Rapid recovery in a child with febrile ulceronecrotic Mucha-Habermann disease following intravenous immunoglobulin administration.

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a lymphocyte-mediated inflammatory skin disorder, is considered a severe variant of pityriasis lichenoides et varioliformis acuta that can lead to a fatal outcome if not managed in a timely fashion. Children with FUMHD can have systemic complications involving various organs. The scarcity of reported cases and the absence of well-designed studies or randomized clinical trials to evaluate different therapeutic modalities pose a major challenge in treating this potentially life-threatening disorder. We report a five-year-old child with FUMHD and seizures treated unsuccessfully with a combination of systemic steroids, methotrexate, dapsone, and oral erythromycin, who improved rapidly and achieved disease control with just a single infusion of low-dose intravenous immunoglobulin.

Homozygous CARD14 variant presenting as infantile erythroderma.

A wide range of inherited and acquired conditions can manifest as infantile erythroderma, among which CARD14-associated papulosquamous eruption (CAPE) is a rare cause. An infant boy presented with a psoriasiform rash that progressed to erythroderma and was unresponsive to topical steroids and cyclosporine. The early onset of the disease, its severity and resistance to conventional treatment were suggestive of a genetic cause. Genetic evaluation revealed a homozygous CARD14 variant of uncertain significance establishing the diagnosis of CAPE, and his parents were heterozygous carriers. There was only minimal improvement in the condition with supportive management and treatment with acitretin. Unfortunately, the child succumbed to sepsis and metabolic complications following a sudden worsening of skin disease. This case highlights the significance of genetic studies in diagnosing treatment-refractory cases of infantile erythroderma and emphasises the importance of early recognition of this rare condition.

Algorithmic approach toward diagnosis of patients with congenital photosensitivity disorders and review of literature.

The congenital photosensitivity disorders present as cutaneous signs and symptoms secondary to photosensitivity, extracutaneous manifestations, and a predisposition to malignancy. Diagnosis of these conditions mainly depend on clinical findings as the molecular analysis is not always feasible. A review of all the related articles collected after a thorough literature search using keywords, "congenital AND photosensitivity NOT acquired" and the individual diseases was done. A total of 264 articles were included in the review. An algorithm for diagnosis of the different congenital photosensitivity disorders based on the various clinical presentations has been proposed. An early suspicion and diagnosis of the different congenital photosensitivity disorders is the cornerstone behind prompt institution of prevention and treatment, and decreasing the associated morbidity.

Upward trends of syphilis in the non-pregnant adults: A six-year report on clinical and epidemiological profile of syphilis from a tertiary care center, India.

Since 2000, a resurgence of syphilis has been noted in many developed and developing countries, especially among men who have sex with men (MSM). Incidence and prevalence of syphilis in pregnant women have been reduced drastically by mandatory screening in early pregnancy. Insufficient data in other populations especially from developing countries limit targeted public health interventions. This study aimed to describe the clinical and epidemiological profile of serologically confirmed syphilis cases among the non-pregnant high-risk group reporting to a tertiary care center in Southern India. A retrospective study was carried out in a tertiary care center in Southern India for 6 years from 2015 to 2020. A total of 265 serologically confirmed syphilis patients were included. A statistically significant increase in positivity from 0.52 to 2.1% was observed in this study (2015 to 2020). Among risk factors, high-risk behavior with multiple heterosexual partners was the commonest (51.3%), followed by marital partners who tested positive (9.4%) and MSM (7.5%). The majority of the patients were diagnosed at the latent stage (79%), followed by secondary syphilis (10%) and tertiary syphilis (8%). A quarter of patients (23%) were coinfected with HIV. Serological non-responsiveness was more common among HIV infected (47 vs. 24%). Sixteen had neurosyphilis and six had ocular involvement. HIV co-infection complicated 50% (8/16) of neurosyphilis patients. Syphilis is still prevalent, especially in high-risk groups including those are attending STI clinics. Further prospective multicentric studies are needed to identify and implement public health measures.

Self-healing cutaneous nodules with fever and arthritis: worrisome presentation of a benign disorder.

A 4-year-old boy with extensive papules and nodules with arthritis was evaluated and followed up. In spite of the initial worrisome presentation, the lesions showed near-complete resolution over a 2-year follow-up period. Click here for the corresponding questions to this CME article.

Coronavirus disease 2019 vaccination in patients with psoriasis: A position statement from India by SIG psoriasis (IADVL Academy).

Coronavirus disease 2019 (COVID-19) pandemic has affected every sphere of life including management of psoriasis. The availability of COVID-19 vaccines has given rise to hope and at the same time some apprehensions as well. With the general population becoming eligible for vaccination, there is some confusion, on the eligibility of patients with different medical conditions and patients on immunosuppressive or immunomodulating medications for COVID-19 vaccination. Dermatologists treating psoriasis patients frequently face questions from them, whether they can undergo coronavirus disease 2019 vaccination. A PUBMED search was performed using the following strategy: 'COVID-19' AND 'Vaccine' AND 'Psoriasis'. We also performed a PUBMED search using the following strategy: 'SARS-CoV-2' AND 'Vaccine' AND 'Psoriasis'. All articles irrespective of language and publication date were included to arrive at this position statement. This position statement deals with the safety, eligibility and modifications of treatment, if needed among psoriasis patients with regards to the coronavirus disease 2019 vaccines currently available in India.

