No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Viral Infections
Abstract
Viruses can cause disease in the skin or mucosa by direct infection or, via a systemic infection, produce secondary skin abnormalities. The chapter reviews the viruses associated with skin lesions, outlining the pathophysiology, the clinical features, diagnostic methods and the approaches to treatment. Primary skin infection following direct contact occurs with poxviruses, some herpesviruses and papillomaviruses leading to visible features which may be readily diagnostic. Less specific skin changes are seen with systemic infections, when infection is often via mucosae or inoculation, for example with parvovirus, measles or coronavirus and for these infections, diagnosis will usually involve body fluid analysis.
Introduction: Giant condylomata acuminata (GCA) is a rare presentation of anogenital wart (AGW), invasive locally but does not metastasize. Combination therapy for GCA is suggested based on modalities and experiences. The combination of TCA and podophyllin has showed good efficacy, followed by electrocautery to eradicate warts. Case: A 24-year-old male had a chief complaint of large warts on the base of the penis that had started to bleed for 4 weeks. The initial lesion appeared 8 months prior as a small varucose papule. The patient is unmarried and has history of sexual contact with sex workers. Physical examination showed multiple verrucous papules, flesh-coloured, cauliflower-like shaped, 5 × 2 × 1 cm in size. The patient tested negative for HIV infection. Histopathological examination showed acanthosis, exophytic growth, parakeratosis, and koilocytosis with no signs of malignancy. This patient received a combination of TCA 90% and podophyllin 25% to initially reduce the tumor size, followed by electrocautery to eradicate the remaining lesions. The tumor showed complete clearance. Discussion: There is no definitive evidence that one therapy is superior to completely eliminating warts. Combination therapy of TCA and podophyllin leads to complete wart clearance, followed by electrocautery to destroy smaller warts.
Background
An outbreak of monkeypox virus infections in non-endemic countries was recognised on May 12, 2022. As of September 29, more than 67 000 infections have been reported globally, with more than 3400 confirmed cases in the UK by September 26. Monkeypox virus is believed to be predominantly transmitted through direct contact with lesions or infected body fluids, with possible involvement of fomites and large respiratory droplets. A case of monkeypox in a health-care worker in the UK in 2018 was suspected to be due to virus exposure while changing bedding. We aimed to measure the extent of environmental contamination in the isolation rooms of patients with symptomatic monkeypox.
Methods
We investigated environmental contamination with monkeypox virus from infected patients admitted to isolation rooms at the Royal Free Hospital (London, UK) between May 24 and June 17, 2022. Surface swabs of high-touch areas in five isolation rooms, of the personal protective equipment (PPE) of health-care workers in doffing areas in three rooms, and from air samples collected before and during bedding changes in five rooms were analysed using quantitative PCR to assess monkeypox virus contamination levels. Virus isolation was performed to confirm presence of infectious virus in selected positive samples.
Findings
We identified widespread surface contamination (56 [93%] of 60 samples were positive) in occupied patient rooms (monkeypox DNA cycle threshold [Ct] values 24·7–37·4), on health-care worker PPE after use (Ct 26·1–35·6), and in PPE doffing areas (Ct 26·3–36·8). Of 20 air samples taken, five (25%) were positive. Three (75%) of four air samples collected before and during a bedding change in one patient's room were positive (Ct 32·7–36·2). Replication-competent virus was identified in two (50%) of four samples selected for viral isolation, including from air samples collected during bedding change.
Interpretation
These data show contamination in isolation facilities and potential for suspension of monkeypox virus into the air during specific activities. PPE contamination was observed after clinical contact and changing of bedding. Contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use, and doffing procedures.
Funding
None.
