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.

Prolonged treatment of dermatophytosis caused by Trichophyton indotinea with terbinafine or itraconazole impacts better outcomes irrespective of mutation in the squalene epoxidase gene.

BACKGROUND: Over the past decades, the increasing incidence of recurrent dermatophytosis associated with terbinafine-resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients. METHODS: Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS-PCR. Based on the culture-positivity and prescribed systemic antifungal, patients were categorised into Group I culture-positive cases treated with systemic terbinafine and Group II culture-positive cases treated with systemic itraconazole, each for a total period of 12 weeks. RESULTS: In the present study, 477 (81.39%) were culture-positive; however, 12 weeks follow-up was available for 294 patients (Group I-157 and Group II-137) who were included for statistical analysis. In both groups [Group I-37/63 (51.4%) and Group II-14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8-12 weeks, the odds of cure rate are significantly better (p < .001) with either itraconazole (Odd Ratio-15.5) or terbinafine (Odd Ratio-4.34). Higher MICs for terbinafine were noted in 41 cases (cured-18 and uncured-23) in Group I and 39 cases (cured-16 and uncured-23) in Group II. From cured (Group I-17/18; 94.4% and Group II-14/16; 87.5%) and uncured (Group I-20/23; 86.9% and Group II-21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having terbinafine MIC ≥ 1or <1 µg/mL (Group I-p = .712 and Group II-p = .69). CONCLUSION: This study revealed that prolonging terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between in vitro data and in vivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis.

Increased prevalence of metabolic syndrome and non-alcoholic fatty liver disease in children with atopic dermatitis: A case-control study from northern India.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects children worldwide, with potential associations to metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Limited research exists on the interplay between AD, MetS, and NAFLD in the pediatric population. This study aimed to investigate the prevalence and potential relationships among AD, MetS, and NAFLD in children. METHODS: A case-control study design was employed, recruiting 50 children with AD (median age: 9.5 years) and 50 age- and sex-matched healthy controls (median age: 11.5 years, p = .051). Data on demographic characteristics, clinical features, disease severity, treatment history, anthropometric measurements, and laboratory evaluations were collected. MetS and NAFLD were diagnosed based on established criteria. RESULTS: The prevalence of MetS was significantly higher in children with AD compared with controls (24% vs. 2%, p = .002). Significant differences for systolic blood pressure (p < .001), diastolic blood pressure (p = .012), and waist circumference (p = .040) were observed between AD patients and controls. Children with AD had higher triglyceride levels (p = .005). NAFLD was exclusively seen in moderate to severe AD cases (6% vs. 0%, p = .242). AD severity showed associations with increased body mass index (p = .020). CONCLUSION: This study highlights the increased prevalence of MetS and the potential association with NAFLD in children with AD. The findings suggest that AD may contribute to the development of metabolic abnormalities at an early age. Further research is needed to elucidate the underlying mechanisms and explore preventive strategies for these interconnected conditions.

Effects of metformin on clinical, hormonal and relevant gene expression parameters in patients with acne: an observational study.

BACKGROUND: Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with polycystic ovarian syndrome (PCOS). However, the benefits of metformin in patients with acne in general are not well established. AIM: To study the effectiveness of metformin treatment in patients with acne but who do not have PCOS and to understand the mechanisms of action of metformin in acne not related to PCOS. METHOD: In this observational study, 30 patients with clinically confirmed acne vulgaris were treated with metformin (1000 mg daily) for 3 months without any other topical or systemic active intervention for their acne. The effect of metformin at the clinical, hormonal and genetic level was assessed. RESULTS: Metformin monotherapy significantly (P < 0.001) decreased the global acne grading score for acne followed by a marginal increase in insulin; with a significant (P = 0.03) increase in insulin-like growth factor-1 (IGF-1). A significant (P < 0.001) decrease in free androgen index resulting from a significant (P < 0.001) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. Homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box protein O1 (FOXO1) expression was significantly (P = 0.006) downregulated with metformin treatment at the mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely HMGCR, SQLE and ACSL5 (P = 0.001, P = 0.03, P = 0.03, respectively) were also downregulated. CONCLUSION: Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FOXO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.

