Phototherapy for the treatment of atopic dermatitis in Singaporean children and adolescents.

BACKGROUND/PURPOSE: Phototherapy has emerged as a safe yet effective form of treatment of atopic dermatitis (AD). Few studies have been done to evaluate the efficacy of phototherapy in Asian children. The aim of this study was to review the phototherapy experience in a cohort of Asian pediatric patients with AD at a tertiary dermatologic center in Singapore. METHODS: A retrospective study of patients 18 years and below with AD who had undergone phototherapy at KK Women's and Children's Hospital, Singapore, over a 4-year period was performed. RESULTS: Sixty-two patients were identified, between ages 4 and 16 years (mean age 11 years) at the time of commencement of phototherapy. Thirty-five (60%) patients were males and 23 (40%) were females. Most patients had moderate to severe disease, with 60.3% of the patients with an initial body surface area (BSA) involvement of 31%-60% and 13.8% of the patients with an initial BSA involvement of 61%-90%. For patients who had undergone narrowband ultraviolet B (NBUVB) and combined ultraviolet A (UVA) and NBUVB phototherapy, the mean reduction of the Eczema Area and Severity Index (EASI) scores were 11.4 and 7.9, respectively. Common side effects experienced include xerosis, pruritus, erythema, and pain. Other reasons for cessation of therapy in the NBUVB group included time commitment difficulty (9.3%), hyperactivity (2.3%), and claustrophobia (2.3%). Two patients that had photochemotherapy (psoralen + UVA) [PUVA] suffered from post-UVA burns requiring cessation of treatment. More than half of the patients (56.9%) treated with phototherapy experienced treatment success with improvement in Investigator Global Assessment and EASI scores. 86.2% of the patients had good compliance to the treatment regime, 12% had poor-compliance, and 3.4% were lost to follow-up. CONCLUSION: Phototherapy is a useful treatment adjunct for moderate to severe AD in Asian children.

Cutaneous adenovirus infection in an immunocompromised child.

Adenoviruses are common viral pathogens in childhood; however, cutaneous manifestations are not well-documented. We present a rare case of cutaneous adenovirus infection in a 23-month-old boy with a background of CD40 ligand deficiency, post bone marrow transplant. The clinical morphology of the skin lesions in our patient, described as skin-colored papules with central crusting, has not been previously described and contributes to the growing literature of cutaneous adenovirus cases.

Degos disease in a child presenting with acute renal failure.

Degos disease, also termed malignant atrophic papulosis, is a rare systemic vaso-occlusive disorder, seldom reported in the pediatric population. The pathognomonic skin lesion in Degos disease is a papule with an atrophic porcelain-white center with an erythematous, telangiectatic rim. The benign form of the disease remains limited to the skin, whereas, in others, it progresses to thrombotic vasculopathy in multiple organs including the gastrointestinal, cardiorespiratory, and central nervous systems, with a high mortality rate. We present a rare case of Degos disease in an adolescent female, presenting as acute renal failure secondary to thrombotic vasculopathy, with the characteristic skin lesion distinctively seen on dermoscopy.

Phenotype and genotype correlation of inherited epidermolysis bullosa in Indonesia.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a group of genodermatoses with considerable clinical and genetic heterogeneity. Clinical diagnosis of the EB subtypes is frequently imprecise and requires confirmation with genetic testing. There is still limited study using genetic testing to identify EB subtypes in Indonesia. This study aims to identify the pathogenic variants of inherited EB patients at the Department of Dermatology and Venereology, Universitas Padjadjaran-Dr Hasan Sadikin General Hospital in Bandung, West Java, Indonesia and to describe the correlation between the phenotype and genotype of our patients. METHODS: Twelve patients clinically diagnosed with EB were included in this study. Genetic testing was performed in collaboration with KK Women's and Children's Hospital, Singapore. RESULTS: Pathogenic variants were identified in the COL7A1 gene in seven patients, namely Dominant Dystrophic EB (DDEB) with mutation types c.5945G>T, c.6218G>A, Recessive Dystrophic EB (RDEB) c.2005C>T, c.6081dup, c.1268C>T, c.1784C>T which are all known mutations. Novel mutations were found in the COL7A1 gene in two patients namely DDEB c.6253G>T and RDEB c.6740C>T. Two EB Simplex (EBS) patients showed mutation KRT14 gene as c.356T>C, c.373C>T which are known mutation. In addition, a novel mutation in LAMA3 gene c.2649del was found in one Junctional EB (JEB) patient. CONCLUSION: The molecular diagnoses of 12 Indonesian EB patients were identified, of which three were novel pathogenic variants. Concordance between the initial clinical diagnosis and genetic testing was only 33%. This demonstrated the importance of early genetic testing for accurate diagnosis, prognostication, management and genetic counselling.

