Cellulitis Revealing a Cryptococcosis-Related Immune Reconstitution Inflammatory Syndrome in a Renal Allograft Recipient

Abstract

Immune reconstitution inflammatory syndrome (IRIS) has rarely been described in the course of disseminated cryptococcosis in solid organ transplant recipients. We report here the case of a renal transplant recipient who developed severe cellulitis in the context of Cryptococcus neoformans-associated IRIS while undergoing reduction of his immunosuppressive therapy. IRIS appeared concomitantly with a dramatic increase of blood CD4+ T cells (94-460/mm 3 ) and required the administration of a short-term steroid therapy to resolve.

Cryptococcosis

“…Drug interactions between fluconazole and immunosuppressive agents should be anticipated due to fluconazole-induced CYP3A4 inhibition, and preemptive adjustment (reduction) in calcineurin inhibitors should be made. Management of immunosuppression in the setting of cryptococcal infection requires recognition of the increased risk of IRIS associated with abrupt withdrawal or reduction of immunosuppression in organ transplant recipients with increased rates of allograft loss reported in some patients [95][96][97]. Stepwise reduction in immunosuppression is recommended, though the approach should be individualized for each patient.…”

“…Meningeal disease is the most frequent and most serious presentation [109]; aseptic meningitis with associated intracranial hypertension and CSF pleocytosis is most commonly observed [100,102,103,105,106,108]. A hallmark histopathologic finding is suppurative or necrotic granulomatous inflammation with yeast seen in tissues despite negative tissue cultures [95,112,116,117]. The presence of a positive CSF culture in cases of suspected cryptococcal IRIS should raise suspicion for direct antifungal failure or resistance, particularly in settings where fluconazole therapy is widely used as the standard of care [88].…”

“…Similarly, withdrawal or reduction of immunosuppressive agents is standard practice in managing infectious complications in SOT recipients [111]. Given the putative risk of IRIS with abrupt withdrawal or discontinuation of immunosuppressive agents in these patients, gradual de-escalation during the initiation of antifungal therapy is advised to reduce the risk of future IRIS [95,111,112].…”

Skin and soft tissue infections in the transplant population

“…Numerous reports exist of cutaneous cryptococcal infections. The host-pathogen interactions in immunocompromised hosts are complex, as demonstrated by a case report of a renal transplant recipient who had cellulitis with necrotic adenitis as a manifestation of cryptococcosis-related immune reconstitution infl ammatory syndrome in the setting of reduced immunosuppression and rising CD4 + lymphocyte count; the patient responded well to treatment with steroids [ 35 ]. A recent report of cutaneous Aspergillus ustus in a lung transplant recipient without any systemic disease describes a new opportunistic fungal pathogen, highlighting the need for biopsy for optimal diagnosis [ 36 ].…”

Immunosuppresseurs et antifongiques

“…[11]. D'une part, elle permet la croissance des levures comme Cryptococcus neoformans dans des conditions de rejet de la greffe ou un syndrome de reconstitution immune [8,50]. Le désé-quilibre de la balance entre les réponses Th1 et Th2 induit par les inhibiteurs de la calcineurine et le MMF serait en cause [9].…”