Authors: Sheliza Halani (From the ∗Department of Medicine, University of Toronto; †Division of Infectious Diseases, Unity Health Toronto), Sean Cai (From the ∗Department of Medicine, University of Toronto; ‡Division of Cardiology), Catherine Zanoria (†Division of Infectious Diseases, Unity Health Toronto), Juan Carlos Monge (From the ∗Department of Medicine, University of Toronto; ‡Division of Cardiology), Sharmistha Mishra (From the ∗Department of Medicine, University of Toronto; †Division of Infectious Diseases, Unity Health Toronto; §MAP Centre for Urban Health Solutions, St. Michael's Hospital, Toronto), Philippe Brouillard (¶Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Montréal; ∥Département de médecine, Université de Montréal, Montréal), Cécile Tremblay (¶Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Montréal; ∥Département de médecine, Université de Montréal, Montréal; ∗∗University of Montreal Hospital Centre (CRCHUM)–Research Centre, Montréal, Quebec, Canada), Ana Isabel Pinho (††Department of Cardiology, São João University Hospital Centre, Porto, Portugal), Guillermo Rodriguez-Nava (‡‡Stanford University School of Medicine, Stanford), Joseph David Cooper (‡‡Stanford University School of Medicine, Stanford; §§Santa Clara Valley Healthcare, San Jose, CA), Supriya Narasimhan (‡‡Stanford University School of Medicine, Stanford; §§Santa Clara Valley Healthcare, San Jose, CA), Peter Kadlecik (¶¶Mid-Atlantic Permanente Medical Group, Rockville, MD), Shreya S. Khera (†Division of Infectious Diseases, Unity Health Toronto; §MAP Centre for Urban Health Solutions, St. Michael's Hospital, Toronto), Darrell H. S. Tan (From the ∗Department of Medicine, University of Toronto; †Division of Infectious Diseases, Unity Health Toronto; §MAP Centre for Urban Health Solutions, St. Michael's Hospital, Toronto; Institutes of ∥∥Medical Science; ∗∗∗Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada)
Categories: Original Study
Source: Sexually Transmitted Diseases
Authors: Sheliza Halani, Sean Cai, Catherine Zanoria, Juan Carlos Monge, Sharmistha Mishra, Philippe Brouillard, Cécile Tremblay, Ana Isabel Pinho, Guillermo Rodriguez-Nava, Joseph David Cooper, Supriya Narasimhan, Peter Kadlecik, Shreya S. Khera, Darrell H. S. Tan
Monkeypox virus is a DNA virus in the orthopoxvirus family, and a multicountry outbreak was declared a Public Health Emergency of International Concern both in 2022 and 2024. Myocarditis is a known complication of many viral infections, and chest pain and electrocardiogram changes may occur from 1 to 4 weeks post-infection. We present 2 clinical cases of mpox-related myocarditis from Canada. We identified 19 additional cases of myocarditis and/or pericarditis in the literature, and data were synthesized with our 2 cases. All 20 patients with available data were hospitalized, 6 of whom were admitted to an intensive care unit. Median time of cardiac symptom onset after initial mpox symptom onset was 5 (range, 0–14) days, elevated troponin was present in 19 of 19 cases (range, 165–21,200 ng/L), arrhythmias were described in 1 patient with Mobitz type 1 and 2 atrioventricular blocks, and echocardiograms showed reduced ejection fraction in 4 of 15 patients. There were no deaths reported. Management of mpox involves symptom control and anti-inflammatories. Recent trials have not shown benefit of tecovirimat compared with placebo in shortening time to lesion resolution; however, in this article, we discuss nuances regarding antivirals in the setting of mpox-related myocarditis.
Disease related to monkeypox virus (MPXV), a zoonotic DNA virus within the orthopoxvirus family, was declared a public health emergency of international concern in 2022 after a multicountry outbreak.^12^ From January 1, 2022, to January 19, 2025, 124,753 laboratory-confirmed mpox cases and 272 deaths have been reported globally.^3^ A majority of mpox cases since the beginning of the 2022 global outbreak have occurred in gay, bisexual, and other men who have sex with men; however, in 2023 and 2024, heterosexual transmission has increased.^45^ Myocarditis is a recognized complication of several systemic viral infections, but little is known about mpox myocarditis due to the paucity of cases. We present 2 clinical cases of mpox myocarditis and situate them alongside 19 cases of mpox myocarditis, myopericarditis, and pericarditis in the literature, focusing on the timeline and variability of cardiac manifestations, laboratory radiographic findings, management, and outcomes. We discuss epidemiology, manifestations, and diagnosis of mpox, as well as a brief overview of myocarditis, mpox management, and mpox prevention.