Genotype of autosomal recessive congenital ichthyosis from a tertiary care center in India.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) refers to non-syndromic ichthyosis caused by mutations in one of the 13 identified genes. There are limited data on the genotype of ARCI and its phenotypic correlation from India. OBJECTIVES: The aim of this study was to characterize the genotype of ARCI among patients from the Indian subcontinent. METHODS: Twenty-eight patients clinically diagnosed as ARCI were recruited prospectively from September 2017 to June 2019 (21 months). DNA was extracted from peripheral blood and analyzed for the 13 described ARCI genes-TGM1, ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, and CASP14 by next-generation sequencing using an in-house panel. The variants identified were confirmed by Sanger sequencing and compared with known pathogenic variants to establish pathogenicity. We also attempted to correlate the phenotype with the genotype. RESULTS: Among the 28 patients recruited (M = 17, F = 11), we identified phenotypes of congenital ichthyosiform erythroderma in 12 (42.9%), 8 with lamellar ichthyosis (28.6%), 5 with intermediate phenotype (17.9%), and 3 with bathing suit ichthyosis (10.7%). Pathogenic and likely pathogenic variants were identified in 22 (78.6%) patients, involving 7 out of the 13 known ARCI genes while 6 (21.4%) did not have pathogenic variants. These included TGM1 mutation in 6 (21.4%), ALOX12B and ALOXE3 in 4 (14.3%) each, NIPAL4 and PNPLA1 in 3 (10.7%) each, and ABCA12 and CERS3 in 1 (3.6%) patient each. Previously unknown pathogenic variants were found in 59.1 % of patients. CONCLUSIONS: Our patients with ARCI were found to have genotypes as previously described in other populations.

Clinicopathological Profile of Childhood Onset Cutaneous Mastocytosis from a Tertiary Care Center in South India.

BACKGROUND: Mastocytosis is characterized by clonal proliferation of mast cells in various organs and can have isolated cutaneous or systemic involvement. Childhood-onset mastocytosis (COM) is usually cutaneous and regresses spontaneously, while adult-onset mastocytosis (AOM) is often persistent with systemic involvement. There is limited data on COM from India. OBJECTIVE: To elucidate the clinicopathological profile of COM. METHODS: We conducted a retrospective chart review of all the patients with histologically proven COM (≤16 years), presenting over 11 years (January 2009 to December 2019) to the Dermatology Department. We compiled the demographic data, clinical characteristics (morphology, extent, distribution), laboratory investigations, histopathology findings, imaging (ultrasound abdomen), c-KIT mutation results, where available, and other associated abnormalities, and grouped them according to the WHO classification for mastocytosis. RESULTS: Among the 66 patients with COM (M: F-1.6:1), 89.4% had onset before 2 years of age. The subtypes were: maculopapular cutaneous mastocytosis (MPCM: 44, 66.7%); mastocytoma of the skin (MOS: 19, 28.8%); diffuse cutaneous mastocytosis (DCM: 2, 3%) and indolent systemic mastocytosis (ISM: 1, 1.5%). Blistering was observed in 29 (43.9%) and Darier sign was elicited in 47 (71.2%) patients. Serum tryptase was elevated in 9/21 (42.9%) patients, but none had systemic mastocytosis. Three patients had c-KIT mutations (two in exon 8 and one in exon 17). Most patients were managed symptomatically and the patient with ISM improved with imatinib. CONCLUSION: MPCM is the most common variant of COM and most patients had a disease onset before 2 years. Overall, COM had a good prognosis with rare systemic involvement, mitigating the need for extensive evaluation routinely in children.

An unusual case of keratinopathic icthyosis: a diagnostic conundrum.

Epidermolytic ichthyosis (EI) is a rare inherited ichthyosis related to heterozygous mutations in the Keratin 1 or Keratin 10 genes. Because of the broad phenotypic spectrum, it is sometimes difficult to differentiate it from other keratinopathic ichthyoses (KI) in clinical practice. We report an intriguing case of KI presenting as generalized ichthyosis in a reticulate pattern surrounding islands of normal skin, epidermolytic hyperkeratosis and binucleate cells on histopathology, and heterozygous mutation in KRT10. Through this case, we would like to demonstrate the importance of genetic studies and genotype-phenotype correlation in diagnosing such challenging cases.

Paraneoplastic Autoimmune Multiorgan Syndrome: A Retrospective Study from a Tertiary Care Center in South India.

