Therapeutic implications of dermoscopic findings in acanthosis nigricans: A clinical and histopathological study.

Acanthosis nigricans is associated with numerous systemic disorders. These include endocrinological conditions such as, diabetes, acromegaly, Cushing's syndrome, thyroid dysfunction, as well as metabolic abnormalities like obesity and polycystic ovarian disease. Its association with visceral malignancy is known. Moreover, Acanthosis nigricans is known to be a cutaneous marker of insulin resistance (IR) and hyperinsulinemia. The primary aim of this study was to study clinical and histopathological patterns of acanthosis nigricans and its correlation with dermoscopic patterns and treatment implications. 103 patients clinically diagnosed as acanthosis nigricans were enrolled in the study. Clinical evaluation, dermoscopy, and skin biopsy was done for histopathological evaluation. Consistency was observed in the changes seen on dermoscopy with clinical and histopathological findings. Common dermoscopy findings were Crista Cutis, Sulcus Cutis, Papillary projections, hyperpigmented dots, crypts, and blotching Dermoscopic findings can be correlated with histopathological features. Dermoscopy allows visualization on higher magnification which helps to pick up subtle changes which are not visible to naked eye. Dermoscopy can be a useful tool to distinguish acanthosis nigricans from other pigmentary disorders in patients who are not willing for histopathological examination and helps in treatment making decisions.

Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study.

BACKGROUND: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. OBJECTIVES: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. PATIENTS/METHODS: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. RESULTS: Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. CONCLUSIONS: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.

The current Indian epidemic of superficial dermatophytosis due to Trichophyton mentagrophytes-A molecular study.

The disease burden of chronic-relapsing and therapy-refractory superficial dermatophytosis dramatically increased in India within the past 5-6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR-ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)-1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte-positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR-ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte-positive showing 151 (93.21%) T mentagrophytes- and 11 (6.79%) T rubrum-positive samples. In this study, we show for the first time a dramatic Indian-wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes "Indian ITS genotype" that might be disseminated Indian-wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.

Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study.

BACKGROUND: Itolizumab, a humanized monoclonal antibody to CD6, is a novel therapeutic agent evaluated in chronic plaque psoriasis. OBJECTIVE: We sought to assess the safety and efficacy of itolizumab in moderate to severe chronic plaque psoriasis. METHODS: A total of 225 patients were randomized (2:2:1) to 2 different itolizumab arms (A or B; A = 4-week loading dose of 0.4 mg/kg/wk followed by 1.6 mg/kg every 2 weeks; B = 1.6/mg every 2 weeks) or placebo. At week 12, the placebo arm was switched to 1.6 mg/kg itolizumab every 2 weeks. The primary end point was the proportion of patients with at least 75% improvement in Psoriasis Area and Severity Index score at week 12. RESULTS: At week 12, 27.0% in arm A (P = .0172 vs placebo), 36.4% in B (P = .0043 vs placebo), and 2.3% in the placebo arm had at least 75% improvement in Psoriasis Area and Severity Index score. At week 28, the proportion with at least 75% improvement in Psoriasis Area and Severity Index score was comparable: 46.1%, 45.5%, and 41.9% for A, B, and placebo, respectively. In weeks 1 to 12, the incidence of all adverse events was comparable across arms (A, 43%; B, 38%; placebo, 47%) and the incidence of infections was not greater than placebo (11.1%, 8.9%, and 18.6% for A, B, and placebo). LIMITATIONS: No active comparator is a limitation. CONCLUSIONS: Itolizumab is an effective and well-tolerated novel biological therapy in moderate to severe psoriasis.

Primary Cutaneous Actinomycosis Mimicking Cutaneous Leishmaniasis.

Actinomycosis is a chronic suppurative bacterial infection commonly seen in the tropics, caused by gram-positive, anaerobic bacilli of the genus Actinomyces. There are very few reported cases of primary cutaneous actinomycosis. It can mimic mycetoma, tuberculosis, nocardiosis, and botryomycosis. A high index of clinical suspicion is required for diagnosis in the absence of sinuses. Even with repeated attempts, cultures are mostly negative; and hence, histology reveals the diagnosis in most cases. Here, we report an unusual case of primary cutaneous actinomycosis in a 21-year-old female patient, following a road traffic accident (RTA). A positive Splendore-Hoeppli phenomenon and special stains demonstrated the ray fungus and helped us reach the diagnosis. The patient was started on oral penicillin G and showed good response.

Clinico-epidemiological profile of genital dermatoses in people living with HIV: A shifting paradigm from venereal to nonvenereal dermatoses.

