‘Monkeypox 2.0’: Case series on a reconditioned virus causing sexually transmissible disease in urban population

Epidemiology of study population

A total of 35 patients were enrolled in our study, of whom 32 were men and 3 were women. Their ages ranged from to 20–56 years an average of 31.7 years. The patients were of Asian, African, or Middle Eastern descent. Twenty-one of these patients were married. Recent sexual exposure was reported in 30 cases (85.5%). The average time from exposure to rash was 1–21 days (average 7.52 days), excluding the patient living with HIV, which was 30 days. Of the sexual exposures, 17 were from sex workers and spa/massage therapists, five were from unmarried partners, three were from marital partners, and others were unspecified. Twenty-eight cases were heterosexual, and two were homosexual. Nine patients (25.7%) used condoms, which did not protect them from the disease. Similar lesions were present in the partner at exposure or later in only 3 cases. We did not obtain any significant contact history with sick animals or handling raw meat from desert animals or camel meat. Travel history was present in five patients within 3 months. There were no cases of households spreading to adults, children, or the elderly who lived in the same household or accommodation. None of the patients had a history of blood transfusions.

Clinical features of our cases

Fever was noted in 26 (74%) of the 35 cases. Fever was mild in eight, moderate in nine, and severe in nine patients. The fever ranged from to 1–21 days, with an average of 4.4 days. The associated features noted were lesion tenderness, itching, headache, sore throat, eye symptoms such as redness and discharge, dysuria, urethral discharge, and gastrointestinal symptoms such as diarrhea and abdominal pain. All except one patient had polymorphic lesions.

The types of skin lesions seen in our cases, in decreasing order of frequency, were necrotic annular pustules (27 cases), pustules (25 cases), papulo-vesicles (20 cases), genital ulcers (16 cases), umbilicated papules (13 cases), erythematous papules (10 cases), crusted papules (3 cases), inguinal ulcer (one case), and maculopapular lesions (one case). The primary and most frequent site of rash was the genitalia in majority of cases (71.4%). Of these, 22 showed penile papules/pustules/ulcers (Figure 1) and 3 females showed labia majora and minora papules or ulcers (Figure 2). The other affected sites (Supplemental material) were in decreasing order of frequency: upper limb (16 cases), abdomen (16 cases), face (15 cases), lower limb (14 cases), chest (13 cases), back of trunk (13 cases), scalp (8 cases), neck (5 cases), lower abdomen and pubic area (4 cases), buttocks (two cases), and inner thighs (1 case). New lesions arose for 1–14 days, with an average of 8 days. The lesions evolved from small papules to papulo-vesicle-like lesions progressing to papulo-pustule, to pustule with erythematous rim, then the center of the pustule changed color to pink, studded with red dots, and then grey and black, forming necrotic papules with annular pustules (Figure 3). During healing the central necrotic scab detached leaving a crateriform lesion, evolving to macules with peripheral scale, and healed mostly without leaving scars. The rash healed within an average of 13.3 days. Two patients had a prolonged course, one of which was newly found to be living with HIV (Figure 4) and the other was a diabetic patient with secondary bacterial infection of the genital ulcer (Figure 5). The vitals were stable in all cases. No hepatosplenomegaly was detected in any of the patients. Lymphadenopathy was found in 22 cases (62.8%) involving inguinal, cervical or submandibular nodes.OPEN IN VIEWER

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Figure 2.

Spectrum of genital lesions in female: discrete flat papules on labia majora reminiscent of condyloma lata, confluent annular necrotic pustules forming an irregular ulcer with scalloped pustular border and satellite pustules some with central necrosis on labia some of which are perianal.

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Figure 3.

Shows evolution of skin lesions from small papule to papulo-vesicle like lesion progressing to papulo-pustule, to pustule with erythematous rim, then umbilicated pustule, then annular pustule with pink center studded with bright red dots, then annular necrotic pustule with inflammatory halo, then a crateriform papule that peeled off and resolved with a pigmented scar.