Juvenile localized scleroderma: A single-centre experience from India.

BACKGROUND: Juvenile localized scleroderma (JLS) or morphoea, a rare chronic autoimmune disease predominantly affects skin, subcutaneous tissue and occasionally the adjacent muscle, fascia and bone. We report the largest single-centre cohort of patients with JLS from India. METHODS: Patients who were diagnosed to have JLS were enrolled from the Paediatric Dermatology Clinic and the Paediatric Rheumatology Clinic of a tertiary care referral hospital in India. Collected data included details of the clinical profile, laboratory investigations and management. RESULTS: We analysed 84 patients with Juvenile localized scleroderma. Median age of disease onset was 5 years, and median age at diagnosis was 8 years. Commonest subtype was linear scleroderma (57 patients, 67.7%) followed by plaque morphoea and generalized morphoea. Fourteen patients (16.6%) were noted to have extracutaneous manifestations (ECMs). These included arthritis in eight (33.3%), brain parenchymal abnormalities in four (4.7%) and pulmonary involvement in two (8.3%) patients. Antinuclear antibody (ANA) was positive in eight/25 patients (32%; diffuse and speckled pattern in four patients each). One amongst these also had elevated anti-dsDNA titres. Positive ANA was found to have no association with ECMs (p 1.000). Patients were treated using methotrexate (61 patients; 72.6%), dexamethasone oral mini-pulse (OMP; 35 patients; 41.6%), calcipotriol (39 patients; 46.4%), topical corticosteroids (32 patients; 38%) and topical tacrolimus (three patients; 3.7%). Using linear regression analysis, administration of dexamethasone OMP and calcipotriol was found to be a predictor of good treatment response (p 0.034 and 0.019, respectively). CONCLUSION: Early use of systemic corticosteroids along with methotrexate may be more beneficial than methotrexate therapy alone.

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Not all black fungus is mucormycosis: A challenging case of Medicopsis romeroi.

In this case of phaeohyphomycosis, fine needle aspiration cytology enabled a rapid diagnosis and prompt treatment. This infection is quite prevalent in immunocompromised individuals; however, the Medicopsis romeroi species is a rare causative agent. These cases are associated with inadequate response to standard antifungal therapy and require discussion.

Correlating clinical and laboratory diagnostic modalities in the diagnosis of epidermolysis bullosa in a resource-poor setting.

BACKGROUND: Mutational analysis and immunofluorescence antigen mapping (IFM) are recommended as the laboratory tools of choice for diagnosing EB. In the past, transmission electron microscopy (TEM) was considered the gold standard, and more recently, clinical diagnostic matrix (CDM) has shown good concordance with next-generation sequencing (NGS). METHODS: In this prospective diagnostic study, a skin biopsy was taken for TEM and IFM in consecutive patients with EB (aged >6 months) diagnosed clinically with CDM. Wherever possible, mutational analysis was done using targeted NGS. RESULTS: Of the 80 patients diagnosed with CDM, skin biopsy specimens of 42 patients were assessed using TEM, and of 59 patients using IFM. NGS was done in 39 patients. Taking NGS as the gold standard for diagnosing EB (n = 39 patients), the concordance with CDM, TEM, and IFM were estimated at 84.6% (33/39), 78.5% (11/14), and 76% (19/25) respectively. CDM showed a substantial agreement with NGS (k = 0.69, p < 0.001). CONCLUSIONS: In comparison to NGS, the highest concordance was seen with CDM followed by TEM and IFM in diagnosing major subtypes of EB.

Randomized controlled trial to compare the effectiveness and safety of low dose dexamethasone oral mini-pulse versus diphenylcyclopropenone contact sensitisation in severe pediatric alopecia areata.

