Case Report: Mixed Airborne Contact Dermatitis-Chronic Actinic Dermatitis Pattern of Parthenium Dermatitis with Response to Tofacitinib Therapy.

Parthenium hysterophorus is the commonest cause of plant dermatitis in India. It classically causes airborne contact dermatitis (ABCD), characterized by pruritic, eczematous, and lichenified lesions involving predominantly the face and flexural areas. Over time, however, a transition to chronic actinic dermatitis (CAD) pattern, with prominent involvement of sun-exposed sites, may occur. Management involves strict protective measures and topical and oral corticosteroids or immunomodulatory agents but often leads to only limited success. We report a patient with a chronic and extensive mixed ABCD-CAD pattern of parthenium dermatitis recalcitrant to conventional treatment, with rapid resolution after initiation of treatment with tofacitinib.

Trans-epidermal extrusion of lepra bacilli from histoid lesions: a risk of continued transmission.

The current goal of Zero Leprosy focuses on the interruption of the transmission of infection within endemic regions. While the role of the skin in the transmission dynamics of leprosy has not been clearly delineated, recent research on the environmental presence of lepra bacilli brings this aspect back into focus. We present a case of lepromatous leprosy with perforated-appearing histoid lesions on the palms and soles, demonstrating the presence of lepra bacilli throughout the epidermis.

An updated clinico-investigative approach to diagnosis of cutaneous hyperandrogenism in relation to adult female acne, female pattern alopecia & hirsutism a primer for dermatologists.

INTRODUCTION: Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied manifestations of hyperandrogenism include seborrhea, acne, infertility, hirsutism, or overt virilization of which adult female acne, hirsutism, and female pattern hair loss are of clinical relevance to dermatologists. AREAS COVERED: We limited our narrative review to literature published during period from 1 January 1985 to Dec 2022 and searched PubMed/MEDLINE, Web of Science (WOS), Scopus, and Embase databases with main search keywords were 'Hyperandrogenism,' 'Female,' 'Biochemical,' 'Dermatological', and 'Dermatology.' We detail the common etiological causes, nuances in interpretation of biochemical tests and imaging tools, followed by an algorithmic approach which can help avoid extensive tests and diagnose the common causes of hyperandrogenism. EXPERT OPINION: Based on current data, total testosterone, sex hormone binding globulin, DHEAS, prolactin, free androgen index, and peripheral androgenic metabolites like 3-alpha diol and androsterone glucuronide are ideal tests though not all are required in all patients. Abnormalities in these biochemical investigations may require radiological examination for further clarification. Total testosterone levels can help delineate broadly the varied causes of hyperandrogenism. Serum AMH could be used for defining PCOM in adults.

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.

A Real-World Study of Steroid-Free Monotherapy with Tofacitinib in Severe and Therapy-Recalcitrant Alopecia Areata, Alopecia Totalis, and Alopecia Universalis Cases: A Retrospective Analysis.

Background: Alopecia areata (AA) presents with noncicatricial alopecia and has multifactorial etiology. Janus Kinase inhibitors (JAKibs) with potential efficacy and favorable side-effect profile are the first class of drugs to receive FDA approval in AA. Objectives: Our primary objective was to assess the complete response rates to tofacitinib monotherapy in severe and recalcitrant AA, alopecia totalis (AT), and alopecia universalis (AU) patients using the latest percentage change in Severity of alopecia tool (SALT) score. We also aimed to analyze the various systemic agents used by these patients prior to the use of tofacitinib. Materials and Methods: Institutional records of 17 patients with severe or refractory AA, AT, and AU treated with tofacitinib monotherapy were analyzed, retrospectively. The response to tofacitinib therapy was determined after calculating percentage change in SALT score. End of treatment was defined as the dose which resulted in a significant response (complete/near complete response was ≥75% hair regrowth from baseline as determined by SALT score). Results: Majority of patients had severe AA (SALT ≥ 50) (n = 9/17, 52.94%), while five patients had AT and three had AU. All patients had received either systemic glucocorticoids (GCS), which included oral mini pulse (OMP) (n = 8), intravenous pulse steroids (n = 4), and daily oral GCS (n = 6) or immunosuppressive agents (ISAs) which included cyclosporine (n = 14) followed by methotrexate (n = 6) and azathioprine (n = 6). Mean SALT score prior to starting tofacitinib was 74.23. Mean dose of tofacitinib used was 13.23 mg (10-15 mg) and mean duration of treatment was 9.23 months. Latest percentage change of SALT score ranged from 70.58% to 100%, with an average of 91.47%. Most patients showed complete/near complete response (13/17, 76.47%). Conclusion: Tofacitinib was found to be safe and effective in severe/refractory AA, AU, and AT patients recalcitrant to other treatment modalities in our study. Further studies are needed to assess the effect of these targeted drugs on JAK-STAT expression or tissue cytokines involved in the pathogenesis of AA using immunohistochemistry.

