Monkeypox virus infection with a syphilitic-roseola-like rash and its histopathologic characterization during 2022 outbreak

A 48-year-old man attended to the Emergency Department with a one-week history of high fever, odynophagia, arthralgias and generalized skin lesions with mild pruritus. The rash started 3 days before consultation with 3 asymptomatic pustules located on right palm, forehead and nasal bridge, with subsequent appearance of multiple round erythematous papules on trunk and upper limbs (Figure 1a), some of them with a central umbilicated pustule (Figure 1b). On the left flank, papules coalesced into plaques with a linear distribution (Figure 1c). Pharyngeal hyperaemia with tonsillar exudates (Figure 1d) and cervical and inguinal lymphadenopathies were also noted. His past medical history included hepatitis B virus infection and secondary syphilis. He defined himself as MSM, acknowledging 2 condomless sexual intercourses consisting of oral and insertive anal sex 10 days prior to symptom onset. Rectal and urethral swabs for real-time polymerase chain reaction (rt-PCR) ruled out gonococcal and chlamydial infection. Herpesvirus rt-PCR of a pustule resulted also negative. Serological tests excluded acute Epstein–Barr Virus, cytomegalovirus, parvovirus B19 and human immunodeficiency virus infection. RPR titres remained stable (1:4) compared with previous controls. Pharyngeal and palm pustules swabs for Monkeypox rt-PCR were both positive. Skin biopsy from upper limb papulopustule showed partial epidermal loss and inflammation (Figure 1e). Remaining keratinocytes were enlarged, with eosinophilic intracytoplasmic inclusions concordant with Guarnieri bodies (Figure 1f). Treponema immunohistochemistry was negative. Patient was treated with topical fusidic acid, topical methylprednisolone and oral acetaminophen. Lesions resolved in 2 weeks. Human monkeypox is an emerging viral zoonosis caused by a virus of the Orthopoxvirus genus characterized by the onset of prodromal symptoms (fever and fatigue) followed by a rash that spreads centrifugally from the face to the entire body. Macules progressively evolve into papules, vesicles, pustules and crusts.1 Since May 2022, more than 57,000 cases have been confirmed in 96 non-endemic countries,2 predominantly affecting MSM with multiple partners and with a high prevalence of anogenital involvement. Sexual intercourses, probably through skin-to-skin contact, may be playing a key role in the transmission of the disease.3 Conversely, our patient had no genital lesions, and skin rash showed some clinical particularities: (1) Truncal syphilitic-roseola-like maculopapular rash admixed with some pustules; (2) Lineal distribution of plaques on the flank reminiscent of Koebner phenomenon. These features led us to first rule out other diagnosis such as disseminated gonococcal infection, secondary syphilis and chickenpox. Exclusion of sexually transmitted diseases (STD) is mandatory in monkeypox infection. Indeed, co-infection with other STDs has been frequently reported,3 and clinical manifestations of Monkeypox can be polymorphic and mimic other entities, making accurate diagnosis difficult. In these cases, skin biopsy may be useful, disclosing typical Guarneri bodies and excluding other possible diagnosis.4 A syphilitic-roseola-like rash has been rarely reported during the present outbreak.5 This fact may represent viral shedding in the viraemic phase of the disease. However, in our patient, these lesions resolved spontaneously, not evolving into vesicles, pustules or crusts, and the possibility of a paraviral immune-mediated phenomenon cannot be excluded. Although no swab or biopsy were obtained from the linear lesions suggestive of Koebner phenomenon, the absence of previous dermatosis, the exclusion of other causes of acute viral exanthem and the well documented viral setting make monkeypox the most likely cause. Cutaneous viral autoinoculation secondary to scratching may be a plausible explanation. Nevertheless, it has not been previously described, and we should be cautious until more case reports and prospective case series consolidate this sign. In summary, early identification of human monkeypox cases is essential to stop virus transmission. It requires an accurate description of the clinical spectrum of the disease, which may include a syphilitic-roseola-like rash and Koebner phenomenon. Atypical cases can be difficult to differentiate from STDs, which should be actively sought. In this scenario, skin biopsy may provide important diagnostic clues. The article has no funding source. None to declared. The patient in this manuscript has given written informed consent to publication of his case details.