Multi-organ clinical manifestations of Mpox: an umbrella review of systematic reviews.

BACKGROUND: Mpox is a severe viral zoonosis that has emerged as a public health concern due to its potential for human-to-human transmission and severe illness. Understanding its clinical manifestations is crucial for effective management and control. Several systematic reviews have assessed various manifestations of Mpox. This umbrella review synthesizes evidence on Mpox's manifestations across different organ systems. METHOD: We conducted an umbrella review, adhering to Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on systematic reviews of Mpox manifestations. We performed a literature search up to 25th September 2023, in databases like PubMed, Embase, and Web of Science. We included systematic reviews of observational studies, case reports, case series, or RCTs reporting any manifestations of Mpox in humans, focusing on a global scope. AMSTAR 2 was used to evaluate the quality of systematic reviews, and data has been synthesized in narrative and tabular manners. RESULTS: A total of 25 systematic reviews were included, uncovering diverse manifestations of Mpox, such as cutaneous, cardiovascular, oral, ophthalmic, gastrointestinal, respiratory, and pregnancy-related. Cutaneous manifestations (up to 100%) were the most prevalent, featuring lesions and rashes. Constitutional symptoms of viral illness were reported in ~ 60% to > 85% of the cases. Significant respiratory symptoms were present in ~ 50% of cases overall. Headaches were the leading neurological symptom present in > 30%. Symptoms of gastrointestinal involvement ranged from 39% (oral lesions) with decreasing frequency to low diarrhea at ~ 5%, with proctitis percentages ranging from high teens to mid-twenties. Ophthalmic manifestations (6% but with wide variations among studies). Many primary studies included in the systematic reviews consisted of case reports and case series. A wide range of manifestations across different organ systems was observed. Negative outcomes for pregnancies were reported, but evidence is limited. Adverse cardiovascular and neurological outcomes were identified, though only a few studies provided insights into these findings. CONCLUSION: Mpox exhibits diverse manifestations, impacting multiple organ systems, with substantial variations. The findings highlight the importance of ongoing, nuanced, and region-specific research and management strategies for Mpox. The reliance on case reports and series underscores the need for more high-quality, long-term studies to deepen our understanding and management of this significant public health concern.

Reactive Lobular Panniculitis in the Setting of Mpox (Monkeypox) Infection.

ABSTRACT: Mpox, previously referred to as monkeypox, was recently deemed a public health emergency in 2022. Our understanding of potential secondary cutaneous manifestations in the setting of this infection is still evolving. We report a rare case of a man who presented with erythematous, painful subcutaneous nodules on his extremities in the setting of recent mpox infection. Biopsy of a lesion from the lower legs revealed a lobular panniculitis with lupus panniculitis-like features on pathology. He was ultimately diagnosed with a unique case of reactive panniculitis secondary to mpox.

Caso probable de síndrome de reconstitución inmune por mpox en una persona con inmunosupresión avanzada por VIH / Probable case of mpox immune reconstitution inflammatory syndrome (IRIS) in a person with HIV disease

Se presenta el caso clínico de persona viviendo con VIH, con mala adherencia a tratamiento, sin vacunación previa para mpox, que evolucionó con un cuadro clínico probable de síndrome de reconstitución inmune posterior a reinicio de TAR, debido a la progresión de las lesiones cutáneas. Recibió tratamiento con tecovirimat por siete días, con evolución clínica favorable. Corresponde al primer caso reportado que recibió terapia con tecovirimat en Chile.

We report a clinical case of a person living with HIV with poor adherence to treatment, no previous mpox vaccination, who had a probable mpox syndrome immune reconstitution after restarting ART, due to worsening of skin lesions. He received treatment with tecovirimat for 7 days, clinically improved and was discharged in good condition. We reported this first clinical case that received tecovirimat in Chile.

[A 19-year-old male migrant with urethritis and vesicular rash]. / Un migrant de 19 ans consulte pour une urétrite et une éruption vésiculeuse.

We report the case of a 19-year-old Malian patient, who presented with urethritis and a vesicular rash during the summer of 2022, following a probable heterosexual intercourse. The epidemic context among the male homosexual population and the clinical picture without genital lesions or lymphadenopathy allowed us to discuss both chickenpox and mpox, the latter being finally confirmed by the detection of Monkeypox virus DNA from vesicular fluid.

Severe mpox in patients with advanced AIDS: long-term disease and fatal outcome.

Herein, we report two cases of severe mpox in patients with advanced acquired immunodeficiency syndrome from Brazil who developed atypical lesions and prolonged illness, one of whom had a fatal outcome. Both patients experienced serious complications involving the perianal and genital regions and prolonged disease with persistent viremia.

Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients.

BACKGROUND: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. CASE PRESENTATIONS: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. CONCLUSIONS: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.

Transverse myelitis associated with Mpox infection.