The COVID‐19 pandemic has represented an unprecedented challenge for the humanity, and scientists around the world provided a huge effort to elucidate critical aspects in the fight against the pathogen, useful in designing public health strategies, vaccines and therapeutic approaches. One of the first pieces of evidence characterizing the SARS‐CoV‐2 infection has been its breadth of clinical presentation, ranging from asymptomatic to severe/deadly disease, and the indication of the key role played by the immune response in influencing disease severity. This review is aimed at summarizing what the SARS‐CoV‐2 infection taught us about the immune response, highlighting its features of a double‐edged sword mediating both protective and pathogenic processes. We will discuss the protective role of soluble and cellular innate immunity and the detrimental power of a hyper‐inflammation‐shaped immune response, resulting in tissue injury and immunothrombotic events. We will review the importance of B‐ and T‐cell immunity in reducing the clinical severity and their ability to cross‐recognize viral variants.
Background: The new coronavirus COVID-19 pandemic has had an unprecedented impact on global health and economic growth. A widely used vaccine is the weakened inactivated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus (Sinopharm). Following major SARS-CoV-2 vaccination campaigns, cutaneous symptoms are on the rise.
Methods: This study is a prospective observational study evaluating cutaneous reactions and time of recovery after Sinopharm vaccination. The cases involved were over the age of 18. The data were anonymized. On the registry's vaccine section, we tracked vaccination dates, skin reactions, and recovery times. All respondents who reported only a cutaneous reaction to the first vaccination dose received a follow-up contact asking about a second vaccination dose cutaneous reaction.
Results: The study included 4560 cases. The mean age of all studied cases was 41.2 ± 6.1 years. There were dermatologic complications in 1190 patients (26.1%). There was induration at the injection site in 495 patients (10.9%), urticaria in 210 patients (4.6%), morbilliform eruption in 375 patients (8.2%), flare of skin site in 105 patients (2.3%), and angioedema in 105 patients (2.3%). The mean recovery days in all studied patients were 2.92 ± 0.94 days with a minimum recovery period of 2 days and a maximum of 7 days.
Conclusions: Because Sinopharm's cutaneous reactions are frequently mild and self-limiting, vaccination should not be discouraged based on these findings. If the first vaccine dose creates a cutaneous reaction, there is no need to skip the second dose.
The magnitude of the 2022 multi-country monkeypox virus outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. We aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhoea and chlamydia testing using a monkeypox virus (MPXV) PCR assay, and identified MPXV DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21 to 37 days later, these three men were free of clinical signs and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed, and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak. Findings of unrecognized or asymptomatic monkeypox (MPXV) virus infections with replication-competent virus in humans suggest a lack of recognized, clinical symptoms could play a role in virus transmission and the magnitude of the 2022 MPXV outbreak.
COVID-19 can present with a range of skin manifestations, some of which specific of the pediatric age. The aim of this systematic literature review was to determine the type, prevalence, time of onset, and evolution of cutaneous manifestations associated with COVID-19 in newborns, children, and adolescents, after excluding multisystem inflammatory syndrome in children (MIS-C). PubMed, Tripdatabase, ClinicalTrials, and Cochrane Library databases were searched using an ad hoc string for case reports/series and observational studies, published between December 2019 and February 2022. Study quality was assessed using the STROBE and CARE tools. Seventy-three (49 case reports/series and 24 studies) out of 26,545 identified articles were included in the analysis. Dermatological lesions were highly heterogeneous for clinical presentation, time of onset, and association with other COVID-19 manifestations. Overall, they mainly affected the acral portions, and typically presented a favorable outcome. Pseudo-chilblains were the most common.
Conclusions: Mucocutaneous manifestations could be the only/predominant and early manifestation of COVID-19 that could precede other more severe manifestations by days or weeks. Therefore, physicians of all disciplines should be familiar with them.What is Known:
• A variety of cutaneous manifestations have been reported in association with COVID-19.
• Urticaria, maculopapular, or vesicular rashes can occur at any age, while chilblains and erythema multiforme are more common in children and young patients.
What is New:
• Skin lesions related to SARS-CoV-2 infection often show a peculiar acral distribution.
