Pigmentary Changes in Systemic Sclerosis are Associated with More Severe Cutaneous Sclerosis and Severity of Other Systems: A Cross-sectional Study from India.

Background: Pigmentary changes of the skin in systemic sclerosis in the form of diffuse hyperpigmentation and salt-and-pepper pigmentation are well documented in the literature; however, its association with disease severity and extent of underlying internal organ involvement has not been well studied. Aims: To assess the correlation between morphology and extent of pigmentary changes with the degree of cutaneous sclerosis and frequency and degree of major organ involvement. Methods: This was a cross-sectional descriptive study conducted in a tertiary care teaching hospital from December 2014 to November 2016. Consecutive patients of systemic sclerosis attending the outpatient department were screened, and patients satisfying the diagnosis as per the American Rheumatism Association criteria were recruited. Skin sclerosis was quantified using modified Rodnan skin score (MRSS), whereas pigmentary changes were calculated in terms of percentage of body surface area involved by rule-of-nine method. Investigations were carried out depending on organ involvement and as per respective specialty consultations with focus on pulmonary, cardiac, and gastrointestinal systems. Results: Of the 50 patients recruited, all had cutaneous involvement in the form of binding down of skin, followed by pigmentary changes. MRSS was significantly higher in patients with any pigmentary alteration (P = 0.03) compared to those without any pigmentary changes. There was a rising trend in between the MRSS severity and the proportion of patients with hyperpigmentation, and it was statistically significant (P = 0.04). Among systemic involvement, lung was involved in the form of interstitial lung disease in 94% patients (n = 47). However, skin pigmentation of any type was associated with lower high-resolution computed tomography scores (P = 0.02). Conclusion: This study shows that in systemic sclerosis patients presenting with pigmentary skin manifestations, cutaneous sclerosis is significantly higher.

An Algorithmic Approach Towards Diagnosis of Patients with Hereditary Reticulate Pigmentary Disorders- A narrative review.

Hereditary reticulate pigmentary disorders include a group of genetic disorders with net-like pigmentation as their predominant presentation. Many of these hereditary reticulate pigmentary disorders have a wide array of cutaneous presentations with overlapping features. Furthermore, some of these disorders also have systemic manifestations. The overlapping features often add confusion and cause delay in the diagnosis. Based on the literature search, we propose an easy-to-follow concise diagnostic algorithm for the same. This would aid in ordering a definite genetic test. A thorough data search was done using data base PubMed using the following keywords. It included "'inherit*' OR 'genetic'" AND "reticulate AND pigment*"'. Thereafter, an individual disease search was done using keywords 'Dowling-Degos disease', 'Dyschromatosis Hereditaria Symmetrica', 'Acropigmentation of Kitamura', 'Dyschromatosis Universalis Hereditaria', 'Naegeli-Franceschetti-Jadasssohn syndrome', 'X-linked reticulate pigmentary disorder' and 'Dyskeratosis congenita'. The search included case reports, series, observational studies, narrative and systematic reviews, clinical trials. Acquired pigmentary disorders were excluded. A total of 1994 articles were retrieved. Finally, 625 articles were included for the review. The articles were narrative review articles (40), case series (23), observational studies (44), and case reports (518). An easy-to-follow clinical diagnostic algorithm based on age of onset, distribution, and other parameters would definitely aid in reaching a provisional diagnosis. And further this approach will help in the genetic workup of a case of hereditary reticulate pigmentary disorder.

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.

Renal Amyloidosis in a Child with Recessive Dystrophic Epidermolysis Bullosa Due to a Novel Variant in COL7A1 Gene.

Secondary amyloidosis may complicate inherited dermatoses, but recessive dystrophic epidermolysis bullosa (RDEB) complicated by renal amyloidosis is rare. We report a case of a 12-year-old male child with RDEB presenting with progressive generalized anasarca for 20 days. Kidney biopsy showed diffuse expansion of mesangial matrix by pale acellular Periodic Acid-Schiff (PAS)-negative amorphous material, which was congophilic on Congo red stain and gave apple green birefringence on polarization and extending along the glomerular basement membrane, suggestive of amyloidosis. Genetic analysis showed a compound heterozygous pathogenic variant in the COL7A1 gene with autosomal recessive inheritance.

Solitary verrucous plaque on a leg.

