Clinical Review

Nail disorders are common among pediatric patients but often are underdiagnosed or misdiagnosed because of their unique disease manifestations. These conditions may severely impact quality of life. There are few nail disease clinical trials that include children. Consequently, most treatment recommendations are based on case series and expert consensus recommendations. We review inflammatory and infectious nail disorders in pediatric patients. By describing characteristics, clinical manifestations, and management approaches for these conditions, we aim to provide guidance to dermatologists in their diagnosis and treatment.

INFLAMMATORY NAIL DISORDERS

Nail Psoriasis

Nail involvement in children with psoriasis is common, with prevalence estimates ranging from 17% to 39.2%.¹ Nail matrix psoriasis may manifest with pitting (large irregular pits) and leukonychia as well as chromonychia and nail plate crumbling. Onycholysis, oil drop spots (salmon patches), and subungual hyperkeratosis can be seen in nail bed psoriasis. Nail pitting is the most frequently observed clinical finding (Figure 1).^2,3 In a cross-sectional multicenter study of 313 children with cutaneous psoriasis in France, nail findings were present in 101 patients (32.3%). There were associations between nail findings and presence of psoriatic arthritis (P=.03), palmoplantar psoriasis (P<.001), and severity of psoriatic disease, defined as use of systemic treatment with phototherapy (psoralen plus UVA, UVB), traditional systemic treatment (acitretin, methotrexate, cyclosporine), or a biologic (P=.003).⁴

Topical steroids and vitamin D analogues may be used with or without occlusion and may be efficacious.⁵ Several case reports describe systemic treatments for psoriasis in children, including methotrexate, acitretin, and apremilast (approved for children 6 years and older for plaque psoriasis by the US Food and Drug Administration [FDA]).² There are 5 biologic drugs currently approved for the treatment of pediatric psoriasis—adalimumab, etanercept, ustekinumab, secukinumab, ixekizumab—and 6 drugs currently undergoing phase 3 studies—brodalumab, guselkumab, risankizumab, tildrakizumab, certolizumab pegol, and deucravacitinib (Table 1).^6-15 Adalimumab is specifically approved for moderate to severe nail psoriasis in adults 18 years and older.

Intralesional steroid injections are sometimes useful in the management of nail matrix psoriasis; however, appropriate patient selection is critical due to the pain associated with the procedure. In a prospective study of 16 children (age range, 9–17 years) with nail psoriasis treated with intralesional triamcinolone (ILTAC) 2.5 to 5 mg/mL every 4 to 8 weeks for a minimum of 3 to 6 months, 9 patients achieved resolution and 6 had improvement of clinical findings.¹⁶ Local adverse events were mild, including injection-site pain (66%), subungual hematoma (n=1), Beau lines (n=1), proximal nail fold hypopigmentation (n=2), and proximal nail fold atrophy (n=2). Because the proximal nail fold in children is thinner than in adults, there may be an increased risk for nail fold hypopigmentation and atrophy in children. Therefore, a maximum ILTAC concentration of 2.5 mg/mL with 0.2 mL maximum volume per nail per session is recommended for children younger than 15 years.¹⁶

Nail Lichen Planus

Nail lichen planus (NLP) is uncommon in children, with few biopsy-proven cases documented in the literature.¹⁷ Common clinical findings are onychorrhexis, nail plate thinning, fissuring, splitting, and atrophy with koilonychia.⁵ Although pterygium development (irreversible nail matrix scarring) is uncommon in pediatric patients, NLP can be progressive and may cause irreversible destruction of the nail matrix and subsequent nail loss, warranting therapeutic intervention.¹⁸

Treatment of NLP may be difficult, as there are no options that work in all patients. Current literature supports the use of systemic corticosteroids or ILTAC for the treatment of NLP; however, recurrence rates can be high. According to an expert consensus paper on NLP treatment, ILTAC may be injected in a concentration of 2.5, 5, or 10 mg/mL according to disease severity.¹⁹ In severe or resistant cases, intramuscular (IM) triamcinolone may be considered, especially if more than 3 nails are affected. A dosage of 0.5 to 1 mg/kg/mo for at least 3 to 6 months is recommended for both children and adults, with 1 mg/kg/mo recommended in the active treatment phase (first 2–3 months).¹⁹ In a retrospective review of 5 pediatric patients with NLP treated with IM triamcinolone 0.5 mg/kg/mo, 3 patients had resolution and 2 improved with treatment.²⁰ In a prospective study of 10 children with NLP, IM triamcinolone at a dosage of 0.5 to 1 mg/kg every 30 days for 3 to 6 months resulted in resolution of nail findings in 9 patients.¹⁷ In a prospective study of 14 pediatric patients with NLP treated with 2.5 to 5 mg/mL of ILTAC, 10 achieved resolution and 3 improved.¹⁶

Intralesional triamcinolone injections may be better suited for teenagers compared to younger children who may be more apprehensive of needles. To minimize pain, it is recommended to inject ILTAC slowly at room temperature, with use of “talkesthesia” and vibration devices, 1% lidocaine, or ethyl chloride spray.¹⁸

Trachyonychia

Trachyonychia is characterized by the presence of sandpaperlike nails. It manifests with brittle thin nails with longitudinal ridging, onychoschizia, and thickened hyperkeratotic cuticles. Trachyonychia typically involves multiple nails, with a peak age of onset between 3 and 12 years.^21,22 There are 2 variants: the opaque type with rough longitudinal ridging, and the shiny variant with opalescent nails and pits that reflect light. The opaque variant is more common and is associated with psoriasis, whereas the shiny variant is less common and is associated with alopecia areata.²³ Although most cases are idiopathic, some are associated with psoriasis and alopecia areata, as previously noted, as well as atopic dermatitis (AD) and lichen planus.^22,24

Fortunately, trachyonychia does not lead to permanent nail damage or pterygium, making treatment primarily focused on addressing functional and cosmetic concerns.²⁴ Spontaneous resolution occurs in approximately 50% of patients. In a prospective study of 11 patients with idiopathic trachyonychia, there was partial improvement in 5 of 9 patients treated with topical steroids, 1 with only petrolatum, and 1 with vitamin supplements. Complete resolution was reported in 1 patient treated with topical steroids.²⁵ Because trachyonychia often is self-resolving, no treatment is required and a conservative approach is strongly recommended.²⁶ Treatment options include topical corticosteroids, tazarotene, and 5-fluorouracil. Intralesional triamcinolone, systemic cyclosporine, retinoids, systemic corticosteroids, and tofacitinib have been described in case reports, though none of these have been shown to be 100% efficacious.²⁴

Nail Lichen Striatus

Lichen striatus involving the nail is uncommon and is characterized by onycholysis, longitudinal ridging, ­splitting, and fraying, as well as what appears to be a subungual tumor. It can encompass the entire nail or may be isolated to a portion of the nail (Figure 2). Usually, a Blaschko-linear array of flesh-colored papules on the more proximal digit directly adjacent to the nail dystrophy will be seen, though nail findings can occur in ­isolation.^27-29 The underlying pathophysiology is not clear; however, one hypothesis is that a triggering event, such as trauma, induces the expression of antigens that elicit a self-limiting immune-mediated response by CD8 T lymphocytes.³⁰

Generally, nail lichen striatus spontaneously resolves in 1 to 2 years without treatment. In a prospective study of 5 patients with nail lichen striatus, the median time to resolution was 22.6 months (range, 10–30 months).³¹ Topical steroids may be used for pruritus. In one case report, a 3-year-old boy with nail lichen striatus of 4 months’ duration was treated with tacrolimus ointment 0.03% daily for 3 months.²⁸

Nail AD

Nail changes with AD may be more common in adults than children or are underreported. In a study of 777 adults with AD, nail dystrophy was present in 124 patients (16%), whereas in a study of 250 pediatric patients with AD (aged 0-2 years), nail dystrophy was present in only 4 patients.^32,33

Periungual inflammation from AD causes the nail changes.³⁴ In a cross-sectional study of 24 pediatric patients with nail dystrophy due to AD, transverse grooves (Beau lines) were present in 25% (6/24), nail pitting in 16.7% (4/24), koilonychia in 16.7% (4/24), trachyonychia in 12.5% (3/24), leukonychia in 12.5% (3/24), brachyonychia in 8.3% (2/24), melanonychia in 8.3% (2/24), onychomadesis in 8.3% (2/24), onychoschizia in 8.3% (2/24), and onycholysis in 8.3% (2/24). There was an association between disease severity and presence of toenail dystrophy (P=.03).³⁵

Topical steroids with or without occlusion can be used to treat nail changes. Although there is limited literature describing the treatment of nail AD in children, a 61-year-old man with nail changes associated with AD achieved resolution with 3 months of treatment with dupilumab.³⁶ Anecdotally, most patients will improve with usual cutaneous AD management.

INFECTIOUS NAIL DISORDERS

Viral Infections

Hand, Foot, and Mouth Disease—Hand, foot, and mouth disease (HFMD) is a common childhood viral infection caused by various enteroviruses, most commonly coxsackievirus A16, with the A6 variant causing more severe disease. Fever and painful vesicles involving the oral mucosa as well as palms and soles give the disease its name. Nail changes are common. In a prospective study involving 130 patients with laboratory-confirmed coxsackievirus CA6 serotype infection, 37% developed onychomadesis vs only 5% of 145 cases with non-CA6 enterovirus infection who developed nail findings. There was an association between CA6 infection and presence of nail changes (P<.001).³⁷

Findings ranging from transverse grooves (Beau lines) to complete nail shedding (onychomadesis)(Figure 3) may be seen.^38,39 Nail findings in HFMD are due to transient inhibition of nail growth and present approximately 3 to 6 weeks after infection.⁴⁰ Onychomadesis is seen in 30% to 68% of patients with HFMD.^37,41,42 Nail findings in HFMD spontaneously resolve with nail growth (2–3 mm per month for fingernails and 1 mm per month for toenails) and do not require specific treatment. Although the appearance of nail changes associated with HFMD can be disturbing, dermatologists can reassure children and their parents that the nails will resolve with the next cycle of growth.

Kawasaki Disease—Kawasaki disease (KD) is a vasculitis primarily affecting children and infants. Although the specific pathogen and pathophysiology is not entirely clear, clinical observations have suggested an infectious cause, most likely a virus.⁴³ In Japan, more than 15,000 cases of KD are documented annually, while approximately 4200 cases are seen in the United States.⁴⁴ In a prospective study from 1984 to 1990, 4 of 26 (15.4%) patients with KD presented with nail manifestations during the late acute phase or early convalescent phase of disease. There were no significant associations between nail dystrophy and severity of KD, such as coronary artery aneurysm.⁴⁵

Nail changes reported in children with KD include onychomadesis, onycholysis, orange-brown chromonychia, splinter hemorrhages, Beau lines, and pincer nails. In a review of nail changes associated with KD from 1980 to 2021, orange-brown transverse chromonychia, which may evolve into transverse leukonychia, was the most common nail finding reported, occurring in 17 of 31 (54.8%) patients.⁴⁴ It has been hypothesized that nail changes may result from blood flow disturbance due to the underlying vasculitis.⁴⁶ Nail changes appear several weeks after the onset of fever and are self-limited. Resolution occurs with nail growth, with no treatment required.

FUNGAL INFECTIONS

Onychomycosis

Onychomycosis is a fungal infection of the nails that occurs in 0.2% to 5.5% of pediatric patients, and its prevalence may be increasing, which may be due to environmental factors or increased rates of diabetes mellitus and obesity in the pediatric population.⁴⁷ Onychomycosis represents 15.5% of nail dystrophies in pediatric patients.⁴⁸ Some dermatologists treat presumptive onychomycosis without confirmation; however, we do not recommend that approach. Because the differential is broad and the duration of treatment is long, mycologic examination (potassium hydroxide preparation, fungal culture, polymerase chain reaction, and/or histopathology) should be obtained to confirm onychomycosis prior to initiation of antifungal management. Family members of affected individuals should be evaluated and treated, if indicated, for onychomycosis and tinea pedis, as household transmission is common.

Currently, there are 2 topical FDA-approved treatments for pediatric onychomycosis in children 6 years and older (Table 2).^49,50 There is a discussion of the need for confirmatory testing for onychomycosis in children, particularly when systemic treatment is prescribed. In a retrospective review of 269 pediatric patients with onychomycosis prescribed terbinafine, 53.5% (n=144) underwent laboratory monitoring of liver function and complete blood cell counts, and 12.5% had grade 1 laboratory abnormalities either prior to (12/144 [8.3%]) or during (6/144 [4.2%]) therapy.⁵¹ Baseline transaminase monitoring is recommended, though subsequent routine laboratory monitoring in healthy children may have limited utility with associated increased costs, incidental findings, and patient discomfort and likely is not needed.⁵¹

Pediatric onychomycosis responds better to topical therapy than adult disease, and pediatric patients do not always require systemic treatment.⁵² Ciclopirox is not FDA approved for the treatment of pediatric onychomycosis, but in a 32-week clinical trial of ciclopirox lacquer 8% use in 40 patients, 77% (27/35) of treated patients achieved mycologic cure. Overall, 71% of treated patients (25/35) vs 22% (2/9) of controls achieved efficacy (defined as investigator global assessment score of 2 or lower).⁵² In an open-label, single-arm clinical trial assessing tavaborole solution 5% applied once daily for 48 weeks for the treatment of toenail onychomycosis in pediatric patients (aged 6–17 years), 36.2% (20/55) of patients achieved mycologic cure, and 8.5% (5/55) achieved complete cure at week 52 with mild or minimal adverse effects.⁵³ In an open-label, phase 4 study of the safety and efficacy of efinaconazole solution 10% applied once daily for 48 weeks in pediatric patients (aged 6 to 16 years) (n=60), 65% (35/60) achieved mycologic cure, 42% (25/60) achieved clinical cure, and 40% (24/60) achieved complete cure at 52 weeks. The most common adverse effects of efina­conazole were local and included ingrown toenail (1/60), application-site dermatitis (1/60), application-site vesicles (1/60), and application-site pain (1/60).⁵⁴

In a systematic review of systemic antifungals for onychomycosis in 151 pediatric patients, itraconazole, fluconazole, griseofulvin, and terbinafine resulted in complete cure rates similar to those of the adult population, with excellent safety profiles.⁵⁵ Depending on the situation, initiation of treatment with topical medications followed by addition of systemic antifungal agents only if needed may be an appropriate course of action.