Context: The protean mucocutaneous manifestations of HIV and the resultant opportunistic infections are well documented. Genital dermatoses can be either venereal or nonvenereal in origin. As the presence of HIV infection greatly increases the chances of acquiring another sexually transmitted pathogen, these are often presumed to be venereal in origin. Aims: The aims of the study were to record the different morphologies of genital skin lesions in seropositive patients and to classify them as venereal or nonvenereal in origin. Settings and Design: This was an observational study undertaken in seropositive patients with genital skin lesions attending the outpatient department of dermatology at a tertiary health-care center. Subjects and Methods: One hundred and seventy-seven seropositive patients with genital lesions were enrolled. A detailed history was taken; the genital and dermatological examination was performed. Statistical Analysis Used: None. Results: Males predominated the study population with the majority (79.1%) falling into the reproductive age group of 15-49 years. Nonvenereal genital dermatoses (59%) outnumbered sexually transmitted infections (STIs) (41%) out of which the most frequently encountered were dermatophytosis, scabies, and intertrigo. Other entities recorded were inflammatory dermatoses, cutaneous adverse drug reactions, and tumors. The most common STIs were herpes genitalis (55.4%) and anogenital warts (32.5%). Conclusion: This study showed that nonvenereal genital dermatoses are more common than STIs in people living with HIV. Our findings reiterate the fact that genital lesions should be approached with caution as a presumptive and hasty diagnosis of STI adds greatly to the morbidity of the patient in terms of guilt and shame, and adversely affects the quality of life.

Nail Changes in Immuno-Bullous Disorders: A Cross-Sectional Study.

Context: Autoimmune blistering (AIBD) disorders affect mucosae, skin, and appendages. Appendageal involvement has not been studied extensively to date. However, they are important as nail changes are commonly encountered during a flare-up of the disease. Aims: To determine the prevalence and patterns of nail changes in various Immunobullous disorders and to study the relationship between the nail changes and the disease duration and severity. Settings and Design: A cross-sectional study was conducted at the Department of Dermatology, venerology, and leprosy at a tertiary care center in Mumbai. Materials and Methods: A cross-sectional study including a total of 74 cases of Immunobullous diseases was conducted and the prevalence of nail changes was determined. The association between the mean number of nail changes and the disease duration and severity was analyzed using ANOVA (Analysis of variance) and unpaired t-test. Statistical Analysis: The Statistical Package for Social Studies (SPSS) software was used for statistical evaluation. Results: We found that the prevalence of nail changes was 91%. There was a significant difference in the mean number of nail changes with respect to the severity grades of mucosal involvement in AIBD (P value < 0.05). There was no significant difference in the mean number of nail changes with respect to the severity grades of Pemphigus vulgaris (PV), Pemphigus foliaceous (PF), subepidermal blistering diseases, and the duration of AIBD. Conclusions: Nails are frequently affected in AIBD. The number of nail changes is related to the severity of mucosal disease but not to duration.

Efficacy and Safety Comparison of Basic Fibroblast Growth Factor-Related Decapeptide 0.1% Solution (bFGFrP) Plus Oral PUVA Combination Therapy with Oral PUVA Monotherapy in the Treatment of Vitiligo.

Background: Phototherapy in its different forms, is mainstay of vitiligo management. Combining treatment modalities like topical calcipotriol (for quicker, more intense repigmentation), Low dose azathioprine with PUVA have proven to be beneficial in management of vitiligo due to different mechanisms of repigmentation and their synergistic effects. Topical bFGF-related decapeptide (bFGFrP) application followed by sun exposure/ UVA phototherapy yields effective repigmentation. bFGFrP has shown to aid the targeted phototherapy in smaller lesions and its combinations with other treatment modalities have been very promising. However, there is paucity of studies on combination treatments; especially oral PUVA along with bFGFrP. This study was aimed at evaluating safety and efficacy of combination of bFGFrP with Oral PUVA in vitiligo (larger body surface area 20% or more). Materials and Methods: Phase IV, randomized, multicentre study (N = 120) in adult patients with stable vitiligo of 6 months treatment period with monthly follow up visits. Psoralen (Tab. Melanocyl) dosage 0.6 mg/kg orally 2 h before exposure to UVA phototherapy. Oral PUVA therapy, initially, at an irradiation dose 4 J/cm2 (PUVA group), followed by increments 0.5 J/cm2 every four sittings if tolerated for twice weekly. Primary end point was improvement in extent of repigmentation (EOR) in target lesion (at least 2 cm × 2 cm in greatest dimension, without leukotrichia), while secondary endpoints were improvement in patient global assessment (PGA) and safety at end of 6 months of treatment period in bFGFrP + oral PUVA combination group and Oral PUVA monotherapy group. Results: End of 6 months, significantly greater EOR >50%) was achieved in 61.8% (34 patients, n = 55) from combination group while 30.2% (16 patients, n = 53) from the oral PUVA monotherapy group (n = 53). Regarding Grade of repigmentation (GOR), complete repigmentation was observed 5.5% (3 patients, n = 55) in combination group whereas no patient showed complete repigmentation in monotherapy group (p ≤ 0.05), PGA showed significant overall improvement in combination group (p ≤ 0.05); 6 patients (10.9%) from combination group Vs one (1.9%) showed complete improvement. During treatment period, there were no reported adverse events. Conclusions: Addition of bFGFrP to oral PUVA therapy resulted in intense and faster induction of repigmentation than oral PUVA monotherapy with favorable safety profile.

