'Case of the Month' from the Medical University of Graz, Austria: pustules with ulceronecrotic centre - monkeypox virus is facing us.

A 60-year-old man presented due to two centrally crustose pustules on the penis of 1 week duration. The patient denied any unprotected sexual intercourse; however, admitted protected sexual contact with a male random acquaintance. The patient denied any local trauma, manipulation, or previous pathologies at that or any other site. He also reported having a fever the day before. He was diagnosed with HIV 14 years previously and maintained a good immune-virological control under antiretroviral treatment. In addition to his history of HIV, he had a history of high blood pressure, depression, and gastro-oesophageal reflux disease. He took candesartan-hydrochlorothiazide, escitalopram, pantoprazole, and trazodone hydrochloride medication on a regular basis. On clinical examination, two sharply demarcated pustules, centrally coated with a necrotic crust were visible on the penis (Fig. 1). Palpating them, they had a hard, infiltrated form. No inguinal lymphadenopathy was present. The oral cavity, as well as palmoplantar region, were unsuspicious. He had no exanthema on the body and had no signs of follicular involvement. However, during the whole-body examination, multiple umbilicated pustules were detected in the perianal region, clinically highly suspicious for monkeypox virus (MPXV) infection. Pustule exudate was collected, and PCR testing confirmed MPXV. Syphilis serology showed no active infection (rapid plasma reagin test negative; Treponema pallidum particle agglutination test [1:1280], screening test reactive, T. pallidum membrane particle agglutination test immunoglobulin M negative). Furthermore, hepatitis B and hepatitis C were excluded serologically. As PCR for Neisseria gonorrhoeae was negative, diagnosis of a disseminated gonococcal infection was unlikely. The pustule was tested for 11 relevant sexually transmitted infections (STIs) including: Chlamydia trachomatis, N. gonorrhoeae, herpes simplex virus 1 (HSV-1) and (HSV-2), Haemophilus ducreyi, Mycoplasma genitalium, Mycoplasma hominis, T. pallidum, Trichomonas vaginalis, Ureaplasma parvum, and Ureaplasma urealyticum, all of which were negative. The MPXV infection was reported to the local health department and patient was sent to quarantine. The patient was advised to abstain from any physical and sexual contact until the complete healing of the pustules and to present for a control visit in order to guarantee complete healing. After 1 month the patient came back to the department of dermatology and presented with complete healing of the lesions (Fig. 2). In the case of genital pustules and/or ulcers generally infections (sexually transmitted or transmittable) should be considered. The pathogens T. pallidum, HSV-1 and HSV-2, and more, seldomly Haemophilus ducreyi are known to elicit vesico-pustules or ulcers at first sight. In May 2022 an outbreak in central Europe of the zoonotic MPXV infection was observed [1-3]. By 25 August 2022, >17 000 cases had been reported in European countries [4]. The MPXV, a double-stranded DNA virus, belongs to the group of orthopoxviruses, that seldomly cause infections in humans, except in Africa where it is endemic [1, 3]. Transmission is not only possible via respiratory droplets, but also by direct skin-to-skin contact with infected lesions [1, 3]. Diagnosis is usually made via PCR testing of skin (pustules and/or crusts), oropharyngeal swab, or of blood [1-3]. Screening of STIs is highly recommended in patients suspicious for MPXV infection. The vast majority of those who are infected, belong to the group of men who have sex with men (MSM) with a median age of 35–38 years [1-3]. A considerable number of those infected have HIV [2]. The incubation period is believed to range up to 21 days, followed by prodromes, including fever, myalgia, arthralgia, lymphadenopathy, headache, or fatigue amongst others [1, 3]. According to the latest outbreak and due to observational cohort studies most patients present with fever (62–72%) and adenopathy (56%–85%) [1, 2]. Only some days after the fever does the typical rash on the face and body appear [1]. This rash might transform from macular to papular, vesicular, pustular, and crustose stages [1, 3]. The typical clinical feature of MPXV is umbilicated pustules, with or without an ulceronecrotic centre. According to the latest data from observational cohort studies and case series the main sites that are affected are the genitals and perianal region, followed by trunk or extremities [1-3]. Many patients have only a small number of lesions (20 or much more frequently even less) [1, 2]. Patel et al. [3] reported about a median of five lesions in their observation of 197 cases. It is of outmost importance to keep in mind that even patients with solitary lesions due to MPXV infection (11% in the observational study of Patel et al. [3]) may present to clinicians [1, 3]. Solitary lesions due to MPXV may easily be misdiagnosed with other solitary genital lesions, like syphilis I or lymphogranuloma venereum (the invasive variants of C. trachomatis). In the case of the perianal region being affected, anal pain and even proctitis are common and often need pain medication or even hospitalisation [1-3]. Antiviral treatment with tecovirimat or cidofovir is possible, but uncommon in the clinical setting [1, 2]. A specific treatment (including vaccination) is currently not available, and usually not necessary in this self-limiting disease, as most cases follow a mild course [1, 3]. Lesions heal within 2–4 weeks and in some cases leave a mild scar [3]. A patient with MPXV infection is contagious until all sores have crusted over, all scabs have fallen off, and an intact, new skin has formed. However, it is still under debate, whether and how long after complete healing of (muco-)cutaneous lesions, MPXV can be transmitted (e.g., via semen [1]) and the European Centre for Disease Prevention and Control (ECDC) recommends condom usage for 12 weeks after recovery from a MPXV infection. Partner notification should be based on national guidelines and national public health authorities. In general, it is recommended that sexual partners and close contacts should self-monitor for at least 21 days after contact with a patient with MPXV. Vaccination against smallpox is believed to offer protection in a high percentage, and some countries recommend vaccination in risk groups, including clinicians, laboratory personnel, those who have contact with MPXV-infected individuals, and the MSM community. Differential diagnosis of multiple genital ulcerated nodular-papular-vesicular lesions include mainly infections with herpes variants, syphilis I–II, and chancre (Table 1). Monkeypox virus infections are on the rise, mimicking clinical aspects of syphilis and herpes variants and should be kept in mind, especially in those patients presenting with pustules and systemic symptoms including mainly fever, myalgia or arthralgia among the MSM community. None of the contributing authors have any conflicts of interest, including specific financial interests, relationships, and affiliations relevant to the subject matter or materials discussed in the manuscript.