A primary vaccine failure cannot be ruled out as an explanation for the missing immunity against measles; however, it is a far less probable explanation given the vaccines high 2-dose effectiveness and the multiple reasons for humoral immunodeficiency depicted above

A primary vaccine failure cannot be ruled out as an explanation for the missing immunity against measles; however, it is a far less probable explanation given the vaccines high 2-dose effectiveness and the multiple reasons for humoral immunodeficiency depicted above. Immune control of measles infection is primarily dependent on T-lymphocyte cytolytic response, whereas humoral immunity seems to play only a minor role in disease control. been receiving Pneumocystis pneumonia prophylaxis with trimethoprim/sulfamethoxazole and herpes simplex virus prophylaxis with valaciclovir. There was no recent travel history, no known animal contact, no recent sexual risk exposure, and no known infectious disease in close contacts. Vaccinations had been completed according to Swiss national recommendations, including 2 documented measles, mumps, and rubella (MMR) vaccine doses in 1993 and 1999. At hospital entry, the patient reported sore throat, unproductive Mibefradil dihydrochloride cough, and fever without chills since 1 day before admission. The clinical exam was only remarkable for pharyngitis and the previously known cervical lymphadenopathy. C-reactive protein was moderately elevated (53 mg/L). The patient was thrombocytopenic (73 G/L) and had a leukocytopenia (1.08 G/L; 0.67 G/L neutrophile granulocytes). A chest x-ray showed no infiltrates, and a rapid-antigen detection test for group A streptococci from a throat swab was negative. Empirical treatment with cefepime was started. Blood cultures and multiplex polymerase Mibefradil dihydrochloride chain reaction (PCR) for respiratory viruses using a nasopharyngeal swab remained negative. Four days after symptom onset, the patient developed a confluent maculopapular rash of the face and upper trunk. Skin biopsy showed a perivascular lymphohistiocytic infiltrate and necrotic keratinocyteschanges compatible with an exanthematous drug eruption. For this reason, trimethoprim/sulfamethoxazole was stopped, and cefepime was switched to meropenem. Besides a progressive craniocaudal evolution of the maculopapular rash (Figure 1B), the patient developed ulcerative stomatitis compatible with Koplik spots (Figure 1A) and bilateral conjunctivitis on day 7 after symptom onset. These findings raised the suspicion of a measles virus infection, although the patient had been vaccinated as a child, as previously described. Positive measles real-time PCR from a throat swab confirmed the suspected diagnosis. In the month before, there had been no measles outbreaks in the patients region of residence, and he was not aware of any contact with a measles-infected individual. Measles IgG and IgM (Serion ELISA classic, Virion/Serion GmbH, Wrzburg, Germany) and rubella virus IgG were negative on day 6 after symptom onset, and mumps virus IgG was borderline positive (93 U/mL; cutoff, 70 U/mL), despite documented prior vaccination with 2 doses. Total IgG was in the lower normal range (8.6 G/L; normal range, 7C16 G/L). Open in a separate window Rabbit polyclonal to Caspase 6 Figure 1. A, Enanthema, no scale available. B, Maculopapular rash (back of the patient), no scale available. C, Computed tomography lung scan with nodular peribronchial infiltrates. D, Histology of the lung section (hematoxylin and eosin stain, 80 magnification) of the patient. Giant cell pneumonitis: numerous syncytial multinuclear giant cells with intracytoplasmic and intranuclear inclusions lining the alveolar Mibefradil dihydrochloride walls, with a background of diffuse alveolar damage. Treatment with intravenous ribavirin, intravenous immunoglobulins, and vitamin A was started. On day 8 after symptom onset, the patient developed progressive dyspnea and hypoxia in addition to the unproductive cough, while the fever persisted. A chest computed tomography scan showed bilateral, in part nodular pulmonary consolidations with Mibefradil dihydrochloride adjacent ground glass infiltrations, compatible with pneumonitis (Figure 1C). Elevated transaminases up to 2 to 3 3 times the upper norm were observed as well. On day 15, he fulfilled the definition of acute respiratory distress syndrome (ARDS) and required invasive ventilation, and on the following day veno-venous extracorporeal membrane oxygenation (VV-ECMO). On day 17 after the onset of symptoms, the patient developed venous bleeding at the puncture site of the VV-ECMO and succumbed to mixed shock and severe pneumonitis. Postmortem examination showed macroscopically severe diffuse micronodular parenchymal consolidations of the lungs. Apart from the aspect of a diffuse alveolar damage, correlating with the clinical picture of ARDS, histology revealed numerous syncytial multinuclear giant cells with intracytoplasmic and intranuclear inclusions lining the alveolar walls, consistent with measles pneumonitis (Figure 1D). DISCUSSION The presented case demonstrates the severity of measles infections in immunocompromised patients and highlights the importance of herd immunity, as rituximab can compromise previously acquired humoral immunity. Measles in immunocompromised patients bears serious complications in about 80% of cases. Pneumonitis Mibefradil dihydrochloride is the principal complication, accounting for most measles-associated deaths [1]. Clinical presentation in immunocompromised patients frequently is atypical, with 27%C40% of patients presenting without a rash [1]. Humoral immunity plays the main role in preventing measles virus infection, with neutralizing antibody titers at the time of exposure correlating with protection from disease [2]. In our patient, a serum sample from before the start of rituximab was not available, but he had received 2 documented MMR vaccine doses before his disease, which induces long-lasting safety in 97% of vaccinated topics [3]. However, at the proper period of analysis, he previously no measurable antibodies to rubella or measles, and he previously borderline mumps IgG. We believe this.