Article, Infectious Diseases

Mumps caused hemophagocytic syndrome: a rare case report

Hemophagocytic syndrome: a “>Case Report

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American Journal of Emergency Medicine

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Mumps caused hemophagocytic syndrome: a rare case report?

Abstract

Mumps-associated hemophagocytic syndrome (HPS) is exception- ally rare. Here, we report a fatal case of concurrent mumps and HPS. A previously healthy 21-year-old male patient was admitted to the Department of Infectious Diseases on October 18, 2011, with complaints of parotid gland pain for 30 days and persistent fever (38.3?C-40?C) for 15 days. Admission examinations showed severe pancytopenia, Liver dysfunction, hyperferritinemia, fibrinopenia, elevated lactalase dehy- drase, bilateral pulmonary inflammation and pleural effusion, abdom- inal lymphadenopathy, and splenomegaly. The patient was accordingly suspected to have mumps-associated HPS and received nutrition support and hormonal therapies as well as platelet transfusions. On hospitalization day 3, the fever stayed high, and painful swelling in the right testicle was reported. A bone marrow biopsy evaluation and serological tests were then performed. Histiocytic hyperplasia and hemophagocytic macrophage infiltration were demonstrated in the bone marrow and antimumps virus immunoglobulin M was detected positive, but bacteria, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus were detected negative in the peripheral blood. The Initial diagnosis of mumps-associated HPS was eventually confirmed. Treat- ments with high doses of methylprednisolone, intravenous immuno- globulin, and etoposide were continued. By hospitalization day 20, patient’s condition was improved, his body temperature and blood counts were almost normal, and the pain and swelling in his parotid glands and right testicle subsided considerably. On hospitalization day 28, however, patient’s condition deteriorated rapidly, and pancytopenia became evident again. On hospitalization day 33, the patient died of multiple organ dysfunction.

Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis, is defined by the Reclassification Working Group of the Histiocyte Society and the World Health Organization (WHO) Committee on Histiocytic/Reticulum Cell Proliferations as a macro- phage-related histiocytic disorder that meets the following diagnostic criteria: (1) persistent fever (N 38.5?C, lasting >=7 days); (2) spleno- megaly; (3) hematologic abnormalities including anemia (hemoglobin level b 9 g/dL) and thrombocytopenia (b 100000 cells/uL); (4) hemo- phagocytosis in bone marrow, spleen, or lymph node; and (5) one of the following abnormalities: hypertriglyceridemia (N 2 nmol/L) and hypofi- brinogenemia (b 150 mg/dL) [1]. An HPS can be either primary or secondary, depending on its Underlying etiology [1-3]. Primary HPS, also known as familial or genetic HPS, is an inherited autosomal recessive disorder in which mutations occur in several genes (eg, PRF1, UNC13D, SH2D1A, and RAB27A) known critical to the control of

? Source of support: Scientific development fund of Shan-dong Public Health Bureau: 2011HZ 047.

proliferation and activation of histiocytes, which result in excessive generation and/or activation of histiocytes and, consequently, the exaggerated immune response characteristic of HPS. It is estimated that primary HPS occurs in a frequency of 1 in 50000 births and 70% of primary HPS cases occurs in the first year of life [3]. Secondary or acquired HPS occurs as a disorder secondary to and in association with various infections (mostly by viruses, but also by bacteria, fungi, protozoa, and parasites), malignancies, autoimmune or metabolic diseases, which has been comprehensively reviewed [3-6]. However, HPS in mumps virus infection has been rarely reported; search of the PubMed database has identified only 1 study [7].

Mumps, also known as epidemic parotitis, is a contagious disease caused by the mumps virus [8]. Primarily affecting the parotid glands commonly in unvaccinated young children [9], mumps leads to painful swelling of parotid glands and, in some cases, meningitis, orchitis, oophoritis, or pancreatitis. The disease is usually diagnosed on clinical grounds, and no confirmatory laboratory testing is necessary. In general, mumps alone is self-limiting; complications and mortality from mumps are rare [10]. However, here, we report a fatal case of HPS complicated by mumps.