A Sensorised Glove to Detect Scratching for Patients with Atopic Dermatitis.

In this work, a lightweight compliant glove that detects scratching using data from microtubular stretchable sensors on each finger and an inertial measurement unit (IMU) on the palm through a machine learning model is presented: the SensorIsed Glove for Monitoring Atopic Dermatitis (SIGMA). SIGMA provides the user and clinicians with a quantifiable way of assaying scratch as a proxy to itch. With the quantitative information detailing scratching frequency and duration, the clinicians would be able to better classify the severity of itch and scratching caused by atopic dermatitis (AD) more objectively to optimise treatment for the patients, as opposed to the current subjective methods of assessments that are currently in use in hospitals and research settings. The validation data demonstrated an accuracy of 83% of the scratch prediction algorithm, while a separate 30 min validation trial had an accuracy of 99% in a controlled environment. In a pilot study with children (n = 6), SIGMA accurately detected 94.4% of scratching when the glove was donned. We believe that this simple device will empower dermatologists to more effectively measure and quantify itching and scratching in AD, and guide personalised treatment decisions.

Juvenile xanthogranulomas in Asian children.

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytic disorder. It can rarely be associated with systemic involvement. There is a paucity of literature on JXG in Asian children. We aim to describe the epidemiology, clinical features, systemic associations, histological features and outcome of a cohort of Asian children with JXG, and review the literature on the condition. We retrospectively reviewed the demographic, clinical and histological data of patients less than 16 years of age, diagnosed with JXG at our tertiary pediatric hospital between January 2002 and April 2019. A total of 147 children with JXG were identified, with a slight male preponderance of 53.1%. The median age of the onset was 15.5 months, with 69.4% presenting before 2 years of age. There was no racial predilection. The most frequently involved site was the head and neck region (44.2%). The majority of patients (76.2%) presented with a solitary lesion. Spontaneous resolution was documented in 57.7% of our patients with mean duration to resolution of 18.8 months. The proportion and speed of resolution did not differ in children with single or multiple lesions. No ophthalmologic complications were detected in our study cohort. JXG in children is generally limited to the skin and is rarely associated with systemic involvement, including the eye. Unless clinically indicated, the results from our study does not support routine screening for juvenile myelomonocytic leukemia, eye or systemic complications, even in the setting of multiple cutaneous JXGs.

Two Histologic Patterns of Lymphomatoid Papulosis Occurring in a Child: A Matter of Timing?

There are several histologic patterns seen in lymphomatoid papulosis, with the possibility of different subtypes occurring in the same patient. We report a case of lymphomatoid papulosis presenting with 2 histologic subtypes (types A and B) occurring concomitantly in a 10-year-old child, and postulate that the different subtypes occur dependent on the age of the lesion biopsied. Incidentally, one of the biopsies also shows a rarely seen pattern of pseudoepitheliomatous hyperplasia in a pediatric lymphomatoid papulosis patient.

Cellular neurothekeoma occurring at the site of radiation therapy in a child with medulloblastoma.

Cellular neurothekeoma is a rare, benign cutaneous neoplasm. We report a case of cellular neurothekeoma arising on the mid-back of a 10-year-old boy within the previous radiation therapy field for medulloblastoma. Clinical features of cellular neurothekeoma in children are similar to those in adults, except that there have been no reports of local recurrence in children following surgical excision, and the presence of atypical histological features does not predict clinical behavior. Recognition of this entity in children is important to avoid misdiagnosis and overly aggressive treatments.

Pediatric patch testing in a multi-ethnic Asian population: A retrospective review.