• Mucocutaneous lesions of various type may be the only/predominant manifestation of COVID-19; they could present in paucisymptomatic and severely ill patients and occur at different stages of the disease.
The newly emerged coronavirus disease 2019 (COVID‐19), induced by a novel strain of the coronavirus family, named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is a rapidly spreading global threat. This virus affects a fair number of tissues in the human body by availing itself of potential target receptors like Angiotensin‐Converting Enzyme 2 (ACE2). Presenting with diverse clinical manifestations, COVID‐19 has raised the urge for extensive research in different medical fields, including dermatology. Developing a comprehensive knowledge of cutaneous manifestations is highly important as it can help us in early diagnosis and better management of the ongoing pandemic. The dermatological presentations of COVID‐19 are classified into main categories of vascular and non‐vascular (exanthematous) patterns. Though not yet fully confirmed, the pathogenesis of these cutaneous presentations has been suggested to be more related to the overactivation of the immune system. In this review, we discuss in detail the clinical features of the diverse skin lesions in COVID‐19 patients and the imperative role of the immune system in their pathogenesis and development. Furthermore, we will discuss the reasons behind the accentuation of skin lesions in COVID‐19 compared to the same virus family predecessors.
Background
In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain.
Methods
This multicentre, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. We enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Participant data were collected by means of interviews conducted by dermatologists or specialists in sexually transmitted infections and were recorded using a standard case report form. Outcomes assessed in all participants with a confirmed diagnosis were demographics, smallpox vaccination, HIV status, exposure to someone with monkeypox, travel, mass gathering attendance, risk factors for sexually transmitted infections, sexual behaviour, signs and symptoms on first presentation, virological results at multiple body sites, co-infection with other sexually transmitted pathogens, and clinical outcomes 14 days after the initial presentation. Clinical outcomes were followed up until July 13, 2022.
Findings
181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0–42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per μL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0–10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs 32 [6], absolute difference 9 [95% CI 8–10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19–44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28–62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practising oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7–13).
Interpretation
In our cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak.
Funding
None.
Objective To characterise the clinical features of monkeypox infection in humans.
Design Descriptive case series.
Setting A regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022.
Participants 197 patients with polymerase chain reaction confirmed monkeypox infection.
Results The median age of participants was 38 years. All 197 participants were men, and 196 identified as gay, bisexual, or other men who have sex with men. All presented with mucocutaneous lesions, most commonly on the genitals (n=111 participants, 56.3%) or in the perianal area (n=82, 41.6%). 170 (86.3%) participants reported systemic illness. The most common systemic symptoms were fever (n=122, 61.9%), lymphadenopathy (114, 57.9%), and myalgia (n=62, 31.5%). 102/166 (61.5%) developed systemic features before the onset of mucocutaneous manifestations and 64 (38.5%) after (n=4 unknown). 27 (13.7%) presented exclusively with mucocutaneous manifestations without systemic features. 71 (36.0%) reported rectal pain, 33 (16.8%) sore throat, and 31 (15.7%) penile oedema. 27 (13.7%) had oral lesions and 9 (4.6%) had tonsillar signs. 70/195 (35.9%) participants had concomitant HIV infection. 56 (31.5%) of those screened for sexually transmitted infections had a concomitant sexually transmitted infection. Overall, 20 (10.2%) participants were admitted to hospital for the management of symptoms, most commonly rectal pain and penile swelling.
Conclusions These findings confirm the ongoing unprecedented community transmission of monkeypox virus among gay, bisexual, and other men who have sex with men seen in the UK and many other non-endemic countries. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema. These presentations should be included in public health messaging to aid early diagnosis and reduce onward transmission.
Background
Persons living with HIV/AIDS have a higher incidence of virus‐related and tobacco/alcohol‐related cancers. This study is the first to estimate the effect of HIV versus HIV‐negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study.
Methods
The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV‐negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age‐standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010.
Results
Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV‐negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV‐positive (N = 30 [81.1%]) than the HIV‐negative veterans with OPSCC (N = 50 [67.6%]), although this difference was not significant (p = .135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk.