The patient was a 21-year-old male college student. He had no history of hematologic disorders. After 30 days of painful swelling in both parotid glands (Fig. A) and 15 days of persistent fever (38.3?C- 40?C), he was admitted to the Department of Infectious Diseases on October 18, 2011. Admission physical, blood cell test, liver function test, lactalase dehydrase test, plasma fibrinogen test, chest computed tomography, and paratid gland computed tomography examinations showed the following: mild/severe fever (38.2?C-40.5?C), severe pancytopenia (white cell count: 0.35 x 103/uL; Red blood cell count: 2.51 x 106/uL; platelets count: 84 x 103/uL), liver dysfunction (alanine transaminase: 187 U/L; aspartate aminotransferase: 120 U/L; and ?– glutamyl transpeptidase: 112 U/L), hyperferritinemia (ferritin N 2000 ng/L), elevated lactalase dehydrase (2142 U/L vs reference range 120- 230 U/L), fibrinopenia (0.44 g/L vs reference range 2-4 g/L), bilateral pulmonary inflammation and pleural effusion (Fig. B), abdominal lymphadenopathy, splenomegaly, and right paratid glandmegaly. Accordingly, the patient fulfilled 4 of the 5 Histiocyte Society and WHO diagnostic criteria for HPS described above, and a mumps- associated HPS was suspected. Given the severe illness, nutrition support and hormonal therapies (methylprednisolone 400 mg/d, intravenous ?-globulin 20 g/d, etoposide-VP16, 100 mg every other day) and platelet transfusions were immediately started. On hospi- talization day 3, however, the fever stayed high 39.6?C, and painful swelling in the right testicle was complained (Fig. C). The little improvement prompted to reconsider the original diagnosis.

It is well established that pathologic abnormalities in bone marrow are the hallmark of HPS and, therefore, 1 of the 5 Histiocyte Society and WHO diagnostic criteria for HPS. To minimize the possibility of

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Fig. Images showing swollen parotid glands (A), pulmonary pleural effusion (B), swollen right testicle (C), and hemophagocytic macrophages (D) in a 21-year old male patient with mumps-associated HPS.

mistreatment due to misdiagnosis, a bone marrow biopsy evaluation was performed. The results showed histiocytic hyperplasia and an increased number of hemophagocytic macrophages (3.6%) in the bone marrow (Fig. D).

Moreover, confirmatory diagnosis of HPS requires laboratory tests complementary to bone marrow biopsy evaluation [11]. Serological analyses were also performed at the same time of the biopsy evaluation. The results demonstrated that the peripheral blood specimen was positive for antimumps virus immunoglobulin M but negative for bacteria, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus. The initial diagnosis of mumps-associated HPS was confirmed, and treatments with high doses of methylprednisolone, intravenous immu- noglobulin, and etoposide were continued. By hospitalization day 20, patient’s condition was improved, his body temperature and blood counts were restored to near normal values, and the pain and swelling in his parotid glands and right testicle subsided considerably. On hospitalization day 28, however, patient’s condition deteriorated rapidly with unexplained reasons, and pancytopenia became evident again. On

hospitalization day 33, the patient died of multiple organ dysfunction.

In summary, we have reported a rare but highly fatal case of mumps-associated HPS. Given the increasing risk of mumps reemer- gence in recent days [12], it is clinically important to alert physicians in intensive care units and departments of emergency medicine and infectious diseases to this syndrome.

Quqntai Xing PhD Department of Infectious Diseases Qilu Hospital of Shandong University

107 Wenhua West Road, Jinan, Shandong 250012, China

E-mail address: [email protected]

Peixiang Xing MD

Department of Laboratory Tests Qilu Hospital of Shandong University

Jinan, Shandong, China

http://dx.doi.org/10.1016/j.ajem.2013.02.006

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