Oral mini pulse (OMP) corticosteroids and diphencyclopropenone (DPCP) contact sensitisation are commonly used treatment modalities in severe cases of Alopecia areata (AA) in children but with scarce studies comparing the two modalities in children. In this study we aimed to compare the effectiveness and safety of dexamethasone OMP with DPCP contact sensitization in severe non progressive AA in children. This randomized open label study was undertaken in 30 children less than 18 years of age with extensive non progressive AA divided in two groups. Group I included 15 patients who received dexamethasone (5 mg/week) OMP as five tablets of 0.5 mg dexamethasone (i.e., 2.5 mg dexamethasone) on two consecutive days in a week. Group II included 15 patients who were treated with DPCP contact sensitization. The treatment was continued in all patients for 24 weeks. Patients were followed up every 4 weeks and records were maintained. Response rate was 100% in OMP group and 53.3% in DPCP group at 24 weeks. In Group I, complete regrowth was seen in 20% patients, and cosmetically acceptable regrowth in 66.7% while in Group II, complete regrowth was not seen in any of the patients, and cosmetically acceptable regrowth in 20% (p = 0.001). Hair regrowth started at mean duration of 7.7 weeks in Group I, while 11.3 weeks in Group II. Response rate of treatment with dexamethasone OMP leads to a significantly faster and better hair regrowth compared to DPCP contact immunotherapy in non-progressive extensive AA in children.

Comparison of overall efficacy and safety of oral versus subcutaneous methotrexate in severe psoriasis.

Subcutaneous (SC) methotrexate (MTX) is considered to be associated with a higher and predictable linear bioavailability as compared to oral MTX. Although various studies have reported SC MTX to be safe and effective in psoriasis, prospective head-to-head comparative trials on oral versus SC MTX are limited. To compare the efficacy and safety of SC versus oral MTX in severe psoriasis. It was a prospective, single-blinded, randomized controlled trial, in 100 eligible, adult patients of severe psoriasis randomized into two groups. Group-A (n = 50) patients were started on oral MTX at a full dose of 0.3 mg/kg/week (maximum 25 mg/week) given for 12 weeks or till achieving PASI90 [90% reduction in Psoriasis Area Severity Index (PASI) from baseline], whichever was earlier and group-B (n = 50) patients received SC MTX in the same dose and duration. MTX was then tapered gradually at 5 mg every 2 weeks and stopped. All patients were followed-up for 24 weeks post-treatment with monthly assessment of PASI and Dermatology Life Quality Index (DLQI) scores. Baseline demographic profiles of patients in both the groups were comparable. The mean ± SD baseline PASI scores were group-A: 15.1 ± 3.2 versus group-B:15.7 ± 3.3 (p = 0.35). The number of patients that achieved PASI90 at or before 12 weeks of treatment was numerically higher in group-B (39/50, 78%) versus group-A (31/50, 62%; p = 0.08) and the time to achieve PASI90 was significantly lesser (p < 0.001).Also, the percentage(%) decline in DLQI was significantly higher in group-B(p = 0.003). The overall side-effect profile was comparable between groups (p = 0.31), but the frequency of gastrointestinal side-effects was significantly less in group-B (p = 0.04). Among those patients who achieved a PASI90 response by week12, relapse rates were comparable during the subsequent 24-week follow-up period [group-A: 12/31 (39%), group-B: 11/39 (28%), and p-value = 0.33]. SC MTX results in a significantly faster achievement of PASI90 and greater reduction in DLQI as compared to oral MTX in patients who are candidates for systemic therapy with a comparable safety profile. CTRI/2018/01/011373, date of registration: 15 January, 2018; trial registered prospectively.

Effectiveness of topical pilocarpine in refractory oral lesions of pemphigus vulgaris: Results from an open-label, prospective, pilot study.

