Faculty Bibliography

SUMMARYThe traditional landscape of dermatophyte infections has changed over the past decade. The emergence and global expansion of Trichophyton indotineae have highlighted the impact of irrational and uncontrolled antifungal and topical corticosteroid use, presented treatment challenges, and highlighted the deficiencies of currently available diagnostic methods. Trichophyton mentagrophytes genotype VII, which has until recently been associated with animal reservoirs, is now associated with human-to-human transmission and is frequently related to sexual transmission. Infections associated with emerging dermatophytes are notable for atypical presentations that may include widespread, inflamed lesions, terbinafine resistance, and frequent relapse. The classic presentation of tinea lesions is frequently obscured by the application of topical corticosteroids, leading to delays in clinical recognition, diagnosis, and appropriate treatment, perpetuating further misuse of topical medications. Deep or invasive dermatophytoses, including Majocchi's granuloma, may occur in immunocompromised patients. The introduction of matrix-assisted laser desorption/ionization-time of flight mass spectrometry and molecular detection of dermatophytes has improved the diagnostic landscape for dermatophytes. However, currently, most assays do not specifically detect T. indotineae or T. mentagrophytes genotype VII, hindering the diagnosis and surveillance. Sequencing of the internal transcribed spacer (ITS) region is required for definitive identification. Terbinafine and azole resistance is common in T. indotineae and increasingly being reported for other species. While nomenclatural changes have been introduced and debated over many decades, the last decade has seen the introduction of new genera, e.g., Nannizzia, Paraphyton, and Lophophyton. An overview of currently recognized dermatophyte species, complexes, and genera is presented here, describing phylogenetic, ecological, and biochemical relatedness. The ethical conundrum of the name Trichophyton indotineae is also discussed.

Granulomatous inflammation of the skin can arise in patients with inflammatory disorders, malignancy, infections, and in reactions to medications or foreign bodies. Granulomatous disorders describe a group of diseases marked by the presence of granulomatous inflammation in the dermis and can be categorized into infectious and non-infectious causes. Inflammatory, non-infectious granulomatous disorders including granuloma annulare (GA), necrobiosis lipoidica, rheumatic nodules, cutaneous sarcoidosis, reactive granulomatous dermatitis (RGD), and necrobiotic xanthogranulomas (NXG) can occur in the setting of underlying systemic disease, and some cutaneous granulomatous disorders, including including GA, RGD and NXG, may rarely be associated with malignancy. Due to the varied clinical and histologic presentations of granulomatous infiltrates, and given rare presentations and ongoing debates regarding strength of disease associations, potential for confusion may arise among clinicians when approaching the diagnosis, differentiation and systemic evaluation of granulomatous disorders. Given the potential of certain granulomatous disorders to herald a new diagnosis of a malignancy, it is imperative that dermatologists approach granulomatous inflammation systemically in order to ensure best patient outcomes. We review clinical presentations and histologic findings of GA, RGD, and NXG and discuss the associations of these granulomatous disorders with malignancy. Further, we provide a framework for clinicians to pursue additional diagnostic evaluation for underlying malignancy in these conditions.

Dermatophytoses (synonymous with tinea) are superficial fungal infections of the skin, hair, and nails, typically caused by dermatophytes in the genera of Trichophyton and Microsporum. Dermatophyte infections are common and are estimated to affect roughly 20-25% of the global population. Historically, tinea infections have been treated with short courses of topical and/or oral antifungal therapies, however, the last decade has seen increasing antifungal treatment failure. Trichophyton (T.) indotineae (previously termed Trichophyton mentagrophytes-genotype VIII) has emerged as the primary species driving antifungal treatment failure worldwide. Clinically, T. indotineae infection may present as a typical dermatophyte infection, or atypically may mimic eczema, psoriasis, or other inflammatory dermatoses. Patients are often strikingly itchy and may be using topical steroid creams inappropriately in combination with antifungal and antibiotic agents. Terbinafine, once considered a first-line oral agent for tinea infections, often fails against T. indotineae, for which prolonged courses of itraconazole (often at higher than typical dermatophyte dosing) are now regarded as the treatment of choice. Fluconazole and griseofulvin demonstrate limited efficacy. Antifungal susceptibility testing may guide treatment choices but is not well established for dermatophytoses. Dermatologists should be aware of an approach to evaluating and treating refractory dermatophyte infections. Increased awareness among clinicians, including in infectious diseases, primary care, and the emergency room, is also important to facilitate early recognition, appropriate management, and timely referral. Dermatologists may play a key role in promoting antifungal stewardship and educating other clinician groups about emerging dermatophyte infections. In this review, we detail T. indotineae with a focus on clinical presentation, diagnostic confirmation, and treatment.

Granuloma annulare (GA) is an inflammatory skin disease typically characterized by an erythematous eruption consisting of papules and annular plaques. GA can have a severe impact on quality of life, especially when widespread. GA can be difficult to treat and often recurs after treatment is stopped; there remain no FDA-approved therapies. In recent years, there has been significant progress in understanding the epidemiology, disease associations, and molecular pathogenesis of GA. Patients with GA are more likely to have hyperlipidemia, diabetes mellitus, and autoimmune diseases including thyroiditis, rheumatoid arthritis, and systemic lupus erythematosus. These associations further underscore the importance of recognizing GA and evaluating for comorbid disease. Accurate diagnosis of GA requires distinguishing it from its clinical and histologic mimics, some of which share annular morphology or granulomatous inflammation. Molecular work has suggested a T-cell mediated pathogenesis and identified key cytokines and other signals that drive macrophage accumulation and activation in tissue. Emerging therapies that block these cytokine signals are showing promise in the clinic. In this article, we provide an updated overview of the epidemiology, disease associations, clinical and histopathologic characteristics, molecular pathogenesis, and treatment of GA.