Case Presentation:
A 62 year-old female with a history of asthma and rheumatoid arthritis on abatacept presented to the hospital with ten days of fevers to 102 and abdominal pain. She reported daily fevers occurring at various times during the day. The abdominal pain was constant, sharp, diffuse, and associated with nausea and an episode of non-bloody, non-bilious vomiting. One week prior to symptom onset she had completed a five-day prednisone taper for an asthma exacerbation. Her social history was notable for her occupation as a nurse practitioner, with previous work as a physician in the Dominican Republic over 25 years ago. She reported recent travel to Mexico two months prior to admission. Her admission labs were notable for a WBC count of 9.14 K/mL with a left shift and 5% atypical lymphocytes, AST 298 m/L, ALT 146 m/L, and alkaline phosphatase of 338 m/L. A RUQ US and abdominal CT scan were unremarkable. She was empirically started on broad spectrum antibiotics. She continued to have daily fevers to 103. Daily blood cultures were negative. Respiratory studies (influenza, RSV), a hepatitis panel, other viral studies (EBV, CMV, HSV, VZV, HIV), evaluation for tick-borne diseases, and T-spot were unremarkable. An MRI of the abdomen revealed splenic enlargement with innumerable T2 hypointense lesions throughout the spleen and hepatic enlargement. A chest CT showed a left upper lobe nodule with irregular margins and a peri-lesional halo. 9 days into hospitalization the urine histoplasma antigen returned positive and serum histoplasma antigen was greater than assay, confirming a diagnosis of disseminated histoplasmosis.
Discussion:
Pulmonary histoplasmosis presents with fever, cough and chest pain, while disseminated infection is often associated with fever and hepatosplenomegaly. TNF inhibitors are known to increase the risk of histoplasmosis. Abatacept, similar to TNF inhibitors, suppresses cellular immunity, predisposing patients to fungal infections. Abatacept has been associated with blastomycosis, aspergillosis, and systemic Candida, but reports of abatacept-associated histoplasmosis are rare. The patient’s travel to Mexico one month prior to symptom onset is highly suggestive of recent exposure. Steroid use may have further predisposed her to active infection. Although reactivation of a prior infection is possible given prior residence in an endemic area, it is not favored as the primary driver of histoplasmosis infections in patients on TNF inhibitors. As more than half of adults from endemic areas have been exposed, if reactivation predominated, the incidence should be much higher than the observed 1-2 cases per 10,000.
Conclusions:
Histoplasmosis should be considered in patients on TNF inhibitors or abatacept with a compatible clinical presentation and prior exposure. Gathering a comprehensive travel history to endemic areas is particularly important, as recent exposure is the likely cause of histoplasmosis for patients on these medications.