An individual in their 20s, assigned male sex at birth, and using daily tenofovir disoproxil fumarate-emtricitabine as HIV preexposure prophylaxis (PrEP) presented to the emergency department (ED) with a 6-day history of fevers reaching 38°C, fatigue, sweats, and groin adenopathy. There was an erythematous papular rash in the pubic region and penis, with associated phimosis and erythematous papular lesions on the neck, right hand, and left lower extremity. Eight days before symptom onset, they had sex with 4 new partners, including insertive and receptive anal sex with inconsistent condom use. They received azithromycin 5 days prior, as a partner had tested positive for chlamydia, and received one 2.4 M unit dose of benzathine penicillin treatment for early latent syphilis (rapid plasma reagin, 32) 1 month prior. Mpox vaccination status was not documented. An extensive infectious workup was performed including mpox testing by polymerase chain reaction (PCR) on blood, urine, and swabs of the throat, nasopharynx, and multiple skin lesions. The patient was discharged from the ED with close follow-up.
On the seventh day of symptoms, the patient noted progressive phimosis, new sores in the mouth, blistering of groin lesions, ongoing sweats and chills, and progressive fatigue. They also noted nonpositional chest tightness and dyspnea. They returned to the ED, and the troponin, which had been normal at the previous visit, had risen to 178 ng/L, and then peaked at 306 ng/L 7 hours later. An electrocardiogram (ECG) showed sinus rhythm with minimal ST elevation in lead II. On examination, there were erythematous papules and pustules on the extremities and face. Electrolytes, creatinine, white blood cell count, and liver enzymes were within normal limits. The patient was admitted with a working diagnosis of mpox infection with myocarditis. Given erythema of the pubic region and possible concomitant bacterial cellulitis, intravenous cefazolin was started. Cardiology consultation was performed, and they offered a differential diagnosis of mild myocarditis, stress cardiomyopathy, or demand ischemia; acute coronary syndrome was thought to be less likely given ECG findings and lack of risk factors.
Naproxen was initiated as an anti-inflammatory, and oral tecovirimat 600 mg twice daily for 14 days was initiated the subsequent day. Ultrasound of the groin showed multiple hypoechoic lymph nodes in both inguinal regions, favored to be reactive with no abscesses. The chest x-ray result was normal. On the 10th day of symptoms (third day of hospital admission), the initial mpox PCR testing demonstrated MPXV (clade II) in all the tested specimens. Hepatitis B surface antigen, hepatitis C serology, fourth-generation HIV antigen/antibody testing, SARS-CoV-2 PCR, blood cultures, urine culture, herpes simplex virus (HSV)-1/HSV-2/varicella zoster virus PCR from a perineal swab, throat swab for gonorrhea/chlamydia nucleic acid amplification testing, and rectal swab culture for gonorrhea were all negative. Syphilis rapid plasma reagin was stable compared with a month prior, at 32. Creatine kinase (CK) was 85 U/L, erythrocyte sedimentation rate was 31 mm/h, and C-reactive protein (CRP) was 55.2 mg/L. Transthoracic echocardiogram showed normal left ventricular function (ejection fraction [EF], 64%), no regional wall motion abnormalities, mild eccentric left ventricular hypertrophy, and severely dilated left atrium. There was no pericardial effusion. They were discharged on the fourth hospital day given clinical improvement and normalization in troponin. They were prescribed oral cephalexin to complete a total 7-day course of antibiotics, the remainder of the course of tecovirimat, and naproxen as needed. The patient had some residual exertional dyspnea and chest tightness on the sixth day after discharge, with a troponin of 64 ng/L; however, they were asymptomatic by approximately 1 month after initial symptom onset.
