We report the case of a 32-year-old man who was admitted to a hospital in Southern Florida in July 2022. He was known to have HIV infection with a cluster of differentiation 4 (CD4) level of 185, was not compliant with his antiretroviral therapy, and had a drug abuse history positive for 3,4-methylenedioxy-methamphetamine (MDMA). The patient had no travel history 30 days before admission.

The patient presented to the emergency room with shortness of breath, fever, cough, and left-sided chest wall pain. The onset of symptoms occurred 5 days before, and the degree of symptoms was mild and constant. The patient denied any sore throat, nausea, or vomiting. Physical examination revealed a pustular skin rash, consisting of generalised exanthema with small white and red papules.

On arrival at the emergency room, he was found to be in a state of sepsis with lactic acidosis. He underwent chest radiography and was found to have 40% left-sided pneumothorax. Chest radiography also showed minimal atelectasis in the left mid-lung, with a small pleural effusion at the base of the left lung. He had sinus tachycardia with a heart rate of 101 beats/min, which returned to sinus rhythm after resorption of the pneumothorax. He tested negative for SARS-CoV-2 antigen and influenza A and B antigens. The patient was administered a single dose of azithromycin as an intravenous infusion and ceftriaxone. The patient was admitted to the hospital for further management.

Physicians from the departments of internal medicine, family medicine, infectious diseases, pulmonology, and critical care were involved in patient care. On day 1 of admission, the patient was afebrile. He was placed on a bi-level positive airway pressure (BiPAP) machine due to respiratory distress, insufficiency, and subjective weakness. The patient was shifted to the telemetry unit with contact and droplet precautions in view of skin lesions. The skin lesions were located on his face, lips, posterior neck, right hand, left antecubital area, left elbow, left forearm, right upper chest, back, right and left torso, abdominogenital region, buttocks, right posterior thigh, left thigh, bilateral lower legs, right inner ankle, and left medial foot. The lesions were multiple and scattered, characterised by macules, vesicles, and papules with dry scabs in some areas, associated with a moderate degree of pain, without any drainage, and with intact peri-wound areas (Fig. 1). The pain associated with the lesions resolved over the next 4 days. He was also diagnosed with generalised progressive macular hypomelanosis secondary to HIV infection. The laboratory investigations conducted on that day are presented in Table 1.

Skin lesions at admission day 1. A Face. B Bilateral lip. C Upper chest. D Right upper chest. E Right arm. F Right forearm. G Abdomen. H Right leg. I Left leg

A new diagnosis of syphilis was made, and a monkeypox polymerase chain reaction (PCR) test was performed. The patient was started on oral antiretroviral drugs, including bictegravir, emtricitabine, and tenofovir, and continued to receive intravenous azithromycin and ceftriaxone.

On day 2 of admission, intravenous acyclovir injection was added to his treatment plan because of a skin rash associated with moderate pain. Chest radiography showed no interval change compared to the prior examination. Over the next few days, the patient became saturated with room air and was comfortable with no new acute symptoms, shortness of breath, or pain. The skin lesions appeared to be more vesicular, and some of them were crusting; hence, they were suspected to be shingles. The patient’s blood and sputum cultures were negative for any pathological organisms. Intramuscular injection of benzathine penicillin G was administered for syphilis.

The following day (day 5), the results of the monkeypox PCR test were confirmed to be positive. The skin lesions appeared fragile, characterised by papules and vesicles, with no associated pain (Fig. 2). The patient continued to be in isolation with airborne, contact, and droplet precautions in place, and an order was placed for tecovirimat, a Food and Drug Administration (FDA)-approved drug for treating smallpox. He was additionally prescribed empirical oral sulfamethoxazole/trimethoprim. Azithromycin and acyclovir were then discontinued.

Skin lesions at admission day 3. A, B Face. C Nose. D Bilateral hands. E Right forearm. F Left foot

Over the next few days, the patient’s skin lesions progressed to multiple lesions, disseminated with vesicular, pustulous character, and crusting was noticed at some sites (Figs. 3 and 4). In addition, he reported feeling better, and his physical examination findings were unremarkable. The patient was well saturated in room air, with oxygen supplementation as needed to maintain an oxygen saturation level above 92%. Another dose of benzathine penicillin G intramuscular injection was administered, but tecovirimat was yet to be administered.

Skin lesions at admission day 5. A Face. B Posterior neck. C Right upper chest. D, E, F Back. G Right torso. H Left torso. I Sacrum and buttocks

Skin lesions at admission day 5. A Left forearm. B Right hand. C Right thigh. D Left thigh. E Left lateral thigh. F Right leg. G Right inner ankle. H Left leg. I Left foot

On day 11, the patient was discharged from the hospital against medical advice. Upon leaving, the patient was instructed to keep himself covered and wear a mask. The patient’s vital signs were stable, and no drainage was noted in any of the lesions. The Infectious Diseases Department and the government were notified.