BACKGROUND: The literature suggests a beneficial role of cholinomimetic agents in the treatment of pemphigus. In the present open-label, prospective pilot study, we assessed the effectiveness of topical pilocarpine 2% eye-drops in the treatment of recalcitrant oral lesions of pemphigus. METHODS: Twenty patients with recalcitrant oral lesions of pemphigus were recruited and instructed to apply pilocarpine 2% eye-drops twice daily on the resistant oral lesions for 180 days. The systemic immunosuppression at the time of inclusion in the present study was continued at the same dose throughout the study duration. The photographs of the lesions were obtained at baseline and an interval of 30 days. The area representing the erosion was measured on clinical photographs using the imageJ software (National Institute of Health). Visual analogue scale and oral health impact profile-14 questionnaire were used to assess the degree of subjective improvement. Anti-desmoglein 1 and 3, and anti-acetylcholine M3 receptor antibodies were measured both in serum and saliva; at baseline and at the completion of the study. RESULTS: Twenty patients were recruited in this pilot study. Mean total duration of illness was 3.4±1.3 years. The mean area of the erosions decreased significantly from 142.01±130.05 mm2 to 44.38±67.78 mm2 at study completion at 180 days (p 0.002, paired t-test). Repeated measures ANOVA demonstrated a significant trend in the reduction of the mean area of the erosions from baseline to day 180 (p 0.002). Mean VAS decreased significantly from 7.2±1.0 at baseline to 5.1±1.9 at day 180 (paired t-test, p 0.001). Mean OHIP-14 decreased significantly from 10.1±2.7 at baseline to 8.4±2.9 at day 180. No significant difference was observed between pre- and post-treatment levels of anti-desmoglein 1, anti-desmoglein 3, and anti-acetylcholine M3 receptor antibodies, in both serum and saliva. LIMITATIONS: The depth component in the erosions could not be measured. An orabase formulation could be used in future studies to facilitate retention of the medication at the site of application. CONCLUSION: Topical pilocarpine holds potential for the treatment of recalcitrant oral lesions of pemphigus vulgaris. It probably brings about re-epithelialization without imparting any immunomodulatory activity. This article is protected by copyright. All rights reserved.

Antinuclear antibody pattern and autoantibody profiling of systemic sclerosis patients in a tertiary referral center in North India.

Antinuclear antibody (ANA) pattern and autoantibody (autoAb) profiling of 150 adult systemic sclerosis (SSc) patients concerning their clinical association and diagnostic significance were analyzed by indirect immunofluorescence (IIF), immunoblot, and fluorescence enzyme immunoassay. One hundred and forty-three (95.3%) patients had positive ANA: DNA topoisomerase I (topo I)-like pattern-84(56%); speckled pattern-44(29.3%);centromere pattern-7(4.6%); and nucleolar pattern-4(2.6%). Three distinct topo I-like immunofluorescence patterns were detected at 1:40 dilution. Topo I-like pattern (32/75-limited cutaneous systemic sclerosis (lcSSc) vs. 52/75-diffuse cutaneous systemic sclerosis (dcSSc); p < 0.001) was found to be associated with dcSSc subset and speckled pattern (lcSSc 28/75 vs. dcSSc 16/75; p < 0.03) with lcSSc subset. One hundred and thirty-eight (92%) patients were positive for SSc-associated autoAbs. The frequency distribution of autoAbs to topo I, centromere A (CENP A) and centromereB (CENP B), RNA polymerase III (RP11, RP155), fibrillarin (U3RNP), nucleolus organizer region (NOR)-90, Th/To, PM-Scl75, PM-Scl100, Ku, platelet-derived growth factor receptor (PDGFR) and Ro-52, were 87(58%), 9(6%), 8(5.3%), 6(4%), 9(6%), 0, 6(4%), 6(4%), 8(5.3%), 5(3.3%), 11(7.3%),0 and 46(30.6%), respectively. Topo I autoAb was strongly associated with dcSSc (35/75 lcSSc vs. 52/75 dcSSc; p < 0.004), Raynaud's (p < 0.003), interstitial lung disease (ILD) (p < 0.001) and pulmonary arterial hypertension (PAH) (p < 0.04). This study helps in defining SSc clinical subset, prognostic markers of disease severity, characterization of the topo I-like ANA pattern, and provides a definite association between the ANA patterns and corresponding autoAb.

Comparison of the efficacy and cost-effectiveness of an immunologically targeted low-dose rituximab protocol with the conventional rheumatoid arthritis protocol in severe pemphigus.