Conclusions
The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV‐positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.
Background:
COVID-19 vaccines are currently the most effective interventions in controlling and preventing severe disease progression. Dermatologic reactions to COVID-19 vaccinations may be rare among clinical trial participants. However, since global mass vaccination became a reality, these adverse effects may become more widespread, and different skin reactions would arise.
Objective:
To systematically review the cutaneous adverse reactions in cases subject to vaccines for COVID-19.
Methods:
We searched the PubMed, SCOPUS, Web of Science, and Embase databases, identifying the relevant records and including the eligible observational ones. After assessing the methodological quality of the included studies, we qualitatively and quantitatively synthesized the data regarding the cutaneous side effects experienced by those in the studies' population.
Results:
Overall, 36 studies were included in our systematic review, with the majority being cross-sectional. We found that pain, erythema, and swelling were the most common local side effects, while different types of rashes, urticaria, and angioedema were the most non-local. Few cases also reported experiencing flare-ups of their underlying diseases or developing newly-onset diseases of various etiologies. Our meta-analyses also found that while viral vector-based vaccines are, though insignificantly, safer in injection site complaints, individuals who received mRNA vaccines developed significantly fewer non-local cutaneous adverse events.
Discussion:
Cutaneous reactions to the COVID-19 vaccines are similar to common cutaneous drug eruptions and COVID-19 cutaneous manifestations. However, we believe that further high-quality research is needed to assess better how and why cutaneous reactions occur in different vaccines.
Background:
Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined.
Methods:
We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections.
Results:
We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having <10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported.
Conclusions:
In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.
Importance:
Molluscum contagiosum (MC) is a highly contagious skin condition. Lesions may persist for months to years, and no US Food and Drug Administration-approved medications are currently available in the US.
Objective:
To assess the efficacy and safety of berdazimer gel, 10.3%, a novel topical nitric oxide-releasing medication, in the treatment of MC.
Design, setting, and participants:
This was a multicenter, vehicle-controlled, double-blind, phase 3 randomized clinical trial (B-SIMPLE4) conducted in 55 clinics (mostly dermatology and pediatric) in the US from September 1, 2020, to July 21, 2021. Eligible participants were 6 months or older and had from 3 to 70 raised MC lesions. Patients with sexually transmitted MC or with MC only in the periocular area were excluded.
Interventions:
Patients were randomized to treatment with berdazimer gel, 10.3%, or vehicle gel, applied as a thin layer to all lesions once daily for 12 weeks.
Main outcomes and measures:
The primary efficacy end point was complete clearance of all MC lesions at week 12. Safety and tolerability measures included adverse event frequency and severity, and assessment of local skin reactions and scarring. Data analyses were performed from August 31, 2021, to September 14, 2021.
Results:
A total of 891 participants were randomized, 444 to berdazimer, 10.3% (mean [range] age, 6.6 [0.9-47.5] years; 228 [51.4%] male; 387 [87.2%] White individuals), and 447 to vehicle (mean [range] age, 6.5 [1.3-49.0] years; 234 [52.3%] female; 382 [85.5%] White individuals). In the intention-to-treat population, 88.5% (393 patients) in the berdazimer group and 88.8% (397 patients) in the vehicle group had a lesion count performed at week 12. At week 12, 32.4% (144 patients) in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% (88 patients) in the vehicle group (absolute difference, 12.7%; odds ratio, 2.0; 95% CI, 1.5-2.8; P < .001) with 14.4% (64 patients) of the berdazimer group discontinuing treatment because of MC clearance compared with 8.9% (40 patients) of the vehicle group. Adverse event rates were low. The most common adverse events were application-site pain and erythema, mostly mild in severity. Adverse events leading to discontinuation affected 4.1% (18 patients) of the berdazimer group and 0.7% (3 patients) of the vehicle group. The most common local skin reaction was mild to moderate erythema.