A cisgender man in his 30s on emtricitabine/tenofovir disoproxil fumarate for HIV PrEP presented with penile and scrotal blister-like lesions, and pelvic lymphadenopathy 4 days after last sexual activity with a male partner. Thereafter, he developed headache and 2 days of fever. He had not previously received mpox vaccination. On day 4 of symptoms, he presented to primary care, and a penile lesion swab was positive for HSV-2 and MPXV by PCR. He was treated with valacyclovir. He had development of rash on the extremities, trunk, back, and axilla. On approximately day 11 of illness, he presented to the ED with difficulty urinating, requiring placement of a urinary catheter. Troponin I was elevated at 833 ng/L, CK was 237 U/L, and CRP was 36.3 mg/L. He did not experience any dyspnea, chest pain or heaviness, or palpitations, and the result from ECG was normal. In conjunction with cardiology, viral myocarditis was the leading diagnosis. Brain natriuretic peptide (BNP) was normal. He was prescribed tecovirimat 600 mg orally twice daily for 14 days and was discharged on day 13 of illness (48 hours after admission) with removal of urinary catheter before discharge. Syphilis serology, HIV Ag/Ab, and urine gonorrhea/chlamydia testing were negative.
At an outpatient visit on day 17, he had brown macular lesions on the arms, chest, and back and one erythematous papule on the chest, which was positive for MPXV by PCR. Repeat troponin and CK on day 17 were normal. The result of an outpatient echocardiogram done on day 31 was normal.
A literature search was initially conducted using PubMed in August 2022 and updated on January 29, 2025, using search terms related to myopericarditis, myocarditis, pericarditis, mpox, and monkeypox. We further reviewed bibliographies of included articles, and relevant review articles were identified. We included original cases and excluded other reviews that synthesized cases that we had already identified. We identified 21 total cases of mpox-associated myocarditis, pericarditis, and/or myopericarditis including the 2 cases presented previously (Table 1).^4678910111213141516171819^ Cases have been described in Canada, the United States, Puerto Rico, Portugal, Spain, Italy, and France. These include 1 case of pericarditis alone, 12 cases of myocarditis alone, 5 cases of myopericarditis, and 3 cases of clinically suspected myocarditis. Patients ranged between 21 and 51 years of age, and all were assigned male sex at birth. All 20 patients where data were available were hospitalized (range, 2–19 days), and at least 6 were admitted to an intensive or coronary care unit or intermediate care unit. Four patients were living with HIV, and 5 were using HIV PrEP.
Median time to cardiac symptom onset after initial mpox symptom onset was 5 days (range, 0–14 days). Chest discomfort was noted in 17 of 20 patients and dyspnea in 6 of 20 patients. Where data were available, elevated troponin was present in 19 of 19 cases of myocarditis/myopericarditis ranging from 165 to 21,200 ng/L. Where data were available, CRP ranged from 9.3 to 154.5 mg/L. Electrocardiograms in the myocarditis/myopericarditis cases included the diffuse or territorial ST changes in 7 of 18 cases, T-wave inversions in 2 of 18, nonspecific changes in 2 of 18, sinus tachycardia in 3 of 18, and elevated PR segment in aVR lead and depressed PR in peripheral and thoracic leads in 1 of 18, and the ECG results were normal in 7 of 18 cases. Arrhythmias were only described in one report, in which the patient with the PR changes described previously developed Mobitz type 1 and 2 atrioventricular blocks, which required atropine and dopamine, without cardiac pacing.^10^ Echocardiogram findings in the myocarditis and myopericarditis cases included the reduced EF in 4 of 15, and segmental hypokinesis or akinesia in 2 of 15, and at least 2 patients had a pericardial effusion. In 10 cases where cardiac magnetic resonance imaging (MRIs) were performed, there were gadolinium enhancement consistent with necrosis, myocardial edema/injury, and/or acute myocarditis and/or myopericarditis.
