Biologics in congenital ichthyosis: are they effective?

BACKGROUND: Congenital ichthyoses (CI) comprise a heterogeneous group of genetic diseases requiring lifelong treatment and having a major effect on quality of life. Conventional treatments reduce scaling and skin discomfort; however, they usually have little or no effect on erythema and pruritus. The identification of cytokine alterations in CI raised the possibility of repurposing available biologics. Several case reports in the literature report successes using different biologics. OBJECTIVE: We aimed to report the effects of biologics in real life. METHODS: This was a retrospective, observational, international multicenter study of patients with CI treated with at least one biologic for a minimum of 3 months. The effect of the biologics was evaluated using an Investigator Global Assessment-Change (IGA-C) scale. A comprehensive literature search was performed in parallel. RESULTS: A total of 98 patients were included, with a mean age of 19.7 years and both sexes equally represented. Patients with Netherton syndrome (NS) or congenital ichthyosiform erythroderma (CIE) represented the majority of patients (30% and 21.4%, respectively). Most patients (84.7%) had a severe or very severe form of CI. The most frequently used biologics were inhibitors targeting interleukin-17 (IL-17), IL-12/IL-23, or the IL-4 receptor. The mean duration of treatment was 22+20.1 months. There were 45 responders (45.9%), including 18 patients (18.3%) who were good responders; all had an erythrodermic CI subset and received one of the three main biologics. In 2 NS and CIE, IL-12/IL-23 and IL-4 receptor inhibitors tended to be most effective. Review of the literature revealed a shorter mean duration of use of biologics (11.5+8.5 months) and higher percentage of responders (85.7%), suggesting reporter bias. CONCLUSION: This series identified subsets of CI that may respond to biologics and will aid in designing future clinical trials of biologics for CI.

Self-induced panniculitis in adolescence: Three cases and review of the literature.

Self-induced trauma is a rare cause of panniculitis in adolescents and may be associated with undiagnosed underlying psychological conditions. The condition often poses a diagnostic challenge as patients usually present with non-specific signs and symptoms, and often a concealed history of self-induced trauma. Here, we present three adolescent patients with self-induced traumatic panniculitis. All three patients were repeatedly admitted with non-specific cutaneous lesions as well as multiple somatic complaints. After extensive evaluation to exclude organic causes, psychiatric assessment eventually revealed underlying psychosomatic disorders as a cause of the self-induced trauma.

Self-improving dystrophic epidermolysis bullosa: First report of clinical, molecular, and genetic characterization of five patients from Southeast Asia.

Self-improving dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by significant improvement in skin fragility within the first few years of life. Genetic inheritance has previously been reported as autosomal dominant or recessive with both forms harboring mutations in COL7A1. To date, there have been no reports of this rare clinical entity from various Southeast Asian ethnicities. Here, we describe the clinical and molecular features of five patients from the Southeast Asia region who presented with predominantly acral-distributed blisters and erosions in the first few days of life. Blistering resolved over several months, without appearance of new blisters. By immunofluorescence, intraepidermal retention of Type VII collagen was observed in all patient skin biopsies when investigated with antibody staining. Genetic analysis of four patients revealed pathogenic variants in COL7A1 which have not been previously reported. The clinical diagnosis in these rare patients is confirmed with molecular histology and genetic characterization.

Palmoplantar keratoderma, oral involvement, and homozygous CTSC mutation in two brothers from Cambodia.

Haim-Munk syndrome (HMS) and Papillon-Lefevre syndrome (PLS) are phenotypic variants of palmoplantar keratoderma (PPK) with progressive early-onset periodontitis and dental caries. HMS and PLS have been associated with homozygous or compound heterozygous mutations in the lysosomal protease gene Cathepsin C (CTSC). There have been only a few documented cases of CTSC mutations in patients from South-East Asia. We report the clinical findings of two Cambodian brothers who presented with diffuse, demarcated PPK with transgrediens extending to the elbows and knees, as well as pachyonychia and dental caries. Arachnodactyly and periodontitis were also found in the older brother. Next-generation sequencing unveiled a homozygous missense variant in CTSC (NM_001814.5: c.1337AC: p.(Asp446Ala)) in both brothers. Both parents were heterozygous for the variant, while an unaffected older brother was homozygous for the wild-type allele. Our study adds to the spectrum of mutations and associated clinical presentations for this rare genodermatosis.

