Emerg Infect DisEmerging Infect. DisEIDEmerging Infectious Diseases1080-60401080-6059Centers for Disease Control and Prevention22931858343771612-023510.3201/eid1809.120235Letters to the EditorLetterMeasles and Secondary Hemophagocytic LymphohistiocytosisSecondary Hemophagocytic LymphohistiocytosisIariaChiaraLeonardiMaria SilvanaBudaAgataToroMaria LuisaCascioAntonioAzienda Ospedaliera Piemonte-Papardo, Messina, Italy (C. Iaria);and Policlinico “G. Martino” University Hospital, Messina (M.S. Leonardi, A. Buda, M.L. Toro, A. Cascio)Address for correspondence: Antonio Cascio, Programma di Infettivologia Speciale, Medicina Tropicale e delle Migrazioni e Parassitologia, Policlinico “G. Martino”, Via Consolare Valeria n. 1, 98125 Messina, Italy; email: acascio@unime.it9201218915291529LupoJ , BernardS , WintenbergerC , BaccardM , VabretA , AntonaD , Fatal measles without rash in immunocompetent adult, France. Emerg Infect Dis. 2012;18:5213 .10.3201/eid1803.111300Keywords: Measlespneumoniahemophagocytosispancytopeniasecondary hemophagocytic lymphohistiocytosisviruses

To the Editor: We found interesting the article by Lupo et al. about a case of fatal measles in an immunocompetent 29-year-old woman (Fatal measles without rash in immunocompetent adult, France; http://dx.doi.org/10.3201/eid1803.111300). Perhaps, however, the possible diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH) should also have been considered in that setting.

HLH is a potentially fatal hyperinflammatory syndrome characterized by histiocyte proliferation and hemophagocytosis. HLH may be inherited (i.e., primary, familial, generally occurring in infants) or may occur at any age secondary to infection, malignancy, or rheumatologic disease. Secondary HLH is determined according to clinical criteria from the HLH Study Group of the Histiocyte Society, which require >5 of the following for a diagnosis: fever; splenomegaly; cytopenia (affecting >2 cell lineages); hypertriglyceridemia or hypofibrinogenemia; hemophagocytosis in the bone marrow, spleen, or lymph nodes; low or absent natural killer cell cytotoxicity; hyperferritinemia; and elevated levels of soluble CD25.

We conducted a PubMed search and found 5 articles that described 6 cases of HLH in patients with measles (15). Pneumonia was described in all of them (15), and central nervous system involvement was described in 3 (1,4). Four cases occurred in children, 3 of them immunocompetent (1,35). The 2 adults were an immunocompetent 18-year-old man who had acute respiratory distress (2) and a 19-year-old man with acute lymphocytic leukemia who had measles pneumonia and acute hemorrhagic leukoencephalitis (1). The only fatal case occurred in an immunocompromised 8-year-old boy with giant-cell pneumonia (3).

The identification of hemophagocytosis in bone marrow aspirate represents only 1 of the 5–8 criteria needed for a diagnosis of HLH; conversely, a bone marrow aspirate lacking hemophagocytosis does not rule out the diagnosis of HLH. Still, we believe HLH should be considered for any patient with fever and pancytopenia, especially in the presence of respiratory distress or multiorgan dysfunction. An appropriate therapy could save the patient (Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature; http://dx.doi.org/10.1002/hon.960).

Suggested citation for this article: Iaria C, Leonardi MS, Buda A, Toro ML, Cascio A. Measles and secondary hemophagocytic lymphohistiocytosis [letter]. Emerg Infect Dis [serial on the internet]. 2012 Sep [date cited]. http://dx.doi.org/10.3201/eid1809.120235