Eight patients received tecovirimat, 7 received anti-inflammatories (high-dose acetylsalicylic acid, naproxen, or ibuprofen), 1 received “anti-aggregation medication,”^8^ 5 received colchicine, and 5 received at least one of an antihypertensive, β-blocker, and/or an angiotensin-converting enzyme inhibitor. Two of the 8 patients who received tecovirimat were those described previously (cases 1 and 2). Symptom recovery information is available for 9 6 had symptom recovery within 1 to 3 days of hospital admission; 2 had symptom recovery when assessed in follow-up at approximately 1 and at 1.5 months, respectively; and 1 had recovered before discharge on day 19 (but unclear exact date of symptom resolution). Follow-up MRIs were done in 2 cases, at 4 and 8 weeks, respectively, which both showed normal findings.^78^ A patient who had reduced EF showed improvement on a day 9 echocardiogram, and his EF ultimately normalized.^10^ There have been no known deaths from mpox-related myocarditis or pericarditis.
One case has been reported of mpox with elevated creatinine phosphokinase, and a separate case of mpox with atrial fibrillation has also been reported, but the details of these cases are not described further here as the patients were not diagnosed with myocarditis.^2021^
Monkeypox virus is classified into clades Ia, Ib, IIa, and IIb.^22^ Clade I MPXV is seen predominantly in Central Africa, with fewer cases reported in other countries related to travel.^22^ The multicountry outbreak that began in 2022 was driven by clade II MPXV (previously called the West African clade).^22^ Case fatality rate has been reported to be higher with clade I mpox infection compared with clade II,^23^ and there is a 56.6% increased risk (although not statistically significant) of hospitalization with mpox in individuals living with HIV compared with individuals who are HIV negative.^24^
The clinical presentation of mpox involves evolution of skin lesions through 4 stages, which are macules, papules, vesicles, and papules, and thereafter scabs develop which fall off when the skin heals.^25^ Individuals can present with prodromal symptoms such as include fever, lymphadenopathy, malaise, and headache.^25^ However, the presentation of mpox can involve an atypical evolution of lesions, lesions at asynchronous stages, cutaneous lesions in the absence of a prodrome or systemic symptoms, and/or anogenital lesions or proctitis alone.^2627^ Manifestations may be subtle in the setting of prior vaccination or infection.^28^ Other associated symptoms can include pharyngitis, oral lesions, cervical lesions, or vulvar disease.^2529^ Rarer complications of mpox are keratitis; myocarditis; epiglottitis; peritonsillar abscess; pneumonitis; neurologic complications such as encephalitis, or secondary bacterial infections; and hemophagocytic lymphohistiocytosis.^430,31S^
In a patient with myocarditis and mucocutaneous symptoms of mpox with compatible epidemiologic risk factors, the literature collectively suggests that mpox testing via PCR should performed for diagnosis and implementation of other health preventative interventions. Polymerase chain reaction testing for mpox can be performed from swabs of skin lesions if applicable or from swabs collected from nasopharyngeal, rectal, or vaginal mucosa. Blood and urine for mpox PCR testing can also be of value in establishing the diagnosis. In considering whether a patient has mpox, clinicians should also identify opportunities for screening for other sexually transmitted infections (e.g., hepatitis B, hepatitis C, HIV, syphilis, and gonorrhea and chlamydia testing from relevant anatomic sites) and vaccination (e.g., hepatitis B) among those at risk for these conditions.
Myocarditis is an inflammatory disease of the cardiac myocytes and can be an acute, subacute, or chronic condition. Patients with myocarditis have highly variable clinical presentations, ranging from nonspecific symptoms such as fatigue, to chest pain, arrhythmias, heart failure, or even sudden death.^32S^ Among infectious etiologies of myocarditis and pericarditis, viruses are the most common in industrialized countries, at up to 69% in a study from England and Wales.^33S^ Enteroviruses make up 25% of viral myocarditis, and other viral etiologies include adenoviruses, influenza, herpesviruses, among others.^33S,34S^ Infectious etiologies also include bacteria (e.g., Mycoplasma pneumoniae, Chlamydia species including Chlamydia trachomatis, Mycobacterium tuberculosis), fungi, and parasitic causes.^33S,35S,36S^ In South and Central America, Trypanosoma cruzi, the protozoon that causes Chagas disease, is an important etiology to consider.^37S^ Mpox should be a considered as a possible etiology of myocarditis and pericarditis in patients who have a compatible clinical syndrome and/or relevant exposure history.