Rumpel-Leede Phenomenon-An alarming rash with benign etiology in 4 healthy infants.

The Rumpel-Leede phenomenon (RLP) is a rare clinical presentation and in some cases shown to be related to serious systemic conditions. In children, it has been described in association with idiopathic thrombocytopenic purpura and Henoch-Schönlein purpura. We present a series of pediatric cases of RLP with mechanical etiologies that had a benign course. We propose minimal investigations for pediatric RLP cases who are systemically well and have a clear suggestive history of a mechanical cause.

Drug reaction with eosinophilia and systemic symptoms in a cohort of Asian children.

BACKGROUND/OBJECTIVES: Drug reaction with eosinophilia and systemic symptoms (DRESS) is rare but potentially fatal in children. Fever and rash, which are salient features of DRESS, may mimic other commonly encountered pediatric conditions. We profiled the DRESS cases in a tertiary children's hospital in Singapore. METHODS: The medical records of all pediatric DRESS patients diagnosed from 2006 to 2016. Data on epidemiology, inciting drugs, clinical, pathologic manifestations, and treatment were assessed. RESULTS: Ten patients aged 4-16 years old were diagnosed with DRESS within the 10-year period. Drugs implicated were antibiotics, such as trimethoprim-sulfamethoxazole, and anticonvulsants, such as carbamazepine, phenobarbitone, and levetiracetam. All patients had fever and pruritic exanthems. Desquamation, purpura, and oral mucositis were also observed. Lymphadenopathy, hepatomegaly, and facial edema occurred frequently. There was liver involvement in all cases, but none progressed to liver failure. Seven patients had eosinophilia, and nine had atypical lymphocytosis. Other laboratory abnormalities included low hemoglobin, thrombocytosis, and prolonged coagulation times. All patients received systemic corticosteroids of varying durations and dosages. Systemic steroids were weaned after 19 days to 4 months. Disease resolution, with liver enzyme levels returning to normal, occurred within 28-90 days. One patient developed TSH-receptor-antibody-positive hyperthyroidism 6 months after the onset of DRESS, while another patient developed chronic urticaria 4 months after resolution of DRESS. CONCLUSION: Early recognition of DRESS is important to ensure that the inciting drug is discontinued, and supportive treatment started expediently. Liver involvement was very common but responded well to systemic steroids.

Should we biopsy melanonychia striata in Asian children? A retrospective observational study.

BACKGROUND AND OBJECTIVES: Melanonychia striata is common in children of darker-skinned Asian races, while subungual melanoma is extremely rare and it is difficult to make a diagnosis clinically. However, performing nail unit biopsies in children is particularly challenging and can result in permanent nail dystrophy. The aim of this study was to review the clinical and histologic characteristics of melanonychia striata in pediatric patients of Asian descent to aid in the clinical decision regarding nail biopsy. METHODS: Sixty-two pediatric patients presenting with melanonychia striata involving single or multiple nails at two tertiary pediatric dermatology clinics in Singapore between 2005 and 2015 were reviewed. Clinical and histopathological data were analyzed, including age at onset, age at presentation, location, color, width, presence of Hutchinson's sign, pseudo-Hutchinson's sign, nail dystrophy, length of follow-up, and clinical evolution. Histopathological assessment was performed by three senior dermatopathologists independently for cases that underwent a nail biopsy. RESULTS: No cases of subungual melanoma were detected in our series. Solitary melanonychia of the thumbnail with a single uniform color was the most common presentation. Pseudo-Hutchinson's sign was commonly observed. Consensus in histological diagnosis emerged amongst all three dermatopathologists in only half of the cases biopsied. CONCLUSION: The occurrence of melanoma in Asian children presenting with melanonychia is extremely rare. We recommend clinical follow-up and anticipatory guidance for these patients and nail unit biopsy only in the presence of high-risk clinical features.

Epstein-Barr virus positive diffuse large B-cell lymphoma presenting with vaginal sloughing and ulcerated skin nodule.

Malignant lymphomas presenting in the female genital tract are extremely rare. We report a case of Epstein-Barr virus associated diffuse large B-cell lymphoma of the genital tract and skin in a 60-year-old woman on long-term azathioprine.

