Rubella associated with hemophagocytic syndrome. First report in a male and review of the literature.

A 22-year-old man was admitted to our hospital because of fever, skin rash and epistaxis. Physical examination revealed fever (39.5°C), generalized purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positive and the IgG titers increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have rubella-associated hemophagocytic syndrome. We report herein the first case in a man and the sixth case of rubella-associated hemophagocytic syndrome in the literature by search in Pub Med till March 2012.

old man was admitted to our hospital because of fever, skin rash and epistaxis. Physical examination revealed fever (39.5°C), generalized purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone marrow aspiration hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positi the IgG titers increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have associated hemophagocytic syndrome. We report herein the first case in a man and the associated hemophagocytic syndrome in the literature by search in Pub Med Haemophagocytic syndrome (HS) is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of lymphocytes or histiocytes with uncontrolled haemophagocytosis and cytokine overproduction. 1 The characterised by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinaemia. HS can be either primary, with a genetic etiology, or secondary associated with malignancies, autoimmune diseases, or infections. 2 is a viral infection typically characterized by rash, fever, and lymphadenopathy. The rash is usually an erythematous, discrete maculopapular exanthem that begins on the face and spreads caudally. It usually disappears within three days but may persist for HS associated with rubella is uncommon. We report the first case of rubella virus old man was admitted to our hospital because of fever, skin rash and epistaxis. Physical examination revealed fever (39.5°C), generalized purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positive and the IgG titers increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have report herein the first case in a man and the associated hemophagocytic syndrome in the literature by search in Pub Med lymphadenopathy. The rash is usually an erythematous, discrete maculopapular exanthem that begins on the face and spreads caudally. It usually disappears within three days but may persist for eight days.
HS associated with rubella is uncommon. We report the first case of rubella virus-associated HS in a -old man and we review all reported cases of rubella associated with HS in the literature by search in Pub Med till March 2012.
year-old man was admitted to infectious diseases department with a 9-day history of fever, eruption, epistaxis and asthenia. Before admission, he had taken to a local hospital for fever and sore throat. He had treated with Cefpodoxime for 7 days. On admission, physical examination revealed fever (39.7°C), generalized purpura and petechiae on the soft palate. There were several enlarged cervical, axillary and inguinal lymph nodes that were soft and tender.
Abdominal examination revealed splenomegaly. Laboratory tests revealed the following: normocytic-normochromic anemia (hemoglobin 9.8 g/dL), white blood cell count 1700 cells/mm 3 (neutrophils, 3%), platelet count 6 x10 9 /L. Results of the liver function tests were normal. Serum ferritin level was 6220 ng/mL and fibrinogen 132 mg/dl. Bone marrow aspiration and biopsy (Figure 1) revealed hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positive and the IgG titers increased from 16 to 50 UI/mL in 3 days. The rubella serology was sought following the clinical and epidemiological context. Tests for common bacterial, mycobacterial, viral, fungal, auto-immune and tumoral causes of HS were negative. Therefore, he was diagnosed to have rubella-associated HS. The patient was treated by supportive measures including platelet transfusion. On discharge, physical examination was normal and her white blood cell count was 3500/mm 3

Discussion.
We found in the literature five reports of rubella-associated HS in women. [3][4][5][6][7] (Table 1) But, to our knowledge this is the first report in a man.
HS can be divided into primary or genetic HS and secondary or reactive HS. Primary HS usually occurs early in life and is associated with a higher mortality rate, while secondary HS occurs later in life and generally carries a better prognosis. 8 Diagnosis of HS relies on specific clinical, laboratory, and histopathological findings proposed by the Histiocyte Society in 1991 and updated in 2004. 9,10 The prognosis of infection-associated HS is better than other types of secondary HS. Risdall et al. introduced the term ''virus-associated hemophagocytic syndrome'' and set down criteria for its separation from malignant histiocytosis. 11,12 The bone marrow hypoplasia may be due to the direct effect of viruses on the hemopoietic cells. The most common agents causing this syndrome are viruses, predominantly the herpes group, including Epstein-Barr virus, Herpes simplex, and Cytomegalovirus. 2 Acquired HS is mostly associated with underlying diseases such as immunodeficiency, hematologic neoplasia, or autoimmune disease. Infection-associated HS is most common in immunocompromised patients such as renal transplant or lymphoma. 11 The occurrence of HS in apparently immunocompetent patients may be explained by the basis of transient immunoparesis. There is no specific treatment for rubella. The anti-rubella vaccination represent the only way to prevent serious complications thus it should be indicated either in boys. Supportive therapy to address nutritional status, concomitant anemia, hemorrhagic complications, and secondary infections is therefore essential to optimize treatment outcomes.

Conclusion.
Rubella is a benign disease. HS may be observed in rubella, if bone marrow aspiration is performed on patients with cytopenia. Treatment consists on supportive care. No specific therapy for rubella infection is available. The evolution is generally favorable.