Measles is a highly contagious viral disease caused by a virus belonging to the Paramyxoviridae family, genus Morbillivirus.1 Maculopapular rash appears 3 or 4 days after the onset of fever, malaise, and headache in conjunction with cough, coryza, and conjunctivitis. Measles virus is transmitted by airborne respiratory droplets entering the respiratory tract or by direct contact with respiratory secretions. The disease is largely self-limiting in immunocompetent and immunized individuals.2 The incidence of measles has increased in the last 2 years and is currently considered a re-emerging disease. Patients who survive the virus can develop respiratory and neurological complications.3 The exanthem following measles infection is clinically distinctive but can be confused it with other infectious or allergic exanthems. Histopathologic study of skin biopsies can help to stablish a correct diagnosis.
A 32-year-old healthy man consulted to the Dermatology Department with a 4-day history of fever. Skin rash and dry cough developed the day before admission. On examination, the patient was febrile (38.9°C). Scarcely confluent, craniocaudally distributed, macular exanthema was present. Palms and soles were spared. Serous conjunctivitis and discrete photophobia were present. Palpable cervical and submandibular adenopathy were noted. Examination of the oral cavity revealed whitish macules on an erythematous base on both mucous membranes, such as “grains of salt on a red background.” Blood tests revealed lymphopenia (200 cells/mL) and elevated glutamic pyruvic transaminase (185 IU/L). All other parameters were normal. Chest radiograph was normal. The patient was admitted for symptomatic treatment and air isolation. Serological tests and a punch biopsy were performed. Measles-specific IgM antibodies confirmed the diagnosis.
Histopathologic study of skin biopsy showed mild superficial perivascular dermatitis with vacuolar interface dermatitis and focal vesicular dermatitis in follicular and interfollicular epidermis. Focal keratinocytic dysmaturation and apoptosis were observed. Hyperkeratosis with parakeratosis was also noted (Fig. 1). Major changes were observed in follicular and sebaceous epithelia. Multiple dyskeratotic keratinocytes were present in follicles and sebaceous glands. Multinucleated keratinocytes showed a glassy cytoplasm and 3–6 irregularly shaped nuclei with indistinct nucleoli (Fig. 2). The dermis showed a mild superficial, perivascular, and periadnexal lymphocytic and eosinophilic infiltrate. Electron microscopy of follicular syncytial epithelial giant cells (SEGCs) showed isolated capsid particles within the cytoplasm and secretory vesicles, measuring approximately 40–60 nm in diameter (Fig. 3).
Measles, a member of the Paramyxoviridae family, is an enveloped virus with a single-strand, negative-sense RNA genome. The hemagglutinin protein communicates with extracellular receptors and initiates cell-to-cell binding, whereas the fusion protein is responsible for cell membrane fusion and formation of the multinucleated giant cells, which are characteristics of measles.2
Migratory movements and the decrease in vaccination rates have led to numerous outbreaks of measles both in Europe and the United States In classic measles, cutaneous changes present as an enanthem (Koplik spots) followed by an exanthem in a cephalocaudal distribution.1 Primary viremia causes viral dissemination through lymphoid tissues and Warthin–Finkeldey giant cells. Secondary viremia involves other organs through infected lymphocytes and monocytes with subsequent formation of SEGCs.4 Although it is usually a self-limited infection, possible complications include otitis media, pneumonia, laryngotracheobronchitis, diarrhea, and encephalitis. No specific antiviral therapy exists for measles, and treatment most often consists of supportive care.
Despite being considered a re-emerging disease, only 7 cases of measles with a histopathological description have been reported in the 21st century (Table 1).5–10 Only in 1 case was electron microscopy used to demonstrate the presence of the virus inside infected cells.10 The distinctive findings include multinucleated keratinocytes, necrotic keratinocytes, and a dermal perifollicular and perivascular lymphocytic and eosinophilic infiltrate. Some authors reported similar changes occurring in follicular epithelia, acrosyringia, and sebaceous glands, consistent with the findings in our case. With the use of electron microscopy, we were able to demonstrate that dermal SEGCs contained capsid material within the cytoplasm of infected cells. Viral particles were not seen inside the nuclei.
In summary, measles is a highly contagious re-emerging viral disease, and early detection is needed to prevent its spread and restrain the epidemic. Skin biopsy can aid in establishing a definitive diagnosis. Multinucleated epidermal giant keratinocytes, and follicular and sebaceous gland involvement are very common histological features in measles. The evidence of measles virus particles inside infected cells can be demonstrated with electron microscopy.
1. Davies N. Measles
: what you can do. Br J Nurs Mark Allen Publ. 2018;27:116.
2. Bhattacharjee S, Yadava PK. Measles
virus: background and oncolytic virotherapy. Biochem Biophys Rep. 2018;13:58–62.
3. Wyplosz B, Lafarge M, Escaut L, et al. Fatal measles
pneumonitis during Hodgkin's lymphoma. BMJ Case Rep. 2013;2013. doi: .
4. Lapadat R, Nam MW, Mehrotra S, et al. Mulberry cells in the thyroid: Warthin-Finkeldey-like cells in hashimoto thyroiditis-associated lymphoma. Diagn Cytopathol. 2017;45:212–216.
5. Yoshida M, Yamada Y, Kawahara K, et al. Development of follicular rash in measles
. Br J Dermatol. 2005;153:1226–1228.
6. Scrivener Y, Marcil T, Lipsker D, et al. Measles
: a follicular disease (in French). Ann Dermatol Venereol. 2011;138:111–115.
7. Sheikine Y, Hawryluk EB, Burgin S, et al. Histopathology of measles
exanthem: a case with characteristic features and eosinophils. J Cutan Pathol. 2012;39:667–670.
8. Levy L, Nasereddin A, Rav-Acha M, et al. Prolonged fever, hepatosplenomegaly, and pancytopenia in a 46-year-old woman. PLoS Med. 2009;6:e1000053.
9. Tirado M, Adamzik K, Böer-Auer A. Follicular necrotic keratinocytes—a helpful clue to the diagnosis of measles
. J Cutan Pathol. 2015;42:632–638.
10. Sidhu HK, Lanoue J, Nazarian R, et al. Histopathology of measles
: report of 2 cases with new findings. Am J Dermatopathol. 2015;37:563–566.