BACTERIAL INFECTIONS

Acute Paronychia

Acute paronychia is a nail-fold infection that develops after the protective nail barrier has been compromised.⁵⁶ In children, thumb-sucking, nail-biting, frequent oral manipulation of the digits, and poor skin hygiene are risk factors. Acute paronychia also may develop in association with congenital malalignment of the great toenails.⁵⁷

Clinical manifestations include localized pain, erythema, and nail fold edema (Figure 4). Purulent material and abscess formation may ensue. Staphylococcus aureus as well as methicillin-resistant S aureus and Streptococcus pyogenes are classically the most common causes of acute paronychia. Treatment of paronychia is based on severity. In mild cases, warm soaks with topical antibiotics are indicated. Oral antibiotics should be prescribed for more severe presentations. If there is no improvement after 48 hours, surgical drainage is required to facilitate healing.⁵⁶

FINAL THOUGHTS

Inflammatory and infectious nail disorders in children are relatively common and may impact the physical and emotional well-being of young patients. By understanding the distinctive features of these nail disorders in pediatric patients, dermatologists can provide anticipatory guidance and informed treatment options to children and their parents. Further research is needed to expand our understanding of pediatric nail disorders and create targeted therapeutic interventions, particularly for NLP and psoriasis.

Nail disorders are common among pediatric patients but often are underdiagnosed or misdiagnosed because of their unique disease manifestations. These conditions may severely impact quality of life. There are few nail disease clinical trials that include children. Consequently, most treatment recommendations are based on case series and expert consensus recommendations. We review inflammatory and infectious nail disorders in pediatric patients. By describing characteristics, clinical manifestations, and management approaches for these conditions, we aim to provide guidance to dermatologists in their diagnosis and treatment.

INFLAMMATORY NAIL DISORDERS

Nail Psoriasis

Nail involvement in children with psoriasis is common, with prevalence estimates ranging from 17% to 39.2%.¹ Nail matrix psoriasis may manifest with pitting (large irregular pits) and leukonychia as well as chromonychia and nail plate crumbling. Onycholysis, oil drop spots (salmon patches), and subungual hyperkeratosis can be seen in nail bed psoriasis. Nail pitting is the most frequently observed clinical finding (Figure 1).^2,3 In a cross-sectional multicenter study of 313 children with cutaneous psoriasis in France, nail findings were present in 101 patients (32.3%). There were associations between nail findings and presence of psoriatic arthritis (P=.03), palmoplantar psoriasis (P<.001), and severity of psoriatic disease, defined as use of systemic treatment with phototherapy (psoralen plus UVA, UVB), traditional systemic treatment (acitretin, methotrexate, cyclosporine), or a biologic (P=.003).⁴

Topical steroids and vitamin D analogues may be used with or without occlusion and may be efficacious.⁵ Several case reports describe systemic treatments for psoriasis in children, including methotrexate, acitretin, and apremilast (approved for children 6 years and older for plaque psoriasis by the US Food and Drug Administration [FDA]).² There are 5 biologic drugs currently approved for the treatment of pediatric psoriasis—adalimumab, etanercept, ustekinumab, secukinumab, ixekizumab—and 6 drugs currently undergoing phase 3 studies—brodalumab, guselkumab, risankizumab, tildrakizumab, certolizumab pegol, and deucravacitinib (Table 1).^6-15 Adalimumab is specifically approved for moderate to severe nail psoriasis in adults 18 years and older.

Intralesional steroid injections are sometimes useful in the management of nail matrix psoriasis; however, appropriate patient selection is critical due to the pain associated with the procedure. In a prospective study of 16 children (age range, 9–17 years) with nail psoriasis treated with intralesional triamcinolone (ILTAC) 2.5 to 5 mg/mL every 4 to 8 weeks for a minimum of 3 to 6 months, 9 patients achieved resolution and 6 had improvement of clinical findings.¹⁶ Local adverse events were mild, including injection-site pain (66%), subungual hematoma (n=1), Beau lines (n=1), proximal nail fold hypopigmentation (n=2), and proximal nail fold atrophy (n=2). Because the proximal nail fold in children is thinner than in adults, there may be an increased risk for nail fold hypopigmentation and atrophy in children. Therefore, a maximum ILTAC concentration of 2.5 mg/mL with 0.2 mL maximum volume per nail per session is recommended for children younger than 15 years.¹⁶

Nail Lichen Planus

Nail lichen planus (NLP) is uncommon in children, with few biopsy-proven cases documented in the literature.¹⁷ Common clinical findings are onychorrhexis, nail plate thinning, fissuring, splitting, and atrophy with koilonychia.⁵ Although pterygium development (irreversible nail matrix scarring) is uncommon in pediatric patients, NLP can be progressive and may cause irreversible destruction of the nail matrix and subsequent nail loss, warranting therapeutic intervention.¹⁸

Treatment of NLP may be difficult, as there are no options that work in all patients. Current literature supports the use of systemic corticosteroids or ILTAC for the treatment of NLP; however, recurrence rates can be high. According to an expert consensus paper on NLP treatment, ILTAC may be injected in a concentration of 2.5, 5, or 10 mg/mL according to disease severity.¹⁹ In severe or resistant cases, intramuscular (IM) triamcinolone may be considered, especially if more than 3 nails are affected. A dosage of 0.5 to 1 mg/kg/mo for at least 3 to 6 months is recommended for both children and adults, with 1 mg/kg/mo recommended in the active treatment phase (first 2–3 months).¹⁹ In a retrospective review of 5 pediatric patients with NLP treated with IM triamcinolone 0.5 mg/kg/mo, 3 patients had resolution and 2 improved with treatment.²⁰ In a prospective study of 10 children with NLP, IM triamcinolone at a dosage of 0.5 to 1 mg/kg every 30 days for 3 to 6 months resulted in resolution of nail findings in 9 patients.¹⁷ In a prospective study of 14 pediatric patients with NLP treated with 2.5 to 5 mg/mL of ILTAC, 10 achieved resolution and 3 improved.¹⁶

Intralesional triamcinolone injections may be better suited for teenagers compared to younger children who may be more apprehensive of needles. To minimize pain, it is recommended to inject ILTAC slowly at room temperature, with use of “talkesthesia” and vibration devices, 1% lidocaine, or ethyl chloride spray.¹⁸

Trachyonychia

Trachyonychia is characterized by the presence of sandpaperlike nails. It manifests with brittle thin nails with longitudinal ridging, onychoschizia, and thickened hyperkeratotic cuticles. Trachyonychia typically involves multiple nails, with a peak age of onset between 3 and 12 years.^21,22 There are 2 variants: the opaque type with rough longitudinal ridging, and the shiny variant with opalescent nails and pits that reflect light. The opaque variant is more common and is associated with psoriasis, whereas the shiny variant is less common and is associated with alopecia areata.²³ Although most cases are idiopathic, some are associated with psoriasis and alopecia areata, as previously noted, as well as atopic dermatitis (AD) and lichen planus.^22,24

Fortunately, trachyonychia does not lead to permanent nail damage or pterygium, making treatment primarily focused on addressing functional and cosmetic concerns.²⁴ Spontaneous resolution occurs in approximately 50% of patients. In a prospective study of 11 patients with idiopathic trachyonychia, there was partial improvement in 5 of 9 patients treated with topical steroids, 1 with only petrolatum, and 1 with vitamin supplements. Complete resolution was reported in 1 patient treated with topical steroids.²⁵ Because trachyonychia often is self-resolving, no treatment is required and a conservative approach is strongly recommended.²⁶ Treatment options include topical corticosteroids, tazarotene, and 5-fluorouracil. Intralesional triamcinolone, systemic cyclosporine, retinoids, systemic corticosteroids, and tofacitinib have been described in case reports, though none of these have been shown to be 100% efficacious.²⁴

Nail Lichen Striatus

Lichen striatus involving the nail is uncommon and is characterized by onycholysis, longitudinal ridging, ­splitting, and fraying, as well as what appears to be a subungual tumor. It can encompass the entire nail or may be isolated to a portion of the nail (Figure 2). Usually, a Blaschko-linear array of flesh-colored papules on the more proximal digit directly adjacent to the nail dystrophy will be seen, though nail findings can occur in ­isolation.^27-29 The underlying pathophysiology is not clear; however, one hypothesis is that a triggering event, such as trauma, induces the expression of antigens that elicit a self-limiting immune-mediated response by CD8 T lymphocytes.³⁰

Generally, nail lichen striatus spontaneously resolves in 1 to 2 years without treatment. In a prospective study of 5 patients with nail lichen striatus, the median time to resolution was 22.6 months (range, 10–30 months).³¹ Topical steroids may be used for pruritus. In one case report, a 3-year-old boy with nail lichen striatus of 4 months’ duration was treated with tacrolimus ointment 0.03% daily for 3 months.²⁸

Nail AD

Nail changes with AD may be more common in adults than children or are underreported. In a study of 777 adults with AD, nail dystrophy was present in 124 patients (16%), whereas in a study of 250 pediatric patients with AD (aged 0-2 years), nail dystrophy was present in only 4 patients.^32,33

Periungual inflammation from AD causes the nail changes.³⁴ In a cross-sectional study of 24 pediatric patients with nail dystrophy due to AD, transverse grooves (Beau lines) were present in 25% (6/24), nail pitting in 16.7% (4/24), koilonychia in 16.7% (4/24), trachyonychia in 12.5% (3/24), leukonychia in 12.5% (3/24), brachyonychia in 8.3% (2/24), melanonychia in 8.3% (2/24), onychomadesis in 8.3% (2/24), onychoschizia in 8.3% (2/24), and onycholysis in 8.3% (2/24). There was an association between disease severity and presence of toenail dystrophy (P=.03).³⁵

Topical steroids with or without occlusion can be used to treat nail changes. Although there is limited literature describing the treatment of nail AD in children, a 61-year-old man with nail changes associated with AD achieved resolution with 3 months of treatment with dupilumab.³⁶ Anecdotally, most patients will improve with usual cutaneous AD management.

INFECTIOUS NAIL DISORDERS

Viral Infections

Hand, Foot, and Mouth Disease—Hand, foot, and mouth disease (HFMD) is a common childhood viral infection caused by various enteroviruses, most commonly coxsackievirus A16, with the A6 variant causing more severe disease. Fever and painful vesicles involving the oral mucosa as well as palms and soles give the disease its name. Nail changes are common. In a prospective study involving 130 patients with laboratory-confirmed coxsackievirus CA6 serotype infection, 37% developed onychomadesis vs only 5% of 145 cases with non-CA6 enterovirus infection who developed nail findings. There was an association between CA6 infection and presence of nail changes (P<.001).³⁷

Findings ranging from transverse grooves (Beau lines) to complete nail shedding (onychomadesis)(Figure 3) may be seen.^38,39 Nail findings in HFMD are due to transient inhibition of nail growth and present approximately 3 to 6 weeks after infection.⁴⁰ Onychomadesis is seen in 30% to 68% of patients with HFMD.^37,41,42 Nail findings in HFMD spontaneously resolve with nail growth (2–3 mm per month for fingernails and 1 mm per month for toenails) and do not require specific treatment. Although the appearance of nail changes associated with HFMD can be disturbing, dermatologists can reassure children and their parents that the nails will resolve with the next cycle of growth.

Kawasaki Disease—Kawasaki disease (KD) is a vasculitis primarily affecting children and infants. Although the specific pathogen and pathophysiology is not entirely clear, clinical observations have suggested an infectious cause, most likely a virus.⁴³ In Japan, more than 15,000 cases of KD are documented annually, while approximately 4200 cases are seen in the United States.⁴⁴ In a prospective study from 1984 to 1990, 4 of 26 (15.4%) patients with KD presented with nail manifestations during the late acute phase or early convalescent phase of disease. There were no significant associations between nail dystrophy and severity of KD, such as coronary artery aneurysm.⁴⁵

Nail changes reported in children with KD include onychomadesis, onycholysis, orange-brown chromonychia, splinter hemorrhages, Beau lines, and pincer nails. In a review of nail changes associated with KD from 1980 to 2021, orange-brown transverse chromonychia, which may evolve into transverse leukonychia, was the most common nail finding reported, occurring in 17 of 31 (54.8%) patients.⁴⁴ It has been hypothesized that nail changes may result from blood flow disturbance due to the underlying vasculitis.⁴⁶ Nail changes appear several weeks after the onset of fever and are self-limited. Resolution occurs with nail growth, with no treatment required.

FUNGAL INFECTIONS

Onychomycosis

Onychomycosis is a fungal infection of the nails that occurs in 0.2% to 5.5% of pediatric patients, and its prevalence may be increasing, which may be due to environmental factors or increased rates of diabetes mellitus and obesity in the pediatric population.⁴⁷ Onychomycosis represents 15.5% of nail dystrophies in pediatric patients.⁴⁸ Some dermatologists treat presumptive onychomycosis without confirmation; however, we do not recommend that approach. Because the differential is broad and the duration of treatment is long, mycologic examination (potassium hydroxide preparation, fungal culture, polymerase chain reaction, and/or histopathology) should be obtained to confirm onychomycosis prior to initiation of antifungal management. Family members of affected individuals should be evaluated and treated, if indicated, for onychomycosis and tinea pedis, as household transmission is common.

Currently, there are 2 topical FDA-approved treatments for pediatric onychomycosis in children 6 years and older (Table 2).^49,50 There is a discussion of the need for confirmatory testing for onychomycosis in children, particularly when systemic treatment is prescribed. In a retrospective review of 269 pediatric patients with onychomycosis prescribed terbinafine, 53.5% (n=144) underwent laboratory monitoring of liver function and complete blood cell counts, and 12.5% had grade 1 laboratory abnormalities either prior to (12/144 [8.3%]) or during (6/144 [4.2%]) therapy.⁵¹ Baseline transaminase monitoring is recommended, though subsequent routine laboratory monitoring in healthy children may have limited utility with associated increased costs, incidental findings, and patient discomfort and likely is not needed.⁵¹

Pediatric onychomycosis responds better to topical therapy than adult disease, and pediatric patients do not always require systemic treatment.⁵² Ciclopirox is not FDA approved for the treatment of pediatric onychomycosis, but in a 32-week clinical trial of ciclopirox lacquer 8% use in 40 patients, 77% (27/35) of treated patients achieved mycologic cure. Overall, 71% of treated patients (25/35) vs 22% (2/9) of controls achieved efficacy (defined as investigator global assessment score of 2 or lower).⁵² In an open-label, single-arm clinical trial assessing tavaborole solution 5% applied once daily for 48 weeks for the treatment of toenail onychomycosis in pediatric patients (aged 6–17 years), 36.2% (20/55) of patients achieved mycologic cure, and 8.5% (5/55) achieved complete cure at week 52 with mild or minimal adverse effects.⁵³ In an open-label, phase 4 study of the safety and efficacy of efinaconazole solution 10% applied once daily for 48 weeks in pediatric patients (aged 6 to 16 years) (n=60), 65% (35/60) achieved mycologic cure, 42% (25/60) achieved clinical cure, and 40% (24/60) achieved complete cure at 52 weeks. The most common adverse effects of efina­conazole were local and included ingrown toenail (1/60), application-site dermatitis (1/60), application-site vesicles (1/60), and application-site pain (1/60).⁵⁴

In a systematic review of systemic antifungals for onychomycosis in 151 pediatric patients, itraconazole, fluconazole, griseofulvin, and terbinafine resulted in complete cure rates similar to those of the adult population, with excellent safety profiles.⁵⁵ Depending on the situation, initiation of treatment with topical medications followed by addition of systemic antifungal agents only if needed may be an appropriate course of action.

