A case of cutaneous Scedosporium apiospermum infection in a patient on a janus kinase inhibitor

Scedosporium apiospermum is a mold that is usually found in soil and polluted water, but has also been linked to contaminated ambient air in hospitals. This fungus typically behaves as a rare opportunistic pathogen affecting immunocompromised patients in whom disseminated disease can readily occur, causing shock and multiorgan failure. We report the first case of cutaneous Scedosporium apiospermum infection in a patient with rheumatoid arthritis treated with a Janus kinase inhibitor. We also reviewed other cutaneous manifestations of Scedosporium apiospermum reported between 2003 and 2022.

Dear Editor, Scedosporium apiospermum is a mold that causes many types of infections, particularly in immunocompromised hosts. This fungal organism is typically found in soil or polluted water, and infections in humans result from inhalation or direct inoculation from trauma. 1 There have been reported cases involving the respiratory tract, central nervous system, eye, skin, soft tissue, and bone. 2 Immunocompetent patients typically have superficial or localized infection of the skin or cornea, 3 whereas immunocompromised patients can manifest hematogenous dissemination affecting multiple organ systems. 4 On the skin, lesions typically appear as nodules or erythematous to violaceous papules or bullae with woody induration. 5 Mycetomas have been reported in immunocompetent patients after trauma. 5 The majority of cutaneous manifestations, however, affect immunocompromised patients in whom no trauma was reported. We report here the first case of this organism causing an opportunistic cutaneous infection in a patient on a Janus kinase (JAK) inhibitor, and review other cutaneous manifestations of Scedosporium apiospermum reported between 2003 and 2022.
A 72-year-old woman with a history of rheumatoid arthritis on tofacitinib 10 mg once daily, presented with a 1-month history of an enlarging, itchy, nodular plaque on the left forearm ( Figure 1a). A skin biopsy revealed extensive chronic and granulomatous inflammation, with multinucleated giant cells and areas of necrosis ( Figure 2a). While an AFB stain was negative for mycobacteria, a GMS stain highlighted a focal collection of septate hyphae within a giant cell (Figure 2b). A fungal culture identified the causative organism as Scedosporium apiospermum.
On follow up examination, scaly violaceous papules and furuncles on the left extensor forearm were evident. Tofacitinib was discontinued and antifungal therapy was initiated. While the antifungal agent with the most evidence of effectiveness against Scedosporium infections is voriconazole, itraconazole 100 mg once daily was started due to formulary constraints. 6 Upon reevaluation 1 month later, interim improvement in the number of nodules was noted, but induration at the proximal and distal edges persisted (Figure 1b). The patient continued the same regimen for an additional month, at which time almost complete flattening of the nodules was observed (Figure 1c).
A literature review for reported cases between 2003 and 2022 found a total of 33 instances, including our own, reporting cutaneous Scedosporium apiospermum infections. Table 1 lists these cases and their clinical features and outcomes. While many factors determine the publication rate of articles concerning specific diseases, the low number of cases (1.7 cases annually), suggests that cutaneous Scedosporium apiospermum infections are fairly rare. Only three patients were immunocompetent, and all three cases resulted after trauma to the skin. The remaining cases were in immunocompromised patients, including transplant recipients, previous diagnoses of leukemia, and those on immunosuppressive agents for diseases, such as rheumatoid arthritis, ulcerative colitis, and temporal arteritis.
In our review, we found that successful treatment has been reported with voriconazole, fluconazole, and itraconazole. In a majority of these anti-fungal regimens, reduction or absolute withdrawal of the immunosuppressive agent was also completed until resolution of the infection. Surgical management was also used in six cases.
In summary, Scedosporium apiospermum is rare opportunistic fungal pathogen most commonly affecting immunocompromised patients, in whom disseminated disease leads to increased mortality. Early detection of this organism, discontinuation of immunosuppressive agent, and treatment with a systemic antifungal agent, is critical for positive outcome.

ACKNOWLEDGEMENT
We thank J. Michael Gagnier M.D. for interpretation of the histopathology and for preparation of the photomicrographs.

CONFLICT OF INTEREST
None to declare.