A Case of Fever of Unknown Origin in the Setting of an Uncommon Exposure History & Nonspecific Symptoms

Background: This case of fever of unknown origin with a broad differential illustrates the potential for multiple diseases to co-occur. Case Presentation: A 46-year-old female with a past medical history of malaria and TB presented with cough, shortness of breath, cyclical fever up to 103°F, diffuse rash, BRBPR, joint pain, multiple liver nodules, night sweats, and 20-lb weight loss following travel to Burma 6 months prior. Physical exam revealed tachycardia with irregular rhythm and a holosystolic murmur, suprapubic tenderness, 2+ lower extremity edema, and scattered small, round pruritic, erythematous rashes throughout all 4 extremities. Several fungal, parasitic, viral, and bacterial infectious etiologies were considered. Labs were significant for the following etiologies: infectious- EBV DNA and Brucellosis, Bartonella Hensleae, Coccidioides, and hepatitis A antibodies; Malignancy- protein gap IgG 2x upper limit; Autoimmune- anti-dsDNA 1:640, CRP 9.7, protein:creatinine ratio 62.1 with decreased C3/C4, positive Coombs, positive ANA, elevated ACE-I levels, and anti-smooth muscle/anti-cardiolipin/anti-RNP/myeloperoxidase antibodies, leading to a broad autoimmune differential. Imaging showed multiple liver nodules, and liver biopsy revealed extramedullary hematopoiesis and diagnosis of stage III High Grade B Cell Lymphoma with CD20+, BCL-2+, Myc+, Ki67>90% cytology. Despite this diagnosis, there was clear concurrent autoimmune manifestation and the treatment team suspected rheumatologic etiology over malignancy prior to diagnosis. Conclusion: This unusual case shows how autoimmune and malignant symptomatology can co-occur, generating a clinical picture that is persistently nonspecific. This case also raises the question of how autoimmune disease can trigger malignancy.