Anti CD-6 Monoclonal Antibodies in the Management of Generalised Pustular Psoriasis.

Generalised pustular psoriasis (GPP) is an uncommon, severe, life-threatening variant of psoriasis requiring careful therapeutic approach. Conventional treatment modalities have unsatisfactory outcomes, poor side effect profiles and toxicities that have led to an emerging use of biological therapies. Itolizumab, an anti-CD-6 humanised monoclonal IgG1 antibody, is approved for the management of chronic plaque psoriasis in India. We share our experience of using this drug in three cases of GPP that were failing conventional therapies. Its upstream effect on co-stimulatory pathway in disease pathogenesis is the postulated mechanism. Our experience warrants further large-scale exploration of the role of itolizumab in the management of GPP, which would benefit this severely affected population of patients. Although the definite pathogenesis of GPP is unknown fully, molecules blocking CD-6, which plays a role in the interaction between T cells and antigen-presenting cells (APCs), are expected as new promising treatment options for GPP.

Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) Task Force against Recalcitrant Tinea (ITART) Consensus on the Management of Glabrous Tinea (INTACT).

BACKGROUND AND AIMS: Dermatophytosis has always been a common superficial mycosis in India. However, the past 6-7 years have seen an unprecedented increase in the number of patients affected by recurrent, chronic, recalcitrant and steroid modified dermatophytosis involving the glabrous skin (tinea corporis, tinea cruris and tinea faciei). Importantly, there has been a notable decrease in clinical responsiveness to commonly used antifungals given in conventional doses and durations resulting in difficult-to-treat infections. Considering that scientific data on the management of the current epidemic of dermatophytosis in India are inadequate, the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) Task force Against Recalcitrant Tinea (ITART) has formulated a consensus statement on the management of dermatophytosis in India. METHODS: Seventeen dermatologists with a focussed interest in dermatophytosis participated in a Delphi consensus method, conducted in three rounds. They responded as either "agree" or "disagree" to 132 statements prepared by the lead experts and gave their comments. Consensus was defined as an agreement of 80% or higher concurrence. Statements on which there was no consensus were modified based on the comments and were then recirculated. The results were finally analysed in a face-to-face meeting and the responses were further evaluated. A draft of the consensus was circulated among the participants and modified based on their inputs. RESULTS: Consensus was achieved on 90 of the 132 statements. Direct microscopy using potassium hydroxide mount was recommended in case of diagnostic difficulty on clinical examination. Counselling of patients about strict adherence to general measures and compliance to treatment was strongly recommended as the key to successful management of dermatophytosis. A combination of systemic and topical antifungal drugs was recommended for the treatment of glabrous tinea in the current scenario. Topical corticosteroid use, whether used alone or in combination with other components, was strongly discouraged by all the experts. It was suggested that topical antifungals may be continued for 2 weeks beyond clinical resolution. Itraconazole and terbinafine were recommended to be used as the first line options in systemic therapy, whereas griseofulvin and fluconazole are alternatives. Terbinafine was agreed to be used as a first line systemic agent in treatment naïve and terbinafine naïve patients with glabrous tinea. Regular follow-up of patients to ensure compliance and monitoring of clinical response was recommended by the experts, both during treatment and for at least 4 weeks after apparent clinical cure. Longer duration of treatment was recommended for patients with chronic, recurrent and steroid modified dermatophytosis. CONCLUSION: Consensus in the management of dermatophytosis is necessary in the face of conventional regimens proving ineffective and dearth of clinical trials re-evaluating the role of available antifungals in the wake of evolving epidemiology of the infection in the country. It needs to be backed by more research to provide the required level of evidence. It is hoped that this consensus statement improves the quality of care for patients with dermatophytosis, which has emerged as a huge public health problem, imposing considerable financial burden on the country.

Poikilodermatous Mycosis Fungoides with Erosive Lesions.

Mycosis fungoides (MF) is the commonest form of cutaneous T-cell lymphoma. Many clinical subtypes and variants of MF have been described, one of which is poikilodermatous MF variant. Erosions and bullous lesions in a patient with poikilodermatous MF is a rare presentation. We present one such rare case of poikilodermatous MF with erosive lesions in a 40-year-old male.

Acral Acanthosis Nigricans in a Case of Scleroderma.

Acanthosis nigricans (AN) is a dermatosis characterized by velvety, papillomatous, brownish-black, hyperkeratotic plaques, typically on the intertriginous surfaces and neck. The majority (80%) of AN occurs idiopathically or in benign conditions such as endocrinopathies like diabetes mellitus, polycystic ovary syndrome; metabolic syndrome and/or heritable disease. Malignancy-associated AN is rare. AN may rarely be associated with autoimmune diseases including systemic lupus erythematosus, due to antibodies to the insulin receptor, so-called type B insulin resistance. Here we report a case of AN in a case of diffuse progressive systemic sclerosis without evidence of insulin resistance.