BACTERIAL INFECTIONS

Acute Paronychia

Acute paronychia is a nail-fold infection that develops after the protective nail barrier has been compromised.⁵⁶ In children, thumb-sucking, nail-biting, frequent oral manipulation of the digits, and poor skin hygiene are risk factors. Acute paronychia also may develop in association with congenital malalignment of the great toenails.⁵⁷

Clinical manifestations include localized pain, erythema, and nail fold edema (Figure 4). Purulent material and abscess formation may ensue. Staphylococcus aureus as well as methicillin-resistant S aureus and Streptococcus pyogenes are classically the most common causes of acute paronychia. Treatment of paronychia is based on severity. In mild cases, warm soaks with topical antibiotics are indicated. Oral antibiotics should be prescribed for more severe presentations. If there is no improvement after 48 hours, surgical drainage is required to facilitate healing.⁵⁶

FINAL THOUGHTS

Inflammatory and infectious nail disorders in children are relatively common and may impact the physical and emotional well-being of young patients. By understanding the distinctive features of these nail disorders in pediatric patients, dermatologists can provide anticipatory guidance and informed treatment options to children and their parents. Further research is needed to expand our understanding of pediatric nail disorders and create targeted therapeutic interventions, particularly for NLP and psoriasis.

Nail disorders are common among pediatric patients but often are underdiagnosed or misdiagnosed because of their unique disease manifestations. These conditions may severely impact quality of life. There are few nail disease clinical trials that include children. Consequently, most treatment recommendations are based on case series and expert consensus recommendations. We review inflammatory and infectious nail disorders in pediatric patients. By describing characteristics, clinical manifestations, and management approaches for these conditions, we aim to provide guidance to dermatologists in their diagnosis and treatment.

INFLAMMATORY NAIL DISORDERS

Nail Psoriasis

Nail involvement in children with psoriasis is common, with prevalence estimates ranging from 17% to 39.2%.¹ Nail matrix psoriasis may manifest with pitting (large irregular pits) and leukonychia as well as chromonychia and nail plate crumbling. Onycholysis, oil drop spots (salmon patches), and subungual hyperkeratosis can be seen in nail bed psoriasis. Nail pitting is the most frequently observed clinical finding (Figure 1).^2,3 In a cross-sectional multicenter study of 313 children with cutaneous psoriasis in France, nail findings were present in 101 patients (32.3%). There were associations between nail findings and presence of psoriatic arthritis (P=.03), palmoplantar psoriasis (P<.001), and severity of psoriatic disease, defined as use of systemic treatment with phototherapy (psoralen plus UVA, UVB), traditional systemic treatment (acitretin, methotrexate, cyclosporine), or a biologic (P=.003).⁴

Topical steroids and vitamin D analogues may be used with or without occlusion and may be efficacious.⁵ Several case reports describe systemic treatments for psoriasis in children, including methotrexate, acitretin, and apremilast (approved for children 6 years and older for plaque psoriasis by the US Food and Drug Administration [FDA]).² There are 5 biologic drugs currently approved for the treatment of pediatric psoriasis—adalimumab, etanercept, ustekinumab, secukinumab, ixekizumab—and 6 drugs currently undergoing phase 3 studies—brodalumab, guselkumab, risankizumab, tildrakizumab, certolizumab pegol, and deucravacitinib (Table 1).^6-15 Adalimumab is specifically approved for moderate to severe nail psoriasis in adults 18 years and older.

Intralesional steroid injections are sometimes useful in the management of nail matrix psoriasis; however, appropriate patient selection is critical due to the pain associated with the procedure. In a prospective study of 16 children (age range, 9–17 years) with nail psoriasis treated with intralesional triamcinolone (ILTAC) 2.5 to 5 mg/mL every 4 to 8 weeks for a minimum of 3 to 6 months, 9 patients achieved resolution and 6 had improvement of clinical findings.¹⁶ Local adverse events were mild, including injection-site pain (66%), subungual hematoma (n=1), Beau lines (n=1), proximal nail fold hypopigmentation (n=2), and proximal nail fold atrophy (n=2). Because the proximal nail fold in children is thinner than in adults, there may be an increased risk for nail fold hypopigmentation and atrophy in children. Therefore, a maximum ILTAC concentration of 2.5 mg/mL with 0.2 mL maximum volume per nail per session is recommended for children younger than 15 years.¹⁶

Nail Lichen Planus

Nail lichen planus (NLP) is uncommon in children, with few biopsy-proven cases documented in the literature.¹⁷ Common clinical findings are onychorrhexis, nail plate thinning, fissuring, splitting, and atrophy with koilonychia.⁵ Although pterygium development (irreversible nail matrix scarring) is uncommon in pediatric patients, NLP can be progressive and may cause irreversible destruction of the nail matrix and subsequent nail loss, warranting therapeutic intervention.¹⁸

Treatment of NLP may be difficult, as there are no options that work in all patients. Current literature supports the use of systemic corticosteroids or ILTAC for the treatment of NLP; however, recurrence rates can be high. According to an expert consensus paper on NLP treatment, ILTAC may be injected in a concentration of 2.5, 5, or 10 mg/mL according to disease severity.¹⁹ In severe or resistant cases, intramuscular (IM) triamcinolone may be considered, especially if more than 3 nails are affected. A dosage of 0.5 to 1 mg/kg/mo for at least 3 to 6 months is recommended for both children and adults, with 1 mg/kg/mo recommended in the active treatment phase (first 2–3 months).¹⁹ In a retrospective review of 5 pediatric patients with NLP treated with IM triamcinolone 0.5 mg/kg/mo, 3 patients had resolution and 2 improved with treatment.²⁰ In a prospective study of 10 children with NLP, IM triamcinolone at a dosage of 0.5 to 1 mg/kg every 30 days for 3 to 6 months resulted in resolution of nail findings in 9 patients.¹⁷ In a prospective study of 14 pediatric patients with NLP treated with 2.5 to 5 mg/mL of ILTAC, 10 achieved resolution and 3 improved.¹⁶

Intralesional triamcinolone injections may be better suited for teenagers compared to younger children who may be more apprehensive of needles. To minimize pain, it is recommended to inject ILTAC slowly at room temperature, with use of “talkesthesia” and vibration devices, 1% lidocaine, or ethyl chloride spray.¹⁸

Trachyonychia

Trachyonychia is characterized by the presence of sandpaperlike nails. It manifests with brittle thin nails with longitudinal ridging, onychoschizia, and thickened hyperkeratotic cuticles. Trachyonychia typically involves multiple nails, with a peak age of onset between 3 and 12 years.^21,22 There are 2 variants: the opaque type with rough longitudinal ridging, and the shiny variant with opalescent nails and pits that reflect light. The opaque variant is more common and is associated with psoriasis, whereas the shiny variant is less common and is associated with alopecia areata.²³ Although most cases are idiopathic, some are associated with psoriasis and alopecia areata, as previously noted, as well as atopic dermatitis (AD) and lichen planus.^22,24

Fortunately, trachyonychia does not lead to permanent nail damage or pterygium, making treatment primarily focused on addressing functional and cosmetic concerns.²⁴ Spontaneous resolution occurs in approximately 50% of patients. In a prospective study of 11 patients with idiopathic trachyonychia, there was partial improvement in 5 of 9 patients treated with topical steroids, 1 with only petrolatum, and 1 with vitamin supplements. Complete resolution was reported in 1 patient treated with topical steroids.²⁵ Because trachyonychia often is self-resolving, no treatment is required and a conservative approach is strongly recommended.²⁶ Treatment options include topical corticosteroids, tazarotene, and 5-fluorouracil. Intralesional triamcinolone, systemic cyclosporine, retinoids, systemic corticosteroids, and tofacitinib have been described in case reports, though none of these have been shown to be 100% efficacious.²⁴

Nail Lichen Striatus

Lichen striatus involving the nail is uncommon and is characterized by onycholysis, longitudinal ridging, ­splitting, and fraying, as well as what appears to be a subungual tumor. It can encompass the entire nail or may be isolated to a portion of the nail (Figure 2). Usually, a Blaschko-linear array of flesh-colored papules on the more proximal digit directly adjacent to the nail dystrophy will be seen, though nail findings can occur in ­isolation.^27-29 The underlying pathophysiology is not clear; however, one hypothesis is that a triggering event, such as trauma, induces the expression of antigens that elicit a self-limiting immune-mediated response by CD8 T lymphocytes.³⁰

Generally, nail lichen striatus spontaneously resolves in 1 to 2 years without treatment. In a prospective study of 5 patients with nail lichen striatus, the median time to resolution was 22.6 months (range, 10–30 months).³¹ Topical steroids may be used for pruritus. In one case report, a 3-year-old boy with nail lichen striatus of 4 months’ duration was treated with tacrolimus ointment 0.03% daily for 3 months.²⁸

Nail AD

Nail changes with AD may be more common in adults than children or are underreported. In a study of 777 adults with AD, nail dystrophy was present in 124 patients (16%), whereas in a study of 250 pediatric patients with AD (aged 0-2 years), nail dystrophy was present in only 4 patients.^32,33

Periungual inflammation from AD causes the nail changes.³⁴ In a cross-sectional study of 24 pediatric patients with nail dystrophy due to AD, transverse grooves (Beau lines) were present in 25% (6/24), nail pitting in 16.7% (4/24), koilonychia in 16.7% (4/24), trachyonychia in 12.5% (3/24), leukonychia in 12.5% (3/24), brachyonychia in 8.3% (2/24), melanonychia in 8.3% (2/24), onychomadesis in 8.3% (2/24), onychoschizia in 8.3% (2/24), and onycholysis in 8.3% (2/24). There was an association between disease severity and presence of toenail dystrophy (P=.03).³⁵

Topical steroids with or without occlusion can be used to treat nail changes. Although there is limited literature describing the treatment of nail AD in children, a 61-year-old man with nail changes associated with AD achieved resolution with 3 months of treatment with dupilumab.³⁶ Anecdotally, most patients will improve with usual cutaneous AD management.

INFECTIOUS NAIL DISORDERS

Viral Infections

Hand, Foot, and Mouth Disease—Hand, foot, and mouth disease (HFMD) is a common childhood viral infection caused by various enteroviruses, most commonly coxsackievirus A16, with the A6 variant causing more severe disease. Fever and painful vesicles involving the oral mucosa as well as palms and soles give the disease its name. Nail changes are common. In a prospective study involving 130 patients with laboratory-confirmed coxsackievirus CA6 serotype infection, 37% developed onychomadesis vs only 5% of 145 cases with non-CA6 enterovirus infection who developed nail findings. There was an association between CA6 infection and presence of nail changes (P<.001).³⁷

Findings ranging from transverse grooves (Beau lines) to complete nail shedding (onychomadesis)(Figure 3) may be seen.^38,39 Nail findings in HFMD are due to transient inhibition of nail growth and present approximately 3 to 6 weeks after infection.⁴⁰ Onychomadesis is seen in 30% to 68% of patients with HFMD.^37,41,42 Nail findings in HFMD spontaneously resolve with nail growth (2–3 mm per month for fingernails and 1 mm per month for toenails) and do not require specific treatment. Although the appearance of nail changes associated with HFMD can be disturbing, dermatologists can reassure children and their parents that the nails will resolve with the next cycle of growth.

Kawasaki Disease—Kawasaki disease (KD) is a vasculitis primarily affecting children and infants. Although the specific pathogen and pathophysiology is not entirely clear, clinical observations have suggested an infectious cause, most likely a virus.⁴³ In Japan, more than 15,000 cases of KD are documented annually, while approximately 4200 cases are seen in the United States.⁴⁴ In a prospective study from 1984 to 1990, 4 of 26 (15.4%) patients with KD presented with nail manifestations during the late acute phase or early convalescent phase of disease. There were no significant associations between nail dystrophy and severity of KD, such as coronary artery aneurysm.⁴⁵

Nail changes reported in children with KD include onychomadesis, onycholysis, orange-brown chromonychia, splinter hemorrhages, Beau lines, and pincer nails. In a review of nail changes associated with KD from 1980 to 2021, orange-brown transverse chromonychia, which may evolve into transverse leukonychia, was the most common nail finding reported, occurring in 17 of 31 (54.8%) patients.⁴⁴ It has been hypothesized that nail changes may result from blood flow disturbance due to the underlying vasculitis.⁴⁶ Nail changes appear several weeks after the onset of fever and are self-limited. Resolution occurs with nail growth, with no treatment required.

FUNGAL INFECTIONS

Onychomycosis

Onychomycosis is a fungal infection of the nails that occurs in 0.2% to 5.5% of pediatric patients, and its prevalence may be increasing, which may be due to environmental factors or increased rates of diabetes mellitus and obesity in the pediatric population.⁴⁷ Onychomycosis represents 15.5% of nail dystrophies in pediatric patients.⁴⁸ Some dermatologists treat presumptive onychomycosis without confirmation; however, we do not recommend that approach. Because the differential is broad and the duration of treatment is long, mycologic examination (potassium hydroxide preparation, fungal culture, polymerase chain reaction, and/or histopathology) should be obtained to confirm onychomycosis prior to initiation of antifungal management. Family members of affected individuals should be evaluated and treated, if indicated, for onychomycosis and tinea pedis, as household transmission is common.

