Case Presentation: A 31-year-old male with no significant past medical history presented with fever, chills, night sweats, and rash. One week prior, he underwent incision and drainage of a perirectal abscess and was started on a 7-day course of trimethoprim/sulfamethoxazole (TMP-SMX). On the second day following the procedure, he developed fevers, chills, night sweats, and rash, which persisted until his presentation to the hospital five days later. On arrival to the Emergency Department, the patient was found to have a fever of 104.4F. On physical exam, he was well-appearing. He had a faint blanching morbilliform rash on his trunk with extension to the proximal extremities. The perirectal abscess had largely resolved with no visible erythema or drainage and minimal scabbing and tenderness. Initial laboratory testing showed pancytopenia (WBC 1.29 K/uL, hemoglobin 12.0 g/dL, platelets 89 K/u). He had significantly elevated inflammatory markers (D-Dimer 25375 ng/mL and ferritin 19350 ng/mL). He additionally had a mild AKI, transaminitis, and coagulopathy. Over subsequent days, many of these laboratory abnormalities significantly worsened, including the pancytopenia and transaminitis. He had rising inflammatory markers with development of hypertriglyceridemia. Initial peripheral smear showed Rouleaux formation, rare schistocytes, and atypical lymphocytes, with no blasts or dysplastic leukocytes. CT chest/abdomen/pelvis with IV contrast showed hepatosplenomegaly. Bone marrow aspirate revealed hemophagocytosis. The patient was started on 10 mg/m2 IV dexamethasone for presumed hemophagocytic lymphohistiocytosis (HLH). Soon after initiating steroids, he clinically improved and was discharged on a slow steroid taper. Five months following initial presentation, his laboratory markers of HLH had all resolved, other than a persistent mild indirect predominant hyperbilirubinemia (TBili 1.6), and steroids were discontinued. No malignancy or other systemic condition were identified during the workup. The patient remains asymptomatic and continues to follow closely with Hematology.
Discussion: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory hematologic condition that is often aggressive with high mortality, particularly when not identified early. HLH can be inherited or sporadic and is often associated with malignancy, infection, or rheumatologic and immunodeficiency disorders [1]. In rare instances, HLH has been associated with medications, including antibiotics [2-7]. The mechanism of the association between medications and HLH is unclear [2,3]. Patients with HLH are typically treated as per the HLH-94 protocol, with dexamethasone and etoposide used as mainstays of treatment [8]. Given the patient’s nontoxic appearance as well as initial positive response to steroids, this patient was not given etoposide or any other medications and responded well to a prolonged steroid taper. The causative agent for HLH in this patient was likely TMP-SMX given the time course from the offending agent, no use of other medications, no other significant medical history, and no underlying malignancy or other systemic condition. His improvement with only steroids may also be supportive of medication-induced HLH.
Conclusions: Medication induced HLH is a rare and poorly understood phenomenon. Our case report discusses a potential successful course of treatment with a favorable outcome in a patient with HLH secondary to trimethoprim/sulfamethoxazole.