Cryptococcal meningoencephalitis relapse after an eight-year delay: an interplay of infection and immune reconstitution

Abstract

We report a case of a symptomatic relapse of HIV-related cryptococcal meningoencephalitis 8 years after the first diagnosis on the background of immune reconstitution. The findings as well as the clinical course suggests a combination of smouldering localized infection and enhanced inflammatory reaction related to immune restoration due to antiretroviral therapy. A combination of antifungal and anti-inflammatory therapy resulted in clinical and radiological improvement. Our case challenges the concept that immune reconstitution inflammatory syndrome and microbiological relapse are dichotomous entities.

Cryptococcal Meningitis: Diagnosis and Management Update

“…A consensus case definition of cryptococcal paradoxical IRIS defines the clinical syndrome as one occurring after treatment of the initial cryptococcal meningitis followed by ART initiation with subsequent clinical deterioration manifesting as one of the following: aseptic meningitis, intracranial lesions, lymphadenopathy, pneumonitis or pulmonary nodules, or cutaneous soft tissue lesions (65). The reported incidence of paradoxical cryptococcal IRIS is highly variable in incidence, ranging between 8-49%, presenting as soon as 4 days and up to 6 years after ART initiation, and carrying a mortality rate of 0-36% (65-67). Better microbiologic therapy and achieving CSF sterility is a key principle at reducing the risk of IRIS (68).…”

Gastrointestinal cryptococcoma – Immune reconstitution inflammatory syndrome or cryptococcal relapse in a patient with AIDS?

“…Although, the initial immune recovery coupled with falling HIV-1 viral loads is consistent with IRIS [2] , the subsequent virological failure makes the diagnosis of paradoxical IRIS less clear. In cryptococcosis, IRIS and treatment failure are not always mutually exclusive [6,7] . Ideally, intra-operative cultures would have been performed which could have helped distinguish IRIS from cryptococcal relapse, based on culture sterility vs. growth, respectively.…”

“…In both cases, they simply observed the patients but also emphasized the importance of confirming sterility of contents in the cryptococcoma by culture. In a case report by Katchanov et al, a similar presentation of a central nervous system cryptococcoma was initially treated with antifungals exclusively with radiological worsening until steroids were added to direct therapy at paradoxical IRIS [6] . We have previously reported the challenges and dangers of using corticosteroids for CM because they may be contraindicated in cases of fluconazole-resistant cryptococcal relapse [7] .…”

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

“…A consensus case definition of cryptococcal paradoxical IRIS defines the clinical syndrome as one occurring after treatment of the initial cryptococcal meningitis followed by ART initiation with subsequent clinical deterioration manifesting as one of the following: aseptic meningitis, intracranial lesions, lymphadenopathy, pneumonitis or pulmonary nodules, or cutaneous soft tissue lesions (71). The reported incidence of paradoxical cryptococcal IRIS is highly variable in incidence, ranging between 8–49%, presenting as soon as 4 days and up to 6 years after ART initiation, and carrying a mortality rate of 0–36% (71–73). Better microbiologic therapy and achieving CSF sterility is a key principle at reducing the risk of IRIS (74).…”