BACKGROUND: Pediatric allergic contact dermatitis (ACD) is increasingly prevalent. Patch testing is the gold-standard diagnostic investigation. The aims of our study were to describe the clinical profile of pediatric patients with ACD in a multi-ethnic Asian population and identify the common contact allergens. METHODS: This was a retrospective study involving children and adolescents aged 16 years or younger with clinically suspected ACD who underwent patch testing between January 2007 and March 2020 at two institutions in Singapore. Information pertaining to their demographics, atopy history, clinical presentation, and patch test results was analyzed. RESULTS: A total of 252 patients were included. The mean age was 10.9 years (1.0-16.7 years). The majority were Chinese (79.8%) and girls (57.5%). Many (66.3%) had atopic dermatitis (AD), which was mild. The most common presentation was an acral eczematous rash. The sensitization rate was 50.0%. The most frequent reactions were to nickel sulfate (49.2%) and fragrance mix (19.1%). The overall rate of relevant positive patch tests was 72.5%. Patients with AD were less likely to have a reaction to fragrance mix (p = .019) and more likely to have a reaction to disperse blue (p = .041). Compared to younger children, adolescents were less likely to have a positive patch test (p = .008). Indians were also less likely to have a positive reaction (p = .004). CONCLUSION: Metals and fragrances were the most common allergens causing childhood ACD in Singapore. Patients with AD were less likely to be sensitized to fragrances and more likely to be sensitized to disperse blue dye.

Dupilumab for children and adolescents with atopic dermatitis: An Asian perspective.

Atopic dermatitis (AD) is a common, chronic, recurrent inflammatory skin disease. Poorly controlled AD can lead to reduced quality of life (QoL) and psychosocial impairment. Dupilumab is the first approved monoclonal antibody targeting type 2 inflammation, for adolescent and adult patients with moderate-to-severe AD. We performed a retrospective analysis of the efficacy and safety of dupilumab in a cohort of Asian children and adolescents with moderate-to-severe AD. Clinical response was documented with investigator global assessment (IGA) and eczema area and severity index (EASI) scores. Improvement in QoL was assessed using child dermatology life quality index (CDLQI) or Teenager's quality of life (T-QoL), and caregivers' QoL was assessed using dermatitis family impact (DFI) questionnaire. Twelve patients were recruited, aged between 6 to 18 years of age (mean 13.3 years), with mean duration of AD of 9.8 years. At baseline, the mean IGA score was four and the mean EASI was 48.2. The mean T-QoL and DFI scores at baseline were 18.7 and 19.6, respectively. After 12 to 16 weeks of treatment, the mean IGA score decreased to 2.2. The mean EASI decreased to 19.3 with mean reduction of 28.9. The mean T-QoL decreased to 7.5 with mean reduction of 11.2, and the mean DFI decreased to 8.6 with mean reduction of 11. Adverse events included mild conjunctivitis in two patients and paradoxical head and neck erythema in one patient. Our study supports dupilumab as an effective and safe treatment option for Asian children and adolescents with moderate-to-severe AD.

Acute generalized exanthematous pustulosis in children and adolescents in Singapore: A ten-year retrospective review.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe, cutaneous adverse reaction. Although most commonly caused by drugs, it can also be triggered by infections, especially in children. METHODS: This is a retrospective study involving children and adolescents aged 16 years or younger, diagnosed with AGEP between January 2010 and March 2020 in our tertiary pediatric hospital. Information pertaining to the patient's demographics, clinical presentation and progress, biochemical, microbiological, and histopathological investigations, treatment, and outcomes was analyzed. RESULTS: Eight patients were diagnosed with AGEP with mean age 8.2 years (range: 1.7-16.0 years). None of the patients had a personal or family history of psoriasis. Almost all patients had fever (n = 7, 87.5%). Although all 8 patients had intercurrent illness, 5 cases were attributed to infection, while the other 3 were likely precipitated by drugs. Abnormal hematological and biochemical parameters included a raised absolute neutrophil count (mean: 11.5 × 109 /L, range: 5.0-30.9 × 109 /L), C-reactive protein (mean: 52.5 mg/L, range: 5.0-143.7 mg/L), and erythrocyte sedimentation rate (mean: 38.6 mm/h, range: 6-64 mm/h). All patients developed post-pustular desquamation and subsequently recovered. The mean duration from onset to cessation of acute pustulation was 5.6 days (range: 3.0-10.0 days). One patient developed a recurrent episode of AGEP. CONCLUSION: AGEP is rare and may be more commonly caused by infections in children. The condition is self-limiting with overall good outcomes in this age-group. In cases with concomitant infection and drug use, formal allergy testing should be arranged after resolution of the infection to confirm the underlying etiology.