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Figure 4.

MPOX co-infection with HIV: 3-5 cm annular necrotic plaques affecting left nostril, upper back, leg and glans penis.

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Figure 5.

MPOX in a diabetic patient: Started as umbilicated pustules with intense inflammatory edema of genitalia, progressing to necrotic ulcers on the shaft of the penis, after debridement, and re-epithelization after antibiotics.

Investigations

MPOX PCR tests by PCR were positive in all cases. Other laboratory tests were done selectively according to the patient. An HIV test was done in 21 out of 35 patients and one was positive. Concomitant sexually transmitted infections (STIs), such as syphilis, urethritis, and hepatitis B and C, were ruled out in all tested cases (around 50% of cases). Few showed urine abnormalities like RBCs, WBC’s in urine, mucus thread, and leukocyte esterase positivity despite negative bacterial cultures and negative urethritis screening. Sixteen patients had an elevated CRP with average value of 36.67 mg/dl. Wound culture from genital ulcers grew several Gram-positive and negative bacteria which were treated appropriately.

Skin biopsy was performed in three cases (Figure 6). It showed ballooning degeneration of keratinocytes with eosinophilic inclusion bodies, diffuse neutrophilic infiltrate in the dermis, and peri-adnexal. No leukocytoclastic vasculitis was noted in any of the 3 cases. Biopsy from our patient living with HIV co-infected with MPV showed necrotizing myositis and fasciitis in the muscles and panniculitis with small- and medium-vessel vasculitis and extensive dermal necrotizing thrombotic vasculitis with mixed septal and lobular necrotizing panniculitis in the skin.OPEN IN VIEWER

Sexually active young adults affected

Young sexually active adults were mostly affected with an average age of 31.7 years which is comparable to the reports from other countries. ¹ But compared to the case series by Patel et al ² from Central London where the majority of MPOX infections were in bisexual or gay men, in our series only 5% of these cases reported same-sex contact. The cause of disparity is unknown, but the demographics of Central London, which has a large population of LGBT communities, the presence of a single working expatriate population in this area, and unwillingness to report same-sex behaviour due to legal or moral concerns could be contributing factors for the different demographics.

Route of transmission was mainly high-risk sexual contact

The average incubation period was difficult to precisely calculate, as 31% had multiple contacts with different partners. However, the average time from the last exposure to rash onset was 7.5 days except in the patient living with HIV where the skin lesions took 1 month to develop after the last heterosexual exposure. A higher risk was observed in individuals seeking sex workers or receiving sexual favors from massage therapists (48%). Condoms surprisingly did not give full protection, as nine cases occurred in men who used condoms and developed lesions on the lower abdomen and pubic area initially sparing the penis (Supplemental material Figure 6); this may be because monkeypox viruses can be transmitted by breaks in the skin or other body fluids like saliva. ³ There are reports of MPOX outbreaks from a tattooing center in Spain that resulted in 20 infections ⁴ ; however, we did not have a history of tattoos in our cases. Most sexual contacts were clinically ‘asymptomatic' and thus possibly become temporary carriers and transmitters of the disease. ⁵

Rare non-sexual close contact

One interesting finding was of possible skin-to-skin transmission after one male patient developed lesions after he helped to drain the ‘boils’ of his female coworker with his bare hands.

Predominance of rash in genital and pubic area

Genitalia were predominantly affected sites in our study. The pox virus is adapted to epidermal cells and thus the initial site of infection resulting from direct inoculation may be the skin, mucosal surface, or respiratory tract, as observed in rural African MPOX infections. The virus then spreads through the regional lymphatics to cause viremia and the involvement of the reticuloendothelial system with secondary viremia. ⁶ This could explain why the initial rash and predominant area of affection is genitalia in the majority of our cases and later rash became generalized; contrast this with only 30% genital involvement for endemic African MPOX infections. ⁶

