A Rare Case of Cytomegalovirus Infection Induced Hemophagacytic Lymphohistocytosis Syndrome (HLH)

Introduction:

Haemophagocytic Lymphohistiocytosis (HLH) is a rare immunopathological syndromes of excessive immune activation which results in multiorgan dysfunction and haemophagocytosis. Persistent stimulation of lymphocytes and histiocytes results in hypercytokinemia, leading to characteristic symptoms of HLH. Primary HLH is caused by the genetic mutation and secondary HLH occurs in autoinflammatory and autoimmune disease(macrophage activation syndrome), lymphoma, Iatrogenic immunosupression and healthy persons with infections. HLH is rare disease but has garnered increaed attension over past 10 years.

Case description:

This is 50 year old female patient with significant past medical history of autoimmune hepatitis controlled on Azathioprine for 2 years. She presented to the emergency room with worsening cough, fevers, chills and shortness of breath, and admitted to the Intensive Care Unit (ICU) due to acute respiratory failure and suspicious for septic shock. She was found to have new onset pancytopenia with White Blood Cell count of 0.7 x10 9, Hemoglobin of 6.9, and platelet 77,000. She did not improved with antibiotics and clinical deteriorating with worse hypoxia and suspicion for Acute Respiratory Distress Syndrome. She was Intubated and on pressor support. Mean while patient also developed Dissiminated Intravascular Coagulation which required multiple platelets, packed red blood cell and cryoprecipitate transfusions. Diagnostic bronchoscopy was done. Bronchial washing is positive for Cytomegalovirus (CMV). Serum CMV Polymerase chain reaction(PCR)test shows high viral load. Computed Tomogram (CT) of abdomen also showed splenomegaly. Patient was started on Valganlciclovir, CT guided bone marrow (BM) biopsy showed secondary hemophagocytosis, Consideration with immunosuppression along with systemic CMV infection, pancytopenia, fever, low fibrinogen (<70 mg/dl) and high ferritin (2292 ng/ml), the diagnosis of the hemophagocytic lymphohistocytosis was made. Steroid was added into treatment regimen. Lab works shows gradually decreasing CMV viral load, till undetectable before discharge. Patient clinically improved with the treatment. She was extubated and discharge with Valganciclovir 900mg 3 times daily for 3 months with weekly CMV PCR.

Discussion:

Disseminated CMV associated with HLH is uncommon in adults, this case is a type of secondary HLH. Early recognition and treatment is important. The clinical features raised the suspicion of HLH were fever, cytopenia, organomegaly, coagulopathy, elevated ferritin and hemophagocytic lymphohistocytic in the BM and not responded to initial antibiotics and Granulocyte colony stimulating factor. In this case patient met the 5 of 8 criteria and showed improvement of symptoms after treatment of the primary infection.