Tofacitinib: A Treatment Option for Recalcitrant Polymorphic Light Eruption and Its Mechanistic Rationale.

Background: Polymorphous light eruption is largely characterized by a delayed-type (type IV) hypersensitivity reaction to 1 or more undefined endogenous ultraviolet-induced skin antigens. Objectives: To evaluate the efficacy of tofacitinib in refractory cases of polymorphous light eruption. Methods: Seven patients who had failed multiple systemic treatments or relapsed within 2 weeks of existing systemic agents with concomitant photoprotection were offered tofacitinib after written consent. Results: Initiation of tofacitinib led to a marked reduction of itching (mean ± SD 3.1 ± 1.12 days) followed by clinical resolution (mean ± SD 2.6 ± 1.1 weeks). The duration of therapy ranged from 1 to 3 months (mean ± SD 2 ± 0.63 months), and 4 of 7 patients had a recurrence in 5.5 weeks and were again initiated on tofacitinib with a prompt response. Conclusion: Tofacitinib inhibits Janus kinase (JAK)1 and JAK3 thus it can abrogate the effects of the predominant cytokine milieu of polymorphic light eruption (PMLE) and thus reduce the expression of aberrant inflammatory T lymphocyte expression in PMLE.

Case Report: An Atypical Case of Post-Kala-Azar Dermal Leishmaniasis with Ulcers and Verrucous Lesions: Clinical and Therapeutic Implications.

About 75% cases of post-kala-azar dermal leishmaniasis (PKDL) occur in India. Although the classic description of PKDL is the progression from initial hypopigmented macular lesions to papules to plaques and nodular lesions, atypical morphologies are also seen and are easily missed or misdiagnosed. We report a case of a 27-year-old man who presented to us with multiple acral ulcers and verrucous lesions for 5 years. A diagnosis of PKDL was made based on slit skin smear, histopathology, and quantitative polymerase chain reaction. The patient was given combination therapy with four doses of liposomal amphotericin B and miltefosine 50 mg twice daily for 45 days. In this report, we discuss unusual morphologies of PKDL, the pathway to the diagnosis, and the therapeutic options available along with their efficacy.

A case-control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S-100 and toluidine blue stain and its therapeutic implications.

BACKGROUND: The pathogenesis of prurigo nodularis (PN) is considered to be multifactorial, with numerous cells and cytokines confabulating to produce an aberrant immune response. METHODS: A cross-sectional observational study was done in cases of untreated primary prurigo nodularis cases with histopathological assessment in 49 cases from lesional and nonlesional skin with assessment of epidermal and dermal changes, dermal infiltrate, S-100 and toluidine blue staining to assess the expression of nerve and mast cells. RESULTS: The most common histological changes seen in lesional skin were hyperkeratosis (98%), irregular hyperplasia (69.4%), hypergranulosis (69.4%), subepidermal clefting (6%), vertical collagen bundles (51.0%), and dermal fibrosis (48.9%). Chronic inflammatory infiltrate was seen in all cases (100%) predominantly of lymphocytes (100%) followed by eosinophils (18.4%), plasma cells (8.2%), and neutrophils (2.0%). There was a marked increase in the expression of S-100 (6.92 ± 3.40 vs. 3.94 ± 2.15, P < 0.001) and toluidine blue (4.99 ± 4.47 vs. 1.22 ± 1.28, P < 0.001) in the lesional skin as compared to the nonlesional skin. CONCLUSION: We can infer that the epidermal and dermal pathology in PN is related to the infiltrate of lymphocytes, mast cells, and neural hyperplasia which perpetuate the pathogenesis by triggering the itch-inflammation cycle. Thus, apart from immunosuppressive agents that target lymphocytes and their cytokines, therapy targeted at mast cells and neural proliferation may be needed to treat prurigo nodularis.

A real-world study of low-dose thalidomide in severe erythema nodosum leprosum highlighting its mechanistic rationale in a resource-constrained target population.

