Discussion:
Given the keratinophilic nature of dermatophytes, invasion deeper than the stratum corneum in the skin is rare.1 However, this case demonstrates that increased immunosuppression in patients with superficial dermatophyte infections may predispose to angioinvasive disease involving deeper tissues. The most common predisposing factors associated with invasive dermatophyte infections include: superficial dermatophytosis, solid organ transplant, topical immunosuppressants, gene mutations, diabetes, and trauma.6 The development of our patient’s angioinvasive dermatophyte infection was preceded by increasing immunosuppression with high dose steroids, rituximab, and ibrutinib in the setting of worsening CLL and ITP. It is known that immunosuppressive agents used in hematologic malignancies such as bruton tyrosine kinase inhibitors (ibrutinib) and anti-CD20 monoclonal antibodies (rituximab) are associated with an increased risk of invasive fungal infection.7-10 Classically, these fungal infections include invasive yeast infections such as candidiasis, mold infections including aspergillosis and fusariosis, endemic fungal disease, and classic opportunistic infections such as cryptococcus and pneumocystis jiroveci.8 Invasive dermatophyte infections are rarely considered when increasing a patient’s immunosuppression. In the setting of superficial dermatophyte infections, clinicians should be aware of the possibility of invasive disease when increasing immunosuppression similar to the more classic non-dermatophyte invasive fungal infections. When a superficial dermatophyte infection presents with a dusky appearance and/or leads to pain out of proportion to exam, there should be concern for invasive disease, including necrotizing fasciitis, and early biopsy/surgical intervention should be considered.
Antifungal treatment guidance for invasive dermatophyte infections is scarce. When dermatophyte infections extend beyond the stratum corneum, it is generally recommended to transition from topical to oral therapy. There is not a consensus on the preferred oral antifungal. A recent systematic review of invasive dermatophyte infections showed that the most commonly used agents were terbinafine and itraconazole.6 However, a number of patients were treated with other antifungals including griseofulvin, fluconazole, amphotericin B, and posaconazole.6 There was additional variability in the duration of treatment for the cases reviewed. We treated our patient with oral terbinafine 250 mg daily for 12 weeks. This drug, dose, and duration of therapy in combination with surgical debridement and reduced immunosuppression resulted in clinical clearance of infection.