Neurologic manifestations of mpox (monkeypox) infection are common. Rarely, transverse myelitis has been associated with mpox infection. We describe a case of longitudinally extensive transverse myelitis in a patient with recently diagnosed mpox, presenting as acute flaccid paraplegia. The patient underwent an extensive work-up that included serological and cerebrospinal fluid (CSF) testing and magnetic resonance imaging (MRI). They were treated with tecoviromat, high dose steroids, and intravenous immunoglobulin, followed by plasma exchange. Despite these interventions, there was minimal neurologic improvement. This case underscores the importance of instituting measures designed to prevent mpox infection, including public education initiatives.

CROI 2023: Tuberculosis and Infectious Complications in Persons With HIV.

Novel implementation strategies to increase uptake and adherence to tuberculosis (TB) preventive therapy hold promise for reducing TB incidence in persons with HIV in high-burden settings. In persons who develop drug-susceptible TB, progress to shorten TB treatment continues to be made with the introduction of new drugs and novel treatment strategies that could allow for treatment shortening to 2 months for most people. A global case series provided powerful evidence that mpox should be considered an HIV-related opportunistic infection given its severe manifestations and poor outcomes. Studies of TB and infectious complications in people with HIV presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized herein.

Mpox Infection and Sexually Transmitted Infections: A Cross-Sectional Study from a Secondary Hospital in the May-September 2022 International Outbreak.

The aims of this study were to describe the characteristics of patients infected by mpox in our setting, to determine the prevalence of mpox in samples that are classically used for diagnosing sexually transmitted infections (STIs) such as anal, urethral, pharyngeal, and urine, and to assess the prevalence of coinfection with STIs in the same samples. A cross-sectional study was conducted, collecting all confirmed cases of mpox between June and July 2022 using polymerase chain reaction. Sociodemographic data, HIV and other STI status, and prevalence of mpox and STIs in urethral, anal, pharyngeal, or urine samples were collected. Data from 22 patients were extracted, all of whom were men who have sex with men (MSM) and 54.5% were previously HIV positive. The median age was 43 years. All the skin samples were positive for mpox, followed by anal samples (n = 10, 45.5%). Mpox was isolated in 2 or more samples simultaneously in 12 (54%) cases. Nine (41%) patients were positive for an STI and four of them had more than one STIs (18.2%). Human mpox has been epidemiologically significant among MSM. Mpox should be investigated not only in skin lesions but also in samples classically used for STIs. Mpox, such as other STIs, shares ways of transmission and coinfection may be underdiagnosed.

Neurological Manifestations of Coronavirus Disease 2019 and Mpox in Pediatric Patients and Their Management: A State-of-the-Art Systematic Review.

BACKGROUND: There is an increasing number of cases being reported of neurological manifestations of Coronavirus disease 2019 (COVID-19) infection and Monkeypox (Mpox), both during the course of the infection and as a presenting symptom. We aim to review the neurological manifestations of COVID-19 and monkeypox in pediatric patients and their management. METHODS: We conducted a systematic review that included cohort studies and case series or reports involving a pediatric population of patients with a confirmed COVID-19 or Mpox infection and their neurological manifestations. We searched the following electronic databases: PubMed, EMBASE, and Scopus. RESULTS: From 1136 articles identified, 127 studies were included. Headache, stroke, Guillain-Barré syndrome, seizure, nerve palsies, and multisystem inflammatory syndrome in children were the most common neurological symptoms caused by COVID-19, whereas encephalitis was commonly seen in patients with Mpox. Rare neurological manifestations of COVID-19 included cerebral venous sinus thrombosis, plexopathies, demyelinating disorders, encephalitis, etc., and rare neurological manifestations of Mpox included headache. CONCLUSIONS: Our review highlights the importance of investigating possible neurological manifestations and closely monitoring these patients to develop a better understanding of the treatment strategies that can be adopted.

Otolaryngologic manifestations among MPOX patients: A systematic review and meta-analysis.