BACKGROUND: Corticosteroids remain the main therapy in erythema nodosum leprosum (ENL), and long-term usage in chronic or recurrent ENL is a cause of significant morbidity and mortality. Thalidomide exerts dramatic effect in controlling ENL and helps reduce the dose of steroids, but the cost is a hindrance to its usage. METHODS: Patients of ENL (steroid naïve and steroid-dependent) were recruited over a 1-year period. An escalating dose of low-dose thalidomide with a reducing dose of prednisolone was titrated depending on the control of disease activity. The primary aim was to reduce the dose of steroids to the lowest effective dose, and the secondary aim was to stop. RESULTS: Sixteen patients of ENL were studied (mean duration of ENL 22.1 months, 15 severe ENL), and a majority (11/16, 68%) were on steroids with a mean duration of 11.27 months. All patients had steroid-related side effects (cushingoid habitus 81.8%, weight gain 54.5%, diabetes mellitus 9%, hyperlipidemia 18.18%, cataract 18.1%, osteoporosis 36.3%, striae 36.3%, acneiform eruptions 18.1%, and myopathy 9%). Steroids could be tapered in a majority of patients (n = 9) within 3 months (mean 2.44 months) with a low dose of thalidomide (25-150 mg/day, mean 78.3 mg) achieving a significant reduction in prednisolone dose (33.16 mg at baseline; 4.28 mg at 3 months, P < 0.05). Steroids could be stopped in 92% of patients by 3.03 months, and both drugs could be stopped in 80% of cases by 5.83 months. CONCLUSION: The rapid and effective control of ENL with low-dose thalidomide in our series is comparable to the historical efficacy of high-dose thalidomide regimens, making it an affordable therapy in resource-constrained settings and an excellent steroid-sparing agent. The rapid onset of disease control is likely attributable to its action via neutrophils.

Application and future prospects of additive manufacturing in dermatology.

The article discusses the additive manufacturing/3D printing of human skin for advanced applications. Even though this is still in its infancy, additive manufacturing has the potential to revolutionize the field of dermatology and cosmetology.

Paucity of cutaneous manifestations of COVID-19 among inpatients at a referral hospital in India.

Background: Varied cutaneous manifestations of COVID-19 have been described, but most studies are based on photographic or application-based observations, without a direct observed-based evaluation by dermatologists. Objective: To study the types of cutaneous manifestations of COVID-19 among confirmed inpatients admitted to COVID-19 wards and intensive care units (ICUs). Methods: This cross-sectional analysis was conducted at a referral hospital in Delhi, India. Four hundred forty consecutive reverse transcription-polymerase chain reaction (RT-PCR)-confirmed cases diagnosed with moderate or severe COVID-19 and admitted to COVID-19 wards or ICUs, respectively, were included. A cutaneous finding was considered to be associated with COVID-19 if it had been described earlier as a consequence of COVID-19 and was observed at the time of or within the first 48 hours of admission (after excluding drugs and comorbidities as causes). Results: Two hundred seventy patients with moderate COVID-19 were admitted to COVID-19 wards, whereas 170 with severe disease were admitted to ICUs. Only 7 of the 270 ward patients (2.59%) and 3 of the 170 ICU patients (1.76%) had cutaneous findings associated with COVID-19. Conclusion: Cutaneous findings attributable to COVID-19 are infrequent, and we believe that these might have been overestimated or overemphasized in earlier studies. Although coagulopathic findings may be associated with severe COVID-19, causation cannot be established in this cross-sectional study.

Cutaneous side effects of hydroxychloroquine in health care workers in a COVID referral hospital - implications for clinical practice.

The utility of hydroxychloroquine for the prophylaxis and treatment of alarmingly rising COVID-19 infection has been widely explored in several studies. However, its cutaneous adverse effects among health care workers and COVID patients taking prophylactic doses has not been reported. We report cases of palmoplantar among health care workers who were on prophylactic doses of hydroxychloroquine and their management with cetirizine and methylprednisolone.

Polidocanol Sclerotherapy in Pyogenic Granulomas.

BACKGROUND: Polidocanol is a safe sclerosing agent with anesthetic properties and minimal skin toxicity. OBJECTIVE: To evaluate the efficacy, safety, and recurrence rates with polidocanol sclerotherapy in the treatment of pyogenic granulomas (PGs). METHODS AND METHODS: Thirty-nine patients with PG were injected with polidocanol 1% solution. Repeat injections were given weekly in case of incomplete clinical/dermoscopic resolution, until a maximum of 3 sittings. A higher strength (3%) was used for subsequent sessions in those with a minimal response to 1% solution. A final assessment for relapses was performed at 3, 6, and 12 months. RESULTS: All 39 patients achieved complete resolution (100% clearance rate), with most (n = 26) lesions resolving after the first sitting. Side effects noted were postprocedure pain (22), erythema (2), superficial ulceration (2), paresthesias (1), prominent edema (4), thrombophlebitis (1), cyanotic discoloration (1), purpuric staining around injection site (4), and mild local pruritus (1). The procedure was well tolerated across the age spectrum (4-63 years) included. CONCLUSION: We report polidocanol to be a highly effective, safe, and cost-effective sclerosant for treatment of PGs with no recurrences or need for special postprocedure care.