Currently, there are 2 topical FDA-approved treatments for pediatric onychomycosis in children 6 years and older (Table 2).^49,50 There is a discussion of the need for confirmatory testing for onychomycosis in children, particularly when systemic treatment is prescribed. In a retrospective review of 269 pediatric patients with onychomycosis prescribed terbinafine, 53.5% (n=144) underwent laboratory monitoring of liver function and complete blood cell counts, and 12.5% had grade 1 laboratory abnormalities either prior to (12/144 [8.3%]) or during (6/144 [4.2%]) therapy.⁵¹ Baseline transaminase monitoring is recommended, though subsequent routine laboratory monitoring in healthy children may have limited utility with associated increased costs, incidental findings, and patient discomfort and likely is not needed.⁵¹

Pediatric onychomycosis responds better to topical therapy than adult disease, and pediatric patients do not always require systemic treatment.⁵² Ciclopirox is not FDA approved for the treatment of pediatric onychomycosis, but in a 32-week clinical trial of ciclopirox lacquer 8% use in 40 patients, 77% (27/35) of treated patients achieved mycologic cure. Overall, 71% of treated patients (25/35) vs 22% (2/9) of controls achieved efficacy (defined as investigator global assessment score of 2 or lower).⁵² In an open-label, single-arm clinical trial assessing tavaborole solution 5% applied once daily for 48 weeks for the treatment of toenail onychomycosis in pediatric patients (aged 6–17 years), 36.2% (20/55) of patients achieved mycologic cure, and 8.5% (5/55) achieved complete cure at week 52 with mild or minimal adverse effects.⁵³ In an open-label, phase 4 study of the safety and efficacy of efinaconazole solution 10% applied once daily for 48 weeks in pediatric patients (aged 6 to 16 years) (n=60), 65% (35/60) achieved mycologic cure, 42% (25/60) achieved clinical cure, and 40% (24/60) achieved complete cure at 52 weeks. The most common adverse effects of efina­conazole were local and included ingrown toenail (1/60), application-site dermatitis (1/60), application-site vesicles (1/60), and application-site pain (1/60).⁵⁴

In a systematic review of systemic antifungals for onychomycosis in 151 pediatric patients, itraconazole, fluconazole, griseofulvin, and terbinafine resulted in complete cure rates similar to those of the adult population, with excellent safety profiles.⁵⁵ Depending on the situation, initiation of treatment with topical medications followed by addition of systemic antifungal agents only if needed may be an appropriate course of action.

BACTERIAL INFECTIONS

Acute Paronychia

Acute paronychia is a nail-fold infection that develops after the protective nail barrier has been compromised.⁵⁶ In children, thumb-sucking, nail-biting, frequent oral manipulation of the digits, and poor skin hygiene are risk factors. Acute paronychia also may develop in association with congenital malalignment of the great toenails.⁵⁷

Clinical manifestations include localized pain, erythema, and nail fold edema (Figure 4). Purulent material and abscess formation may ensue. Staphylococcus aureus as well as methicillin-resistant S aureus and Streptococcus pyogenes are classically the most common causes of acute paronychia. Treatment of paronychia is based on severity. In mild cases, warm soaks with topical antibiotics are indicated. Oral antibiotics should be prescribed for more severe presentations. If there is no improvement after 48 hours, surgical drainage is required to facilitate healing.⁵⁶

FINAL THOUGHTS

Inflammatory and infectious nail disorders in children are relatively common and may impact the physical and emotional well-being of young patients. By understanding the distinctive features of these nail disorders in pediatric patients, dermatologists can provide anticipatory guidance and informed treatment options to children and their parents. Further research is needed to expand our understanding of pediatric nail disorders and create targeted therapeutic interventions, particularly for NLP and psoriasis.

Bacterial and nonbacterial components of the gut microbiome and their function can accurately differentiate children with autism spectrum disorder (ASD) from neurotypical children, new research shows. 

The findings could form the basis for development of a noninvasive diagnostic test for ASD and also provide novel therapeutic targets, wrote investigators, led by Siew C. Ng, MBBS, PhD, with the Microbiota I-Center (MagIC), the Chinese University of Hong Kong.

Their study was published online in Nature Microbiology. 
 

Beyond Bacteria

The gut microbiome has been shown to play a central role in modulating the gut-brain axis, potentially influencing the development of ASD. 

However, most studies in ASD have focused on the bacterial component of the microbiome. Whether nonbacterial microorganisms (such as gut archaea, fungi, and viruses) or function of the gut microbiome are altered in ASD remains unclear. 

To investigate, the researchers performed metagenomic sequencing on fecal samples from 1627 boys and girls aged 1-13 years with and without ASD from five cohorts in China. 

After controlling for diet, medication, and comorbidity, they identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways that were altered in children with ASD. 

Machine-learning models using single-kingdom panels (archaea, bacteria, fungi, viruses) achieved area under the curve (AUC) values ranging from 0.68 to 0.87 in differentiating children with ASD from neurotypical control children. 

A model based on a panel of 31 multikingdom and functional markers achieved “high predictive value” for ASD, achieving an AUC of 0.91, with comparable performance among boys and girls. 

“The reproducible performance of the models across ages, sexes, and cohorts highlights their potential as promising diagnostic tools for ASD,” the investigators wrote. 

They also noted that the accuracy of the model was largely driven by the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which were less abundant in children with ASD, and may serve as therapeutic targets. 
 

‘Exciting’ Possibilities 

“This study broadens our understanding by including fungi, archaea, and viruses, where previous studies have largely focused on the role of gut bacteria in autism,” Bhismadev Chakrabarti, PhD, research director of the Centre for Autism at the University of Reading, United Kingdom, said in a statement from the nonprofit UK Science Media Centre. 

“The results are broadly in line with previous studies that show reduced microbial diversity in autistic individuals. It also examines one of the largest samples seen in a study like this, which further strengthens the results,” Dr. Chakrabarti added. 

He said this research may provide “new ways of detecting autism, if microbial markers turn out to strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple behavioral assessments could help address the detection gap.

“One limitation of this data is that it cannot assess any causal role for the microbiota in the development of autism,” Dr. Chakrabarti noted. 

This study was supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China, The D. H. Chen Foundation, and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program. Dr. Ng has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie; has received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; is a scientific cofounder and shareholder of GenieBiome; receives patent royalties through her affiliated institutions; and is named as a co-inventor of patent applications that cover the therapeutic and diagnostic use of microbiome. Dr. Chakrabarti has no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Bacterial and nonbacterial components of the gut microbiome and their function can accurately differentiate children with autism spectrum disorder (ASD) from neurotypical children, new research shows. 

The findings could form the basis for development of a noninvasive diagnostic test for ASD and also provide novel therapeutic targets, wrote investigators, led by Siew C. Ng, MBBS, PhD, with the Microbiota I-Center (MagIC), the Chinese University of Hong Kong.

Their study was published online in Nature Microbiology. 
 

Beyond Bacteria

The gut microbiome has been shown to play a central role in modulating the gut-brain axis, potentially influencing the development of ASD. 

However, most studies in ASD have focused on the bacterial component of the microbiome. Whether nonbacterial microorganisms (such as gut archaea, fungi, and viruses) or function of the gut microbiome are altered in ASD remains unclear. 

To investigate, the researchers performed metagenomic sequencing on fecal samples from 1627 boys and girls aged 1-13 years with and without ASD from five cohorts in China. 

After controlling for diet, medication, and comorbidity, they identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways that were altered in children with ASD. 

Machine-learning models using single-kingdom panels (archaea, bacteria, fungi, viruses) achieved area under the curve (AUC) values ranging from 0.68 to 0.87 in differentiating children with ASD from neurotypical control children. 

A model based on a panel of 31 multikingdom and functional markers achieved “high predictive value” for ASD, achieving an AUC of 0.91, with comparable performance among boys and girls. 

“The reproducible performance of the models across ages, sexes, and cohorts highlights their potential as promising diagnostic tools for ASD,” the investigators wrote. 

They also noted that the accuracy of the model was largely driven by the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which were less abundant in children with ASD, and may serve as therapeutic targets. 
 

‘Exciting’ Possibilities 

“This study broadens our understanding by including fungi, archaea, and viruses, where previous studies have largely focused on the role of gut bacteria in autism,” Bhismadev Chakrabarti, PhD, research director of the Centre for Autism at the University of Reading, United Kingdom, said in a statement from the nonprofit UK Science Media Centre. 

“The results are broadly in line with previous studies that show reduced microbial diversity in autistic individuals. It also examines one of the largest samples seen in a study like this, which further strengthens the results,” Dr. Chakrabarti added. 

He said this research may provide “new ways of detecting autism, if microbial markers turn out to strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple behavioral assessments could help address the detection gap.

“One limitation of this data is that it cannot assess any causal role for the microbiota in the development of autism,” Dr. Chakrabarti noted. 

This study was supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China, The D. H. Chen Foundation, and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program. Dr. Ng has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie; has received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; is a scientific cofounder and shareholder of GenieBiome; receives patent royalties through her affiliated institutions; and is named as a co-inventor of patent applications that cover the therapeutic and diagnostic use of microbiome. Dr. Chakrabarti has no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Bacterial and nonbacterial components of the gut microbiome and their function can accurately differentiate children with autism spectrum disorder (ASD) from neurotypical children, new research shows. 

The findings could form the basis for development of a noninvasive diagnostic test for ASD and also provide novel therapeutic targets, wrote investigators, led by Siew C. Ng, MBBS, PhD, with the Microbiota I-Center (MagIC), the Chinese University of Hong Kong.

Their study was published online in Nature Microbiology. 
 

Beyond Bacteria

The gut microbiome has been shown to play a central role in modulating the gut-brain axis, potentially influencing the development of ASD. 

However, most studies in ASD have focused on the bacterial component of the microbiome. Whether nonbacterial microorganisms (such as gut archaea, fungi, and viruses) or function of the gut microbiome are altered in ASD remains unclear. 

To investigate, the researchers performed metagenomic sequencing on fecal samples from 1627 boys and girls aged 1-13 years with and without ASD from five cohorts in China. 

After controlling for diet, medication, and comorbidity, they identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways that were altered in children with ASD. 

Machine-learning models using single-kingdom panels (archaea, bacteria, fungi, viruses) achieved area under the curve (AUC) values ranging from 0.68 to 0.87 in differentiating children with ASD from neurotypical control children. 

A model based on a panel of 31 multikingdom and functional markers achieved “high predictive value” for ASD, achieving an AUC of 0.91, with comparable performance among boys and girls. 

“The reproducible performance of the models across ages, sexes, and cohorts highlights their potential as promising diagnostic tools for ASD,” the investigators wrote. 

They also noted that the accuracy of the model was largely driven by the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which were less abundant in children with ASD, and may serve as therapeutic targets. 
 

‘Exciting’ Possibilities 

“This study broadens our understanding by including fungi, archaea, and viruses, where previous studies have largely focused on the role of gut bacteria in autism,” Bhismadev Chakrabarti, PhD, research director of the Centre for Autism at the University of Reading, United Kingdom, said in a statement from the nonprofit UK Science Media Centre. 

“The results are broadly in line with previous studies that show reduced microbial diversity in autistic individuals. It also examines one of the largest samples seen in a study like this, which further strengthens the results,” Dr. Chakrabarti added. 

He said this research may provide “new ways of detecting autism, if microbial markers turn out to strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple behavioral assessments could help address the detection gap.

“One limitation of this data is that it cannot assess any causal role for the microbiota in the development of autism,” Dr. Chakrabarti noted. 

This study was supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China, The D. H. Chen Foundation, and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program. Dr. Ng has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie; has received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; is a scientific cofounder and shareholder of GenieBiome; receives patent royalties through her affiliated institutions; and is named as a co-inventor of patent applications that cover the therapeutic and diagnostic use of microbiome. Dr. Chakrabarti has no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

TOPLINE:

Combat exposure is strongly associated with chronic pain in active-duty servicewomen and female civilian dependents of military personnel on active duty; a lower socioeconomic status and mental health conditions further increased the likelihood of chronic pain.

METHODOLOGY:

• Researchers analyzed claims data from the Military Health System to identify chronic pain diagnoses among active-duty servicewomen and civilian dependents of individuals on active duty.
• A total of 3,473,401 individuals (median age, 29 years) were included in the study, with 644,478 active-duty servicewomen and 2,828,923 civilian dependents.
• The study compared the incidence of chronic pain during 2006-2013, a period of heightened deployment intensity, with 2014-2020, a period of reduced deployment intensity.
• The primary outcome was the diagnosis of chronic pain.

TAKEAWAY:

• Active-duty servicewomen in the years 2006-2013 had a 53% increase in the odds of reporting chronic pain compared with those in the period between 2014 and 2020 (odds ratio [OR], 1.53; 95% CI, 1.48-1.58).
• Civilian dependents in the years 2006-2013 had a 96% increase in the odds of chronic pain compared with those in the later interval (OR, 1.96; 95% CI, 1.93-1.99).
• In 2006-2013, junior enlisted active-duty servicewomen had nearly a twofold increase in the odds of chronic pain (OR, 1.95; 95% CI, 1.83-2.09), while junior enlisted dependents had more than a threefold increase in the odds of chronic pain (OR, 3.05; 95% CI, 2.87-3.25) compared with senior officers.
• Comorbid mental conditions also were associated with an increased odds of reporting chronic pain (OR, 1.67; 95% CI, 1.65-1.69).

IN PRACTICE:

“The potential for higher rates of chronic pain in women veterans has been theorized to result from differences in support structures, family conflict, coping strategies, stress regulation, and exposure to military sexual trauma,” the authors wrote. “Our results suggest that these contributing factors may carry over to the women dependents of combat veterans in addition, indicating a line of research that requires urgent further exploration.”

SOURCE:

The study was led by Andrew J. Schoenfeld, MD, MSc, of the Center for Surgery and Public Health, Department of Orthopaedic Surgery at Brigham and Women’s Hospital and Harvard Medical School, in Boston. It was published online on July 5, 2024, in JAMA Network Open.

LIMITATIONS:

This study relied on claims-based data, which may have issues with coding accuracy and limited clinical granularity. The population size reduced over time owing to military downsizing, which could impact the findings. The prevalence of chronic pain in the population was likely underestimated because individuals who did not report symptoms or were diagnosed after separation from service were not identified.

DISCLOSURES:

This study was funded by the US Department of Defense. The lead author reported receiving grants and personal fees, serving as the editor-in-chief for Spine, acting as a consultant, and having other ties with various sources outside the submitted work.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Combat exposure is strongly associated with chronic pain in active-duty servicewomen and female civilian dependents of military personnel on active duty; a lower socioeconomic status and mental health conditions further increased the likelihood of chronic pain.

METHODOLOGY:

• Researchers analyzed claims data from the Military Health System to identify chronic pain diagnoses among active-duty servicewomen and civilian dependents of individuals on active duty.
• A total of 3,473,401 individuals (median age, 29 years) were included in the study, with 644,478 active-duty servicewomen and 2,828,923 civilian dependents.
• The study compared the incidence of chronic pain during 2006-2013, a period of heightened deployment intensity, with 2014-2020, a period of reduced deployment intensity.
• The primary outcome was the diagnosis of chronic pain.