PURPOSE: MPOX has numerous otolaryngologic presentations that have been recognized as clinically important, especially with the onset of the 2022 outbreak. However, how these features vary across region and outbreak have yet to be elucidated or supported by meta-analysis. The objective of this study is to identify the otolaryngologic manifestations of MPOX across previous and current outbreaks and among endemic and non-endemic regions. BASIC PROCEDURES: Data sources of MEDLINE (PubMed), the Cochrane Library, Scopus, Embase, Web of Science, Google Scholar, and OpenGrey were searched through August 2022. All observational studies reporting data on laboratory-confirmed MPOX patients with otolaryngologic symptoms were included. Two authors independently performed the screening process while a third resolved disagreements. Data were extracted into a structured form by two authors independently. We performed a meta-analysis of the prevalence of otorhinolaryngologic symptoms using MetaXL software (version 5.3) under a random-effects model. MAIN FINDINGS: 38 studies with 5952 patients were included. The four most prevalent manifestations were headache at 31 % (95 % CI [0.16-0.49], I 2  = 99 %), sore throat at 22 % (95 % CI [0.09-0.37], I 2  = 99 %), cough at 16 % (95 % CI [0.05-0.30], I 2  = 99 %), and cervical lymphadenopathy at 10 % (95 % CI [0.01-0.26], I 2  = 100 %). Otolaryngologic features were more prevalent in previous outbreaks as compared to the 2022 outbreak including 37 % prevalence of headache (95 % CI [0.11-0.66], I 2  = 100 %), 33 % prevalence of cough (95 % CI [0.21-0.47], I 2  = 98 %), 27 % prevalence of sore throat (95 % CI [0.07-0.53], I 2  = 99 %), 15 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.428], I 2  = 100 %), 13 % prevalence of oral ulcers (95 % CI [0.02-0.30], I 2  = 99 %), 6 % prevalence of oral exanthem (95 % CI [0.00-0.17], I 2  = 99 %), 5 % prevalence of dysphagia (95 % CI [0.00-0.18], I 2  = 99 %), and 5 % prevalence of tonsillar signs (95 % CI [0.00-0.13], I 2  = 99 %). Features that were more prevalent in endemic areas versus non-endemic areas include 27 % prevalence of cough (95 % CI [0.14-0.41], I 2  = 99 %), 15 % prevalence of oral ulcers (95 % CI [0.02-0.36], I 2  = 99 %), 6 % prevalence of tonsillar signs (95 % CI [0.00-0.18], I 2  = 99 %), and 19 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.48], I 2  = 100 %), while the only feature more prevalent in non-endemic areas was headache with a prevalence of 36 % (95 % CI [0.24-0.47], I 2  = 96 %). PRINCIPAL CONCLUSIONS: In this systematic review and meta-analysis, four symptoms - headache, sore throat, cough, and cervical lymphadenopathy - were found to be the most prevalent otolaryngologic features of MPOX. Otolaryngologic manifestations of MPOX were more pronounced in prior outbreaks and in endemic areas as compared to the 2022 outbreak and non-endemic areas. These findings may aid MPOX recognition in an otolaryngology setting.

Risk factors for mortality and clinical presentation of monkeypox.

OBJECTIVES: To describe risk factors for mortality and clinical characteristics in patients with mpox infection at a reference hospital in Mexico. DESIGN: A prospective cohort study was conducted from September to December 2022 at Hospital de Infectología La Raza National Medical Center. METHODS: Study participants were patients that met operational definition of confirmed case of mpox according to WHO criteria. Information was obtained through a case report form that included epidemiological, clinical, and biochemical information. The follow-up period was from initial evaluation for hospitalization until discharge due to clinical improvement or death. Written informed consent was obtained from all participants. RESULTS: Seventy-two patients were included in the analysis, 64 of 72 (88.9%) were people with HIV (PWH). Of the total of patients 71 of 72 (98.6%) were male, with a median age of 32 years old [95% confidence interval (CI), interquartile range (IQR) 27-37]. Coinfection with sexually transmitted infections was reported in 30 of 72 (41.7%). The overall mortality was five of 72 (6.9%). The incidence of mortality rate in PWH was 6.3%. Median days from onset of symptoms to death from any cause during hospitalization was 50 days (95% CI, IQR 38-62). Risk factors for mpox mortality in the bivariate analysis were CD4 + cells count ≤100 cells/µl at the time of assessment RR 20 (95% CI, IQR 6.6-60.2) ( P  < 0.001), absence of antiretroviral therapy RR 6.6 (95% CI, IQR 3.6-12.1) ( P  = 0.001) and ≥50 skin lesions at presentation RR 6.4 (95% CI, IQR 2.6-15.7) ( P  = 0.011). CONCLUSIONS: The clinical presentation between PWH and non-HIV patients was similar in this study, however, reported mortality was associated with advanced-HIV disease.

Otolaryngologic manifestations of Mpox: the Atlanta outbreak.

BACKGROUND: In 2022, Mpox (MPX) has become clinically relevant as otolaryngologists are evaluating this exotic disease process due to its many otolaryngologic manifestations. AIMS/OBJECTIVE: To characterize our cohort of otolaryngology-relevant MPX confirmed cases. MATERIALS AND METHODS: A descriptive case series was performed via retrospective review. Adult patients who underwent inpatient or emergency department otolaryngology consultation at an Emory University-affiliated tertiary care level hospital for MPX were included. RESULTS: Seven patients (age 18-58 years; median 32 years) were identified. All patients were male. Six patients (86%) were black and six patients (86%) were HIV positive with varied immunocompetence. Otolaryngology was consulted for lymphadenopathy (n = 2), pharyngeal involvement (n = 1), and airway evaluation (n = 4). All 6 patients with active MPX developed the classic rash, which developed after oropharyngeal symptoms in 3 patients. Three patients had laryngeal involvement. CONCLUSION: MPX manifests with symptoms requiring otolaryngology expertise, especially when the airway is involved. Infectious disease consultation is key. Mpox can be identified with a specific constellation of demographic identifiers and physical exam findings, which is key to determining appropriate treatment and protection for the consulting otolaryngologist. SIGNIFICANCE: This is the first otolaryngologic study of Mpox and first description of Mpox laryngeal involvement.