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Hemophagocytic Syndrome: Revisiting a Classic Diagnosis

Díaz, Hortensia Álvarez MD*; García Rodríguez, Jose Francisco MD*; García Jiménez, Antonio MD

Infectious Diseases in Clinical Practice: November 2008 - Volume 16 - Issue 6 - p 414
doi: 10.1097/IPC.0b013e318181fa4d
Letter to the Editor

*Departments of Internal Medicine and †Intensive Care Unit Hospital Arquitecto Marcide-Profesor Novoa Santos Ferrol, A Coruña, Spain

No conflicts of interest for any authors have been declared.

Comments: Hemophagocytic syndrome seems to be a clinical presentation of many conditions. Disseminated tuberculosis must be considered in the setting of a broad differential diagnosis, and it will be reviewed below.

To the Editor:

Hemophagocytic syndrome is characterized by dysregulation of reticuloendothelial system, leading to phagocytosis of platelets, lymphocytes, and erythrocytes, in the setting of malignancy, autoimmune disease, or intracellular pathogens.

A 48-year-old white man without relevant medical history was admitted to the hospital because of abdominal distention developed 6 months earlier. The patient looked unwell, feverish, and bradypsychic and was without focal neurologic disturbances. There were no peripheral lymphadenopathies and no heart murmur or rub, breath sounds were diminished over the lower right lung field, abdomen was distended with ascites, and there was pitting edema in both lower extremities. Blood test revealed pancytopenia, hypoalbuminemia, dissociated cholestasis, acute renal failure, increased inflammatory and lymphocyte-induced parameters (including β2-microglobulin), autoantibodies (antinuclear antibodies, anti-Ro antibodies, anti-smooth muscle antibodies), and serum tumor markers (CA19.9 and CA125). Peritoneal fluid demonstrated mononuclear cell shift, adenosine deaminase (ADA) above 70 IU/L, increased CA125 and CA19.9, negative cytology, culture, and acid-fast bacillus. Bone marrow biopsy showed normal cells. Tuberculin skin testing was nonreactive. Clinical status became worse 48 hours after admission, and the patient was transferred to intensive care unit. Tuberculostatic agents were started (isoniazid, rifampin, pirazinamide). A thoracic and abdominal computed tomographic scan showed bilateral pleural effusion, ascites, splenomegaly, and mild pericardial effusion. Blood and bone marrow cultures were negative, as well as multiple serologies, including HIV. Omentum biopsy showed granulomas with positive Ziehl-Neelsen staining. Clinical course, peritoneal fluid, and serum analyses showed a dramatic improvement 2 weeks after the initiation of tuberculostatic agents. At 4 weeks, bone marrow and peritoneal fluid cultures grew Mycobacterium tuberculosis complex on Lowenstein medium. Our patient continues tuberculostatic treatment, and his clinical status and cytopenias have been recovered 5 months later.

In the presence of hepatosplenomegaly, polyserositis (with increased ADA levels), and pancytopenia, we must consider hemophagocytic syndrome associated with disseminated tuberculosis.1 Empiric tuberculostatic medication should be initiated, above all if the disease progresses rapidly, whereas pathological or microbiological results are in progress. On the other hand, in the setting of non-Hodgkin lymphoma, ADA may be increased2; in addition, high β2-microglobulin level may appear in patients with tuberculosis.3 Autoimmune diseases should be also kept in mind, although high titers of autoantibodies have been observed in tuberculosis.4 Finally, malignant conditions must be considered, although CA19.9 and CA125 have been reported in liver disease and any benign condition that stimulates production of peritoneal fluid.5 Therefore, early suspicious diagnosis becomes a challenge because different management and outcome will be associated.

Hortensia Álvarez Díaz, MD*

Jose Francisco García Rodríguez, MD*

Antonio García Jiménez, MD†

*Departments of Internal Medicine and

†Intensive Care Unit

Hospital Arquitecto Marcide-

Profesor Novoa Santos

Ferrol, A Coruña, Spain

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© 2008 Lippincott Williams & Wilkins, Inc.