BACKGROUND: Various dosing protocols of rituximab have been used in pemphigus. B-cell repopulation following rituximab treatment can be considered a forerunner of clinical relapse. Immunologically guided dosing may remove the need for fixed timepoint maintenance dosing, hence being more cost-effective and perhaps safer. AIM: To compare the overall efficacy and cost-effectiveness of a low-dose rituximab regimen (500 mg, 2 weeks apart) with immunologically guided, ultralow-dose (200 mg) top-up infusions on immunological relapse vs. the use of a rheumatoid arthritis (RA) protocol with rituximab 500 mg repeat infusion to treat clinical relapse in severe pemphigus, over a 1-year period, METHODS: In total, 23 patients with severe pemphigus were randomized into Group A (RA protocol: 1000 mg given as two doses, 2 weeks apart) and Group B (low-dose rituximab 500 mg given as two doses, 2 weeks apart). Both groups also received short-term oral corticosteroids, and underwent clinical and immunological (3-monthly flow cytometry assessments of B-cell subtypes) monitoring. Group A received a top-up dose of rituximab 500 mg upon clinical relapse, while Group B received an ultralow top-up dose (200 mg) following detection of B-cell repopulation, which was intended to prevent clinical relapse. Outcome parameters [complete remission off treatment (CROT), relapse (clinical and immunological), total corticosteroid dose and direct cost of therapy] were compared. RESULTS: The mean ± SD time to CROT (Group A, 27.1 ± 1.6 weeks; Group B, 26 ± 1.2 weeks, P = 0.09) and the cumulative prednisolone dose (P = 0.28) were comparable between the two groups. In Group A, 3 of 9 (33.3%) patients had clinical relapse (mean ± SD time of 9.3 ± 0.4 months). In Group B, B-cell repopulation was seen in 10 of 11 (90.9%) patients within a mean time of 8.4 ± 2.4 months, and a single top-up dose of 200 mg successfully prevented clinical relapse. The overall cost of therapy was 37.4% cheaper in Group B. CONCLUSION: An immunologically guided low-dose rituximab regimen can be an equally effective but more affordable alternative to conventional rituximab regimens in pemphigus.

Atypical Wiskott-Aldrich syndrome without thrombocytopenia partially responding to omalizumab therapy.

Primary immunodeficiencies with eczema can be easily misdiagnosed as atopic eczema, and thus require a high degree of awareness for diagnosis. Wiskott-Aldrich syndrome (WAS) is a rare disease and the fact that WAS without microthrombocytopenia has not been reported to date makes this case more interesting. As the patient's predominant problem was eczema and he had high circulating IgE antibodies in his serum, omalizumab was chosen as an appropriate steroid-sparing treatment option, as it has been shown to be effective in previous studies.

Psychological morbidity in pemphigus patients in clinical remission and its relation with clinico-demographic parameters.

BACKGROUND AND OBJECTIVES: Significant psychological morbidity exists in patients with active pemphigus. Pemphigus being a chronic disease, psychological morbidity may exist in pemphigus patients in remission as well. The objectives of the study were to assess the psychological morbidity in pemphigus patients in clinical remission and to correlate it with clinico-demographic parameters. PATIENTS AND METHODS: Pemphigus patients in clinical remission were consecutively included and were asked to respond to the Hindi/English version of Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7) and panic disorder module of PHQ. RESULTS: Of 107 patients recruited, 41 (38.3 %, 95 % CI: 29.1-48.2 %) patients were found to have either depression (33 [30.8 %, 95 % CI: 22.2-40.5 %]) or anxiety (38 [35.5 %, 95 % CI: 26.5-45.4 %] syndrome based on cut-offs of PHQ-9 score and GAD-7 score, respectively. Number of patients with mild, moderate and moderately severe/severe depression syndrome were 26 (24.3 %, 95 % CI: 17.2-33.2 %), 7 (6.5 %, 95 % CI: 0.3-12.9 %) and 0 respectively and patients with mild, moderate, severe anxiety syndrome were 29 (27.1 %, 95 % CI: 19.6-36.2 %), 9 (8.4 %, 95 % CI: 4.5-15.2 %) and 0 respectively. Patients with anxiety or depression syndrome had significantly higher clinical disease activity in the past, number of days spent in dermatology inpatient and significantly shorter clinical remission at the time of assessment as compared to those without these symptoms. CONCLUSIONS: Significant burden of mild/moderate depression or anxiety syndrome associated with past severity of disease and shorter duration of clinical remission was found.