A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications.

BACKGROUND: Prurigo nodularis (PN) is a chronic dermatologic condition manifesting as multiple papulonodular lesions occurring on the background of intense pruritus. PN could be primary or secondary. The exact immune pathogenesis of PN is not yet clear, and multiple pathways are proposed with the JAK-STAT pathway rarely being investigated. AIMS: In this study, our aim was to assess the role of Th cells in PN by comparing the expression of STAT 1, 3, and 6 in involved and normal skin of primary prurigo nodularis. METHODS: A total of 49 clinico-histopathologically proven cases of primary prurigo nodularis were included. Two skin biopsies for each patient from lesional and non-lesional skin were stained with STAT 1, 3, and 6, and the nuclear staining pattern in the epidermis was graded as strong, moderate, weak, or none. RESULTS: Statistically significant expression of STAT 3 and STAT 6 staining was seen in the epidermis of the lesional skin as compared to non-lesional skin. CONCLUSION: Our study showed a marked dominance of STAT 3 and STAT 6 staining in the epidermis which signifies that the keratinocytes play an important role in PN and suggest that Th2, Th17, and Th22 cytokines mediate the tissue response in PN.

Case Report: Successful Outcome of Primary Infertility with Multidrug Therapy in a Long-Standing Case of Hypogonadism Resulting from Lepromatous Leprosy: Shattering the Dogma of Irreversible Infertility in Leprosy.

We present a case of primary infertility with features of hypogonadism in a male patient with lepromatous leprosy who had remained undiagnosed for 3 years. On investigation, azoospermia and deranged gonadotropin levels with normal serum testosterone were noted and the patient was initiated on multibacillary-multidrug therapy with the primary aim of treating the disease. Although the cutaneous lesions improved within 6 weeks, remarkably infertility was reversed in 2 months-with concomitant normalization of luteinizing hormone, follicle stimulating hormone, and sperm count-an outcome that was unexpected. While reiterating leprosy as a cause of infertility, we discuss the probable mechanism for the efficacy of multidrug therapy in what seemed to be an irreversible outcome of advanced lepromatous leprosy.

Current Use of Ivermectin in Dermatology, Tropical Medicine, and COVID-19: An Update on Pharmacology, Uses, Proven and Varied Proposed Mechanistic Action.

Ivermectin is a broad-spectrum antiparasitic drug with anti-inflammatory, anti-viral, anti-bacterial, and anti-tumor effects. In this review, we discuss the history, pharmacology, multimodal actions, indications in dermatology and tropical medicine, therapeutic and prophylactic use of ivermectin in COVID-19, safety, adverse effects, special considerations, and drug interactions of ivermectin.

Immunopathogenesis of Dermatophytoses and Factors Leading to Recalcitrant Infections.

The pathogenesis of dermatophytic infections involves the interplay of three major factors: the dermatophyte, the inherent host defense, and the adaptive host immune response. The fungal virulence factors determine the adhesion and invasion of the skin while the immune response depends on an interaction of the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMP) with pattern recognition receptors (PRRs) of the host, which lead to a differential Th (T helper) 1, Th2, Th17, and Treg response. While anthropophilic dermatophytes Trichophyton rubrum and now increasingly by T. interdigitale subvert the immune response via mannans, zoophilic species are eliminated due to a brisk immune response. Notably, delayed-type hypersensitivity (Th1) response of T lymphocytes causes the elimination of fungal infection, while chronic disease caused by anthropophilic species corresponds to toll-like receptor 2 mediated IL (interleukin)-10 release and generation of T-regulatory cells with immunosuppressive potential. Major steps that determine the ultimate clinical course and chronicity include genetic susceptibility factors, impaired epidermal and immunological barriers, variations in the composition of sebum and sweat, carbon dioxide tension, skin pH, and topical steroid abuse. It is important to understand these multifarious aspects to surmount the problem of recalcitrant dermatophytosis when the disorder fails conventional therapeutic agents.