Clinical spectrum of human monkeypox: An Italian single‐centre case series

Dear Editor, Since May 2022, numerous clusters of human monkeypox (MP) have been documented in nonendemic countries, especially in men that have sex with men (MSM),1– 5 raising concerns as to whether the changing epidemiology of MP may represent a public health issue in groups engaging in highrisk sexual behaviours throughout Europe.6 MP is a selflimiting, viral zoonotic disease, manifesting with a typical rash, tender lymphadenopathy and systemic symptoms such as fever and malaise.7 Persontoperson transmission is thought to occur through direct contact with skin lesions and respiratory droplets, but spread with sexual fluids has been suggested as well.7,8 Herein, we report on six individuals diagnosed with MP from 6 June to 20 June, 2022, at the Sexually Transmitted Diseases (STDs) outpatient service of our Dermatology Unit (Table 1). Positivity for MP DNA was confirmed on both pharyngeal and vesicopustular fluid swabs (realtime polymerase chain reaction) for all cases. All patients identified themselves as MSM and disclosed to have had several unprotected sexual intercourses in the preceding months. Five had history of prior STDs and three travelled abroad in the 2 weeks preceding the onset of symptoms. None had been vaccinated for smallpox and they did not recall contact with animals known as MP reservoirs. Cutaneous manifestations typically consisted of isolated, 3– 6 mm, whitetoyellowish vesicopustular lesions, going through several stages of evolution to show brownish crusted umbilication at the centre (Figure 1a). Depending on stage, dermoscopy showed whitish structureless areas (Figure 1a, inset), surrounded by a millimetric halo of perilesional erythema, with either a yellowish area or brownish crusts at the centre. New lesions continued to develop after presentation in 3/6 patients. Resolution occurred with a certain degree of atrophic scarring about 3 weeks after onset (Figure 1b). Active medical treatment (e.g. tecovirimat) was not required. The genital area was the most commonly affected body site (5/6 patients). However, mucosal lesions at the glans were seen only in 2/6 cases. Involvement of the lips (3/6), chin (2/6), hands (4/6) and perianal region (2/6) was also recorded, consistent with reported sexual activities (Figure 1c). Single lesions on the posterior neck, forehead, thigh and shoulder were present in one case each. Atypical clinical varieties were observed in 2/6 cases. Patient n.3 developed extensive perilesional erythema (Figure 1d) one week after presentation. Signs of maceration at mucosal sites (glans and inner foreskin) were also observed (Figure 1e). In patient n.5, who had been on oral prednisone for several months due to an unrelated disorder, a pustule evolving into a giant (>2 cm), ulcerated lesion was noted (Figure 1f). Histopathology was available for 4/6 patients. In all cases, a central area of fullthickness epidermal necrosis with adjacent acanthosis and keratinocyte degeneration, corresponding to the umbilicated pustular stage, was observed. At higher magnification, direct cytopathic changes were documented, including the presence of multinucleated keratinocytes, Btype inclusions9 and ground glasslike eosinophilic nuclei. The underlying dermis revealed a fullthickness inflammatory infiltrate consisting of lymphocytes, neutrophils and eosinophils in a perieccrine and perivascular distribution. Direct contact, autoinoculation and viremia may all account for the observed lesional distribution. Nevertheless, the striking preference for sites involved in sexual contacts seems to favour the former route of transmission.1,8 Further complicating matters, with its varied clinical presentation MP may pose a challenge in terms of differential diagnosis, with possible mimics being herpes simplex, molluscum contagiosum, syphilis, handfootandmouth disease, orf/milker's nodule, nodular scabies, pytiriasis lichenoides et varioliformis acuta, chickenpox and more rarely other poxvirus infections, such as cowpox. The recent MP outbreak has been attributed to the waning of crossprotective herd immunity for smallpox and possibly to novel MP virus mutations;6 however, no definitive explanation has been provided yet. Interestingly, only half of our cases were travelassociated, implying viral circulation within the local MSM community and crediting the concept of a new MP cluster in Milan, Italy.10