TAKEAWAY:

• Active-duty servicewomen in the years 2006-2013 had a 53% increase in the odds of reporting chronic pain compared with those in the period between 2014 and 2020 (odds ratio [OR], 1.53; 95% CI, 1.48-1.58).
• Civilian dependents in the years 2006-2013 had a 96% increase in the odds of chronic pain compared with those in the later interval (OR, 1.96; 95% CI, 1.93-1.99).
• In 2006-2013, junior enlisted active-duty servicewomen had nearly a twofold increase in the odds of chronic pain (OR, 1.95; 95% CI, 1.83-2.09), while junior enlisted dependents had more than a threefold increase in the odds of chronic pain (OR, 3.05; 95% CI, 2.87-3.25) compared with senior officers.
• Comorbid mental conditions also were associated with an increased odds of reporting chronic pain (OR, 1.67; 95% CI, 1.65-1.69).

IN PRACTICE:

“The potential for higher rates of chronic pain in women veterans has been theorized to result from differences in support structures, family conflict, coping strategies, stress regulation, and exposure to military sexual trauma,” the authors wrote. “Our results suggest that these contributing factors may carry over to the women dependents of combat veterans in addition, indicating a line of research that requires urgent further exploration.”

SOURCE:

The study was led by Andrew J. Schoenfeld, MD, MSc, of the Center for Surgery and Public Health, Department of Orthopaedic Surgery at Brigham and Women’s Hospital and Harvard Medical School, in Boston. It was published online on July 5, 2024, in JAMA Network Open.

LIMITATIONS:

This study relied on claims-based data, which may have issues with coding accuracy and limited clinical granularity. The population size reduced over time owing to military downsizing, which could impact the findings. The prevalence of chronic pain in the population was likely underestimated because individuals who did not report symptoms or were diagnosed after separation from service were not identified.

DISCLOSURES:

This study was funded by the US Department of Defense. The lead author reported receiving grants and personal fees, serving as the editor-in-chief for Spine, acting as a consultant, and having other ties with various sources outside the submitted work.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Combat exposure is strongly associated with chronic pain in active-duty servicewomen and female civilian dependents of military personnel on active duty; a lower socioeconomic status and mental health conditions further increased the likelihood of chronic pain.

METHODOLOGY:

• Researchers analyzed claims data from the Military Health System to identify chronic pain diagnoses among active-duty servicewomen and civilian dependents of individuals on active duty.
• A total of 3,473,401 individuals (median age, 29 years) were included in the study, with 644,478 active-duty servicewomen and 2,828,923 civilian dependents.
• The study compared the incidence of chronic pain during 2006-2013, a period of heightened deployment intensity, with 2014-2020, a period of reduced deployment intensity.
• The primary outcome was the diagnosis of chronic pain.

TAKEAWAY:

• Active-duty servicewomen in the years 2006-2013 had a 53% increase in the odds of reporting chronic pain compared with those in the period between 2014 and 2020 (odds ratio [OR], 1.53; 95% CI, 1.48-1.58).
• Civilian dependents in the years 2006-2013 had a 96% increase in the odds of chronic pain compared with those in the later interval (OR, 1.96; 95% CI, 1.93-1.99).
• In 2006-2013, junior enlisted active-duty servicewomen had nearly a twofold increase in the odds of chronic pain (OR, 1.95; 95% CI, 1.83-2.09), while junior enlisted dependents had more than a threefold increase in the odds of chronic pain (OR, 3.05; 95% CI, 2.87-3.25) compared with senior officers.
• Comorbid mental conditions also were associated with an increased odds of reporting chronic pain (OR, 1.67; 95% CI, 1.65-1.69).

IN PRACTICE:

“The potential for higher rates of chronic pain in women veterans has been theorized to result from differences in support structures, family conflict, coping strategies, stress regulation, and exposure to military sexual trauma,” the authors wrote. “Our results suggest that these contributing factors may carry over to the women dependents of combat veterans in addition, indicating a line of research that requires urgent further exploration.”

SOURCE:

The study was led by Andrew J. Schoenfeld, MD, MSc, of the Center for Surgery and Public Health, Department of Orthopaedic Surgery at Brigham and Women’s Hospital and Harvard Medical School, in Boston. It was published online on July 5, 2024, in JAMA Network Open.

LIMITATIONS:

This study relied on claims-based data, which may have issues with coding accuracy and limited clinical granularity. The population size reduced over time owing to military downsizing, which could impact the findings. The prevalence of chronic pain in the population was likely underestimated because individuals who did not report symptoms or were diagnosed after separation from service were not identified.

DISCLOSURES:

This study was funded by the US Department of Defense. The lead author reported receiving grants and personal fees, serving as the editor-in-chief for Spine, acting as a consultant, and having other ties with various sources outside the submitted work.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A higher intake of ultraprocessed foods increases the risk for systemic lupus erythematosus (SLE) by over 50% in women. The risk doubled in those with anti–double-stranded DNA antibodies.

METHODOLOGY:

• Researchers assessed 204,175 women from two Nurses’ Health Study cohorts from 1984 to 2016.
• Participants completed semiquantitative food frequency questionnaires every 4 years for the assessment of dietary intake.
• Incident SLE cases were self-reported and confirmed using medical records, with 212 cases identified.

TAKEAWAY:

• A higher cumulative average daily intake of ultraprocessed foods was associated with a 56% increased risk for SLE (95% confidence interval [CI], 1.04-2.32).
• The risk for anti–double-stranded DNA antibody-positive SLE was more than doubled (hazard ratio, 2.05; 95% CI, 1.15-3.65).
• Sugar or artificially sweetened beverages were associated with a 45% increased risk for SLE (95% CI, 1.01-2.09).
• No significant interactions with body mass index were observed in the association between ultraprocessed food intake and SLE.

IN PRACTICE:

This study is too preliminary to have practical application.

SOURCE:

The study was led by Sinara Rossato, PhD, Harvard T.H. Chan School of Public Health, Boston. It was published online in Arthritis Care & Research.

LIMITATIONS:

The study’s generalizability is limited due to the predominantly White female population of registered nurses. The relatively high baseline age of participants may not fully capture the peak incidence age range for SLE. The observational nature of the study cannot establish causality between ultraprocessed food intake and SLE risk.

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors did not declare any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A higher intake of ultraprocessed foods increases the risk for systemic lupus erythematosus (SLE) by over 50% in women. The risk doubled in those with anti–double-stranded DNA antibodies.

METHODOLOGY:

• Researchers assessed 204,175 women from two Nurses’ Health Study cohorts from 1984 to 2016.
• Participants completed semiquantitative food frequency questionnaires every 4 years for the assessment of dietary intake.
• Incident SLE cases were self-reported and confirmed using medical records, with 212 cases identified.

TAKEAWAY:

• A higher cumulative average daily intake of ultraprocessed foods was associated with a 56% increased risk for SLE (95% confidence interval [CI], 1.04-2.32).
• The risk for anti–double-stranded DNA antibody-positive SLE was more than doubled (hazard ratio, 2.05; 95% CI, 1.15-3.65).
• Sugar or artificially sweetened beverages were associated with a 45% increased risk for SLE (95% CI, 1.01-2.09).
• No significant interactions with body mass index were observed in the association between ultraprocessed food intake and SLE.

IN PRACTICE:

This study is too preliminary to have practical application.

SOURCE:

The study was led by Sinara Rossato, PhD, Harvard T.H. Chan School of Public Health, Boston. It was published online in Arthritis Care & Research.

LIMITATIONS:

The study’s generalizability is limited due to the predominantly White female population of registered nurses. The relatively high baseline age of participants may not fully capture the peak incidence age range for SLE. The observational nature of the study cannot establish causality between ultraprocessed food intake and SLE risk.

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors did not declare any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A higher intake of ultraprocessed foods increases the risk for systemic lupus erythematosus (SLE) by over 50% in women. The risk doubled in those with anti–double-stranded DNA antibodies.

METHODOLOGY:

• Researchers assessed 204,175 women from two Nurses’ Health Study cohorts from 1984 to 2016.
• Participants completed semiquantitative food frequency questionnaires every 4 years for the assessment of dietary intake.
• Incident SLE cases were self-reported and confirmed using medical records, with 212 cases identified.

TAKEAWAY:

• A higher cumulative average daily intake of ultraprocessed foods was associated with a 56% increased risk for SLE (95% confidence interval [CI], 1.04-2.32).
• The risk for anti–double-stranded DNA antibody-positive SLE was more than doubled (hazard ratio, 2.05; 95% CI, 1.15-3.65).
• Sugar or artificially sweetened beverages were associated with a 45% increased risk for SLE (95% CI, 1.01-2.09).
• No significant interactions with body mass index were observed in the association between ultraprocessed food intake and SLE.

IN PRACTICE:

This study is too preliminary to have practical application.

SOURCE:

The study was led by Sinara Rossato, PhD, Harvard T.H. Chan School of Public Health, Boston. It was published online in Arthritis Care & Research.

LIMITATIONS:

The study’s generalizability is limited due to the predominantly White female population of registered nurses. The relatively high baseline age of participants may not fully capture the peak incidence age range for SLE. The observational nature of the study cannot establish causality between ultraprocessed food intake and SLE risk.

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors did not declare any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

A Seattle plastic surgeon who illegally restricted patients from posting negative reviews about his practice and directed his staff to post fake positive reviews will pay $5 million for violating Washington state’s consumer protection law.

According to a July 1 consent decree, Javad Sajan, MD, and his practice Allure Esthetic must pay $1.5 million in restitution to 21,000 patients and $3.5 million to the state for manipulation of patient ratings.

The settlement resolves a federal lawsuit brought by Washington State Attorney General Bob Ferguson that accused the doctor of illegally suppressing patients’ negative reviews by “forcing” them to sign nondisclosure agreements (NDAs) before they received care. In an April decision, US District Judge Ricardo S. Martinez sided with the state, ruling that Allure Esthetic’s actions violated the federal Consumer Review Fairness Act (CRFA).

“Writing a truthful review about a business should not subject you to threats or intimidation,” Mr. Ferguson said in a July 2 statement. “Consumers rely on reviews when determining who to trust, especially services that affect their health and safety. This resolution holds Allure accountable for brazenly violating that trust — and the law — and ensures the clinic stops its harmful conduct.”

In court documents, Dr. Sajan’s attorneys had argued that the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them.

The surgeon’s practice is “pleased to have resolved its case with the Attorney General’s Office,” according to a statement provided by Dr. Sajan’s attorney. “The cooperative settlement, while not admitting fault and resolving claims asserted by both sides, allows Allure Esthetic to continue to focus on its core mission of providing compassionate care to patients and serving the community. The decision to settle was not an easy one, but it was necessary to allocate time and resources where they matter most — the patients.” 

The dispute stemmed from NDAs that Dr. Sajan’s practice required patients to sign starting in 2017, according to Mr. Ferguson’s complaint. The terms instructed patients to contact the business directly if they had concerns rather than post a negative review.

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the lawsuit. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents.

In addition, Mr. Ferguson accused Dr. Sajan of creating fake positive accounts of patient experiences and buying fake followers on social media. State investigators found Dr. Sajan directed Allure Esthetic’s employees to create fake Gmail accounts to post the false reviews, many of which are still online today, according to the state’s complaint.

Mr. Ferguson also claimed Dr. Sajan and his practice manipulated social media to appear more popular by purchasing followers through an online vendor. The practice also allegedly used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media.

After filing the lawsuit, Mr. Ferguson’s office uncovered further evidence of Dr. Sajan’s efforts to influence his professional reputation through fabrication, according to the July 2 release. Allure Esthetic “rigged” “best doctor” competitions hosted by local media outlets by paying staff and contractors to vote for Dr. Sajan as “best plastic surgeon” in the region, according to the release. The staff cast as many votes as websites allowed, despite not being patients of Allure Esthetic.

The practice also allegedly edited before-and-after photos of patients to make their results appear better and kept tens of thousands of dollars in rebates intended for its patients.

In addition to paying $5 million, the consent decree requires Dr. Sajan and his practice also:

• Stop posting or influencing consumer reviews; perform a full audit of all public reviews on Google, Yelp, and other third-party review platforms; and request removal of every review Allure Esthetic was involved in creating, posting, or shaping in any manner.
• Remove all misleading “before-and-after” photographs of plastic surgery procedures from its website and social media and stop altering photographs of future procedures.
• Cease use of and attempts to enforce all illegal NDAs and notify patients who previously signed them that they are released from the terms of those NDAs.
• Pay a third-party forensic accounting firm to perform a full, independent audit of Allure Esthetic’s consumer rebate program to identify consumers who are owed rebates that were unlawfully claimed by Allure Esthetic.

Additionally, the attorney general’s office will continue to monitor Allure Esthetic, and upon request, the practice must provide information that demonstrates its compliance with the consent decree for the next 10 years.

The practice must also develop internal policies and implement a training program to educate staff about nondeceptive advertising and compliance with consumer protection laws.

Dr. Sajan and his practice agreed to the terms of the consent decree, and the settlement is not considered an admission of liability.

A version of this article first appeared on Medscape.com.

A Seattle plastic surgeon who illegally restricted patients from posting negative reviews about his practice and directed his staff to post fake positive reviews will pay $5 million for violating Washington state’s consumer protection law.

According to a July 1 consent decree, Javad Sajan, MD, and his practice Allure Esthetic must pay $1.5 million in restitution to 21,000 patients and $3.5 million to the state for manipulation of patient ratings.

The settlement resolves a federal lawsuit brought by Washington State Attorney General Bob Ferguson that accused the doctor of illegally suppressing patients’ negative reviews by “forcing” them to sign nondisclosure agreements (NDAs) before they received care. In an April decision, US District Judge Ricardo S. Martinez sided with the state, ruling that Allure Esthetic’s actions violated the federal Consumer Review Fairness Act (CRFA).

“Writing a truthful review about a business should not subject you to threats or intimidation,” Mr. Ferguson said in a July 2 statement. “Consumers rely on reviews when determining who to trust, especially services that affect their health and safety. This resolution holds Allure accountable for brazenly violating that trust — and the law — and ensures the clinic stops its harmful conduct.”

In court documents, Dr. Sajan’s attorneys had argued that the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them.

