28 DAYS LATER

Case Presentation: A 55-year-old woman with a history of rheumatoid arthritis presented for generalized weakness, dysuria, nausea, and dizziness of 1 week duration. She developed progressive weakness with associated decreased exercise tolerance, nausea, and diarrhea. Her oral intake decreased. There was no inciting event and did not note any recent close contacts with similar symptoms.Her rheumatoid arthritis had been previously severe and uncontrolled, requiring multiple large joint replacements. Her symptoms had markedly improved with an increased regimen of methotrexate 20mg weekly, infliximab, leflunomide, and prednisone 3mg daily. She also has been seen recently for increasing pain of her left knee. The patient was hypotensive, tachycardic, and tachypneic with new oxygen requirements, her knee was noted to be slightly effused and warm to touch, but without erythema. Chest X-ray was unremarkable. She had a profoundly elevated CRP. She was also noted to have an elevated creatinine, transaminitis, and thrombocytopenia. An aspirate of the left knee demonstrated a WBC count of 700.The patient became increasingly hypotensive despite fluid resuscitation. She required vasopressor support for presumed shock. She developed lab abnormalities consistent with DIC; the blood smear was notable for numerous schistocytes and encapsulated organisms within several neutrophils consistent with disseminated histoplasmosis. The urine and blood tests for histoplasma antigen exceeded the upper limit reported by the lab.The patient was started on appropriate antimicrobials, however the patient continued to deteriorate clinically and subsequently succumbed to multiple organ failure from complications attributed to her disseminated histoplasmosis. 15 days after the patient passed away, the culture from her knee aspirate resulted positive for h. capsulatum after 28 days of incubation

Discussion: Histoplasmosis is a fungal infection caused by histoplasma capsulatum, a dimorphic fungi endemic to the Mississippi and Ohio River Valleys. While typically self-limited in immunocompetent hosts, histoplasmosis can lead to progressive multiple organ failure that can be fatal to immunocompromised hosts as our case demonstrates.While hospitalists in this geographic distribution are familiar with histoplasma respiratory infections in immunocompromised patients, prosthetic joint infection (PJI) by this organism is exceedingly rare, with only 7 reported cases. Of these cases, 5 occurred to a prosthetic knee joint like our case. Additionally, one other case shared the comorbidity of rheumatoid arthritis, suggesting that this condition or its associated management is a risk factor for developing PJI caused by h capsulatum. Finally, all these cases were united in their difficulty in identifying h. capsulatum as the causative organism.While our case shares similarities with cases already reported in medical literature, it also has noteworthy differences. Our identified histoplasma on blood smear with positive serology and urine studies supporting the diagnosis. The other cases all opted for surgical management with either removal of the infected prosthetic or resection with washout, whereas our patient did not have a surgical intervention. Our case was also notable for the patient succumbing to complications of disseminated histoplasmosis.

Conclusions: Histoplasmosis PJI can have a varied presentation making it difficult to establish a diagnosis for this rare cause of PJI in immunocompromised patients.