Measles, also known as rubeola, is still a major cause of childhood deaths througout the world. It is caused by a RNA paramyxovirus and is spread by airborne contact. Ulcerated lesions in the mouth are an early sign of the disease and are called Koplik spots. A very rare late complication is subacute sclerosing panencephalitis (SSPE) caused by a mutated defective virus.
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EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Rubeola
PATHOGENESIS CHARACTERIZATION Paramyxovirus
After infection, the virus enters the epithelium of the upper respiratory tract or the conjunctiva
Initial replication phase of 4–6 days:
Virus reaches the reticuloendothelial system and particularly affects the liver and spleen via lymphatics and blood vessels with further replication
Giant cells with multiple nuclei are formed by cell fusion (Warthin-Finkeldey giant cells)
First, cytotoxic T-cells and natural killer cells limit the spread of the virus
B-cells are activated, which produce specific antibodies that eliminate the virus
8th and 12th days:
Virus travels free in the blood or in mononuclear cells and arrives at the target organs:
Epithelial tissues of the eye, lungs, intestines, and stomach where additional virus replication occurs, which causes the exanthem
The extent and the intensity of the skin rash is determined by the number of the infected cells and is an allergic reaction to the virus in the epithelium
An intact, cell-mediated immune response causes the exanthema and is necessary for the elimination of the virus and the virus is no longer histologically demonstrable after the exanthema has developed
CHARACTERIZATION SUBACUTE SCLEROSING PAN-ENCEPHALITIS (SSPE)
Subacute sclerosing panencephalitis (SSPE): early diagnosis, prognostic factors and natural history.
Division of Neurology, King Khalid University Hospital, Riyadh, Saudi Arabia.
J Neurol Sci 1996 Aug;139(2):227-34 Abstract quote
We studied the value of long video-split electroencephalographic monitoring (VSEEG) in detecting myoclonus in nearly SSPE and evaluated the natural history and outcome-affecting factors.
The 32 newly diagnosed patients had VSEEG to detect myoclonus and its correlations with EEG periodic complexes. Disease progression was monitored by a special "outcome score'; the chi-square test and multi-variable statistics analysed the outcome score in relation to different variables, such as age at onset, sex, duration of symptoms at presentation, CSF measles antibody titre, type and interval between periodic complexes (EEG discharges). Myoclonus or atonia occurred in all patients and was time-related to the EEG periodic complexes; in 32% of patients, myoclonus or atonia were not clinically evident. The EEG periodic complexes were of 3 types: Type I (16 patients) periodic giant delta waves; Type II (10 patients) periodic giant delta waves intermixed with rapid spikes or fast activity; and Type III (6 patients), long spike-wave discharges interrupted by giant delta waves. Outcome score was associated with symptoms duration (P < 0.01) and EEG periodic complexes (P < 0.05). Symptom duration was inversely related to final outcome (multi-variable analysis).
Long VSEEG monitoring greatly improves early diagnosis and detection of subtle atonia or segmental myoclonus. Prognostic factors were the type of EEG periodic complexes and duration of symptoms at presentation.
MRI findings in subacute sclerosing panencephalitis.
Anlar B, Saatci I, Kose G, Yalaz K.
Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey.
Neurology 1996 Nov;47(5):1278-83 Abstract quote
Thirty-four MRI studies of 26 patients with subacute sclerosing panencephalitis are reported.
Lesions of high signal intensity on T2-weighted images are the most common finding; they frequently involve the periventricular or subcortical white matter. Lesions tend to start in the cortex-subcortical white matter and progress with periventricular white matter involvement and diffuse cerebral atrophy. Pial and parenchymal contrast enhancement, local mass effect of parenchymal lesions, and involvement of the splenic portion of the corpus callosum are not infrequent. Basal ganglia and brainstem lesions were rare in this series.
Although cortical and subcortical lesions have some correlation with clinical findings, the extent and location of the periventricular white matter lesions and cerebral atrophy did not reflect the neurologic status in many patients.
Changing epidemiological features of subacute sclerosing panencephalitis.
Anlar B, Kose G, Gurer Y, Altunbasak S, Haspolat S, Okan M.
Hacettepe University Dept. of Pediatric Neurology, Ankara, Turkey.
Infection 2001 Aug;29(4):192-5 Abstract quote
BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a chronic central nervous (CNS) system infection caused by measles virus. Because changing immunization practices affect the epidemiology of measles and consequently SSPE, we examined the epidemiological data of our SSPE registry.
