Erythematous maculopapular rash in monkeypox virus infection: A retrospective case series of 30 patients.

Abstract

Monkeypox (MPX) is a zoonotic disease caused by an orthopoxvirus usually causing self-limiting outbreaks in Africa. Since May 2022, an unprecedented outbreak has spread globally.1 The classical presentation of MPX disease associates fever, headache, myalgia, lymphadenopathy, sore throat and pleiomorphic skin lesions. Typical skin lesions are papules, vesicles and pustules that ulcerate, become umbilicated and then crops. However, the clinical presentation of MPX disease is sometimes aspecific and can mislead diagnosis.2, 3 We conducted a single centre retrospective study in Paris, France, to analyse MPX patients presenting with an erythematous maculopapular rash. All patients gave oral consent to participate and the study was approved by a Research Ethics Committee. Between 21st May and 28th July 2022, 439 patients had a PCR-confirmed MPX infection in this centre. Thirty patients (30/439, 6.8%) presented an erythematous maculopapular rash (Table 1; Figure 1). Patients were all men except one male to female transgender and 93% had sex with men. Among the 30 patients, 25 (83%) presented concomitant typical MPX vesiculopustular skin lesions and 15 (50%) presented concomitant pharyngitis (Figure 1). Of note, five patients (17%) had no typical MPX skin lesions and presented only with an erythematous maculopapular rash and a pharyngitis. Rashes appeared in a median of 3.5 days [IQR 2–6] after symptoms' onset. Dermatological examination revealed aspecific maculopapular rashes, always affecting the trunk and sometimes extending to the limbs or face. Three patients were hospitalized: one for aphagious pharyngitis, one for blepharitis and one for phimosis with urinary retention. All rashes resolved in a few days without specific treatment. The prescription of an antibiotic therapy before the apparition of the rash was reported in 17 cases (59%), mostly amoxicillin (n = 13) for suspected bacterial pharyngitis. In patients with antibiotics, the rash followed antibiotic use after a median of 1 day [IQR 1–2]. Among the 13 patients for whom EBV blood PCR was done, all had a replication. Of note, EBV blood PCR was performed in seven patients of the centre with MPX without a rash and found EBV replication in the seven cases. Histopathological findings were similar in the six patients who had a cutaneous biopsy to rule out a severe drug reaction. It consisted of a superficial lymphocytic infiltrate consistent with maculopapular exanthema of drug or viral origin. The immunohistochemical EBV marker (EBER) was always negative and there was no specific MPX histological pattern to guide diagnosis. In this centre, rashes frequency is estimated at 6.8% of MPX patients, which makes it less frequent than other recent reviews (8.0%–13.7%).3-5 Half the patients in this study had an association of rash and pharyngitis leading to antibiotics prescription to treat a suspected bacterial pharyngitis. MPX diagnosis may reduce the use of unnecessary antibiotic prescribing. MPX rashes could be related to different physiopathological mechanisms including an aspecific MPX cutaneous tropism or concomitant viral EBV replication with cutaneous manifestation.6, 7 Rashes onset in 59% of patients after antibiotic therapy might also suggest a drug reaction or an infectious mononucleosis-like antibiotic reaction.8 A primary EBV infection is much less probable even though clinical presentation can be misleading.9 An erythematous maculopapular rash was observed in 13 patients without prior antibiotic therapy making it a specific skin manifestation of MPX infection. Maculopapular rashes are not uncommon in MPX. They are associated to pharyngitis in half of the cases and to typical skin lesions in 83% of the cases. In an epidemic context, MPX infection should thus be considered in patients with an erythematous maculopapular rash even without associated skin lesions. None. There are no conflict of interest. The patients in this article have given written informed consent to publication of their case details.