The patient is a 42 year old male with HIV (CD4 116, VL 33K) with poor adherence to antiretroviral therapy who presented to clinic with 3-6 months of anorexia and one week of cough and fevers. He was febrile to 39.4C, started on treatment for pneumonia, and admitted to the hospital. Imaging showed centrilobular nodules. He underwent bronchoscopy which was negative for infection and malignancy. He had a subcarinal lymph node biopsy which was unremarkable. Fevers resolved, and he was discharged with a course of doxycycline and antiretroviral therapy.
The patient returned to clinic 3.5 weeks later with fever to 39.1C and a new cough. Chest CT showed evolution of nodules with mixed improvement and worsening. A repeat bronchoscopy was negative for infection or malignancy. A transbronchial biopsy showed lymphohistiocytic infiltrates with multinucleate giant cells. Fevers resolved. He was believed to have inadequately treated pneumonia and discharged with an additional antibiotic course.
The patient returned to clinic 3.5 weeks later with fevers, fatigue, and anorexia. He was febrile to 38.8C. CD4 count was 34 with an undetectable viral load. Chest CT again showed bilateral nodules. He remained persistently febrile despite antibiotics. He underwent biopsy of an enlarging lung nodule and was started on empiric treatment for myocobacterium avium complex (MAC) infection. After extensive review, the pathology demonstrated lymphomatoid granulomatosis (LYG). He was started on prednisone and rituximab with prompt resolution of fevers. MAC treatment was stopped and subsequently restarted after a sputum culture turned positive. The primary etiology of fevers was LYG for which he continues chemotherapy.
Discussion:
LYG is thought to be an EBV associated B cell lymphoproliferative disorder that most commonly involves the lungs, though the skin and nervous system may also be affected. Since there is significant overlap between LYG and other pulmonary diseases in both clinical presentation and radiographic findings, the diagnosis is a pathologic diagnosis. The pathology shows lymphoid infiltrates and areas of necrosis as well as invasion of blood vessel walls with lymphoid infiltrate (Figure 1). Immunohistochemical testing shows CD20+ B cells and LYG is graded based on the quantity of EBV positive B cells. LYG is commonly associated with immunosuppression and generally has a median survival of 14 months. Mainstays of treatment include steroids, rituximab, and chemotherapy similar to what is used for diffuse large B cell lymphoma.
Conclusions:
The differential diagnosis for fever of unknown origin in an immunocompromised HIV positive person is broad, including both infectious and non-infectious etiologies. Since cough was his main localizing symptom, the pulmonary system was evaluated repeatedly over multiple hospitalizations spanning 3 months and after several antibiotic courses for pneumonia. This case highlights the challenges in identification of subacute infections and rare malignancies as well as correlating pathologic findings with clinical symptoms.