Hemophagocytic Lymphohistiocytosis in a Remote Kidney Transplant Recipient Triggered by HSV Infection With Complete Recovery: An Educational Case Report.

Rationale: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive immune activation. It is more commonly seen in children but increasingly recognized in adults. Primary HLH relies on a genetic predisposition, whereas secondary HLH develops in the context of infections, malignancies, or autoimmune diseases. Hemophagocytic lymphohistiocytosis has been rarely described in patients on immunosuppressive therapy after kidney transplant. Here, we describe a case of HLH in a patient with a remote history of kidney transplant, triggered by a viral infection.

Presenting concerns: A 45-year-old female, with a kidney transplant in 2009 for IgA nephropathy, presented with fever, vomiting, and back pain of 1-week duration. She was on triple immunosuppression consisting of daily doses of prednisone 5 mg, azathioprine 100 mg, and tacrolimus extended release 1 mg, and a baseline creatinine of 130 µmol/L.

Diagnosis: Initial investigations showed anemia, leukopenia, elevated serum creatinine, transaminitis, and markedly increased ferritin of 67 600 µg/L which prompted a bone marrow biopsy to rule out HLH. The bone marrow showed an increased proportion of CD68+ cells (macrophages) with more than 5 in 1000 hemophagocytic macrophages. Her soluble IL-2 receptor (CD25) level was 3406 pg/mL (606-2299 pg/mL) which was mildly elevated. She fulfilled 4 of the 8 criteria for HLH and with an H score was 223 which suggested a diagnosis of HLH with 96.9% probability. An extensive secondary workup for possible triggers for HLH led to a swab from genital ulcers that was positive for herpes simplex virus (HSV) type 2. The polymerase chain reaction (PCR) in the blood for HSV type 2 was also positive.

Interventions: Given the diagnosis of HSV type 2 as the putative trigger for HLH, she was started on parenteral acyclovir for 2 weeks followed by oral valacyclovir for 2 more weeks. In the context of infection, the azathioprine was stopped while low-dose steroid and tacrolimus were continued.

Outcomes: With the initiation of treatment for HSV infection, leukopenia, creatinine, and transaminases improved along with ferritin levels. At her 6-month follow-up, her blood counts and liver enzymes had normalized, and ferritin was 566 µg/L.

Teaching points: Hemophagocytic lymphohistiocytosis is a rare disease in kidney transplant recipients with a high mortality rate. It can occur even in remote kidney transplant recipients so a high degree of suspicion is necessary to lead to a prompt diagnosis. Infections are common triggers for secondary HLH. Early identification and treatment of the triggering infection may improve outcomes.