The immune reconstitution inflammatory syndrome: a cause of death in persons on antiretroviral therapy?

The availability of antiretroviral therapy (ART) has significantly improved the quality of life of persons with HIV infection. However, new problems have arisen as a consequence of this treatment. An immune reconstitution inflammatory syndrome (IRIS) in which patients experience a paradoxical worsening of their clinical condition may occur during recovery of the immunity. Thus far, there is no laboratory test available to diagnose IRIS. The diagnosis therefore remains clinical and by exclusion. In this paper, we describe the autopsy findings of three HIV-infected patients who died at the Antwerp University hospital directly or indirectly related to IRIS. One patient died following a disseminated cryptococcocal and Mycobacterium avium complex (MAC) infection. Two other patients died with a disseminated aspergillosis infection after receiving corticosteroids to decrease IRIS induced inflammatory signs. These three patients show the difficulties faced by clinicians in diagnosing IRIS and the importance of performing autopsies in persons with HIV infection who die despite receiving ART.

Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings.

In many resource-limited settings, cryptococcal meningitis (CM) contributes up to 20% of all deaths with further complications due to Immune Reconstitution Inflammatory Syndrome (IRIS). We present a case report on a patient who developed CM-IRIS and then subsequent CM-relapse with a fluconazole-resistant organism and then later CM-IRIS once again, manifesting as cystic cryptococcomas, hydrocephalus, and sterile CSF. In this case we, demonstrate that CM-IRIS and persistent low level cryptococcal infection are not mutually exclusive phenomena. The management of IRIS with corticosteroids may increase the risk of culture positive CM-relapse which may further increase the risk of recurrent IRIS and resulting complications including death. We also highlight the role of imaging and fluconazole resistance testing in patients with recurrent meningitis and the importance of CSF cultures in guiding treatment decisions.

Burkitt's lymphoma in Uganda: the role of immunohistochemistry in diagnosis.

BACKGROUND: Haematoxylin and eosin staining has remained the standard diagnostic method for Burkitt's lymphoma. Ancillary tests including immunohistochemistry, not widely available in developing countries, are important tools in verifying the diagnosis of lymphomas with equivocal morphological findings. OBJECTIVE: To evaluate the reliability of haematoxylin and eosin staining in the diagnosis of Burkitt's lymphoma using immunohistochemistry as the gold standard. DESIGN: Cross sectional study. SETTING: Department of Pathology laboratory, Makerere University Medical School, Uganda. SUBJECTS: One hundred and thirty eight formalin fixed paraffin embedded biopsies of Burkitt's lymphoma diagnosed from January 2001 to December 2005. RESULTS: Of the 138 tumours, 88.4% were extra-nodal: jaw 36.2%, ovary 21%, gastrointestinal tract 12.3% other abdominal 11.6%. Males (55.8%) predominated. The sensitivity and specificity of haematoxylin and eosin were 93.2% and 50% respectively. The positive and negative predictive values were 91.7% and 55.6%. CONCLUSION: Histology using haematoxylin and eosin staining is sensitive in the diagnosis of Burkitt's lymphoma but not very specific. Immunohistochemical staining with CD20, Ki-67 and bcl-2 is necessary for difficult cases.