Monkeypox and Malignant Syphilis Coinfection in an HIV Patient

To the Editor: Monkeypox, an orthopoxvirus of the Poxviridae family, was recently declared a public health emergency by the World Health Organization because of the increasing number of cases in several African countries and the potential for spread beyond the continent. In addition, HIV-infected individuals are disproportionately affected by monkeypox, often presenting with severe or atypical clinical manifestations that may delay diagnosis.1,2 A 27-year-old man with a history of HIV infection presented to the emergency department of our hospital with painful crusted ulceronecrotic lesions on the right cheek, right thigh, and left leg of approximately 1 month's duration (Fig. 1A). He denied any systemic symptoms. A punch biopsy of the cheek was performed for histopathologic and microbiologic analysis, and the patient was discharged with close follow-up by our dermatology service. Microbiologic results (bacterial cultures) showed coinfection with Staphylococcus aureus and Corynebacterium diphtheriae. The Corynebacterium diphthteriae strain was shown to be nontoxigenic after the Elek test (modified immunodiffusion) and was interpreted as a contaminating agent. Tests for mycobacteria [Ziehl–Neelsen staining, mycobacterial culture, and polymerase chain reaction (PCR) nucleic acid analysis for Mycobacterium tuberculosis], fungi (fungal culture), and leishmania (PCR study) were negative. Based on these results, treatment with oral levofloxacin and topical mupirocin was initiated. The histopathology report (Figs. 2A–D) subsequently showed a mixed inflammatory infiltrate predominantly in the dermis with abundant plasma cells accompanied by spirochetal aggregates identified by immunostaining for Treponema pallidum. Consequently, the patient received an intramuscular injection of 2.4 million units of benzathine penicillin G. Despite this treatment, the lesions did not improve and increased in size (Fig. 1B). At this point, the patient was admitted to hospital for close monitoring and further investigations. While in hospital, he was diagnosed with poorly controlled HIV infection (>20,000 viral copies with <100 CD4 lymphocytes in the blood count). In addition, he developed ulcerated pseudopustular lesions on the right eyelid, clinically suggestive of viral infection (Fig. 1C). Similarly, lesions on the rest of the body progressed and new ulcers (Fig. 1D) and Kaposi sarcoma lesions (confirmed by biopsy) appeared on the face (Fig. 1E) and oral mucosa. A new biopsy of the right eyelid and PCR tests for herpesvirus and monkeypox were performed. PCR results confirmed monkeypox infection, and histologic analysis showed globular keratinocytes with eosinophilic intracytoplasmic inclusions compatible with Guarnieri bodies, further suggesting monkeypox infection (Figs. 2E and F). Based on these findings, treatment with tecovirimat at a standard dose of 600 mg twice daily for 14 days and 1% trifluridine eye drops every 4 hours was initiated. The patient completed the treatment with a satisfactory response and the skin lesions resolved with healing, showing repigmentation in the periphery. He was discharged 2 weeks later with an adequate CD4 count and no active skin lesions. Finally, 3 months later, the scars had decreased in size and had almost regained pigmentation (Fig. 1F).FIGURE 1.: Clinical presentation of the lesions through the course of the disease. A, Ulceronecrotic plaque, 6 × 6 cm, fibrinous surface, and violaceous margins on the right cheek when the patient presented to the emergency department. B, The same plaque increased in size (until 9 × 7 cm) after 1 week of treatment with 2.4 million units of penicillin G benzathine. C–E, Lesions 3 weeks after onset. In panel C, several ulcerated pseudovesicles are seen on the right upper and lower eyelids, suggesting viral infection. In panel D, a new ulcer is seen in the left antebrachial region, and in panel E several violaceous papules are seen on the left cheek, later identified as Kaposi sarcoma. F, Main lesion after 3 months of treatment. Reduction of the lesion with no signs of activity and residual dyschromia.FIGURE 2.: Histologic appearance of the lesions. A–D, 5 mm punch biopsy of right cheek ulcer (panel A hematoxylin–eosin staining ×4, panel B, hematoxylin–eosin staining ×10, panel C, hematoxylin–eosin staining ×20, panel D, immunohistochemistry for Treponema pallidum ×20). Histology of the lesion on the cheek showed pseudoepitheliomatous hyperplasia with an inflammatory infiltrate in the dermis with a predominance of plasma cells. Immunohistochemistry (D) showed aggregates of spirochetes. E and F, 4 mm punch biopsy of a pseudovesicle of the right lower eyelid (panel E, hematoxylin–eosin staining ×10, panel F, hematoxylin–eosin staining ×40). The palpebral biopsy showed ballooning keratinocytes with eosinophilic intracytoplasmic bodies with a ground-glass appearance, and the nucleus displaced to the periphery, compatible with Guarnieri bodies (best seen in panel F and indicated with red arrow), suggesting monkeypox infection.Several case series, such as that by Mitjà et al1 and the narrative review by Saldana et al,2 suggest that systemic complications of monkeypox, including disseminated or life-threatening presentations, are more common in patients with CD4 cell counts <100 cells/mm3. These patients may develop ecchymotic or hemorrhagic lesions, large necrotic ulcers, or wart-like formations without the typical appearance of rounded ulcers with necrotic centers and raised borders. These findings suggest that monkeypox may manifest differently in people with advanced HIV and could potentially be considered an AIDS-defining condition.1,3 In addition, severe forms of the disease are more susceptible to bacterial or fungal superinfection,2 which clinicians should promptly investigate and treat. In addition, health care providers should screen for other sexually transmitted infections when mpox infection is suspected, because 20%–30% of patients with confirmed mpox infection are coinfected with other sexually transmitted infections.4,5 To the authors' knowledge, although cases of syphilis and monkeypox coinfection have been documented, this report presents the first case of simultaneous viral inclusions of monkeypox and T. pallidum in the biopsy of an HIV-positive patient, highlighting the atypical and sometimes severe manifestations of mpox in individuals with low CD4 counts.