ReferencesPearl PL, Abu-Farsakh H, Starke JR, Dreyer Z, Louis PT, Kirkpatrick JB Neuropathology of two fatal cases of measles in the 1988–1989 Houston epidemic. Pediatr Neurol. 1990;6:12630 10.1016/0887-8994(90)90046-42340030Komatsuda A, Chubachi A, Miura AB Virus-associated hemophagocytic syndrome due to measles accompanied by acute respiratory failure. Intern Med. 1995;34:2036 10.2169/internalmedicine.34.2037787329Nakano T, Shimono Y, Sugiyama K, Nishihara H, Higashigawa M, Komada Y, Clinical features of measles in immunocompromised children. Acta Paediatr Jpn. 1996;38:2127 10.1111/j.1442-200X.1996.tb03472.x8741308Yamamoto K, Otake M, Takayanagi M Therapeutic effect of cyclosporin A combined with methylprednisolone pulse therapy on hemophagocytic syndrome with the central nervous system involvement [in Japanese] No To Hattatsu. 2002;34:667111808211Joshi R, Phatarpekar A, Currimbhoy Z, Desai M Haemophagocytic lymphohistiocytosis: a case series from Mumbai. Ann Trop Paediatr. 2011;31:13540 10.1179/1465328111Y.000000000921575318
Emerg Infect DisEmerging Infect. DisEIDEmerging Infectious Diseases1080-60401080-6059Centers for Disease Control and Prevention10.3201/eid1809.120749ArticleLupoJulienTimsitJean-FrançoisMorandPatriceCentre Hospitalier Universitaire de Grenoble and Université Joseph Fourier, Grenoble, FranceAddress for correspondence: Julien Lupo, Laboratoire de Virologie, Institut de Biologie et Pathologie Centre Hospitalier Universitaire de Grenoble, BP 217, Grenoble Cedex 9 38043, France; email: jlupo@chu-grenoble.frIariaC , LeonardiMS , BudaA , ToroML , CascioA . Measles and secondary hemophagocytic lymphohistiocytosis [letter]. Emerg Infect Dis. 2012;18:1529 .10.3201/eid1809.120235

In Response: We thank Iaria et al. (1) for their comments on our letter reporting an unusual case of fatal measles without rash in an immunocompetent woman who manifested cytopenias and an intractable acute respiratory distress syndrome (2). The authors suggest that secondary hemophagocytic lymphohistiocytosis (HLH) could have been considered in this patient. Our reply supplies supplementary clinical and laboratory findings that could be useful for discussion.

During our patient’s hospitalization, we were able to investigate 6/8 diagnostic criteria for HLH proposed by the Histiocyte Society (3). Of these, only 2 or 3 were found: persistent fever at 38.5°C; hypertriglyceridemia at 267 mg/dL (analysis performed at day 7); and cytopenias, which preferentially affected erythrocytes and lymphocytes. (Thrombocytopenia was moderate at >100 × 109 platelets/L, and no neutropenia was found [>2 × 109 neutrophils/L].) Liver function was not affected; no hepatomegaly was found, and alanine aminotransferase, aspartate aminotransferase, and bilirubin levels remained within reference ranges. Physical examinations did not detect splenomegaly, and laboratory findings did not show hypofibrinogenemia or ferritin level exceeding 500 ng/mL. A bone marrow biopsy performed on day 2 of hospitalization did not show hemophagocytosis. Studies of natural killer cell function and soluble CD25, which are also proposed diagnostic criteria for HLH, were not performed.

Overall, we found that the arguments in favor of HLH were too limited to consider this diagnosis and initiate an aggressive therapeutic approach based on immunosuppressive drugs. Even if, in the event of HLH, an early and appropriate treatment can be life-saving, the destruction of the remaining immune functions might also be lethal for the patient.

Suggested citation for this article: Lupo J, Timsit J-F, Morand P. Measles and secondary hemophagocytic lymphohistiocytosis [letter]. Emerg Infect Dis [Internet]. 2012 Sep [date cited]. http://dx.doi.org/10.3201/eid1809.120749

ReferencesIaria C, Leonardi MS, Buda A, Toro ML, Cascio A Measles and secondary hemophagocytic lymphohistiocytosis [letter] Emerg Infect Dis. 2012;18:1529 10.3201/eid1809.120235Lupo J, Bernard S, Wintenberger C, Baccard M, Vabret A, Antona D, Fatal measles without rash in Immunocompetent adult, France. Emerg Infect Dis. 2012;18:5213 10.3201/eid1803.11130022377448Janka GE Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012;63:23346 10.1146/annurev-med-041610-13420822248322