Violaceous Nodules on the Leg of an Alemtuzumab-Treated Kidney Transplant Recipient: Answer

Le résumé fourni par la source

(Continued from page e28) ANSWER: DEEP DERMATOPHYTOSIS The incisional biopsy demonstrated marked pseudoepitheliomatous hyperplasia of the epidermis overlying a dense mixed inflammatory infiltrate extending through the dermis and superficial subcutis. Numerous neutrophil-rich microabscesses and “dirty” necrotic foci were present between collagen bundles and around downgrowing squamous epithelium (Figure 2). The squamous cells showed preserved maturation and only minimal cytologic atypia, without stromal desmoplasia, favoring reactive pseudoepitheliomatous hyperplasia rather than invasive squamous cell carcinoma. Special stains for bacteria and mycobacteria (Gram and Ziehl–Neelsen) were negative. On hematoxylin–eosin sections, only very subtle hyphal profiles were suspected within the necrotic inflammatory debris (Fig. 3B).FIGURE 3.: A, Grocott methenamine silver stain highlighting numerous septate fungal hyphae within necrotic dermis and adjacent adnexal structures. B, High-power hematoxylin–eosin section showing neutrophil-rich necrotic dermal debris in which fungal elements are subtly appreciated (arrow). C, Potassium hydroxide preparation from lesional scale demonstrating abundant branching septate hyphae, confirming dermatophyte infection.Grocott methenamine silver (GMS) stain highlighted abundant slender, septate fungal hyphae and spores within the dermis and microabscesses (Fig. 3A). A potassium hydroxide preparation from lesional scale showed numerous branching septate hyphae, and culture yielded Trichophyton rubrum, establishing the diagnosis of deep dermatophytosis (Fig. 3C). DISCUSSION Deep dermatophytosis is a rare form of invasive dermatophyte infection in which dermatophytes extend beyond the epidermis and hair follicles into the dermis and, in some cases, the subcutis or deeper tissues.1 Recent systematic reviews have identified just more than 100 reported patients worldwide, largely in the context of profound or iatrogenic immunosuppression, including solid-organ transplantation, advanced HIV infection, inherited defects in antifungal immunity such as CARD9 deficiency, and intensive immunosuppressive regimens.2,3 Clinically, deep dermatophytosis often presents with firm dermal nodules, ulcerated plaques, or tumor-like lesions on the extremities or face, frequently in association with superficial tinea or onychomycosis and mimicking bacterial abscesses, panniculitis, vasculitis, or cutaneous neoplasms. Topical therapy alone is inadequate because of the depth of involvement, and delayed recognition is common.1–3 Histologically, deep dermatophytosis characteristically shows exuberant pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate rich in neutrophils and, in some cases, suppurative granulomas or abscess-like collections. This pattern can closely simulate well-differentiated squamous cell carcinoma or keratoacanthoma, particularly in transplant patients in whom the clinical threshold for diagnosing carcinoma is low. In multiple series and case reports, the dominant histologic clue has been dermal microabscesses with subtle or atypical fungal forms that are difficult to appreciate on routine hematoxylin–eosin sections, underscoring the importance of PAS and GMS stains to demonstrate septate hyphae in the dermis and adnexal structures.1,2 In this case, the main histologic differential diagnoses included atypical mycobacterial infection, leishmaniasis, bacillary angiomatosis, and invasive squamous cell carcinoma. Atypical mycobacterial infections typically show necrotizing or suppurative granulomas with Fite-positive bacilli. Leishmaniasis reveals dermal infiltrates containing intracytoplasmic amastigotes on Giemsa or hematoxylin–eosin sections. Bacillary angiomatosis is characterized by a lobular capillary proliferation with neutrophils and granular amphophilic material containing Warthin–Starry–positive bacilli.4–6 In contrast, this biopsy showed a predominantly epidermal pseudoepitheliomatous response with neutrophilic microabscesses, numerous dermal fungal elements on GMS, and negative stains for bacteria and mycobacteria, supporting deep dermatophytosis rather than these alternatives. Similar pseudoepitheliomatous, neutrophil-rich patterns have been reported in transplant-associated deep T. rubrum infection, where lesions on the lower limbs or face were initially suspected to represent bacterial infection or nonmelanoma skin cancer.1–3 Our patient had several converging risk factors: solid-organ transplantation, diabetes, and very recent exposure to lymphocyte-depleting alemtuzumab followed by augmented immunosuppression for suspected antibody-mediated rejection. Alemtuzumab induces prolonged depletion of CD4+ and CD8+ T cells and is associated with a substantial burden of opportunistic infections, including invasive fungal disease, particularly when combined with additional immunosuppressive therapies.7,8 Deep or disseminated dermatophyte infections have been described in similar settings of intensified immunosuppression for solid-organ transplant rejection, underscoring how the “net state” of immunosuppression, rather than any single agent, drives risk. The patient responded to oral terbinafine 250 mg daily, consistent with case series and systematic reviews that support terbinafine as a preferred first-line agent for deep dermatophytosis in solid-organ transplant recipients, with itraconazole or newer azoles as alternatives or adjuncts, while accounting for relevant drug–drug interactions. Invasive or disseminated disease may require combination therapy and treatment for many months, alongside careful search for extracutaneous involvement and, where possible, reduction of immunosuppression.1–3 This case illustrates how deep dermatophytosis can masquerade as keratoacanthoma-like squamous neoplasia in an alemtuzumab-treated kidney transplant recipient. For dermatopathologists and clinicians, key red flags include (1) tender nodules or ulcerated plaques on the lower extremities of a heavily immunosuppressed patient, particularly with concomitant tinea or onychomycosis; (2) pseudoepitheliomatous hyperplasia with neutrophilic microabscesses out of proportion to cytologic atypia; and (3) antibiotic-refractory “cellulitis” or “abscesses” in which special stains have not yet been performed. Prompt biopsy with PAS/GMS, KOH examination, culture, and early systemic antifungal therapy are crucial to prevent progression to deep or disseminated invasive dermatophyte infection in this high-risk population.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.