IADVL SIG Recalcitrant Dermatophytosis Position Statement on Super Bioavailable Itraconazole.

Itraconazole (ITZ) has been the mainstay of oral antifungal treatment for the current epidemic of recalcitrant dermatophytosis (RD) in India. Recently, a newer formulation of ITZ, super bioavailable itraconazole (SUBA-ITZ), is made available in the market by many pharmaceutical companies. It is important for dermatologists to understand the pharmacokinetic properties of SUBA-ITZ vis-a-vis conventional pellet formulation to use it effectively and safely. Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) has established a special interest group for recalcitrant dermatophytosis (SIG-RD) to strengthen research, continuing medical education, and industry collaboration on the subject. This position statement on SUBA-ITZ by SIG-RD is an attempt to address current pieces of evidence and the position of this new formulation in the management of RD.

Comparison of outcomes of azathioprine, leflunomide and allergen avoidance in patients with patch test-positive pigmented contact dermatitis: a randomized comparative study.

BACKGROUND: Pigmented contact dermatitis (PCD) is a noneczematous form of allergic contact dermatitis characterized by dermal hyperpigmentation. Allergen avoidance is the cornerstone of therapy, but it is difficult to achieve. The use of immunosuppressives seems rational, but data are lacking. OBJECTIVES: To compare outcomes with azathioprine (AZA), leflunomide and allergen avoidance (AA) in patients with PCD. METHODS: A comparative study was conducted on 28 patients with patch test-positive PCD who were randomly allocated to one of three treatment groups: AZA 2 mg kg-1 daily for 24 weeks + AA (n = 10); leflunomide (LEF) 20 mg daily for 24 weeks + -AA (n = 8); AA alone (n = 10). Patients were followed up for an additional 24 weeks. The Dermal Pigmentation Area and Severity Index (DPASI) score and Hindi Melasma Quality of Life scale (MELASQOL) were used to assess hyperpigmentation and quality of life (QoL). respectively. RESULTS: Hair colorants (n = 12) and paraphenylenediamine (n = 8) were the most common allergens. Mean (SD) DPASI score decreased from 30.97 (3.69), 32.35 (3.90) and 31.86 (3.47) to 13.78 (4.25), 21.67 (2.99) and 20.64 (3.82) at 48 weeks in the three groups, respectively (P < 0.001); the maximum percentage decline was seen with AZA (56%). Mean (SD) MELASQOL score was reduced in the three treatment groups from 48.0 (6.46), 46.75 (3.69) and 46.6 (4.65) to 19.6 (6.98), 24.5 (5.80) and 24.0 (5.49), respectively, at 48 weeks (P < 0.001). Reductions in DPASI and Hindi MELASQOL scores were significantly correlated. The most frequent adverse event was transaminitis in both the AZA and LEF groups. CONCLUSIONS: Patients on AZA achieved a statistically significantly greater reduction in DPASI and MELASQOL score; therefore, AZA may fulfil an unmet need in PCD treatment. An objective reduction in hyperpigmentation was paralleled by an improvement in QoL score, reiterating the need for active management of this disease.

Use of tofacitinib in baricitinib-refractory atopic dermatitis: An example of JAK inhibitor switching.

Atopic dermatitis (AD) is predominantly mediated by a T-helper 2 immune system response. While JAK inhibitors have gained treatment approval for AD, data regarding interclass efficacy and therapeutic rationale is lacking. We report a patient with recalcitrant AD who failed baricitinib but demonstrated an excellent response to the pan-JAK inhibitor tofacitinib.

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.

Therapeutic Updates on the Management of Tinea Corporis or Cruris in the Era of Trichophyton Indotineae: Separating Evidence from Hype-A Narrative Review.

The emergence and spread of Trichophyton indotineae (T. indotineae) has led to a sea change in the prescription practices of clinicians regarding the management of dermatophytic skin infections. An infection easily managed with a few weeks of antifungals, tinea corporis or cruris, is now often chronic and recurrent and requires prolonged treatment. Rising resistance to terbinafine, with documented squalene epoxidase (SQLE) gene mutations, and slow clinical response to itraconazole leave clinicians with limited treatment choices. However, in these testing times, it is essential that the tenets of antifungal stewardship be followed in making therapeutic decisions, and that the existing armamentarium of antifungals be used in rationale ways to counter this extremely common cutaneous infection, while keeping the growing drug resistance among dermatophytes in check. This review provides updated evidence on the use of various systemic antifungals for dermatophytic infection of the glabrous skin, especially with respect to the emerging T. indotineae species, which is gradually becoming a worldwide concern.