Lymphocytic Thrombophilic Arteritis: A Possible Association with Minocycline.

We describe a case of lymphocytic thrombophilic arteritis in a 15-year-old girl who had previously taken minocycline for a year. Cutaneous polyarteritis nodosa and lymphocytic thrombophilic arteritis share many features and may both be triggered by minocycline. There may be a long latency between drug exposure to minocycline and development of disease.

Transient Neonatal Zinc Deficiency Caused by a Novel Mutation in the SLC30A2 Gene.

This is a case report of a 4-month-old full-term, fully breastfed boy who presented with a persistent periorificial and groin rash associated with poor weight gain and irritability. His serum zinc level was low. The mother's breast milk zinc level was found to be low despite her serum zinc levels being normal, confirming the diagnosis of transient neonatal zinc deficiency. Mutational analysis revealed a novel mutation in the mother's SLC30A2 gene, which encodes a zinc transporter expressed in mammary gland epithelial cells.

Multidisciplinary management of chronic atopic dermatitis in children and adolescents: a prospective pilot study.

BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic disorder affecting 10-20% of children and is associated with psychological issues and impaired quality of life (QoL). The role of psychosocial support in the treatment of AD is increasingly important. We studied the impact of a multidisciplinary clinic (MDC) in the management of AD in a tertiary children's hospital in Singapore. METHODS: We performed a prospective pilot interventional study on 34 pediatric patients with AD and concomitant psychosocial impairment. Patients were recruited into an MDC, comprising a dermatologist, clinical psychologist and medical social worker. AD severity was scored using Scoring Atopic Dermatitis (SCORAD), while QoL was assessed using the Children's Dermatology Life Quality Index Questionnaire (CDLQI) and Family Dermatology Life Quality Index Questionnaire (FDLQI). Biopsychosocial assessments and interventions were also performed. Eighty-three percent of patients received cognitive behavioral therapy, while 40% received social work intervention. RESULTS: There was an overall improvement in mean SCORAD, CDLQI, and FDLQI scores across MDC visits. A correlation between AD severity and QoL was established. A patient satisfaction survey showed improvement in severity, understanding, and control of the disease. CONCLUSION: Our study suggests the effectiveness of a multidisciplinary approach in managing pediatric AD patients with psychosocial co-morbidities.

Progressive scarring facial lesions in a boy.

Hydroa vacciniforme is a photosensitivity disorder characterized by the childhood onset of necrotic vesiculopapules on exposed areas. We present a case of a 10-year-old boy with a 1-year history of papular lesions over his face. In this report, we discuss the in-depth histology of hydroa vacciniforme, and the management options.

Ulcerated Giant Dermatofibroma following Routine Childhood Vaccination in a Young Boy.

INTRODUCTION: The development of cutaneous neoplasms at immunization sites following vaccination is uncommon, and only few have been reported in the literature worldwide. We report an unusual case of an ulcerated giant dermatofibroma that developed as a chronic nonhealing plaque in the immunization scar of a young boy after vaccination. CASE REPORT: A 13-month-old Chinese boy presented with an unusual skin reaction on the vaccination site at the right anterolateral thigh following a routine intramuscular injection of '5-in-1' (diphtheria, tetanus, pertussis, polio and Haemophilus influenzae B) vaccine at 4 months of age. The immunization site developed a slightly raised papule with a central punctum that progressively grew in size, ulcerated and showed occasional bleeding over a span of 9 months. On follow-up, the lesion showed a chronic granulomatous reaction with surrounding induration and a central scarring. The right inguinal lymph node was palpable. Ultrasound of the lesion showed only nonspecific focal skin thickening. An incisional skin biopsy with careful histopathological evaluation revealed microscopic features consistent with an ulcerated giant dermatofibroma. CONCLUSION: Neoplastic development in immunization scars following vaccination is a rare occurrence and, hence, makes this case a diagnostic challenge. A high index of suspicion is crucial in atypical presentations of a common skin lesion, as typified by this case. Careful history taking and clinicopathological correlation of clinical findings with gross and microscopic findings along with targeted immunohistological staining is often essential to aid early diagnosis.