We present the case of a female in her 70s who presented with a solitary verrucous plaque on her left leg accompanied by painful oral erosions. Various differential diagnoses were considered, like lichen simplex chronicus, hypertrophic lichen planus, and chromoblastomycosis. We diagnosed pemphigus vegetans (PVeg) on a nonintertriginous site through comprehensive clinical examination and histopathological and immunopathological evaluations. This case highlights the importance of considering PVeg in the differential diagnosis of solitary verrucous plaques, even in atypical extra-flexural anatomical locations.

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.

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.

Facial Segmental Infantile Haemangioma: A Cutaneous Mosaicism Quandary.

Mosaicism has long been considered the underlying mechanism of segmental infantile hemangiomas (SIH). This was a prospective pilot case-control study conducted with the objective to quantify the percentage overlap of silhouettes of facial SIH with those of Blaschko lines (the most well studied archetypical pattern of mosaicism on face) as compared to other mosaic disorders on face. Lesional silhouettes of 8 patients with SIH (Group A) and 6 patients with other facial dermatosis known to have blaschkoidal distribution (Group B), were overlapped on a standardized template with Blaschkoidal lines on the frontal view of face. The alignment was done via the auto align tool of Photoshop and the percentage of overlap was calculated with an online image comparison software (IMGonline.com.ua). There was a significant difference in mean overlap in Group A (72.92 ± 15.6 %) as compared to Group B (90.1 ± 4.3%; P=0.018). Hence, we concluded that facial SIH do not follow lines of Blaschko.

Infantile hemangiomas: a dermatologist's perspective.

Infantile hemangioma (IH), the most common vascular tumor in pediatrics, is thought to arise from aberrant stem cell responses to stimuli such as hypoxia. This review explores the diverse manifestations, complications, and management strategies for IH, emphasizing the importance of a multidisciplinary approach. The epidemiology and risk factors associated with IH, including connections to prematurity, low birth weight, and family background, are discussed. The intricate pathogenesis involving hemangioma stem cells, KIAA1429, hypoxia, and the renin-angiotensin system is examined. The natural history and clinical features, as well as extracutaneous involvements such as hepatic IH, PHACES syndrome, and LUMBAR syndrome, are detailed. Complications such as ulceration, functional impairment, hypothyroidism, and cosmetic concerns are highlighted. The differential diagnosis and diagnostic modalities, including colorimeters, high-frequency ultrasonography, and imaging techniques, are discussed. Management approaches, including the use of propranolol, atenolol, corticosteroids, alternative systemic treatments, topical therapy, laser therapy, and surgery, are comprehensively reviewed. The evolving landscape of IH management is underscored, with ongoing research exploring alternative treatments and individualized approaches based on IH characteristics.

Clinico-Epidemiologic Profile of Non-Syndromic Congenital Ichthyosis - A Retrospective Chart Review of 107 Patients.

Background: Congenital ichthyoses are a rare Mendelian group of disorders affecting the integument with a heterogeneous clinical presentation amongst which scaling is a constant feature. There is scanty epidemiologic data regarding the clinical profile and histologic patterns of inherited ichthyosis from resource-poor countries. Aims and Objectives: The study was aimed at assessing the clinic-epidemiologic characteristics associated with the different forms of non-syndromic congenital ichthyosis. Materials and Methods: This was a retrospective chart review of ichthyosis patients that presented between July 2016 and Jun 2020. Details including demographic profile, clinical characteristics along with any relevant investigations done were included. Results: During the study period of 4 years, 107 patients with congenital non-syndromic ichthyosis were seen. The most frequent diagnosis was of common ichthyoses, followed by autosomal recessive congenital ichthyosis, epidermolytic ichthyosis and erythrokeratoderma, in decreasing order. Conclusion: Important clinical findings like erythema and the type of scales as well as histological differences including an absent or reduced granular layer in ichthyosis vulgaris can help differentiate among the clinical phenotypes of inherited non-syndromic ichthyosis especially in resource-poor settings. Also, there is a high prevalence of vitamin D deficiency and hence a need for screening for the same in all patients of congenital ichthyosis including the milder phenotypes.

Association of Attention Deficit Hyperactivity Disorder with the Use of Oral Propranolol in Infantile Haemangiomas: An Ambispective Comparative Study.