Oral vitamin D versus acitretin in congenital non-syndromic ichthyosis: double blinded, randomized controlled trial.

BACKGROUND: Vitamin D has emerged as a promising treatment for congenital ichthyosis for which no comparative studies exist. METHODOLOGY: In this randomized, double-blinded study, patients with congenital ichthyosis received either Vitamin D 2000 IU/day (group A) or acitretin 0.5 mg/kg/day (group B) for 24 weeks. The primary outcome was improvement in the Visual Index for Ichthyosis Severity (VIIS) and Ichthyosis Area Severity Index (IASI). Secondary outcomes included Ichthyosis Quality of Life Index-32 (IQoL-32), mRNA expression of RORγt and IL-17 and adverse events. RESULTS: Twenty-four patients completed the study. Group A (n = 11) showed a significant decrease in VIIS (p = 0.023) and IASI (p = 0.026) at 12 but not 24 weeks. Group B (n = 13) showed a significant decrease in IASI at 24 weeks only (p = 0.016). The IQoL-32 improved over 24 weeks in both groups. A significant decrease in the mRNA expression of RORγt (p = 0.048) and IL-17 (p = 0.023) was seen only in group A. There was no significant difference between the two treatment arms in terms of VIIS, IASI and IQol-32 at 12 and 24 weeks. No serious adverse events were observed. CONCLUSION: Vitamin D maybe an alternative to acitretin in the treatment of congenital ichthyosis where it reduces the expression of RORγt and IL-17.

Effects of metformin on experimentally induced acne on rabbit ear.

Evidence for the effectiveness of metformin in the treatment of acne is limited. To assess its efficacy, comedones were experimentally induced in young New Zealand rabbit ear using Isopropyl Myristate (IM) followed by metformin treatment (30 mg/kg bodyweight) for 60 days with continued IM application. In another group, to check whether metformin pre-treatment affects subsequent comedone development by IM, metformin was given for 14 days and then withdrawn (14 days) followed by comedone development with IM and metformin treatment. At different time points, dermatoscopic images of rabbit ear were taken for clinical assessment. Blood and biopsy samples were taken for hormonal assessment, histological examination and gene expression. Histologically confirmed acne model was developed in rabbit ear. Follicular size increased significantly (p = 0.0004 in both groups) upon IM application. Metformin significantly decreased comedones size as observed in dermatoscopic (p = 0.0003 in group I, p = 0.0190 in group II) and histological examination (p = 0.0313 in group I and II). However, size of comedones developed after metformin pretreatment was significantly (p < 0.0001) smaller. The lipid content of sebaceous glands decreased with metformin without any significant changes in the assessed hormones and genetic expression. Overall, metformin was found to be clinically effective in experimentally induced acne and can be used in humans.

Sociodemographic characteristics and spectrum of Malassezia species in individuals with and without seborrhoeic dermatitis/dandruff: A comparison of residents of the urban and rural populations.

Seborrhoeic dermatitis/dandruff (SD/D) is a common, persistent, relapsing inflammatory condition affecting the areas rich in sebaceous glands. SD/D is widely prevalent in India but Malassezia species implicated are not well studied. To estimate the prevalence and spectrum of Malassezia species causing SD/D and understand the sociodemographic characteristics of SD/D in rural and urban populations, a total of 200 SD/D patients and 100 healthy controls (HC) from both rural and urban backgrounds were enrolled in this study. SD/D severity was clinically graded as mild, moderate, severe, and very severe. The isolates were identified by phenotypic characters and confirmed by ITS2 PCR-RFLP and sequencing of the ITS region of rDNA. Severe (59%) and very severe (71%) form of SD/D was higher in the rural population compared to the urban population (P = .004). The isolation rate of Malassezia was significantly higher in overall SD/D patients scalp (82%) compared to HC (67%) (P = .005). From the scalp of SD/D patients, M. globosa (36.2%) was predominantly isolated followed by M. restricta (31.3%), M. furfur (15.7%), a mixture of M. globosa and M. restricta (12%) or M. arunalokei (4.8%). Similarly, M. globosa (49.3%) was predominately isolated from the scalp of HC followed by M. restricta (22.4%). M. restricta was significantly higher in the scalp of SD/D patients compared to HC and/or nasolabial fold of both SD/D patients and HC (P = .0001). Our findings indicate that M. restricta has a high association with SD/D. More severe disease frequency was observed in the rural population. PRECIS: Dandruff is associated with Malassezia restricta and very severe cases are higher in rural population, probably due the poor hygiene. Moderate to severe hair loss and itching were strongly associated with dandruff. Use of soaps to cleanse scalp appears to be better than shampoo in preventing dandruff.

