Molecular profiling of an Indian EB cohort - a single centre experience.

INTRODUCTION: Epidermolysis bullosa (EB) encompasses rare hereditary skin conditions marked by skin fragility, nail dystrophy, and minor trauma-induced skin blisters. This study aims to identify genetic variants in Indian EB patients and examine the relationship between genotypic and phenotypic manifestations. MATERIAL AND METHOD: EB patients seen consecutively over a period of 5 years at Outpatient Department of Dermatology. Baseline demographic data, birth history, family history, skin manifestation at birth, past medical history, current cutaneous manifestations, and the evolution of the disease were assessed and recorded. Genetic variants were identified using targeted gene panel sequencing of 23 EB-related genes, and a genetic-phenotype analysis was performed. RESULTS: Our study included 65 patients with EB. Among 65 EB patients, 38 dystrophic EB cases (58.46%), 12 junctional EB (18.46%), 12 epidermolysis bullosa simplex (18.46%), and 3 Kindler EB (4.62%) were reported. Dominant and recessive forms of dystrophic EB accounted for 16.92% and 41.4%, respectively. We identified 75 unique genetic variants, 58.67% newly discovered and 41.33% previously reported. Compound heterozygous variations were more frequent (55.55%) than homozygous ones (44.44%) in recessive dystrophic EB patients. Junctional EB patients harboured LAMB3 gene mutations more frequently, while epidermolysis bullosa simplex patients showed KRT5 and KRT14 gene missense heterozygous mutations. Kindler EB patients had homozygous mutations in the FERTM1 gene. CONCLUSION: Our study unveiled several novel genetic variants; severe phenotypes associated with nonsense genetic variants. These findings offer valuable insights for future clinical assessments and tailored management strategies.

Direct immunofluorescence on plucked hair outer root sheath can predict relapse in pemphigus vulgaris.

BACKGROUND: Prospective research is lacking on the utility of plucked hair outer root sheath direct immunofluorescence (ORS DIF) in the prediction of relapse in pemphigus vulgaris (PV) and the correlation of ORS DIF positivity with serum desmoglein antibody titers. METHODS: We performed a prospective cohort study enrolling 80 PV patients in complete clinical remission at a tertiary care center in North India. Study participants underwent ORS DIF at baseline, which was repeated every 3 months. Skin biopsy DIF was done at study inclusion, repeated at 3 months, and upon clinical relapse. An antidesmoglein antibody titer was assessed concurrently with ORS DIF in a subset of patients. Patients on adjuvant therapy had their adjuvant therapy withdrawn either at the initial visit, at 3 months, or at a 6-month follow-up. Our objectives were to determine the association between positive ORS DIF and clinical relapse, the correlation between positive ORS DIF and skin biopsy DIF, and between positive ORS DIF and positive antidesmoglein antibody titers (when concurrently done). RESULTS: Twenty-two patients (27.5%) had a clinical relapse. Baseline immunological markers significantly associated with relapse are ORS DIF positivity with IgG (16/36 [45.44%] P = 0.005) and C3 (12/29 [41.37%] P = 0.047) and greater intensity of baseline IgG and C3 positivity in ORS DIF (IgG, P = 0.002; C3, P = 0.033). Notably, a significant correlation was observed between baseline positive ORS DIF and skin biopsy DIF (IgG, ρ = 0.695; C3, ρ = 0.498). Positive ORS DIF strongly correlated with positive anti-Dsg3 antibody titers (φs = 0.815; P < 0.01). Early withdrawal of adjuvant immunosuppressant (within 3 months) (P = 0.007) and positive ORS DIF were also associated with relapse (P = 0.017). CONCLUSION AND RELEVANCE: ORS DIF is a reliable predictor of PV clinical relapse and demonstrated robust correlations with skin biopsy DIF and antidesmoglein antibody titers. Periodic assessment of ORS DIF aids in determining new-onset positivity that heralds clinical relapse.

Direct immunofluorescence demystified: Essential insights and recent advances for dermatologists.

Direct immunofluorescence (DIF) is widely used in dermatopathology for the diagnosis of autoimmune blistering diseases (AIBDs), cutaneous vasculitis, and connective tissue disorders. Although it is easy and useful to perform, it needs technical expertise and experience for proper interpretation. The yield of DIF depends on multiple factors including the adequacy, transportation, storage, processing, and interpretation of the biopsy specimen. Effective collaboration between the dermatologist and dermatopathologist along with meticulous clinico-pathological correlation is crucial for accurately interpreting DIF in the appropriate clinical context. In this narrative review of DIF in dermatology, we discuss the indications of DIF, recent updates on the selection of optimum biopsy sites, basic techniques of DIF including the classical transport medium and its alternatives, processing and staining technique, patterns in various diseases, advancements such as serration pattern analysis, and latest recommendations on the use of DIF in cutaneous disorders.