The surgeon’s practice is “pleased to have resolved its case with the Attorney General’s Office,” according to a statement provided by Dr. Sajan’s attorney. “The cooperative settlement, while not admitting fault and resolving claims asserted by both sides, allows Allure Esthetic to continue to focus on its core mission of providing compassionate care to patients and serving the community. The decision to settle was not an easy one, but it was necessary to allocate time and resources where they matter most — the patients.” 

The dispute stemmed from NDAs that Dr. Sajan’s practice required patients to sign starting in 2017, according to Mr. Ferguson’s complaint. The terms instructed patients to contact the business directly if they had concerns rather than post a negative review.

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the lawsuit. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents.

In addition, Mr. Ferguson accused Dr. Sajan of creating fake positive accounts of patient experiences and buying fake followers on social media. State investigators found Dr. Sajan directed Allure Esthetic’s employees to create fake Gmail accounts to post the false reviews, many of which are still online today, according to the state’s complaint.

Mr. Ferguson also claimed Dr. Sajan and his practice manipulated social media to appear more popular by purchasing followers through an online vendor. The practice also allegedly used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media.

After filing the lawsuit, Mr. Ferguson’s office uncovered further evidence of Dr. Sajan’s efforts to influence his professional reputation through fabrication, according to the July 2 release. Allure Esthetic “rigged” “best doctor” competitions hosted by local media outlets by paying staff and contractors to vote for Dr. Sajan as “best plastic surgeon” in the region, according to the release. The staff cast as many votes as websites allowed, despite not being patients of Allure Esthetic.

The practice also allegedly edited before-and-after photos of patients to make their results appear better and kept tens of thousands of dollars in rebates intended for its patients.

In addition to paying $5 million, the consent decree requires Dr. Sajan and his practice also:

• Stop posting or influencing consumer reviews; perform a full audit of all public reviews on Google, Yelp, and other third-party review platforms; and request removal of every review Allure Esthetic was involved in creating, posting, or shaping in any manner.
• Remove all misleading “before-and-after” photographs of plastic surgery procedures from its website and social media and stop altering photographs of future procedures.
• Cease use of and attempts to enforce all illegal NDAs and notify patients who previously signed them that they are released from the terms of those NDAs.
• Pay a third-party forensic accounting firm to perform a full, independent audit of Allure Esthetic’s consumer rebate program to identify consumers who are owed rebates that were unlawfully claimed by Allure Esthetic.

Additionally, the attorney general’s office will continue to monitor Allure Esthetic, and upon request, the practice must provide information that demonstrates its compliance with the consent decree for the next 10 years.

The practice must also develop internal policies and implement a training program to educate staff about nondeceptive advertising and compliance with consumer protection laws.

Dr. Sajan and his practice agreed to the terms of the consent decree, and the settlement is not considered an admission of liability.

A version of this article first appeared on Medscape.com.

A Seattle plastic surgeon who illegally restricted patients from posting negative reviews about his practice and directed his staff to post fake positive reviews will pay $5 million for violating Washington state’s consumer protection law.

According to a July 1 consent decree, Javad Sajan, MD, and his practice Allure Esthetic must pay $1.5 million in restitution to 21,000 patients and $3.5 million to the state for manipulation of patient ratings.

The settlement resolves a federal lawsuit brought by Washington State Attorney General Bob Ferguson that accused the doctor of illegally suppressing patients’ negative reviews by “forcing” them to sign nondisclosure agreements (NDAs) before they received care. In an April decision, US District Judge Ricardo S. Martinez sided with the state, ruling that Allure Esthetic’s actions violated the federal Consumer Review Fairness Act (CRFA).

“Writing a truthful review about a business should not subject you to threats or intimidation,” Mr. Ferguson said in a July 2 statement. “Consumers rely on reviews when determining who to trust, especially services that affect their health and safety. This resolution holds Allure accountable for brazenly violating that trust — and the law — and ensures the clinic stops its harmful conduct.”

In court documents, Dr. Sajan’s attorneys had argued that the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them.

The surgeon’s practice is “pleased to have resolved its case with the Attorney General’s Office,” according to a statement provided by Dr. Sajan’s attorney. “The cooperative settlement, while not admitting fault and resolving claims asserted by both sides, allows Allure Esthetic to continue to focus on its core mission of providing compassionate care to patients and serving the community. The decision to settle was not an easy one, but it was necessary to allocate time and resources where they matter most — the patients.” 

The dispute stemmed from NDAs that Dr. Sajan’s practice required patients to sign starting in 2017, according to Mr. Ferguson’s complaint. The terms instructed patients to contact the business directly if they had concerns rather than post a negative review.

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the lawsuit. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents.

In addition, Mr. Ferguson accused Dr. Sajan of creating fake positive accounts of patient experiences and buying fake followers on social media. State investigators found Dr. Sajan directed Allure Esthetic’s employees to create fake Gmail accounts to post the false reviews, many of which are still online today, according to the state’s complaint.

Mr. Ferguson also claimed Dr. Sajan and his practice manipulated social media to appear more popular by purchasing followers through an online vendor. The practice also allegedly used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media.

After filing the lawsuit, Mr. Ferguson’s office uncovered further evidence of Dr. Sajan’s efforts to influence his professional reputation through fabrication, according to the July 2 release. Allure Esthetic “rigged” “best doctor” competitions hosted by local media outlets by paying staff and contractors to vote for Dr. Sajan as “best plastic surgeon” in the region, according to the release. The staff cast as many votes as websites allowed, despite not being patients of Allure Esthetic.

The practice also allegedly edited before-and-after photos of patients to make their results appear better and kept tens of thousands of dollars in rebates intended for its patients.

In addition to paying $5 million, the consent decree requires Dr. Sajan and his practice also:

• Stop posting or influencing consumer reviews; perform a full audit of all public reviews on Google, Yelp, and other third-party review platforms; and request removal of every review Allure Esthetic was involved in creating, posting, or shaping in any manner.
• Remove all misleading “before-and-after” photographs of plastic surgery procedures from its website and social media and stop altering photographs of future procedures.
• Cease use of and attempts to enforce all illegal NDAs and notify patients who previously signed them that they are released from the terms of those NDAs.
• Pay a third-party forensic accounting firm to perform a full, independent audit of Allure Esthetic’s consumer rebate program to identify consumers who are owed rebates that were unlawfully claimed by Allure Esthetic.

Additionally, the attorney general’s office will continue to monitor Allure Esthetic, and upon request, the practice must provide information that demonstrates its compliance with the consent decree for the next 10 years.

The practice must also develop internal policies and implement a training program to educate staff about nondeceptive advertising and compliance with consumer protection laws.

Dr. Sajan and his practice agreed to the terms of the consent decree, and the settlement is not considered an admission of liability.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients taking a glucagon-like peptide 1 receptor agonist (GLP-1 RA) experience only a modest delay in gastric emptying of solid foods and no significant delay for liquids, compared with those receiving placebo, indicating that patients may not need to discontinue these medications before surgery.

METHODOLOGY:

• GLP-1 RAs, while effective in managing diabetes and obesity, are linked to delayed gastric emptying, which may pose risks during procedures requiring anesthesia or sedation due to potential aspiration of gastric contents.
• Researchers conducted a meta-analysis to quantify the duration of delay in gastric emptying caused by GLP-1 RAs in patients with diabetes and/or excessive body weight, which could guide periprocedural management decisions in the future.
• The primary outcome was halftime, the time required for 50% of solid gastric contents to empty, measured using scintigraphy. This analysis included data from five studies involving 247 patients who received either a GLP-1 RA or placebo.
• The secondary outcome was gastric emptying of liquids measured using the acetaminophen absorption test. Ten studies including 411 patients who received either a GLP-1 RA or placebo were included in this analysis.

TAKEAWAY:

• The mean gastric emptying halftime for solid foods was 138.4 minutes with a GLP-1 RA and 95.0 minutes with placebo, resulting in a pooled mean difference of 36.0 minutes (P < .01).
• No significant difference was found in the gastric emptying time for liquids between the GLP-1 RA and placebo groups. Furthermore, the amount of gastric emptying noted at 4 or 5 hours on the acetaminophen absorption test was comparable between these groups.
• The gastric emptying time for both solids and liquids did not differ between GLP-1 RA formulations or between short-acting or long-acting GLP-1 RAs.

IN PRACTICE:

“Based on current evidence, a conservative approach with a liquid diet on the day before procedures while continuing GLP-1 RA therapy would represent the most sensible approach until more conclusive data on a solid diet are available,” the authors wrote.

SOURCE:

The study, led by Brent Hiramoto, MD, MPH, of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The small number of studies utilizing some diagnostic modalities, such as breath testing, precluded a formal meta-analysis of these subgroups. The results could not be stratified by indication for GLP-1 RA (diabetes or obesity) because of insufficient studies in each category.

DISCLOSURES:

The lead author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. One author declared serving on the advisory boards of three pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients taking a glucagon-like peptide 1 receptor agonist (GLP-1 RA) experience only a modest delay in gastric emptying of solid foods and no significant delay for liquids, compared with those receiving placebo, indicating that patients may not need to discontinue these medications before surgery.

METHODOLOGY:

• GLP-1 RAs, while effective in managing diabetes and obesity, are linked to delayed gastric emptying, which may pose risks during procedures requiring anesthesia or sedation due to potential aspiration of gastric contents.
• Researchers conducted a meta-analysis to quantify the duration of delay in gastric emptying caused by GLP-1 RAs in patients with diabetes and/or excessive body weight, which could guide periprocedural management decisions in the future.
• The primary outcome was halftime, the time required for 50% of solid gastric contents to empty, measured using scintigraphy. This analysis included data from five studies involving 247 patients who received either a GLP-1 RA or placebo.
• The secondary outcome was gastric emptying of liquids measured using the acetaminophen absorption test. Ten studies including 411 patients who received either a GLP-1 RA or placebo were included in this analysis.

TAKEAWAY:

• The mean gastric emptying halftime for solid foods was 138.4 minutes with a GLP-1 RA and 95.0 minutes with placebo, resulting in a pooled mean difference of 36.0 minutes (P < .01).
• No significant difference was found in the gastric emptying time for liquids between the GLP-1 RA and placebo groups. Furthermore, the amount of gastric emptying noted at 4 or 5 hours on the acetaminophen absorption test was comparable between these groups.
• The gastric emptying time for both solids and liquids did not differ between GLP-1 RA formulations or between short-acting or long-acting GLP-1 RAs.

IN PRACTICE:

“Based on current evidence, a conservative approach with a liquid diet on the day before procedures while continuing GLP-1 RA therapy would represent the most sensible approach until more conclusive data on a solid diet are available,” the authors wrote.

SOURCE:

The study, led by Brent Hiramoto, MD, MPH, of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The small number of studies utilizing some diagnostic modalities, such as breath testing, precluded a formal meta-analysis of these subgroups. The results could not be stratified by indication for GLP-1 RA (diabetes or obesity) because of insufficient studies in each category.

DISCLOSURES:

The lead author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. One author declared serving on the advisory boards of three pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients taking a glucagon-like peptide 1 receptor agonist (GLP-1 RA) experience only a modest delay in gastric emptying of solid foods and no significant delay for liquids, compared with those receiving placebo, indicating that patients may not need to discontinue these medications before surgery.

METHODOLOGY:

• GLP-1 RAs, while effective in managing diabetes and obesity, are linked to delayed gastric emptying, which may pose risks during procedures requiring anesthesia or sedation due to potential aspiration of gastric contents.
• Researchers conducted a meta-analysis to quantify the duration of delay in gastric emptying caused by GLP-1 RAs in patients with diabetes and/or excessive body weight, which could guide periprocedural management decisions in the future.
• The primary outcome was halftime, the time required for 50% of solid gastric contents to empty, measured using scintigraphy. This analysis included data from five studies involving 247 patients who received either a GLP-1 RA or placebo.
• The secondary outcome was gastric emptying of liquids measured using the acetaminophen absorption test. Ten studies including 411 patients who received either a GLP-1 RA or placebo were included in this analysis.

TAKEAWAY:

• The mean gastric emptying halftime for solid foods was 138.4 minutes with a GLP-1 RA and 95.0 minutes with placebo, resulting in a pooled mean difference of 36.0 minutes (P < .01).
• No significant difference was found in the gastric emptying time for liquids between the GLP-1 RA and placebo groups. Furthermore, the amount of gastric emptying noted at 4 or 5 hours on the acetaminophen absorption test was comparable between these groups.
• The gastric emptying time for both solids and liquids did not differ between GLP-1 RA formulations or between short-acting or long-acting GLP-1 RAs.

IN PRACTICE:

“Based on current evidence, a conservative approach with a liquid diet on the day before procedures while continuing GLP-1 RA therapy would represent the most sensible approach until more conclusive data on a solid diet are available,” the authors wrote.

SOURCE:

The study, led by Brent Hiramoto, MD, MPH, of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The small number of studies utilizing some diagnostic modalities, such as breath testing, precluded a formal meta-analysis of these subgroups. The results could not be stratified by indication for GLP-1 RA (diabetes or obesity) because of insufficient studies in each category.

DISCLOSURES:

The lead author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. One author declared serving on the advisory boards of three pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

In one of several recently published studies on the relationship between COVID-19 infection and asthma, asthma symptoms in children declined as the proportion of the US population vaccinated against COVID-19 increased, according to data drawn from the National Survey of Children’s Health (NSCH).

The inverse correlation between symptoms and vaccination was strong and statistically significant, according to investigators led by Matthew M. Davis, MD, Physician in Chief and Chief Scientific Officer, Nemours Children’s Health, Wilmington, Delaware.

“With each increase of 10 percentage points in COVID-19 vaccination coverage, the parent-reported child asthma symptoms prevalence decreased by 0.36 percentage points (P < .05),” Dr. Davis and his coinvestigators reported in a research letter published in JAMA Network Open.
 

Studies Explore Relationship of COVID and Asthma

The reduced risk of asthma symptoms with COVID-19 vaccination in children at the population level is just one of several recently published studies exploring the interaction between COVID-19 infection and asthma, but two studies that posed the same question did not reach the same conclusion.

In one, COVID-19 infection in children was not found to be a trigger for new-onset asthma, but the second found that it was. In a third study, the preponderance of evidence from a meta-analysis found that patients with asthma – whether children or adults – did not necessarily experience a more severe course of COVID-19 infection than in those without asthma.

The NSCH database study calculated state-level change in scores for patient-reported childhood asthma symptoms in the years in the years 2018-2019, which preceded the pandemic and the years 2020-2021, when the pandemic began. The hypothesis was that the proportion of the population 5 years of age or older who completed the COVID-19 primary vaccination would be inversely related to asthma symptom prevalence.