Teledermatology during the COVID-19 pandemic: Experience at a tertiary care centre in North India.

BACKGROUND: Teledermatology has evolved as a valuable option to outpatient visits during the current pandemic. We set up a smartphone-based hybrid model of teledermatology services providing direct care to patients at our center. To analyse patient and physician-experience and acceptability for teledermatology over a 6-month-period, along with clinicodemographic profile of patients. METHODOLOGY: Single-center, retrospective study conducted from May 20, 2020 to October 31, 2020. Patient satisfaction level for teledermatology was assessed on a 4-point scale and compared with the satisfaction level during their previous physical visits prior to COVID-19 pandemic. A physician assessment form was utilised to record the experience of dermatologists while providing teledermatology services. RESULTS: Of 7530 patients registered, a successful consult was provided to 6125 patients (81.34%). Average number of teleconsultations/day rose from 23.60 in May 2020 to 77.96 in October 2020. Mean age of patients availing teledermatology services was 33.60 ± 16.99 years. Average distance to care and travel time were 100.90 ± 171.77 km and 135 ± 222.32 min, respectively. A definitive diagnosis could be ascertained in 5724 patients (93.45%) and in-person visit was recommended to 133 patients (2.2%). Out of 6125 patients, 5229 could be contacted for feedback, 935 (18.18%), 2230 (42.65%), 1749 (33.45%), and 300 patients (5.70%) reported being very satisfied, satisfied, partially satisfied, and unsatisfied, respectively. Of 1914 patients, who had availed in-person OPD facilities prior to the pandemic, 914 patients (49.62%) preferred in-person visits. Of 34 dermatologists surveyed, 88.2% felt comfortable providing teleconsultations and 82.4% felt the need to continue teledermatology services in the upcoming months. CONCLUSIONS: Overall, teledermatology is a valid alternative for in-person dermatology visits during the current crisis; helping with initial triage and further patient management. Further refinement of the process could lead to even more acceptability.

Managing syndromic congenital ichthyosis at a tertiary care institute-Genotype-phenotype correlations, and novel treatments.

Syndromic congenital ichthyoses (CI) are genetically determined disorders of cornification that are characterized by generalized scaling along with systemic symptoms. Data on congenital syndromic ichthyosis from developing countries are scarce. We aimed to assess the prevalence, phenotype-genotype correlation, and management of syndromic CI patients presenting to our outpatient during the specified period this was a retrospective study of congenital syndromic ichthyosis patients attending a dermatology clinic in a tertiary care center from 2105-2018. We reviewed epidemiological and comorbidities data, phenotype-genotype correlations, and treatments of syndromic congenital ichthyosis patients. Six patients of Syndromic CI were diagnosedamongst 86 patients of CI (8.1%). Amongst these, three patients of Sjogren-Larrson syndrome (SLS), two patients of Netherton syndrome (NS), and one of Chanarin-Dorfman disease (CDD) were reported. Next-generation sequencing (NGS) was performed with novel variants reported in one patient each of SLS, NS, and CDD. An atypical phenotype was observed in a patient with NS with associated growth hormone and adrenocorticotropic hormone deficiency but with favorable clinical response to intravenous immunoglobulin. Our reports point towards the unreported pool of genetic mutations in CI from India. Novel mutations were associated with variable cutaneous and systemic involvement.