Therapeutic success of tofacitinib in granuloma annulare: A retrospective case series of 15 patients.

Background Granuloma annulare (GA) is a necrobiotic granulomatous disorder that may sometimes be resistant to treatment, especially the generalised form. Tofacitinib has recently shown promise in the treatment of non-infective granulomatous dermatosis. Objectives In this study, we aimed to evaluate the response of generalised GA to oral tofacitinib. Methods This was a retrospective case series in patients of generalised GA who were treated with oral tofacitinib 5 mg twice a day in a tertiary care centre in north India. Baseline clinical details and histopathological findings were reviewed. Treatment response was noted in the form of clearance of lesions (complete or partial) along with the time taken to achieve the maximum response. Results A total of 15 patients of generalised GA were included in this study, amongst whom nine patients were resistant to conventional therapies whilst the remaining were treatment naïve. Complete clearance of lesions was noted in 11 patients at a mean treatment duration of 4.4 ± 2.1 months whereas clearance was partial in four, with a mean follow-up duration post- treatment in patients who had partial clearance, which is 7.3 ± 2.8 month, with a reduction in erythema and infiltration in those lesions. Adverse effects in the form of hyperlipidemia were observed in two patients. Conclusion Tofacitinib, a JAK-STAT inhibitor is beneficial in treating GA, especially in those with generalised and recalcitrant disease.

Clinical and demographic characteristics of mucous membrane pemphigoid in India: A retrospective analysis.

Background Mucous membrane pemphigoid (MMP) is a rare subepidermal autoimmune blistering disorder. The clinical and demographic parameters of this disease in Indian patients have not yet been elucidated in detail. Objective We aimed to study the clinical and demographic characteristics, disease course, and treatment aspects of MMP patients. Methods The data for this study were obtained by reviewing the case record forms of patients registered in the Autoimmune Bullous Disease (AIBD) Clinic of the Department of Dermatology, Venereology & Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, a tertiary care centre in India. The diagnosis of MMP was established on the basis of clinical and immune-histopathological features which are consistent with standard diagnostic criteria for the disease. Results A total of 52 patients with MMP registered in the AIBD clinic were included. The mean age at disease onset was 50 years and the average age at presentation was 56 years. Females outnumbered males in the study with a ratio of 1.36:1. The oral and ocular mucosae were the most commonly affected sites (82.6% and 63.4% respectively). Visual difficulty was reported by half the patients (26 of 52 patients). IgG, C3, and IgA deposits were detected on direct immunofluorescence (DIF) in 29, 21, and 11 patients, respectively. Serologic analysis was performed in only 7 of the patients and of these, just 1 exhibited a positive result on multivariant ELISA and epidermal pattern of binding on salt split skin indirect immunofluorescence. Most patients were treated with prednisolone (44 of 52). Steroid-sparing adjuvants were used in combination including cyclophosphamide, azathioprine, methotrexate, dapsone, and colchicine. Rituximab was administered in 7 patients with severe or refractory disease. Limitations This is a retrospective analysis of data available from a clinic registry. In patients with negative direct immunofluorescence on biopsy, the diagnosis was based on clinico-pathologic consensus. Conclusion MMP is not as uncommon in India as the paucity of reports suggest. Visual complications are frequent in Indian MMP patients. A high index of suspicion is required for early diagnosis and appropriate treatment to prevent ocular complications.

Clinico-epidemiological characteristics and long-term surgical outcome of basal cell carcinoma treated with standard excision in patients of skin of colour: A retrospective study from Northern India.

Background There is scant data on basal cell carcinoma (BCC) in Indian patients. This retrospective study was conducted to explore epidemiology, risk factors, clinical and pathological aspects, and long-term treatment outcomes of BCC in a cohort of North Indian patients. Methods Data about patients registered in the dermatosurgery clinic between 01 January 2017 and 31 December 2022 with a confirmed diagnosis of BCC was collected. Results Among the 83 patients, 56.6% were females, and the median age was 62 years (6-85 years). Most patients (81.9%) had a single BCC lesion, resulting in a total of 126 assessed lesions. The median size of BCC at presentation was 1.90 cm, with nodular BCC being the most common histopathological subtype (39.7%). Head and neck region involvement was observed in 82.5% of patients, with the malar region, nose, and periorbital region being the most commonly affected sites. Pigmentation was clinically evident in 45.2% of cases. Surgical excision was the primary treatment modality (71.1% of patients). The median follow-up duration was 40 months (6-57 months). Recurrence occurred in five patients, with a longer disease-free survival period observed in the surgically treated group (55.58 ± 0.98 months) compared to patients treated with medical or destructive therapies (43.6 ± 3.482 months) (p = 0.003). Conclusion The data from this hospital-based study indicated a slight predilection for females among North Indian patients with BCC, with most cases occurring during their seventh decade of life. The condition commonly occurred on sun-exposed areas such as the malar region and nose, with a high percentage of pigmented lesions. Recurrence following surgical excision was rare, and overall treatment outcomes were favourable.