Relative to the 2018-2019 years, the mean rate of parent-reported asthma symptoms was 0.85% lower (6.93% vs 7.77%; P < .001) in 2020-2021, when the mean primary series COVID-19 vaccination rate was 72.3%.

The study was not able to evaluate the impact of COVID-19 vaccination specifically in children with asthma, because history of asthma is not captured in the NSCH data, but Dr. Davis contended that the reduction in symptomatic asthma among children with increased vaccination offers validation for the state-level findings.

“Moreover, the absence of an association of COVID-19 vaccination administered predominantly in 2021 with population-level COVID-19 mortality in 2020 serves as a negative control,” he and his colleagues wrote in their research letter.
 

Protection from Respiratory Viruses Seen for Asthma Patients

In an interview, Dr. Davis reported that these data are consistent with previous evidence that immunization against influenza also reduces risk of asthma symptoms. In a meta-analysis published in 2017, it was estimated that live vaccines reduced risk of influenza by 81% and prevented 59%-72% of asthma attacks leading to hospitalizations or emergency room visits.

“The similarity of our findings regarding COVID-19 vaccination to prior data regarding influenza vaccination underscores the importance of preventing viral illnesses in individuals with a history of asthma,” Dr. Davis said. It is not yet clear if this is true of respiratory syncytial virus (RSV). Because of the short time that the RSV vaccine has been available, it is too soon to conduct an analysis.

One message from this study is that “clinicians should continue to encourage COVID-19 vaccination for children because of its general benefits in preventing coronavirus-related illness and the apparent specific benefits for children with a history of asthma,” he said.

While vaccination appears to reduce asthmatic symptoms related to COVID-19 infection, one study suggests that COVID-19 does not trigger new-onset asthma. In a retrospective study published in Pediatrics, no association between COVID-19 infection and new-onset asthma could be made in an analysis of 27,423 children (ages, 1-16 years) from the Children’s Hospital of Philadelphia (CHOP) Care Network.

Across all the pediatric age groups evaluated, the consistent finding was “SARS-CoV-2 positivity does not confer an additional risk for asthma diagnosis at least within the first 18 months after a [polymerase chain reaction] test,” concluded the investigators, led by David A. Hill, MD, PhD, Division of Allergy and Immunology, CHOP, Philadelphia, Pennsylvania.
 

Risk of Asthma Doubled After COVID-19 Infection

However, the opposite conclusion was reached by investigators evaluating data from two cohorts of children ages 5-18 drawn from the TriNetX database, a global health research network with data on more than 250 million individuals. Cohort 1 included more than 250,000 children. These children had never received COVID-19 vaccination. The 50,000 patients in cohort 2 had all received COVID19 vaccination.

To compare the impact of COVID-19 infection on new-onset asthma, the patients who were infected with COVID-19 were compared with those who were not infected after propensity score matching over 18 months of follow-up.

In cohort 1, the rate of new onset asthma was more than twofold greater among those with COVID-19 infection (4.7% vs 2.0%). The hazard ratio (HR) of 2.25 had tight confidence intervals (95% CI, 2.158-2.367).

In cohort 2, the risk of new-onset asthma at 18 months among those who had a COVID-19 infection relative to those without was even greater (8.3% vs 3.1%). The relative risk approached a 3-fold increase (HR 2.745; 95% CI, 2.521-2.99).

The conclusion of these investigators, led by Chia-Chi Lung, PhD, Department of Public Health, Chung Shan Medical University, Taichung City, Taiwan, was that there is “a critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children.”

These health risks might not be as significant as once feared. In the recently published study from Environmental Health Insights, the goal of a meta-analysis was to determine if patients with asthma relative to those without asthma face a higher risk of serious disease from COVID-19 infection. The meta-analysis included studies of children and adults. The answer, according an in-depth analysis of 21 articles in a “scoping review,” was a qualified no.

Of the 21 articles, 4 concluded that asthma is a risk factor for serious COVID-19 infection, but 17 did not, according to Chukwudi S. Ubah, PhD, Department of Public Health, Brody School of Medicine, East Caroline University, Greenville, North Carolina.
 

None of These Questions are Fully Resolved

However, given the disparity in the results and the fact that many of the studies included in this analysis had small sample sizes, Dr. Ubah called for larger studies and studies with better controls. He noted, for example, that the studies did not consistently evaluate mitigating factors, such as used of inhaled or oral corticosteroids, which might affect risk of the severity of a COVID-19 infection.

Rather, “our findings pointed out that the type of medication prescribed for asthma may have implications for the severity of COVID-19 infection in these patients,” Dr. Ubah said in an interview.

Overall, the data do not support a major interaction between asthma and COVID-19, even if the data are not conclusive. Each of the senior authors of these studies called for larger and better investigations to further explore whether COVID-19 infection and preexisting asthma interact. So far, the data indicate that if COVID-19 infection poses a risk of precipitating new-onset asthma or inducing a more severe infection in children with asthma, it is low, but the degree of risk, if any, remains unresolved in subgroups defined by asthma treatment or asthma severity.

Dr. Davis, Dr. Hill, Dr. Lung, and Dr. Ubah reported no potential conflicts of interest. None of these studies received funding from commercial interests.

In one of several recently published studies on the relationship between COVID-19 infection and asthma, asthma symptoms in children declined as the proportion of the US population vaccinated against COVID-19 increased, according to data drawn from the National Survey of Children’s Health (NSCH).

The inverse correlation between symptoms and vaccination was strong and statistically significant, according to investigators led by Matthew M. Davis, MD, Physician in Chief and Chief Scientific Officer, Nemours Children’s Health, Wilmington, Delaware.

“With each increase of 10 percentage points in COVID-19 vaccination coverage, the parent-reported child asthma symptoms prevalence decreased by 0.36 percentage points (P < .05),” Dr. Davis and his coinvestigators reported in a research letter published in JAMA Network Open.
 

Studies Explore Relationship of COVID and Asthma

The reduced risk of asthma symptoms with COVID-19 vaccination in children at the population level is just one of several recently published studies exploring the interaction between COVID-19 infection and asthma, but two studies that posed the same question did not reach the same conclusion.

In one, COVID-19 infection in children was not found to be a trigger for new-onset asthma, but the second found that it was. In a third study, the preponderance of evidence from a meta-analysis found that patients with asthma – whether children or adults – did not necessarily experience a more severe course of COVID-19 infection than in those without asthma.

The NSCH database study calculated state-level change in scores for patient-reported childhood asthma symptoms in the years in the years 2018-2019, which preceded the pandemic and the years 2020-2021, when the pandemic began. The hypothesis was that the proportion of the population 5 years of age or older who completed the COVID-19 primary vaccination would be inversely related to asthma symptom prevalence.

Relative to the 2018-2019 years, the mean rate of parent-reported asthma symptoms was 0.85% lower (6.93% vs 7.77%; P < .001) in 2020-2021, when the mean primary series COVID-19 vaccination rate was 72.3%.

The study was not able to evaluate the impact of COVID-19 vaccination specifically in children with asthma, because history of asthma is not captured in the NSCH data, but Dr. Davis contended that the reduction in symptomatic asthma among children with increased vaccination offers validation for the state-level findings.

“Moreover, the absence of an association of COVID-19 vaccination administered predominantly in 2021 with population-level COVID-19 mortality in 2020 serves as a negative control,” he and his colleagues wrote in their research letter.
 

Protection from Respiratory Viruses Seen for Asthma Patients

In an interview, Dr. Davis reported that these data are consistent with previous evidence that immunization against influenza also reduces risk of asthma symptoms. In a meta-analysis published in 2017, it was estimated that live vaccines reduced risk of influenza by 81% and prevented 59%-72% of asthma attacks leading to hospitalizations or emergency room visits.

“The similarity of our findings regarding COVID-19 vaccination to prior data regarding influenza vaccination underscores the importance of preventing viral illnesses in individuals with a history of asthma,” Dr. Davis said. It is not yet clear if this is true of respiratory syncytial virus (RSV). Because of the short time that the RSV vaccine has been available, it is too soon to conduct an analysis.

One message from this study is that “clinicians should continue to encourage COVID-19 vaccination for children because of its general benefits in preventing coronavirus-related illness and the apparent specific benefits for children with a history of asthma,” he said.

While vaccination appears to reduce asthmatic symptoms related to COVID-19 infection, one study suggests that COVID-19 does not trigger new-onset asthma. In a retrospective study published in Pediatrics, no association between COVID-19 infection and new-onset asthma could be made in an analysis of 27,423 children (ages, 1-16 years) from the Children’s Hospital of Philadelphia (CHOP) Care Network.

Across all the pediatric age groups evaluated, the consistent finding was “SARS-CoV-2 positivity does not confer an additional risk for asthma diagnosis at least within the first 18 months after a [polymerase chain reaction] test,” concluded the investigators, led by David A. Hill, MD, PhD, Division of Allergy and Immunology, CHOP, Philadelphia, Pennsylvania.
 

Risk of Asthma Doubled After COVID-19 Infection

However, the opposite conclusion was reached by investigators evaluating data from two cohorts of children ages 5-18 drawn from the TriNetX database, a global health research network with data on more than 250 million individuals. Cohort 1 included more than 250,000 children. These children had never received COVID-19 vaccination. The 50,000 patients in cohort 2 had all received COVID19 vaccination.

To compare the impact of COVID-19 infection on new-onset asthma, the patients who were infected with COVID-19 were compared with those who were not infected after propensity score matching over 18 months of follow-up.

In cohort 1, the rate of new onset asthma was more than twofold greater among those with COVID-19 infection (4.7% vs 2.0%). The hazard ratio (HR) of 2.25 had tight confidence intervals (95% CI, 2.158-2.367).

In cohort 2, the risk of new-onset asthma at 18 months among those who had a COVID-19 infection relative to those without was even greater (8.3% vs 3.1%). The relative risk approached a 3-fold increase (HR 2.745; 95% CI, 2.521-2.99).

The conclusion of these investigators, led by Chia-Chi Lung, PhD, Department of Public Health, Chung Shan Medical University, Taichung City, Taiwan, was that there is “a critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children.”

These health risks might not be as significant as once feared. In the recently published study from Environmental Health Insights, the goal of a meta-analysis was to determine if patients with asthma relative to those without asthma face a higher risk of serious disease from COVID-19 infection. The meta-analysis included studies of children and adults. The answer, according an in-depth analysis of 21 articles in a “scoping review,” was a qualified no.

Of the 21 articles, 4 concluded that asthma is a risk factor for serious COVID-19 infection, but 17 did not, according to Chukwudi S. Ubah, PhD, Department of Public Health, Brody School of Medicine, East Caroline University, Greenville, North Carolina.
 

None of These Questions are Fully Resolved

However, given the disparity in the results and the fact that many of the studies included in this analysis had small sample sizes, Dr. Ubah called for larger studies and studies with better controls. He noted, for example, that the studies did not consistently evaluate mitigating factors, such as used of inhaled or oral corticosteroids, which might affect risk of the severity of a COVID-19 infection.

Rather, “our findings pointed out that the type of medication prescribed for asthma may have implications for the severity of COVID-19 infection in these patients,” Dr. Ubah said in an interview.

Overall, the data do not support a major interaction between asthma and COVID-19, even if the data are not conclusive. Each of the senior authors of these studies called for larger and better investigations to further explore whether COVID-19 infection and preexisting asthma interact. So far, the data indicate that if COVID-19 infection poses a risk of precipitating new-onset asthma or inducing a more severe infection in children with asthma, it is low, but the degree of risk, if any, remains unresolved in subgroups defined by asthma treatment or asthma severity.

Dr. Davis, Dr. Hill, Dr. Lung, and Dr. Ubah reported no potential conflicts of interest. None of these studies received funding from commercial interests.

In one of several recently published studies on the relationship between COVID-19 infection and asthma, asthma symptoms in children declined as the proportion of the US population vaccinated against COVID-19 increased, according to data drawn from the National Survey of Children’s Health (NSCH).

The inverse correlation between symptoms and vaccination was strong and statistically significant, according to investigators led by Matthew M. Davis, MD, Physician in Chief and Chief Scientific Officer, Nemours Children’s Health, Wilmington, Delaware.

“With each increase of 10 percentage points in COVID-19 vaccination coverage, the parent-reported child asthma symptoms prevalence decreased by 0.36 percentage points (P < .05),” Dr. Davis and his coinvestigators reported in a research letter published in JAMA Network Open.
 

Studies Explore Relationship of COVID and Asthma

The reduced risk of asthma symptoms with COVID-19 vaccination in children at the population level is just one of several recently published studies exploring the interaction between COVID-19 infection and asthma, but two studies that posed the same question did not reach the same conclusion.

In one, COVID-19 infection in children was not found to be a trigger for new-onset asthma, but the second found that it was. In a third study, the preponderance of evidence from a meta-analysis found that patients with asthma – whether children or adults – did not necessarily experience a more severe course of COVID-19 infection than in those without asthma.

The NSCH database study calculated state-level change in scores for patient-reported childhood asthma symptoms in the years in the years 2018-2019, which preceded the pandemic and the years 2020-2021, when the pandemic began. The hypothesis was that the proportion of the population 5 years of age or older who completed the COVID-19 primary vaccination would be inversely related to asthma symptom prevalence.

Relative to the 2018-2019 years, the mean rate of parent-reported asthma symptoms was 0.85% lower (6.93% vs 7.77%; P < .001) in 2020-2021, when the mean primary series COVID-19 vaccination rate was 72.3%.

The study was not able to evaluate the impact of COVID-19 vaccination specifically in children with asthma, because history of asthma is not captured in the NSCH data, but Dr. Davis contended that the reduction in symptomatic asthma among children with increased vaccination offers validation for the state-level findings.

“Moreover, the absence of an association of COVID-19 vaccination administered predominantly in 2021 with population-level COVID-19 mortality in 2020 serves as a negative control,” he and his colleagues wrote in their research letter.
 

Protection from Respiratory Viruses Seen for Asthma Patients

In an interview, Dr. Davis reported that these data are consistent with previous evidence that immunization against influenza also reduces risk of asthma symptoms. In a meta-analysis published in 2017, it was estimated that live vaccines reduced risk of influenza by 81% and prevented 59%-72% of asthma attacks leading to hospitalizations or emergency room visits.

“The similarity of our findings regarding COVID-19 vaccination to prior data regarding influenza vaccination underscores the importance of preventing viral illnesses in individuals with a history of asthma,” Dr. Davis said. It is not yet clear if this is true of respiratory syncytial virus (RSV). Because of the short time that the RSV vaccine has been available, it is too soon to conduct an analysis.