BACKGROUND: Paraneoplastic autoimmune multiorgan syndrome (PAMS), first described as paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome with a diverse spectrum of clinical and immunopathological features associated with an internal neoplasm. MATERIALS AND METHODS: The details of the patients diagnosed with PAMS/PNP from an Indian tertiary center between January 2010 to December 2019 were retrieved from the hospital database. The clinical manifestations, histopathological features, immunofluorescence findings, and other relevant clinical details were obtained. RESULTS: There were eight patients (4 males, 4 females) with PAMS, age ranging from 8 to 46 years (mean 31 years), of whom two were 8-year-old children. The mucocutaneous manifestations were polymorphic and all had recalcitrant oral mucosal involvement. The most common mucosal presentation was pemphigus-like (5/8), and the cutaneous presentation was lichen planus-like (5/8). Castleman's disease (5/8) was the commonest neoplasm followed by thymoma (2/8). Interface dermatitis was seen in all biopsies and three different patterns of direct immunofluorescence were seen, which were intercellular "fish-net" fluorescence in the epidermis (2/8), granular/linear deposition along the basement membrane (4/8) and a combination of both patterns (1/8). Indirect immunofluorescence done on rat bladder in 3 patients showed intercellular "fish-net" fluorescence. Desmoglein levels were not elevated in any of our patients. The follow-up period ranged from 1 to 112.5 months (mean, 23.6 months) with a mortality rate of 12.5%. CONCLUSION: In our study, Castleman's disease was the most common associated malignancy, and the mucocutaneous and histopathological findings were heterogeneous. Timely diagnosis and early intervention improved the outcome in our patients.

Phenotypic variability of a TREX1 variant in Aicardi-Goutieres type 1 patients from the Indian subcontinent.

Aicardi-Goutieres Syndrome (AGS) is a heterogeneous genetic syndrome, manifesting early as encephalopathy and is associated with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, thrombocytopenia and intracranial calcification. The most severe neonatal type, AGS1, is caused by biallelic disease-causing variants in TREX1. In this study, we describe four patients with TREX1-related AGS1 whose phenotype overlaps with intra-uterine infections and neonatal lupus. Exome sequencing identified a previously reported TREX1 variant, c.223dup (NM_016381.5; p. Glu75GlyfsTer82) in all the four patients belonging to the Indian subcontinent. The functional consequence of the disease-causing variant was predicted by using a new combination of bioinformatics softwares. The recurrence of this pathogenic variant indicates a possible founder effect in TREX1 for AGS1 in this population. The phenotypic variability in those with this founder mutation can mimic intrauterine infections and neonatal lupus, thereby leading to misdiagnosis warranting a targeted genetic testing approach to be a part of the diagnostic workup to obtain a definite, early and cost-effective diagnosis in patients from Indian subcontinent with early onset encephalopathy.

The Role of Frozen Section in the Rapid Diagnosis of Severe Cutaneous Adverse Drug Reactions.

CONTEXT: Early diagnosis is the mainstay in the management of severe cutaneous adverse reactions (SCARs) to drugs. AIMS: To study the role of frozen section in the rapid diagnosis of SCARs and the impact on outcome of the affected patients. SETTINGS AND DESIGN: A single-blind, hospital-based study was conducted from December 2014-July 2016. METHODS AND MATERIAL: We biopsied 32 adults with SCARs diagnosed by clinical features and standard criteria. The histopathological features seen on frozen sections were compared to that of paraffin blocks. The impact of rapid diagnosis on the clinical outcome was studied in toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). STATISTICAL ANALYSIS: Z test was used to compare two proportions. Kappa statistic, sensitivity, specificity, positive predictive value, and negative predictive value of the frozen section diagnosis were calculated in TEN/SJS and DRESS using MedCalc software. RESULTS: Frozen and paraffin sections were done in TEN/SJS spectrum (13), DRESS (17), and AGEP (2). The sensitivity, specificity and kappa values for frozen section diagnosis in SJS/TEN and DRESS were 91.7%, 95%, 0.867 and 94.4%, 100%, 0.937 respectively. The concordance between frozen and paraffin section diagnosis was 100% in TEN, SJS, DRESS and AGEP. All the 6 patients with TEN and 2 with AGEP survived. Taking the worst-case scenario, the mortality in SJS was 28.6%. The mortality among patients with DRESS was 11.8%. CONCLUSIONS: Frozen section helps in the rapid diagnosis and early treatment of SCARs and differentiates it from diseases that mimic it.

Learning to pop blisters in epidermolysis bullosa with a simple model.

Epidermolysis bullosa (EB) is a genetic disorder with skin fragility resulting in easy blistering of skin and mucous membranes. A plane of cleavage exists even where there is no visible blister, so new blisters should be drained as soon as possible to prevent their expansion. Although, learning how to drain blisters safely and painlessly without introducing infection is essential, it can be a major challenge, especially for new parents and children. To avoid demonstrating the technique directly on patient's skin, we have devised a simple teaching aid simulating a hand and forearm with multiple blisters, created with readily available materials. In our experience, we have found this low-cost model to be extremely useful to teach patients, families, and professional groups, how to drain EB blisters and it provides an effective, low-cost, painless substitute for real-life blisters, empowering parents and engaging children.

Two cases of CARD14-associated papulosquamous eruption from India.

Identification of CARD14-associated papulosquamous eruption (CAPE) is important as it helps in determining prognosis and management of those affected. We report two siblings with genetically confirmed CAPE presenting with treatment-resistant erythroderma in one patient and patterned psoriatic plaques with facial predominance in the other.