CARD14-associated papulosquamous eruption (CAPE) in a toddler responding to treatment with acitretin.

CARD14-associated papulosquamous eruption (CAPE) is a rare autosomal dominant dermatosis that presents classically in early childhood with clinical features of both psoriasis and pityriasis rubra pilaris (PRP). The disease is known to be refractory to topical and systemic therapies classically used for psoriasis, with the majority of reported cases requiring treatment with biologics, such as ustekinumab and secukinumab. We present a toddler with a clinical presentation consistent with CAPE and found to have a novel heterozygous variant of the CARD14 gene. She was refractory to treatment with topical emollients and topical corticosteroids, but responsive to oral acitretin.

Epidermolysis bullosa with pyloric atresia associated with compound heterozygous ITGB4 pathogenic variants: Minimal skin involvement but severe mucocutaneous disease.

We report a case of junctional epidermolysis bullosa with pyloric atresia (JEB-PA) with minimal skin involvement but severe protein-losing enteropathy and airway involvement. Genetic analysis revealed heterozygous mutations in the ITGB4 gene encoding integrin ß4 protein. Parental testing confirmed inheritance of frameshift variant (c.794dupC) as maternal and splice site variant (c.1608C>T/p.Cys536Cys) as paternal. Immunofluorescence mapping of her skin revealed a subepidermal blister with decreased and frayed integrin ß4 at both the floor and the roof of the blister, while the intestinal mucosa showed complete absence of integrin ß4. We review the literature and discuss the differential expression of integrins in the skin and gastrointestinal tract, as well as the role of chronic inflammation in the pathogenesis of EB.

Moisturisers from birth in at-risk infants of atopic dermatitis - a pragmatic randomised controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a common, chronic dermatosis, with onset of disease often manifesting in early infancy. Past studies evaluating the early use of moisturisers in the prevention of AD had mixed results. OBJECTIVES: To compare the incidence of moderate or severe AD and total incidence of AD in a cohort of 'at-risk' infants treated with moisturisers from the first 2 weeks of life, to a similar group without moisturisers. METHODS: We performed a single-centre, prospective, parallel-group, randomised study in infants with at least 2 first-degree relatives with atopy. Subjects were randomised into either a treatment group with moisturisers or a control group without moisturisers. Participants were assessed at 2, 6, and 12 months for AD and if present, the severity was assessed using SCORAD index. We also compared the overall incidence of AD, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, pH, and incidence of food and environmental sensitisation and allergies between both groups. Genotyping for loss-of-functions mutations in the FLG gene was conducted. RESULTS: A total of 200 subjects were recruited, with 100 subjects in each arm. There was no significant difference in incidence of moderate or severe AD, and total incidence of AD at 12 months between the treatment and control groups. There was a lower mean SCORAD in the treatment group than in the control group, but no significant difference in TEWL, SC hydration, and skin pH. No significant side-effects were reported. CONCLUSIONS: The early use of moisturisers in 'at-risk' infants does not reduce the incidence of moderate-to-severe AD and overall incidence of AD in infancy.

Treatment of cutaneous viral warts in children: A review.

Viral warts or verruca are very common skin infections in children. Although benign, lesions can be extensive, painful, bleed, or lead to cosmetic disfigurement. Although spontaneous resolution can occur, parents often bring their children for treatment, especially when they are symptomatic. Many publications have assessed the efficacy and safety of treatment of warts in adults. However, treatment in children can be challenging due to their immune responses and lower threshold for pain. We review the current literature on the methods, efficacy, and side effect profile of common treatment modalities for cutaneous viral warts in children. There is evidence that salicylic acid and cryotherapy are effective, and although cryotherapy is more effective, there is a higher risk of side effects such as pain and blistering. Combination treatment with salicylic acid and cryotherapy may reduce these side effects. Although there is limited data, other treatment options such as cantharidin, immunotherapy and other mechanical therapies, for example, carbon dioxide lasers, may also be considered, especially for recalcitrant lesions.