Cutaneous Inflammatory Manifestations of Chronic Granulomatous Disease.

This cross-sectional study examines cutaneous inflammatory presentations of chronic granulomatous disease.

Giant Genital Mass: Unveiling a Unique Case of Folliculocystic and Collagen Hamartoma.

Folliculocystic and collagen hamartoma (FCCH) is a rare entity, typically documented in males with tuberous sclerosis complex. Here, we report a unique case of FCCH in a 19-year-old female with an unusual presentation in the external genitalia. The patient presented with a progressively enlarging mass over three years, causing difficulties in walking and sitting. Examination revealed a 10 x 15 cm tender, lobulated, skin-colored tumor with comedo-like openings originating from the right labium majus, with satellite lesions on both labia majora. She had no other symptoms or history suggestive of tuberous sclerosis. Histopathological examination showed dilated hair follicles with keratin, perifollicular fibrosis, and thick dermal collagen bands extending into subcutaneous tissue, confirming FCCH. This case underscores the importance of considering FCCH in the differential diagnosis of genital masses, even without classical clinical associations. Our findings contribute to the limited literature on FCCH and highlight the need for further exploration and awareness within the medical community.

Diagnostic Utility of Multiplex Polymerase Chain Reaction in Patients of Clinically Suspected Pure Neuritic Leprosy by Identifying Mycobacterium leprae in Skin Biopsy Samples and Nasal Swabs.

Pure neuritic leprosy (PNL) often remains underdiagnosed due to the lack of simple, reliable diagnostic tools to detect Mycobacterium leprae. This study aimed to investigate the utility of multiplex polymerase chain reaction (MPCR) in easily accessible and less invasive biopsy sites, including skin biopsy samples and nasal swabs (NSs), to detect M. leprae. A total of 30 (N = 30) clinically suspected and untreated patients with PNL were recruited. Nasal swabs and skin biopsy samples from the innervation territory of an "enlarged nerve" were collected. DNA was extracted and subjected to MPCR (targeting leprae-specific repetitive element [RLEP], 16S rRNA, and SodA genes) and RLEP-PCR (individual gene PCR). The PCR products were analyzed by 3% agarose gel electrophoresis. In 30 patients with clinically suspected PNL, 60% (N = 18) of skin biopsy samples and 53% (N = 16) of NSs were found positive for M. leprae DNA by MPCR, whereas only 23.3% (N = 7) of skin biopsy samples and 10% (N = 3) of NSs were found positive by RLEP-PCR. MPCR demonstrated a greater positivity rate than did RLEP-PCR for detection of M. leprae. Serologic positivity for anti-natural disaccharide-octyl conjugated with bovine serum albumin (ND-O-BSA) antibodies was 80% (16/20), including 35% (7/20) of PNL patients for which the skin MPCR was negative. Both serologic positivity and skin MPCR positivity were observed in 65% of patients (N = 20). Multiplex polymerase chain reaction is a useful tool for detection for M. leprae in skin biopsy samples and NSs in clinically suspected cases of PNL, with the added advantages of being less invasive and technically easier than nerve biopsy.

Clear cell myomelanocytic tumor of ligamentum teres.

Clear cell myomelanocytic tumor (CCMMT) of the falciform ligament/ligamentum teres is a rare hepatic tumor, a variant of the perivascular epithelioid cell tumor (PEComa) family. CCMMT is the rarest variant of hepatic PEComas. Only a few cases of CCMMT have been reported in the English literature. Because of its rarity, less is known about its biological behavior. We present a case of a 31-year-old female who complained of abdominal pain, bilious vomiting, and abdominal fullness over two months. The radiological impression was of focal nodular hyperplasia. The histological examination of the resection specimen revealed a well-circumscribed tumor arranged in fascicles, sheets, and a whorling pattern. The tumor cells were spindle to epithelioid shaped with abundant clear to pale eosinophilic cytoplasm. The tumor cells expressed both myoid (smooth muscle actin) and melanocytic (MelanA and HMB45) markers, while they were negative for hepatocytic and vascular markers. Thus, based on histology and immunohistochemistry, a diagnosis of CCMMT was made. This case presents the diagnostic challenges of CCMMT and discusses the differential diagnosis with a literature review.