Mpox: A recent addition to the differential diagnosis of genital ulcer disease

INTRODUCTION

Mpox, previously called monkeypox, is a zoonotic infection caused by the Mpox virus. The World Health Organization declared Mpox a public health emergency in 2022 and again in 2024 due to rising cases.^[1] It is listed as a priority pathogen that could cause a pandemic. Since the 2022 outbreak, many cases with unusual symptoms have been reported. We describe a rare presentation of Mpox with crusted genital ulcers and arciform erythema over the lower abdomen.

CASE REPORT

A 48-year-old man with uncontrolled diabetes mellitus who returned to Kerala, India, from Ajman, United Arab Emirates (UAE) presented to the dermatology outpatient department with crusted genital ulcers for 10 days, along with fever and fatigue which began on the 2^nd day of the genital lesions. More ulcers developed within 1 week along with a rim of erythema and edema in the suprapubic region. A general practitioner in the UAE had prescribed ciprofloxacin, analgesics, and antacids for 5 days. He denied extramarital heterosexual and homosexual contact and his last marital contact was 3 months before the onset of symptoms.

On examination, he had multiple well-defined, umbilicated papulopustules with hyperpigmented crusts on the corona of the glans penis, shaft, and root of the penis [Figure 1a]. The lesions were firm and exhibited mild tenderness. He also had an arciform erythema of size about 4 cm wide on the suprapubic region, 10 cm below the umbilicus [Figure 1b]. Bilateral tender firm inguinal lymph nodes (1 × 1 cm and 1.5 × 1.5 cm) were palpable. The scrotum and perianal areas were unaffected.

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Figure 1:

(a) Multiple discrete well-circumscribed umbilicated papulopustules with central hyperpigmented crust on the corona of glans penis, root, and shaft of penis. (b) An arciform erythema on the suprapubic region.

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Differential diagnoses considered were Mpox, primary and secondary syphilis. Gram stain was negative. A complete hemogram showed lymphocytosis; urine microscopy was normal; and serology for HIV, hepatitis B, hepatitis C, and syphilis was non-reactive. Real-time polymerase chain reaction (PCR) tested positive for Orthopox and Mpox virus from the nasopharyngeal swab, tissue fluid, and biopsy samples, while urine and serum samples tested negative.

Histopathology showed acanthosis with spongiosis, full-thickness inflammatory infiltrates, intraepidermal pustules, eosinophilic inclusion bodies in keratinocytes, and non-viable “ghost” keratinocytes. Some keratinocytes had ground-glass nuclei, while others had peripherally displaced nuclei [Figures 2 and 3].

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Figure 2:

(a) Histopathology of skin shows epidermis and dermis. Epidermis shows acanthosis (hematoxylin and eosin; ×10). (b) spongiosis and full-thickness inflammation (hematoxylin and eosin; ×10).

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Figure 3:

(a) Histopathology of umbilicated crusted papule shows intraepidermal pustule, (hematoxylin and eosin; ×40). (b) Eosinophilic intracytoplasmic inclusions seen in keratinocytes (red arrow), (hematoxylin and eosin; ×40). (c) Ghost keratinocytes with ground-glass appearance of nuclei and occasional keratinocytes show nucleus pushed to the periphery (hematoxylin and eosin; ×40).

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The patient was treated with oral doxycycline 100 mg twice daily and topical mupirocin cream. He was referred to a government medical college for isolation and further management where he continued the drug for 2 weeks. He was retested every 4 days, and isolation continued until the PCR tests were negative and all the lesions healed. His wife tested negative for Mpox.

DISCUSSION

Mpox is caused by a virus from the Orthopoxvirus genus in the Poxviridae family. The disease transmits from animals to humans (primary) through saliva, respiratory secretions, and skin contact or from person to person (secondary) through respiratory droplets and direct contact with lesions.^[2]

An incubation period of 1–2 weeks is followed by a prodrome of fever, headache, malaise, and lymphadenopathy. The rash typically starts on the face and spreads centrifugally, progressing through papule, vesicle, pustule, and crust stages over 2–3 weeks.^[2]

Since 2022, more cases have involved localized genital lesions, especially among sexually active men who have sex with men or bisexual individuals. Eight distinct published series from 17 countries indicated that between 84% and 100% of reported cases had engaged in sexual activity before developing symptoms.^[3] In this case, even though the patient denies recent sexual contact, lesions being limited to genitalia suggest a probable sexual transmission.

Genital Mpox lesions can be easily mistaken for other more common sexually transmitted infections (STIs), including herpes genitalis. While the lesions of herpes genitalis progress from vesicles to erosions and ulcerations, the papulopustular lesions of Mpox form a hyperpigmented crust. The salient morphology of the other sexually transmitted genital ulcer diseases is summarized [Table 1].

Atypical presentations reported include localized genitourinary rash, verrucous lesions, acute paronychia, subungual ulcers, scrotal and penile shaft edema, and eschar-like lesions.^[2,4-6] Our patient showed a crusted genital ulcer along with an arciform erythema over the suprapubic region.

Although PCR remains the gold standard for diagnosis, histopathology can help rule out other common STIs. Histopathological findings in Mpox include epidermal necrosis, ballooning and reticular degeneration of keratinocytes, multinucleated cells, and a dense mixed inflammatory cell infiltrate with remarkable neutrophil exocytosis.^[7] Mpox shows intracytoplasmic eosinophilic Guarnieri-type inclusion bodies in keratinocytes which can be a useful differentiating histopathological feature from herpes genitalis, where intranuclear eosinophilic inclusion bodies are seen.^[8] Proliferation and swelling of endothelial cells and perivascular infiltration of lymphoid cells and plasma cells are the main histopathological changes seen in syphilis. Treponemes are commonly identified in both primary and secondary lesions using silver staining. Donovanosis shows pseudoepitheliomatous hyperplasia and neutrophilic abscess with moderate numbers of large mononuclear cells with vacuoles containing Donovan bodies. The ulcer of chancroid is characterized by a narrow superficial zone of degenerate leukocytes and fibrin, a broader middle zone with characteristic vascular changes, and a deep zone in which there is plasma cell and lymphocyte infiltrate.^[9]

Most cases of Mpox recover with symptomatic management. Drugs effective against other orthopox viruses such as tecovirimat, brincidofovir, cidofovir, trifluridine ophthalmic solution, and vaccinia immune globulin intravenous have been used to treat severe Mpox.^[10] JYNNEOS and ACAM2000 are two US Food and Drug Administration-approved vaccines for the prevention of Mpox.^[11]

CONCLUSION

Dermatologists should maintain a high index of suspicion for Mpox when evaluating patients with genital ulcer disease. Histopathology can serve as an invaluable tool to establish the diagnosis when real-time PCR is unavailable. Prompt suspicion and isolation of cases will help prevent further transmission of the infection.