Other areas of involvement

Apart from the trunk and limbs, a predilection for the face (60%) and scalp (32%) seems to be a differentiating feature in early disease (Supplemental material Figure 3, 5). Tenderness of the lesions and crowding of lesions in the lower abdomen and pubic area (Supplemental material Figure 6) were also differentiating features from other similar diseases. In our study predictors for secondary infection of ulcers and necessity for cultures and antibiotics/antifungals were as follows: frankly purulent discharge, progressive non-healing skin lesions beyond 2 weeks, enlargement of ulcers more than 1 cm, persistant high fever and edema of the genitalia. Oral lesions were seen in 17% of the cases as papules or erosions (Supplemental material Figure 7). Eye symptoms were observed in 8% of the cases and have been described in detail by Kaufman et al. ⁷

Disease course

The necrotic annular pustules seem to be specific to MPOX skin infection, and we would like to call this the ‘smoke ring sign’. This helps to differentiate MPOX from all other pox viruses and similar diseases early in the course of the disease. The Central London cases ² had erythematous maculopapular rash in 13.7% of cases compared to only one case in our study, and the patient had a history of taking an antibiotic before the onset, and he improved on stopping the antibiotic.

Women with MPOX

Three female patients with MPOX had genital ulcers (Figures 1 and 2) with inconspicuous scattered body lesions. One patient developed conjunctivitis/episcleritis (Supplemental material Figure 7). The lesions on the genitalia in the women were easily ulcerated, were more painful, and needed constant pain medication compared to the male patients.

Urethritis like syndrome in MPOX in the absence of evidence of other STI’s

Another notable feature was dysuria and/or seropurulent discharge (11%) and/or abnormal urine routines (25%) in the absence of investigatory evidence for other sexually transmitted infections, such as gonococcal or common causes of non-gonococcal urethritis, by PCR and culture. This may aid in transmission in the absence of skin lesions. Hematuria, a clinical feature of monkeypox, has also recently been described. ⁸

MPOX in patient co-incidentally detected to be HIV positive

A 34-year-old Nigerian adult male patient was concomitantly diagnosed with HIV, CMV and MPOX when he presented with 3 weeks of a skin rash that started on the genitalia and then spread to the rest of the body. Skin lesions were larger compared to other cases in this series and were located on the trunk limbs and genitalia (Figure 4). Despite starting antiretroviral therapy and ganciclovir, the patient died of his disease 45 days after admission. Tecovirimat wasn’t started due to unavailability. A similar report of genital MPV lesions in a patient living with HIV was treated with tecovirimat with improvement in his condition. ⁹ Unlike our study which had STI screening selectively, other studies have found that a substantial proportion of monkeypox cases may be coinfected with HIV or other STIs, which is why CDC ¹⁰ recommends testing for other sexually transmitted infections once a diagnosis is established. However, compared to previous endemics in Africa, the death rates secondary to MPOX infections outside Africa is low (<5%) ¹¹ according to the current literature.

MPOX in diabetic patient

We had one protracted case of monkeypox in a 41-year-old diabetic male (Figure 5), who presented with typical lesions that rapidly progressed, to genital skin necrosis and swelling and treated with antibiotics and debridement for secondary infection with carbapenem-resistant E. coli. The ulcer healed 3 weeks after with scarring. There is a theoretical review predicting susceptibility and severity of MPV infection in poorly controlled diabetes, which seems to hold true in our diabetic case. ¹²

Investigations in MPOX cases

Skin biopsy of necrotic papules showed viral cytopathic changes (Figure 6) and can be misdiagnosed as herpetic folliculitis, herpes zoster, smallpox, or leukocytoclastic vasculitis, and only PCR can help in this situation. The skin pathology of MPOX lesions has been described previously by Bayer-Garner et al ¹³ and for the current epidemic by Chalali et al. ¹⁴

Differential diagnosis

MPV infection can present only solely as genital ulcers.^14,15 The main differential diagnoses assigned by non-dermatologists who referred such cases are discussed in Supplemental material Table 1, with useful pointers for correct diagnosis.