A man with fever and petechiae
Authors: William L Greene, Joe Craft
Journal: The Lancet (1997)

A 54-year-old man with no previous medical history developed fever (up to 39°C), fatigue, malaise, and mild abdominal discomfort 7 days before admission to our hospital in April, 1996. He consulted his family physician, who found that the results of routine blood tests were normal and diagnosed a viral infection. On the day of admisson, the patient awoke with a diffuse erythematous rash on his face, neck, and legs, and noticed specks of blood on his pillow. On presentation to our Emergency Department, he continued to complain of malaise and fatigue, but denied new symptoms, HIV-1 risk factors, recent travel, contacts with ill people, taking medicines, or a history of alcohol abuse. He had no family or personal history of bleeding disorders. On examination he had a temperature of 38·2°C and diffuse non-palpable, non-blanching petechiae on his face, neck, arms, and legs, as well as ecchymoses on his buccal mucosa. He said that the petechiae were the same as his earlier rash. Several small, non-tender lymph nodes were palpable on the front and sides of his neck and above his right clavicle. His spleen tip was palpable, but his liver was not enlarged. Blood count showed a low platelet count, and he was admitted to hospital. On admission, his white blood count was 9·6×109/L with a differential of 21% polymorphonuclear cells, 9% bands, 50% atypical lymphocytes, and 20% monocytes. His haemoglobin was 15 g/dL. The platelet count was less than 5×109/L. Liver aminotransferases and total bilirubin were mildly elevated, but coagulation parameters and routine biochemistry were normal. Peripheral blood smear showed numerous atypical, enlarged lymphocytes, and only rare platelets (figure). Bone-marrow biopsy showed increased numbers of megakaryocytes but was otherwise normal. Flow cytometry of the blood showed no evidence of a malignant population of cells. There were no antibodies to HIV-1, toxoplasma, hepatitis C, hepatitis B surface antigen, or cytomegalovirus antigen. Monospot was positive, and serum IgM antibodies to Epstein-Barr virus (EBV) were present in high titre. IgG antiplatelet antibodies to the IIb–IIIa glycoprotein complex were also found. He was treated with prednisone (1 mg/kg body weight) and intravenous immunoglobulin (400 mg/kg daily) for 5 days. However, his platelet count remained less than 5×109/L, the peripheral blood smear continued to show more than 50% atypical lymphocytes, and he developed epistaxis requiring nasal packing. Acyclovir and α-interferon were given in an attempt to control the infection, and intravenous anti-Rh antibodies were given to try to decrease the platelet destruction, all to no avail. He continued to have epistaxis, and on the 12th hospital day he had a laparoscopic splenectomy. On the first postoperative day, the platelet count was 30×109/L, rising to 85×109/L the second day, and to 110×109/L the third. After discharge from the hospital, prednisone was tapered off and he remains well. Antiplatelet antibody titres were not repeated after surgery, but the peripheral smear and platelet count remain normal 6 months after discharge. He is presently on no medication. Infectious mononucleosis typically occurs in children and adolescents, but is well known in adults.1Ginsburg A Ginsburg J Infectious mononucleosis in older patients.CMA J. 1982; 127: 1103-1104PubMed Google Scholar The disease usually follows a benign and self-limited course, but complications include haemolytic anaemia, aseptic meningitis, and pericarditis.2Papadakis M Infectious mononucleosis.West J Med. 1982; 137: 141-144PubMed Google Scholar Although mild to moderate decreases in platelet counts may occur in up to half of patients, severe thrombocytopenia is rarely seen.3Carter R Platelet levels in infectious mononucleosis.Blood. 1965; 25: 817-822PubMed Google Scholar The aetiology of severe thrombocytopenia in infectious mononucleosis is immune-mediated, and antiplatelet autoantibodies may be found.4Cyran E Rowe J Blood R Intravenous gammaglobulin treatment for immune thrombocytopenia associated with infectious mononucleosis.Am J Hematol. 1991; 38: 124-129Crossref PubMed Scopus (16) Google Scholar Even when present, severe thrombocytopenia is usually self-limited,5Wong S Bennet B Natural history of severe thrombocytopenia in infectious mononucleosis.Postgrad Med J. 1982; 58: 249-251Crossref PubMed Scopus (8) Google Scholar but spontaneous resolution may take 3 months or more.4Cyran E Rowe J Blood R Intravenous gammaglobulin treatment for immune thrombocytopenia associated with infectious mononucleosis.Am J Hematol. 1991; 38: 124-129Crossref PubMed Scopus (16) Google Scholar Treatment with steroids is only variably successful, and intravenous immunoglobulin has been reported to be successful.5Wong S Bennet B Natural history of severe thrombocytopenia in infectious mononucleosis.Postgrad Med J. 1982; 58: 249-251Crossref PubMed Scopus (8) Google Scholar In this case, neither intervention was beneficial, and the patient required splenectomy because of continued epistaxis. His response was immediate and sustained, and his platelet count is now normal. Physicians should remember that, although unusual, acute infectious mononucleosis occurs in adults and may lead to life-threatening thrombocytopenia. Infectious mononucleosis should be included in the differential diagnosis of possible aetiologies of severe thrombocytopenia in adults.