One message from this study is that “clinicians should continue to encourage COVID-19 vaccination for children because of its general benefits in preventing coronavirus-related illness and the apparent specific benefits for children with a history of asthma,” he said.

While vaccination appears to reduce asthmatic symptoms related to COVID-19 infection, one study suggests that COVID-19 does not trigger new-onset asthma. In a retrospective study published in Pediatrics, no association between COVID-19 infection and new-onset asthma could be made in an analysis of 27,423 children (ages, 1-16 years) from the Children’s Hospital of Philadelphia (CHOP) Care Network.

Across all the pediatric age groups evaluated, the consistent finding was “SARS-CoV-2 positivity does not confer an additional risk for asthma diagnosis at least within the first 18 months after a [polymerase chain reaction] test,” concluded the investigators, led by David A. Hill, MD, PhD, Division of Allergy and Immunology, CHOP, Philadelphia, Pennsylvania.
 

Risk of Asthma Doubled After COVID-19 Infection

However, the opposite conclusion was reached by investigators evaluating data from two cohorts of children ages 5-18 drawn from the TriNetX database, a global health research network with data on more than 250 million individuals. Cohort 1 included more than 250,000 children. These children had never received COVID-19 vaccination. The 50,000 patients in cohort 2 had all received COVID19 vaccination.

To compare the impact of COVID-19 infection on new-onset asthma, the patients who were infected with COVID-19 were compared with those who were not infected after propensity score matching over 18 months of follow-up.

In cohort 1, the rate of new onset asthma was more than twofold greater among those with COVID-19 infection (4.7% vs 2.0%). The hazard ratio (HR) of 2.25 had tight confidence intervals (95% CI, 2.158-2.367).

In cohort 2, the risk of new-onset asthma at 18 months among those who had a COVID-19 infection relative to those without was even greater (8.3% vs 3.1%). The relative risk approached a 3-fold increase (HR 2.745; 95% CI, 2.521-2.99).

The conclusion of these investigators, led by Chia-Chi Lung, PhD, Department of Public Health, Chung Shan Medical University, Taichung City, Taiwan, was that there is “a critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children.”

These health risks might not be as significant as once feared. In the recently published study from Environmental Health Insights, the goal of a meta-analysis was to determine if patients with asthma relative to those without asthma face a higher risk of serious disease from COVID-19 infection. The meta-analysis included studies of children and adults. The answer, according an in-depth analysis of 21 articles in a “scoping review,” was a qualified no.

Of the 21 articles, 4 concluded that asthma is a risk factor for serious COVID-19 infection, but 17 did not, according to Chukwudi S. Ubah, PhD, Department of Public Health, Brody School of Medicine, East Caroline University, Greenville, North Carolina.
 

None of These Questions are Fully Resolved

However, given the disparity in the results and the fact that many of the studies included in this analysis had small sample sizes, Dr. Ubah called for larger studies and studies with better controls. He noted, for example, that the studies did not consistently evaluate mitigating factors, such as used of inhaled or oral corticosteroids, which might affect risk of the severity of a COVID-19 infection.

Rather, “our findings pointed out that the type of medication prescribed for asthma may have implications for the severity of COVID-19 infection in these patients,” Dr. Ubah said in an interview.

Overall, the data do not support a major interaction between asthma and COVID-19, even if the data are not conclusive. Each of the senior authors of these studies called for larger and better investigations to further explore whether COVID-19 infection and preexisting asthma interact. So far, the data indicate that if COVID-19 infection poses a risk of precipitating new-onset asthma or inducing a more severe infection in children with asthma, it is low, but the degree of risk, if any, remains unresolved in subgroups defined by asthma treatment or asthma severity.

Dr. Davis, Dr. Hill, Dr. Lung, and Dr. Ubah reported no potential conflicts of interest. None of these studies received funding from commercial interests.

A variety of skin problems can occur in musicians due to the repetitive movements of playing instruments.^1,2 Musicians’ nails are continuously exposed to the mechanical forces and chemical substances characteristic of their instruments.³ Occupational nail alterations in musicians caused by repetitive physical trauma, allergic contact dermatitis, and/or infection may lead to disability and compromise their professional career.³

We conducted a systematic review of the literature on the clinical features of musical instrument–related nail alterations to optimize the management and prevention of these conditions.

Methods

We conducted a systematic review of PubMed, Scopus, and Google Scholar databases for eligible publications on instrument-related nail alterations in musicians using the search terms musicians with nail, onychopathy, and Raynaud. No time or language criteria were applied. Reviews, editorials, and articles not related to the topic were excluded. Bibliographies/reference lists were checked to find any additional relevant publications. Relevant articles in English and French were screened by 2 independent reviewers (A.G. and N.L.), and the following data were extracted for qualitative synthesis: sex, age, musical instrument, clinical features, number of years practicing the instrument, laboratory investigations, and disease course.

Results

The literature search yielded 11 publications. Sixteen additional articles were identified by other methods (ie, references, related publications). Overall, 3 full-text articles described general nail alterations but did not describe the clinical data, and 11 publications were editorials, commentaries, reviews, or not relevant. Thirteen contributions fulfilled the inclusion criteria and were eligible for qualitative synthesis. The flow diagram illustrates the screening process (Figure 1).

Twenty-three patients were included. The instruments identified were divided into 2 groups: string instruments (ie, guitar, violin, harp) and percussion instruments (ie, drums, piano, slap bass). Nail alterations were clinically expressed as: (1) modifications of the nail surface; (2) nail bed, soft-tissue, and bone abnormalities; and (3) periungual tissue and distal pulp disorders. All cases are summarized in the Table.^4-16 Three articles described occupational Raynaud phenomenon.^12-14

Comment

Modifications of the Nail Surface—Onychodystrophy, such as deformity or discoloration of the nail plate, was described in 6 patients among a cohort of 295 musicians and an additional 6 patients among 199 musicians with induced skin lesions. This condition was most common in string instrument players and pianists due to injury and irritation.^4,5

One patient, who had been a professional violist for 27 years, presented with lamellar onychoschizia, which corresponds to a horizontal splitting of the nail toward its distal portion (Figure 2). The 3 fingernails of the dominant hand were involved with a V-shaped incision of the distal margin of the nail due to the repetitive friction of the nails with the strings.⁶

Striations of the nail plate were reported in a guitarist who played for 10 years.⁷ Physical examination revealed linear transverse ridges alternating with depressions on the central aspect of the nail plate of the right thumbnail, as the patient was right-handed. This condition, attributed to sustained pressure on the string applied by the thumb, also has been called habit tic deformity.⁷

Nail Bed, Soft-Tissue, and Bone Lesions—Purpura (or hemorrhage) of the nail bed was associated with a percussion instrument (ie, piano) in 1 patient, affecting the second, third, and fourth fingernails of the right hand.⁸ Especially when performing ascending glissando passages, the pianist applies pressure that may damage the finger and cause fingernail purpura. This condition improved after the patient stopping practicing glissandi.⁸

Conclusion

Healthy nails are essential for playing a musical instrument. This review highlights the occurrence of fingertip callosities, paronychia, onycholysis, and subungual hemorrhages among musicians who play instruments. Additionally, the transmission of string-vibratory movements can produce microvascular damage and occupational Raynaud phenomenon in some musicians. These occupational nail disorders are underrecognized and may be underdiagnosed. Thus, musicians and clinicians must be aware of these alterations to adopt preventive measures and to provide adequate treatment.

A variety of skin problems can occur in musicians due to the repetitive movements of playing instruments.^1,2 Musicians’ nails are continuously exposed to the mechanical forces and chemical substances characteristic of their instruments.³ Occupational nail alterations in musicians caused by repetitive physical trauma, allergic contact dermatitis, and/or infection may lead to disability and compromise their professional career.³

We conducted a systematic review of the literature on the clinical features of musical instrument–related nail alterations to optimize the management and prevention of these conditions.

Methods

We conducted a systematic review of PubMed, Scopus, and Google Scholar databases for eligible publications on instrument-related nail alterations in musicians using the search terms musicians with nail, onychopathy, and Raynaud. No time or language criteria were applied. Reviews, editorials, and articles not related to the topic were excluded. Bibliographies/reference lists were checked to find any additional relevant publications. Relevant articles in English and French were screened by 2 independent reviewers (A.G. and N.L.), and the following data were extracted for qualitative synthesis: sex, age, musical instrument, clinical features, number of years practicing the instrument, laboratory investigations, and disease course.

Results

The literature search yielded 11 publications. Sixteen additional articles were identified by other methods (ie, references, related publications). Overall, 3 full-text articles described general nail alterations but did not describe the clinical data, and 11 publications were editorials, commentaries, reviews, or not relevant. Thirteen contributions fulfilled the inclusion criteria and were eligible for qualitative synthesis. The flow diagram illustrates the screening process (Figure 1).

Twenty-three patients were included. The instruments identified were divided into 2 groups: string instruments (ie, guitar, violin, harp) and percussion instruments (ie, drums, piano, slap bass). Nail alterations were clinically expressed as: (1) modifications of the nail surface; (2) nail bed, soft-tissue, and bone abnormalities; and (3) periungual tissue and distal pulp disorders. All cases are summarized in the Table.^4-16 Three articles described occupational Raynaud phenomenon.^12-14

Comment

Modifications of the Nail Surface—Onychodystrophy, such as deformity or discoloration of the nail plate, was described in 6 patients among a cohort of 295 musicians and an additional 6 patients among 199 musicians with induced skin lesions. This condition was most common in string instrument players and pianists due to injury and irritation.^4,5

One patient, who had been a professional violist for 27 years, presented with lamellar onychoschizia, which corresponds to a horizontal splitting of the nail toward its distal portion (Figure 2). The 3 fingernails of the dominant hand were involved with a V-shaped incision of the distal margin of the nail due to the repetitive friction of the nails with the strings.⁶

Striations of the nail plate were reported in a guitarist who played for 10 years.⁷ Physical examination revealed linear transverse ridges alternating with depressions on the central aspect of the nail plate of the right thumbnail, as the patient was right-handed. This condition, attributed to sustained pressure on the string applied by the thumb, also has been called habit tic deformity.⁷

Nail Bed, Soft-Tissue, and Bone Lesions—Purpura (or hemorrhage) of the nail bed was associated with a percussion instrument (ie, piano) in 1 patient, affecting the second, third, and fourth fingernails of the right hand.⁸ Especially when performing ascending glissando passages, the pianist applies pressure that may damage the finger and cause fingernail purpura. This condition improved after the patient stopping practicing glissandi.⁸

Conclusion

Healthy nails are essential for playing a musical instrument. This review highlights the occurrence of fingertip callosities, paronychia, onycholysis, and subungual hemorrhages among musicians who play instruments. Additionally, the transmission of string-vibratory movements can produce microvascular damage and occupational Raynaud phenomenon in some musicians. These occupational nail disorders are underrecognized and may be underdiagnosed. Thus, musicians and clinicians must be aware of these alterations to adopt preventive measures and to provide adequate treatment.

A variety of skin problems can occur in musicians due to the repetitive movements of playing instruments.^1,2 Musicians’ nails are continuously exposed to the mechanical forces and chemical substances characteristic of their instruments.³ Occupational nail alterations in musicians caused by repetitive physical trauma, allergic contact dermatitis, and/or infection may lead to disability and compromise their professional career.³

We conducted a systematic review of the literature on the clinical features of musical instrument–related nail alterations to optimize the management and prevention of these conditions.

Methods

We conducted a systematic review of PubMed, Scopus, and Google Scholar databases for eligible publications on instrument-related nail alterations in musicians using the search terms musicians with nail, onychopathy, and Raynaud. No time or language criteria were applied. Reviews, editorials, and articles not related to the topic were excluded. Bibliographies/reference lists were checked to find any additional relevant publications. Relevant articles in English and French were screened by 2 independent reviewers (A.G. and N.L.), and the following data were extracted for qualitative synthesis: sex, age, musical instrument, clinical features, number of years practicing the instrument, laboratory investigations, and disease course.

Results

The literature search yielded 11 publications. Sixteen additional articles were identified by other methods (ie, references, related publications). Overall, 3 full-text articles described general nail alterations but did not describe the clinical data, and 11 publications were editorials, commentaries, reviews, or not relevant. Thirteen contributions fulfilled the inclusion criteria and were eligible for qualitative synthesis. The flow diagram illustrates the screening process (Figure 1).

Twenty-three patients were included. The instruments identified were divided into 2 groups: string instruments (ie, guitar, violin, harp) and percussion instruments (ie, drums, piano, slap bass). Nail alterations were clinically expressed as: (1) modifications of the nail surface; (2) nail bed, soft-tissue, and bone abnormalities; and (3) periungual tissue and distal pulp disorders. All cases are summarized in the Table.^4-16 Three articles described occupational Raynaud phenomenon.^12-14

Comment

Modifications of the Nail Surface—Onychodystrophy, such as deformity or discoloration of the nail plate, was described in 6 patients among a cohort of 295 musicians and an additional 6 patients among 199 musicians with induced skin lesions. This condition was most common in string instrument players and pianists due to injury and irritation.^4,5

One patient, who had been a professional violist for 27 years, presented with lamellar onychoschizia, which corresponds to a horizontal splitting of the nail toward its distal portion (Figure 2). The 3 fingernails of the dominant hand were involved with a V-shaped incision of the distal margin of the nail due to the repetitive friction of the nails with the strings.⁶

Striations of the nail plate were reported in a guitarist who played for 10 years.⁷ Physical examination revealed linear transverse ridges alternating with depressions on the central aspect of the nail plate of the right thumbnail, as the patient was right-handed. This condition, attributed to sustained pressure on the string applied by the thumb, also has been called habit tic deformity.⁷

Nail Bed, Soft-Tissue, and Bone Lesions—Purpura (or hemorrhage) of the nail bed was associated with a percussion instrument (ie, piano) in 1 patient, affecting the second, third, and fourth fingernails of the right hand.⁸ Especially when performing ascending glissando passages, the pianist applies pressure that may damage the finger and cause fingernail purpura. This condition improved after the patient stopping practicing glissandi.⁸

Conclusion

Healthy nails are essential for playing a musical instrument. This review highlights the occurrence of fingertip callosities, paronychia, onycholysis, and subungual hemorrhages among musicians who play instruments. Additionally, the transmission of string-vibratory movements can produce microvascular damage and occupational Raynaud phenomenon in some musicians. These occupational nail disorders are underrecognized and may be underdiagnosed. Thus, musicians and clinicians must be aware of these alterations to adopt preventive measures and to provide adequate treatment.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.