A rare case of cutaneous Trichosporon asahii infection in an immunocompromised child.

We present an 11-year-old girl who developed neutropenic fever and papulonodular lesions over her limbs and back following chemotherapy for relapsed acute myeloid leukemia. She was found to have cutaneous Trichosporon asahii infection, with no evidence of systemic infection, and responded to treatment with voriconazole. T. asahii infection is rare but often fatal and usually causes disseminated infections in immunocompromised patients. Cutaneous infection is relatively uncommon and rarely occurs in the pediatric population.

Vulvar lymphangiectasia secondary to gastrointestinal tuberculosis infection in a teenager.

We report a rare presentation of vulvar lymphangiectasia that developed secondary to gastrointestinal tuberculosis in a teenager, and its spontaneous resolution after anti-tuberculous treatment was completed.

Pilot study of a customized nanotextile wet garment treatment on moderate and severe atopic dermatitis: A randomized clinical trial.

BACKGROUND: Atopic dermatitis (AD) is a common dermatosis. The cornerstone of eczema management is to repair and maintain skin barrier and hydration, as well as to reduce inflammation. Wet wrap therapy (WWT) is a widely used adjunct to achieve this. The conventional material used for WWT is viscose, which presents drawbacks including discomfort, high cost, and poor durability. Here, we explore the possibility of using customized nanotextile (nanopolyester) for WWT, hoping to prove that this material is non-inferior to viscose in clinical effectiveness and patient acceptance. METHODS: Patients aged 0-18 years with moderate to severe eczema were randomized to receive either viscose (Tubifast™) or nanotextile for WWT. Patients were instructed to apply WWT daily overnight for 2 weeks. Patients' disease severity score (IGA, SCORAD) and quality of life (QoL) score (IDQOL/CDLQI) were measured on day 0, 7, and 14 of treatment. Patient survey was conducted to collect patients' feedback about garment use. RESULTS: Fifty-three children aged 7 months to 17 years were recruited (27 in Tubifast™ and 26 in nanotextile group). Patients in both groups showed significant improvement in disease severity and QoL from baseline (P < .001), and such improvement was similar in both groups. However, nanotextile garment was significantly more comfortable (2.73/10 vs 5.12/10, P = .001), easier to wear (2.78/10 vs 5.24/10, P = .003), and cooler (2.43/10 vs 3.96/10, P = .033) from patients' feedback. CONCLUSION: This study demonstrates that nanomaterial is as effective as conventional viscose in WWT, while superior in patient acceptability. Nanotextile for WWT has good potential in eczema management, especially in patients with suboptimal response to topicals alone.

Associations between health-related quality of life and health care costs among children with atopic dermatitis and their caregivers: A cross-sectional study.

BACKGROUND/OBJECTIVES: Atopic dermatitis is associated with a decreased health-related quality of life and contributes to substantial health care costs. It is important to understand what accelerates health care costs to inform various stakeholders, so they can effectively meet health care needs. This cross-sectional study aims to explore associations between health-related quality of life, health care costs, and cost-accelerating variables. METHODS: Information on health-related quality of life (HRQoL) was collected through generic and disease-specific instruments from caregivers and children <16 years of age with a physician-confirmed diagnosis of atopic dermatitis. The economic impact of atopic dermatitis was evaluated by analyzing information on health service utilization and other health care costs related to managing the condition. RESULTS: Children with high impact on health-related quality of life presented an annual health care cost of US$ 3787 compared with US$ 2548 for moderately impacted and US$ 2258 among children for which the condition had low impact. The severity of atopic dermatitis, disease duration, and a lower health-related quality of life was associated with greater health care costs. Analyses of subdomains of health-related quality of life revealed correlations between "mood" and "personal relationships" on one hand and caregivers' physical health and health care costs on the other hand. CONCLUSIONS: Highly affected HRQoL is associated with increased health care costs and could be a valuable complement to traditional severity assessments. By using HRQoL instruments, burdens and symptoms beyond severity can be identified and addressed with interventions to increase HRQoL and subsequently reduce health care costs.

Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies.

Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet's syndrome-like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.