MATERIALS AND METHODS: Age of onset, age at onset of measles, duration of Latent period and immunization status were examined in cases recorded at the SSPE Registry Center in Turkey between 1975 and 1999.
RESULTS: Age of onset diminished from 13 years before 1994 to 7.6 years after 1995; age at onset of measles declined from 29 months to 20 months and the Latent interval from 9.9 years to 5.9 years. Age at onset of measles and immunization status did not directly affect the duration of the Latent period.
CONCLUSION: Although its incidence has decreased in Turkey, SSPE has been seen at younger ages in recent years. This change cannot be attributed solely to younger age at onset of measles. Factors affecting the duration of the Latent period should be investigated further.
VARIANTS Acute Measles Gastric Infection
Am J Surg Pathol 2001;25:259-262
44-year-old man who was referred for gastroscopy because of abdominal pain.
Routine hematoxylin and eosin staining showed characteristics indicative of so-called ex-Helicobacter pylori-gastritis that had developed after antibiotic treatment 2 years ago
Additional large, bizarre inclusion bodies and clusters of multinucleated giant cells were located in the surface epithelium and within the lamina propria. These giant cells had an appearance similar to that of Warthin-Finkeldey cells, which can be found during the prodromal phase of measles infection
Anti-measles virus immunochemistry showed a strong positivity for measles virus antigen within the giant cells
Case report confirms the systemic character of measles virus infection and confirms that measles viral replication can involve the gastric mucosa in addition to the conjunctiva, lung, and intestina.
Measles-Related Appendicitis Differing Histologic Findings According to the Stage
So-Ya Paik, MD, Jung-Tak Oh, MD, Yoon-Jung Choi, MD, Kye-Won Kwon, MD, and Woo-Ick Yang, MD
From the Department of Diagnostic Pathology, Daejin Medical Center, Gyungee-do, Korea (Drs Paik and Choi); and the Departments of Pediatric Surgery (Dr Oh) and Pathology (Drs Kwon and Yang), Yonsei University College of Medicine, Seoul, Korea.
Arch Pathol Lab Med 2002;Vol. 126, No. 1, pp. 82–84. Abstract quote
Owing to the characteristic Warthin-Finkeldey giant cells found in hyperplastic mucosa-associated lymphoid tissue, it has been emphasized that pathologists can make a diagnosis of measles from appendectomy specimens even in the prodromal stage before diagnostic rashes develop. However, to date, those reported cases of measles-related appendicitis have dealt with the histologic features of the prodromal stage and we found no reports in the English literature describing the histopathologic findings of appendicitis during the full-blown stage of measles.
Here, we describe 2 cases of measles-related appendicitis that show contrasting histologic features according to stage, one discovered during the prodromal stage and the other occurring during the full-blown stage.
This report describes heretofore unreported histopathologic findings of measles-related appendicitis observed during the full-blown stage of the infection and highlights histopathologic changes caused by replication of the virus in different compartments of the same organ during the course of infection.
Measles Virus Infection in the Placenta of Monozygotic Twins
Makiko Ohyama, M.D., Tomoko Fukui, M.D., Yukichi Tanaka, M.D., Keisuke Kato, M.D., Rikuo Hoshino, M.D., Tomoka Sugawara, M.D., Michiko Yamanaka, M.D., Rieko Ijiri, M.D., Tetsutaro Sata, M.D. and Yasufumi Itani, M.D.
Divisions of Neonatology (MO, TF, RH, YI), Pathology (YT, KK, RI), and Obstetrics (TS, MY), Kanagawa Children’s Medical Center, Yokahama, Japan; and Department of Pathology (TS), National Institute of Infectious Diseases, Tokyo, Japan
Mod Pathol 2001;14:1300-1303 Abstract quote
We report a case of monozygotic twins whose mother was infected with measles at 19 weeks’ gestation. One of the twins died in utero at 32 weeks’ gestation.
The placenta of the stillbirth showed massive fibrin deposition, and some residual trophoblasts contained many inclusion bodies positive for measles virus antigen. Fetal organs and cells other than a few splenic lymphocytes showed no evidence of measles virus infection. The placenta of the surviving infant showed focal intervillous fibrin deposits, and only a few syncytiotrophoblasts were positive for measles virus antigen. At present, 7 months after the delivery, the surviving infant has not developed any sign of measles virus infection. Postpartum course of the mother has been uneventful, although high titers of serum anti-measles virus IgM persisted for 6 months after delivery.