Red Flaging Unscientific Prescriptions in Dermatophytosis: An Overview.

Dermatophytosis has acquired an epidemic-like proportion, fuelling a wide gamut of irrational, unethical and unscientific prescriptions. The menace can be attributed to poorly regulated legislative laws controlling the approval of molecules, unscientific marketing gimmicks by the pharmaceutical industry, over-the-counter availability of drugs and lack of awareness and knowledge among the prescribing physicians. In this review, we have attempted to enlist the irrational and unethical prescription patterns for dermatophytosis.

JAK inhibitors in vitiligo: what they hit and what they miss - an immunopathogenesis based exposition of existing evidence.

INTRODUCTION: Vitiligo is an autoimmune disorder which presents as depigmented macules due to selective loss of melanocytes. Heightened expression of Janus Kinase Signal transducers and activators of transcription (JAK STAT) pathway, which mediate cytokines action, suggest that targeting this signaling pathway may be an effective option. AREAS COVERED: A PubMed search was carried out with the broad key words 'JAK,' 'vitiligo' from 2016 to 2023. We also analyzed papers where tissue-based JAK expression was studied, with or without concomitant treatment with JAK inhibitors. We address the role of JAK inhibitors in vitiligo and their effect on repigmentation of lesions. EXPERT OPINION: While JAK inhibitors help in cessation of disease progression, they have no in vivo action on melanocyte proliferation and hence cannot result in re-pigmentation as a monotherapy. There is a need for tissue-based JAK and cytokine-based studies with post-treatment expression data to validate the role of this class of drugs in vitiligo. There is as yet no data to suggest that selective JAK inhibitors are superior to pan JAK inhibitors for vitiligo. JAK inhibitors are useful in active disease and effectively modulate the cytokine mediated autoimmune dammage and makes them singularly superior to oral glucocorticosteroids.

Time to revisit the purported link of leprosy reactions with infective triggers: An unnecessary economic burden for patients.

Existing literature on factors triggering leprosy reactions is based only on case reports and case series, and thus probably gives a biased view. We undertook a case-control study to investigate such purported trigger factors in 42 leprosy reaction patients and 40 non-reactional controls, and the cost of investigations required for the same. Detailed history, clinical evaluation and investigations for triggers were carried out. Infections (typhoid, dental caries) were the most common triggers found, followed by pregnancy. Trigger factors were commoner in the type 2 reaction (T2R) group compared to type 1 (T1R) reaction group. There was however no statistical difference between the two groups. The average estimated cost of investigations was higher in the reactional group and this difference was statistically significant. Hence, except for essential investigations required for initiating steroids, an extensive battery of investigations is unjustified unless the medical history suggests a definitive infective trigger.

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.

An update on the myriad antifungal resistance mechanisms in dermatophytes and the place of experimental and existential therapeutic agents for Trichophyton complex implicated in tinea corporis and cruris.

INTRODUCTION: There is an epidemic emergence of increased resistance in dermatophytes with to antifungal drugs with ergosterol1 (Erg1) and Erg11 mutations to terbinafine and azoles. Apart from mutations, mechanisms that predict clinical failure include efflux pumps, cellular kinases, heat shock proteins (Hsp), and biofilms. Apart from itraconazole and SUBATM (Super-Bioavailable) itraconazole, measures that can be used in terbinafine failure include efflux-pump inhibitors, Hsp inhibitors and judicious use of antifungal drugs (topical + systemic) combinations. AREAS COVERED: A PubMed search was done for the relevant studies and reviews published in the last 22 years using keywords dermatophytes OR Trichophyton, anti-fungal, resistance, mechanism and fungal AND resistance mechanisms. Our aim was to look for literature on prevalent species and we specifically researched studies on Trichophyton genus. We have analyzed varied antifungal drug mechanisms and detailed varied experimental and approved drugs to treat recalcitrant dermatophytosis. EXPERT OPINION: Apart from administering drugs with low minimum inhibitory concentration, combinations of oral and topical antifungals (based on synergy data) and new formulations of existing drugs are useful in recalcitrant cases. There is a need for research into resistance mechanism of the existent Trichophyton strains in therapeutic failures in tinea corporis & cruris instead of data derived from laboratory strains which may not mirror clinical failures.