INTRODUCTION:Hemophagocytic syndrome is a constellation of findings including fever, rash, cytopenias, lymphadenopathy, and hepatosplenomegaly resulting from dysregulation of macrophage activation and proliferation. Secondary forms of the syndrome are associated with infection, autoimmune disorders, and malignancy. We describe a patient who develops hemophagocytic syndrome but has two potential associated causes.
CASE PRESENTATION:A 35 year-old Samoan female presented with 2 months of nonproductive cough, night sweats, chills, and 20 pound weight loss. She also noted recent fevers and hematachezia. She had been maintained on chronic corticosteroids for lupus nephritis and autoimmune hemolytic anemia. Eight years ago, she completed a course of therapy for pan-sensitive disseminated Mycobacterium tuberculosis. She was born in the United States and denied any recent travel. On presentation, she had a temperature of 103.1 °F, BP of 90/60, HR of 110, and RR of 30. Her exam was notable for tachycardia and tachypnea. Laboratory studies demonstrated renal failure, metabolic anion-gap acidosis, WBC of 3.8 with 48% bands, hemoglobin of 10.5, platelets of 105, ferritin of 663, triglycerides of 286, and an albumin of 2.0 with otherwise normal liver function tests. Urine analysis had 2+ protein. HIV was negative. Chest radiograph demonstrated a diffuse bilateral nodular pattern consistent with miliary tuberculosis. Cultures of the blood, sputum, and urine were negative for bacterial pathogens. However, sputum, BAL, and urine specimens were AFB smear positive. Bone marrow biopsy revealed granulomas and erythrophagocytosis. The patient was started initially on rifampin, isoniazid, pyrazinamide, ethambutol, amikacin, and moxifloxicin for the possibility of resistant tuberculosis. However, the cultures subsequently grew pan-sensitive M. tuberculosis . Steroids were continued for lupus and adrenal insufficiency. Notably, during her hospitalization the patient developed a diffuse macular rash, progressive anemia and thrombocytopenia, hyperbilirubinemia, and decreasing fibrinogen levels consistent with the clinical manifestation of hemophagocytic syndrome as appreciated on the bone marrow biopsy performed earlier in her hospital course. Unfortunately, her hospital course has been very complicated and is ongoing at this time.
DISCUSSIONS:Hemophagocytic syndrome results from activation and uncontrolled regulation of macrophages with characteristic findings of phagocytosis of erythrocytes, platelets, and hemopoetic precursors in the reticuloendothelial system. Besides pancytopenia, other findings include fever, maculopapular rash, lymphadenopathy, hepatosplenomegaly, elevated ferritin levels, hyperbilirubinemia, hypertriglyceridemia, and low fibrinogen levels. Primary or congenital forms of hemophagocytic syndrome are typically fatal without immunosuppresion and bone marrow transplantation. Secondary forms of the disease are commonly associated with autoimmune disease, malignancy, and infections. Epstein-Barr virus is the most frequently associated infectious etiology, though fungal, parasitic, bacterial, and other viral infections have also been described. Hemophagocytic syndrome associated with M. tuberculosis has been described in the literature with an approximate mortality rate of 50%. While the pathophysiology is not well delineated, some have speculated that the Th1 immune response triggered by M. tuberculosis may lead to the unregulated immune response seen in hemophagocytic syndrome. Aside from anti-tuberculous medications, some have utilized immunomodulatory therapies such as high dose steroids, plasmapharesis, intravenous immunoglobulin, and splenectomy. Our patient has two potential secondary causes of hemophagocytic syndrome, though the likely culprit is her disseminated tuberculosis infection. A prior review of the literature notes only one similar combination of hemophagocytic syndrome with associated tuberculosis infection and underlying systemic lupus erythematosus.
CONCLUSION:This case highlights an uncommon syndrome associated with two very different diseases. Pancytopenia and other systemic complications are seen in both autoimmune and disseminated infections. However, it is important to consider hemophagocytic syndrome as a potential diagnosis when evaluating pancytopenia and these constellation of findings.
DISCLOSURE:Amali Jayasinghe, No Financial Disclosure Information; No Product/Research Disclosure Information