This case is informative in the following respects: the villous trophoblasts had diagnostic inclusion bodies and ultrastructural evidence of measles virus infection, the degree of viral involvement within the monochorionic placenta was uneven, both of the twins were virtually free from measles virus infection despite the marked involvement of the placenta, and measles virus infection had persisted in the monochorionic placenta for approximately 13 weeks.
- Histologic and molecular correlates of fatal measles infection in children.
Plaza JA, Nuovo GJ.
Department of Pathology, The Ohio State University, Columbus, Ohio 43210-1228, USA.
Diagn Mol Pathol. 2005 Jun;14(2):97-102. Abstract quote
The purpose of this study is to document three cases of fatal measles infection in children who ranged in age from 1 to 6 years old. In each case, there was a rapidly progressive illness marked by severe respiratory and central nervous system disease; in two cases, tonsillar herniation occurred. The lung tissues showed marked interstitial pneumonitis with diffuse endothelial cell and pneumocyte degeneration; occasional multinucleated giant cells were observed.
Brain sections showed a paucicellular inflammatory infiltrate with diffuse neuronal damage. Measles nucleoprotein and measles RNA were detected in each case by immunohistochemistry and reverse transcriptase (RT) in situ PCR, respectively. In the lung tissues, the viral protein and RNA localized primarily to pneumocytes and macrophages; infected endothelial cells were also evident. In the brain sections, the virus-infected cells cytologically had the appearance of neurons and microglial cells. The viral load, defined by the percentage of cells infected in a given field, was very high in the lung, spleen, and brain. Viral infection was associated with a marked increase in the number of cells expressing tumor necrosis factor alpha and concomitant reduction in the cells expressing suppressors of cytokine signaling (SOCS).
It is concluded that measles infection should be in the differential diagnosis of a rapidly progressive illness in young children in the United States and that the pathogenesis is based, in part, on massive viral infection with up-regulation of cytokine expression that likely reflects, in part, down-regulation of inhibitors of cytokine mRNA receptor synthesis.
PROGNOSIS AND TREATMENT CHARACTERIZATION SUBACUTE SCLEROSING PANENCEPHALITIS
Combined treatment with interferon-alpha and ribavirin for subacute sclerosing panencephalitis.
Tomoda A, Shiraishi S, Hosoya M, Hamada A, Miike T.
Department of Child Development, Kumamoto University School of Medicine, Kumamoto, Japan.
Pediatr Neurol 2001 Jan;24(1):54-9 Abstract quote
Two patients with subacute sclerosing panencephalitis (SSPE) are described. They were diagnosed on admission to the hospital with SSPE, as judged on cerebrospinal fluid examination involving reverse transcription followed by polymerase chain reaction, at the second stage of Jabbour's classification.
They first were treated with intraventricular interferon-alpha monotherapy; however, the combination of interferon-alpha and IV ribavirin was started at 8 and 5 months after beginning the interferon-alpha monotherapy, respectively. Although slow progressive brain atrophy was observed in Patient 1 on brain magnetic resonance imaging before the ribavirin therapy, no further progression was noted 11 months after starting combination therapy with ribavirin. The event-related potential study results and audiography of the right ear improved in Patient 1 after the combination therapy was initiated. In Patient 2 the hypertonicity, neurobladder incontinence, and dysphagia improved 3 months after starting the combination treatment.
Although this group of patients is small, these results suggest treatment with intrathecal high-dose interferon-alpha and IV ribavirin is effective in the treatment of SSPE. Early administration of intrathecal high-dose interferon-alpha and IV ribavirin should be considered as a possible therapy for SSPE patients, especially interferon-nonresponding ones.
- MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis.
Vestergaard M, Hviid A, Madsen KM, Wohlfahrt J, Thorsen P, Schendel D, Melbye M, Olsen J.
The Danish Epidemiology Science Centre, Department of Epidemiology and Social Medicine, Aarhus University, Aarhus, Denmark.
JAMA. 2004 Jul 21;292(3):351-7. Abstract quote
CONTEXT: The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination.
OBJECTIVES: To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination.
DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries.
MAIN OUTCOME MEASURES: Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy.
RESULTS: A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure.
CONCLUSIONS: MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology.
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Warthin-Finkeldey cells -Large multinucleated cells with characteristic eosinophilic nuclear and cytoplasmic inclusions. They develop as a result of fusion of heterogeneous plasma cells.
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