Severe Monkeypox Infection in a Patient with AIDS: An Illustrative Case Report ()
1. Introduction
The Monkeypox (Mpox) virus (MPXV) is an orthopoxvirus known to be endemic in Africa [1] , and until recently, cases were rarely seen outside West and Central Africa. Therefore there has been very little research on the subject of human transmission, vaccines or medications for the treatment of MPXV infections. In the United States, a localized outbreak of MPXV infection was reported in Wisconsin in 2003 related to transmission from infected animals imported from Ghana [2] . In 2018 a small number of cases were reported in the United Kingdom [3] and a single case was reported from Israel [4] , both instances linked to travellers from Nigeria. However, since May 2022, multiple cases have been reported worldwide and in a recent update, the World Health Organization (WHO) reported more than 80,000 confirmed cases of mpox involving more than 110 countries [5] . In August of 2022, the United States declared its mpox outbreak a national public health emergency [6] . We report an early and illustrative case of MPXV infection seen at our community teaching hospital in Worcester, Massachusetts.
2. Case Presentation
A 49-year-old gay male was admitted to the hospital when he presented with severe scrotal pain and swelling. He was initially diagnosed as having cellulitis with epididymo-orchitis and following a four-day stay in the hospital where he received parenteral antibiotics, he was discharged home on ciprofloxacin, doxycycline and metronidazole. However, he returned seven days later with worsening perianal pain and swelling and watery diarrhoea. He worked as a painter and lived with a gay male. He reported being sexually active with one male partner, but denied any sexual contact in the 3 weeks prior to this admission. He stated that he had been compliant with the prescribed oral antibiotics. The patient had a history of HIV infection, diagnosed in 2007, with viral suppression while on antiretroviral therapy (ART) till 2016 when he stopped seeing his physicians and stopped his ART. He also reported a history of syphilis (2016), Crohn’s disease, severe allergy to penicillin (anaphylaxis) and trimethoprim-sulpha (severe rash). On admission, he was noted to have a fever (101.5˚F). Examination of the genital area revealed a normal circumcised penis and normal scrotum, but severe inflammation in the perineum and buttock cheeks with thickening of the skin, whitish discoloration in some areas, blackish discoloration in other areas, scattered vesicles and surrounding redness with severe tenderness to palpation. There was no crepitus and no purulent discharge (Figure 1). He also had tender enlarged inguinal lymph nodes bilaterally. His acute symptoms precluded a digital rectal examination. Laboratory workup revealed normal white cell count, creatinine and liver enzymes. RPR was positive (1:1), HIV viral load: 607,000 copies/mL, CD4 count: 47/µL, he had negative serology for HBV and HCV, and tested negative for chlamydia and gonorrhoea. Blood cultures were negative. A surgical consultation was obtained for deep tissue biopsy for pathology and he was initiated on IV tigecycline along with combination antiretroviral therapy: bictegravir/emtricitabine/tenofovir alafenamide. He was also placed on azithromycin and atovaquone for Mycobacterium avium and pneumocystis prophylaxis respectively. In spite of broad antibiotic coverage, he remained febrile and his buttock cellulitis kept progressing with appearance of new vesicles and some pustules. On day 3 of his hospitalization, he developed pustules with central umbilication on his face (Figure 2(a), Figure 2(b)) and over his buttocks. He also developed a pustule over the palmar surface of his right hand, (Figure 3) multiple pinhead white lesions over the scrotum, (Figure 4) and two purulent ulcers on his penis. There were no lesions in the oral cavity. At this time, he was placed in contact and respiratory isolation precautions. Samples from the lesions on his face were tested for herpes virus (HSV) and MPXV and he was initiated on IV acyclovir. Two days later, the PCR test for MPXV returned positive (non-variola orthopox DNA detected). The PCR for HSV was negative. Acyclovir was discontinued and he was started on oral tecovirimat 600 mg twice a day. Over the next two days, he continued experiencing low grade fevers and he developed new pustules scattered over his arms and back (Figure 5). The lesions on his face
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Figure 1. Severe cellulitis of buttocks.
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Figure 2. (a) Pustules with central umbilication on the right side of the face; (b) Umbilicated pustule on the left side of the face.
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Figure 4. Eruption of vesicles and pustules on the scrotum.
increased in size but some appeared to be drying up and crusting with some haemorrhage (Figure 6(a), Figure 6(b)) and the lesions on his buttock had progressed to pustules (Figure 7). After three days of starting tecovirimat, the patient began improving with resolution of fever and crusting of pustules. He was discharged from the hospital after completing 14 days of parenteral antibiotics
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Figure 6. (a) Crusted lesions on right side of face; (b) Crusted lesion on left side of face.
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Figure 7. Multiple pustules on buttocks.
and he completed a 14-day course of tecovirimat as an outpatient. No secondary cases of mpox infection were detected among hospital staff including the surgery team who performed biopsy of the perianal area prior to the institution of isolation precautions. Histopathology of buttock lesion was non-diagnostic revealing epidermal psoriasiform hyperplasia (Figure 8(a)) with superimposed reactive cytological atypia and focal necrosis, and florid dermal acute and chronic inflammation (Figure 8(b)). No viral inclusions, plasma cells or giant cells were identified. Special stains were negative for acid-fast bacilli and fungus. No malignancy was detected either. He followed up in the Infectious Diseases outpatient office 1 week after discharge from the hospital. All his skin lesions had subsided (Figures 9(a)-(c)) except for the buttocks where he had persistent painful erosions (Figure 10) which took another 2 months for full resolution. (Figure 11) On detailed inquiry, he reported that he had had receptive anal sex 3 weeks prior to onset of his buttock lesions. His male sexual partner did not have any
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Figure 8. (a) Hematoxylin-eosin section (10×) of buttock showing psoriasiform hyperplasia of epidermis and inflammatory infiltrate deep in the dermis; (b) Hematoxylin-eosin section (40×) of buttock showing mixed inflammatory Infiltrate in dermis.