Timing of cardiac symptom onset after an infectious trigger is variable.^38S^ For instance, after a viral infection, chest pain and ECG changes may occur from 1 to 4 weeks post-infection, followed by heart failure symptoms at 2 weeks to 3 months.^39S^ In the setting of myocarditis from T. cruzi infection, symptoms can occur after a few weeks of parasite inoculation and last weeks to months.^37S^ The criterion standard for diagnosis of myocarditis is endomyocardial biopsy, which can show inflammatory infiltrates within the myocardium associated with myocyte necrosis; however, in clinical practice, endomyocardial biopsy is reserved for sicker patients or situations when etiopathogenesis is relevant for treatment.^32S,39S^ Therefore, diagnosis often relies on clinical suspicion, in combination with supportive biomarkers (troponin, CRP, erythrocyte sedimentation rate); ECG findings, which can include ST-segment deviations, T-wave inversions, and/or cardiac arrhythmias; transthoracic echocardiogram findings such as increased left ventricular thickness and/or decreased function; and typical cardiac MRI abnormalities (based on the updated Lake Louise criteria).^39S–41S^ Other supportive criteria of myocarditis include pericardial effusion or an abnormality in the left ventricular systolic function.^41S^ Because self-limited viral infections remain the most common cause of myocarditis,^42S^ the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases advises against routinely performing viral serologies for workup of infectious causes of myocarditis.^39S^ Management of myocarditis is largely supportive and includes anti-inflammatories as well as assessment and management of cardiac complications.
Management of mpox includes oral and topical analgesia and anti-inflammatories for symptom control, and for patients with proctitis, stools softeners and laxatives can be considered. For mpox, the antiviral drug tecovirimat has shown protection against infection and death in animal models with poxvirus disease.^43S^ The PALM-007 and STOMP trials recently found no benefit of tecovirimat compared with placebo in shortening time to lesion resolution in clade I and II disease, respectively; PALM-007 also showed no mortality benefit.^44S,45S^ Of note, however, the median number of days to symptom resolution in PALM-007 was numerically smaller (7 vs. 8) in the stratum of participants who initiated treatment within 7 days of symptom onset compared with those initiating treatment later.^46S^ Because the median time of cardiac symptom onset after initial mpox symptom onset was 5 (range, 0–14) days in our review, it is conceivable that early initiation of tecovirimat in mpox myocarditis may be helpful. In addition, cidofovir and brincidofovir have been shown in a mouse study to reduce viral replication of clade IIa and IIb MPXV in the respiratory tract of mice,^47S^ although human data are limited. Infectious diseases clinician consultation would be strongly recommended in the setting of mpox-related myocarditis or pericarditis to decide whether any such antivirals should be initiated.^46S,47S^
Regarding mpox prevention, a third-generation replication-incompetent smallpox vaccine containing Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) virus (Imvamune or Jynneos) is authorized for mpox vaccination in many countries.^48S^ Two doses of 0.5 mL administered subcutaneously, 4 weeks apart, are recommended in individuals 18 years or older based on risk of mpox infection from current guidelines.^49S–51S^ Vaccination can be used as mpox postexposure prophylaxis up to 14 days after exposure.^49S–51S^ Myocarditis and/or pericarditis has been reported among persons who received ACAM2000 and Dryvax vaccines.^52S^ With the MVA-BN vaccine, there have been some cardiac adverse events of special interest (AESIs) in vaccine recipients compared with placebo, but no confirmed cases of myocarditis.^53S,54S^ In trials, AESIs occurred in 1.4% of recipients of mpox vaccine and 2.1% of mpox vaccine recipients who previously received smallpox vaccination.^53S^ A retrospective study found an incidence of 3.1 per 1000 doses of AESIs after the MVA-BN vaccine; however, all AESIs were explained by other possible causes.^55S^ Ongoing surveillance to monitor for adverse events related to mpox vaccination is essential.
This review compiles 21 reported cases of myocarditis, pericarditis, and/or myopericarditis presenting as rare complications of mpox infection, including 2 previously unpublished cases. All cases have recovered with no reported deaths. Myocarditis related to mpox vaccination has been described with the ACAM2000 vaccination, with surveillance ongoing. Potential future directions include long-term follow-up of patients to assess residual cardiac symptoms/function and whole genome sequencing to correlate genomic changes with risk of myocarditis and/or pericarditis.