Case Presentation:

A 24–year–old man presented with 2 weeks of fever, malaise, diarrhea, and cough followed by right upper quadrant pain, leg edema, and dyspnea on exertion. He denied previous illnesses or high–risk behavior, took no medications, and reported no travel. He had recently camped out overnight. Temperature 39.7°C, heart rate 80, blood pressure 105/59, respiratory rate 20. He appeared fatigued and was in mild respiratory distress with bibasilar crackles. Heart sounds were normal. There was no jugular venous distention and only trace peripheral edema. Abdomen was mildly distended with right upper quadrant tenderness; liver edge was 6 cm below costal margin. Skin showed no rash, jaundice, or petechiae. Initial laboratory examination was significant for WBC 4.9, hemoglobin 10.6, normal electrolyte panel, AST 73, ALT 80, total protein 5.5, albumin 2.6, and gross proteinuria. Pulmonary vasculature was mildly congested on chest x–ray. Right upper quadrant ultrasound revealed hepatomegaly and a benign–appearing gall bladder. He was started on doxycycline to cover rickettsial organisms. Blood cultures remained negative and viral studies were initiated. On hospital day 4, right upper quadrant pain and respiratory distress increased. AST and ALT were increased to 255 and 216, respectively. Ferritin was grossly increased at 4179. HIV PCR was negative but cytomegalovirus (CMV) PCR returned at 240,000. We diagnosed the patient as having impending hemophagocytic lymphohistiocytosis (HLH) secondary to cytomegalovirus, and initiated valganciclovir. Subsequent HLH–directed testing revealed triglycerides of 486, IL2 receptor level of 3900 pg/mL (ref range 0–1033 pg/mL) and normal Natural Killer cell function. Renal biopsy revealed minimal change nephropathy, a change also associated with HLH. The patient had steady clinical improvement and discharged on day 14.

Discussion:

Hospitalists commonly encounter patients with fever and protean symptoms without clear source; clinical decline of these patients presents a diagnostic and therapeutic challenge. While secondary HLH is rare, misdiagnosis or under–recognition may contribute to low perceived prevalence. HLH is a disorder of the mononuclear phagocytic system: impairment of natural killer (NK) and cytotoxic T–lymphocyte activity results in uncontrolled immune activation. Secondary HLH is associated with infections, hematologic malignancy, autoimmune disease, and drugs. It resembles the systemic inflammatory response syndrome, and progresses to multi–organ dysfunction. Mortality is high, 75–95%. As cases of HLH complicating CMV infection in immunocompetent adults are rare, no standard therapy exists. To our knowledge, this is the first case of HLH due to CMV forestalled with antiviral therapy.

Conclusions:

This case exemplifies how awareness of advances in understanding and management of HLH can lead to earlier recognition and treatment of this often fatal illness.