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Figure 9. (a) Resolution of lesions on right side of face; (b) Resolution of lesions on right side of face; (c) Resolution of a pustule on the right hand.
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Figure 10. Persistent inflammation with erosions and discharge on buttocks.
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Figure 11. Complete resolution of buttock lesions after 2 months.
lesions on his skin, oral or genital mucosa, remained asymptomatic throughout this period and proceeded to receive two doses of the mpox vaccine. The patient did not know of anyone in his contact circle who had skin or genital lesions. The patient provided written consent for publication of this case report
3. Discussion
The differential diagnosis for our patient’s perianal lesions included atypical HSV infection, condylomata lata (syphilis), condylomata accuminata (HPV) with superadded bacterial infection, or an unusual bacterial, viral or fungal infection in a patient with AIDS, or cutaneous malignancy associated with AIDS. He was initiated on broad antibiotic therapy, and tigecycline was chosen considering patient’s severe allergy to penicillin and trimethoprim-sulfa. When the patient developed new vesicles and pustules in spite of the broad antibiotics, he was initiated on parenteral acyclovir to cover for possible disseminated HSV infection.
The differential diagnoses for the widespread pustules included disseminated HSV, molluscum contagiosum or cutaneous cryptococcosis. However, deroofing the pustules did not reveal the classic pasty material seen in the latter two conditions. His serology for cryptococcus was also negative. He continued experiencing new lesions in spite of broad coverage with antibiotics and acyclovir. Once the diagnosis of mpox was established by the PCR test, acyclovir was discontinued and he was started on the antiviral medication tecovirimat. This medication has demonstrated efficacy against smallpox in animals [7] , was approved in 2018 for the treatment of smallpox in humans [8] , and has shown efficacy against mpox in animal models [9] . Tecovirimat was offered to the patient under an expanded access investigational new drug protocol of the CDC. Three days of treatment with tecovirimat elapsed before a clinical response was observed. Initial response included a resolution of fever and lack of new skin lesions, along with drying and crusting of older lesions. The patient received a total of 14 days of tecovirimat per the protocol, with monitoring of blood counts, kidney and liver parameters all of which remained normal. Parenteral antibiotics were continued for 14 days secondary to severe perianal cellulitis. Through all this, he also continued pneumocystis and Mycobacterium avium prophylaxis, as well as 3-drug combination ART. There was no evidence of adverse drug-drug interactions between the antiviral agents.
Histopathologic findings of ballooning degeneration and multinucleated syncytial keratinocytes, acanthosis and spongiosis of epidermis (with necrosis in severe cases) and mixed inflammatory dermal infiltrate is characteristic of the skin lesions of mpox infection [10] . The skin biopsy of our patient had some of these features. However, the characteristic keratinocyte changes were not seen. This may be attributable to sampling error (the sample may not have been obtained from primary mpox lesion) and our facility did not have the ability to perform immunohistochemistry or electron microscopy on the tissue sample.
The majority of cases of MPXV infection have been identified in men who have sex with men and transmission is believed to occur through local inoculation during skin and mucosal contact [1] [5] [6] . The anogenital area was the most common location for the skin rash in one large study. [11] The MPXV has also been isolated from seminal fluid [11] [12] . The contact source of infection is not always identified and transmission may occur from asymptomatic individuals which is possibly the mode of transmission in our patient. In one large study, a definite exposure history was obtained in only 23 out of 528 cases. [11] Other groups have also raised the question about sexual transmission from an asymptomatic carrier of MPXV. In two retrospective studies - one from Belgium [13] and the other from France [14] samples obtained for routine STI screening were tested for mpox PCR and 3 out of 4 (Belgium study) and 11 out of 13 (French study) PCR-positive patients were asymptomatic.
Non-sexual transmission has also been reported, via fomites or piercings as was seen in an outbreak at tattoo establishment in Spain [15]
In our patient, there was no history of contact with anyone with a rash, (or who subsequently developed a rash). However, his history of receptive anal sex with his male partner and the development of the most severe infection in the perianal area makes it very likely that asymptomatic transmission occurred via sex from his male partner rather than via fomites. Our patient’s severe perianal infection took almost 3 months for complete resolution.
4. Conclusions
Mpox infection is seen predominantly in gay males and the mode of transmission is most commonly via skin and/or mucosal contact with an individual who has cutaneous or mucosal lesions, but transmission may occur from asymptomatic individuals. Our case adds to the literature on possible transmission by an asymptomatic gay partner.
Perianal lesions are often the most severe and take the longest to heal. Infection with HIV with very low CD4 count (AIDS) likely contributed to this severe atypical manifestation in our patient. Our case report includes images of different stages of typical mpox skin rash, as well as atypical more severe perianal lesions seen in an immunocompromised individual with AIDS. Early recognition of atypical skin lesions could lead to the prompt diagnosis and initiation of tecovirimat to limit severity of disease as well as decrease the risk of transmission.
Our case also adds to the literature regarding the safety and efficacy of tecovirimat in the management of mpox infection. Our patient did not develop any clinical side effects and his CBC, kidney and liver tests remained normal. There was no drug-drug interaction between tecovirimat and ART medications: bictegravir/emtricitabine/tenofovir.