INTRODUCTION: Common illnesses tend to produce atypical manifestations in the immunosuppressed hosts. The advent of human immunodeficiency virus (HIV) endemic has brought an increased incidence of cryptococcosis, particularly in the form of meningitis. Now, atypical presentations of many fungal and granulomatous diseases are increasingly recognized among patients receiving highly active antiretroviral therapy (HAART). We describe a case of cryptococcal mediastinal lymphadenitis due to immune reconstitution inflammatory syndrome (IRIS) following the initiation of HAART.
CASE PRESENTATION: SJ is a 34-year-old heterosexual man who presented with two weeks of fever, night sweats and non-productive cough. He was diagnosed with HIV and acquired immune deficiency syndrome (AIDS) ten months ago. At that time, he developed cryptococcal meningitis with accompanying cryptococcemia. The cerebrospinal fluid (CSF) and serum cryptococcal antigen titers were 1:16 and 1:512, respectively. He was treated with Amphotericin-B, and his symptoms subsided along with clearance of the CSF antigenemia. At discharge, his viral load was >750,000 copies/ml, the CD4+ count 8 cells/μl, and CD4/CD8 ratio 0.04. He was prescribed fluconzale 400 mg/day as secondary prophylaxis. For the last seven months, the patient also received HAART regularly with good compliance.On this admission, his physical examination showed a well-nourished male without distress. He had fevers and diaphoresis. Peripheral lymph nodes were not enlarged. Lung and heart auscultation was normal. Laboratory studies revealed white blood cell count of 5,000 /μl, CD4+ count of 150 cells/μl and an undetectable HIV viral load. Cryptococcal titer was 1:128 in serum and negative in CSF. Imaging of the chest from plain radiographs and computed tomography showed hilar and mediastinal enlargement suggestive of adenopathy. During bronchoscopy, scattered mucosal nodules along tracheal wall with yellow purulent exudates expressed were noted. All cultures, including viral, fungal and mycobacterial, from blood and sputum, were negative. However, cytology of needle aspirate of the mucosal nodules revealed histiocytic granulomatous inflammation with capsulated yeast forms identified as Cryptococcus. The patient was continued on fluconazole with naproxen added. His cough abated and the fever resolved within two weeks. On follow up, the mediastinal adenopathy also regressed over the next four months.
DISCUSSIONS: Mediastinal adenopathy in AIDS patients has typically been associated with either Mycobaterium tuberculosis or Mycobacterium avium complex in cases of suspected infectious etiology. Lymphoma, Kaposi's sarcoma and sarcoidosis make up the differential diagnoses for the non-infectious causes. In a recent literature review, lymphadenitis is noted to be the most common Cryptococcus-related IRIS . Curiously, no viable organism could be cultured from the lymph node aspirates in all the cases; the diagnosis was established by histologic examination. The timing for development of IRIS from initiation of HAART is variable. The risks of developing Cryptococcus-related IRIS include initial viral load, CD4 cell count, CSF antigen titer, as well as HAART introduction within 30 days of the initial cryptococcosis diagnosis . Optimal therapy likely includes continuation of HAART and antifungal drug. But the role of anti-inflammatory agents remains undefined.
CONCLUSION: Introduction of HAART has ushered in an era where uncommon manifestations of common diseases are increasingly recognized. Cryptococcal lymphadenitis/mediastinitis is one such entity. In AIDS patients with prior cryptococcal infection, IRIS-related mediastinitis must be considered in the appropriate presentation. Treatment should involve continued HAART with considerations for the addition of anti-inflammatory agents.
DISCLOSURE: Kenneth Wei, None.