Previous studies have raised concerns about the effects of oral propranolol on the central nervous system in infants, the exact measure and mechanism and the long-term follow-up of which is less well studied. This was an ambispective comparative study of children with infantile haemangioma (IH) followed by a repeat visit 4-10 years after completion of propranolol therapy. Parents were asked about psychologic functioning along with an initial screening examination. All patients were evaluated by a paediatric psychiatrist. After evaluation by the Strength and Difficulties Questionnaire, and subsequently by the paediatric psychiatrist, 2 of 12 patients (16.67%) showed features of attention deficit hyperactivity disorder in comparison to 0 of 40 subjects in the control group (0.0498; α = 0.05). These results indicate an increased risk of neuropsychiatric illnesses such as attention deficit hyperactivity disorder (ADHD) in patients given propranolol for IH, as supporting evidence to previous claims.

Construction and validation of an audio-visual tool to instruct caregivers of patients with pemphigus in photographing skin and oral cavity lesions during tele-consultation: A cross-sectional study.

Background Owing to the lack of standardised audio-visual (A-V) instructions to take photographs, patients with pemphigus faced difficulties during tele-consultation in COVID-19 pandemic. Objective To construct and validate an A-V instruction tool to take photographs of skin and oral cavity lesions of pemphigus. Methods In this observational study, we included patients with pemphigus of either gender seeking tele-consultation, aged 18 years or older. A-V instructions demonstrating skin and oral cavity photography were designed and shared with the patients. They were requested to send pictures of lesions that complied with the instructions. They were then required to complete a 10-item questionnaire for face validation in the two following rounds. The videos were content validated by 14 experts in the field of clinical dermatology. Results Forty-eight patients took part in face validation. A majority of patients, 47 (97.9%) and 45 (93.8%); rated the audio and video quality as being above average, respectively. Forty-seven patients (97.9%) said the instructional videos were useful, and 42 patients (87.5%) said they did not need to take any further images to show how severe their disease was. The average scale content validity index for the instructions on skin imaging and the oral cavity imaging during round 1 of content validation was 0.863 and 0.836, respectively. Limitation Validated instruction videos are in Hindi language and need to be further translated and validated in other local languages for use in non-Hindi speaking regions. Conclusion A-V instructions were useful to take photographs during tele-consultation.

RASopathies: Evolving Concepts in Pathogenetics, Clinical Features, and Management.

RASopathies refers to the group of disorders which are caused by a mutation in various genes of the RAS/MAPK (RAT sarcoma virus/Mitogen activated protein kinase) pathway. It includes many genes with varied functions, which are responsible for cell cycle regulation. As the mutation in one gene affects the entire pathway, there are many overlapping features among the various syndromes which are included under an umbrella term "RASopathies." However, neuroectodermal involvement is a unifying feature among these syndromes, which are caused by germline mutations affecting genes along this pathway. Recently, many other RASopathies have been described to involve blood vessels, lymphatics, and immune system. Also, many cutaneous mosaic disorders have been found to have mutations in the concerned pathway. The purpose of this article is to briefly review the pathogenesis of RASopathies with cutaneous manifestations, and summarise the features that can be helpful as diagnostic clues to dermatologists. As we understand more about the pathogenesis of the pathway at the cellular level, the research on genotype-phenotype correlation and therapeutic options broadens. Targeted therapy is in the clinical and preclinical trial phase, which may brighten the future of many patients.

Ectodermal Dysplasia - An Overview and Update.

Ectodermal dysplasias are a heterogeneous group of disorders that are characterized by abnormal development of ectodermal structures like hair, teeth, nails, and sweat glands. Alhough they were earlier classified according to the structures affected and hence the clinical manifestations, recent developments inch towards a genetic basis for classification. They are currently divided into four groups of disorders based on the pathway involved, which includes the ectodysplasin/nuclear factor-kappa B (NFKB) pathway, wingless-type MMTV integration site family, member 10 ([wingless related integration site] WNT10), tumor protein p63 (TP63), and the structural group. In spite of attempts at the segregation of the various disorders, there is a great degree of overlap in clinical features among the conditions, which makes a thorough history-taking and clinical examination important in helping us arrive at a diagnosis and judge the various systems involved. A multidisciplinary approach forms the crux of the management of patients with ectodermal dysplasias and their families, with a focus on education, counseling, prosthesis, and an overall rehabilitative outlook. Special attention must also be paid to screening family members for varying severities of the disorders, and an attempt must be made at a genetic diagnosis with genetic counseling.