Background/Purpose: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with immunodeficiency associated with the disease itself and immunosuppressive treatment. Infections are very frequent events and one of the main causes of morbidity and mortality. However, fungal infections have a low incidence, being those associated with Cryptococcus neoformans (CN) the most frequently described.

The aim of this study was to describe clinical, biochemical and outcomes of the invasive fungal infection (IFI) produced by CN in patients with SLE assisted in our hospital.

Methods: A retrospective and observational study of the IFIs by CN was carried out in adult patients with SLE (ACR82-97), assisted between January 1, 1993 and 1 May 2018.

Detection of capsular antigen in cerebrospinal fluid (CSF), a positive result of the ink test or isolation of the fungus from sterile sites according to EORTC/MSG 2008 criteria (European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group) were defined as IFI tested by CN. Evolution time of SLE at infection diagnosis, time of hospitalization, SLE activity measured by SLEDAI, clinical manifestations and immunosuppressive treatment were analyzed.

Results: Twenty one SLE patients with IFI were identified, and 7 (33%) of them presented CN infection. Rest of IFIs were caused as follows: 7 (33%) by Candida spp., Aspergillus spp: 2 (14,3%), H. capsulatum: 3 (9,52%), P. jiroveci: 1 (4,8%), H. capsulatum / Alternaria spp (mixed infection): 1 (4,8%). Seven cases infected with CN occurred in women with a mean of 40 years ± 16. Mean evolution time of SLE at fungal infection was 9.7 years (9-180 months). Mean SLEDAI was 10 (0-24). 86% (6/7) of the patients had nephropathy and 57% (4/7) required hemodialysis. 43% (3/7) received treatment with cyclophosphamide but only 2 patients presented neutropenia. 86% (6/7) received corticosteroid therapy with meprednisone at doses greater than 20 mg/day and 29% (2/7) were treated with pulses of methylprednisolone. Other treatments were: Azathioprine, intravenous gammaglobulin, Mycophenolate Mofetil.

All the patients presented symptoms related to meningoencephalitis and Chinese ink test, antigenemia and CSF culture were positive in all cases. In 2 patients, CN was also isolated in the blood culture and in one of them also in sputum (disseminated infections). All were treated with Amphotericin B (liposomal amphotericin B was used in one patient due to renal failure and in another patient associated with fluconazole). Two patients continued with secondary prophylaxis with fluconazole. 5/7 patients died during hospitalization (71.4%), in most cases directly related to the infection.

Conclusion: Invasive fungal disease by Cryptococcus neoformans in SLE patients was associated to active disease, renal compromise and immunosuppressive treatment. Meningoencephalitis was the most prevalent clinical manifestation of cryptococcosis and in all cases the germ was isolated in the CSF. Two patients had a disseminated infection (blood cultures and positive sputum). All were treated with amphotericin B. The mortality was 71.4%.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/invasive-fungal-infection-with-cryptococcal-meningitis-in-patients-with-systemic-lupus-erythematosus/