Conclusions and relevance:
Use of berdazimer gel, 10.3%, for MC appears to demonstrate favorable efficacy and safety with low adverse event rates.
Trial registration:
ClinicalTrials.gov Identifier: NCT04535531.
Pemphigus is a rare autoimmune blistering disease, involving potentially life-threatening conditions often requiring immunosuppression. Currently, the COVID-19 pandemic caused by severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection has become a global public emergency. Vaccines are the most effective defense against COVID-19 infection. However, in clinic, there are cases of new onset or flare of pemphigus following COVID-19 vaccination, where vaccines have manifested significantly desirable risk-benefit profiles for patients. Although Rituximab, as first-line therapy, may impair humoral immunity, pemphigus may not predispose to develop COVID-19 infection compared to a healthy population. Conversely, delay or interruption of immunosuppressants probably results in unfavorable clinical outcomes for disease progression. Overall, clinicians should encourage their patients to undergo the vaccination after a comprehensive assessment. The definite association between COVID-19 vaccination and pemphigus remains to be further elucidated. Herein, we provide an overview of the published studies to date on COVID-19 and pemphigus as well as the exploration of their complicated interplay. In addition, we discuss the management strategies for pemphigus patients in this special period, in an effort to more effectively establish a standard treatment paradigm for this particular patient group.
"COVID toes" is the colloquial name of chilblain-like lesions (CBLL) thought to be a sequela of COVID-19 infection. Over two years and roughly 300 publications later, this association remains controversial. Here we summarize key clinical, serological, biological, histological and immunological evidence that supports and rejects this relationship as well as discuss alternate theories underlying CBLL pathogenesis (Table 1).
Various adverse effects particularly cutaneous manifestations associated with different COVID‐19 vaccines have been observed in practice. To evaluate all patients who presented to our tertiary center with skin manifestations following COVID‐19 vaccines injection from September to December 2021. All patients with skin manifestation within 30 days or less following COVID‐19 vaccination were enrolled in our case‐series. All cases included in our study were diagnosed based on clinical and/or histopathological evaluation and all other possible differential diagnoses were ruled out. Twenty‐five individuals including 16 (64%) males and 9 (36%) females with the mean age of 47± 17.62 years (range 18‐91) were enrolled in our study. Twenty‐two (88%) patients developed lesions after Sinopharm vaccine injection and 3 (12%) cases manifested lesions after the AstraZeneca vaccine. Six (24%) patients developed new‐onset lichen planus (LP) and 1 (4%) patient manifested LP flare‐up. Two (8%) individuals developed psoriasis and 1 (4%) case showed psoriasis exacerbation. One (4%) patient developed new‐onset pemphigus vulgaris (PV) and 1 (4%) case experienced a flare of PV lesions. One (4%) patient manifested Pityriasis lichenoides et varioliformis acuta (PLEVA) flare‐up. Other new‐onset cases were as follows: toxic epidermal necrolysis (TEN) (n=1, 4%), bullous pemphigoid (BP) (n=2, 8%), alopecia areata (AA) (n=2, 8%), pytriasis rosea (n=1, 4%), herpes zoster (n=1, 4%), cutaneous small vessel vasculitis (n=1, 4%), erythema multiform (EM) and urticaria (n=3, 12%), and morphea (n=1, 4%). Physicians should be aware of the possible side effects especially cutaneous manifestations associated with COVID‐19 vaccines. This article is protected by copyright. All rights reserved.
Introduction: Acquired epidermodysplasia verruciformis (EV) is a skin disorder that has been described in individuals with perinatally acquired HIV. Many cases have been identified in sub-Saharan Africa in keeping with the epidemiology of HIV infection compared to the rest of the world, where cases are rare. Epidermodysplasia verruciformis skin lesions may undergo malignant transformation. There are few documented cases of malignant transformation of these skin lesions. We describe a patient with an EV-like skin rash who developed cutaneous squamous cell carcinoma (SCC).
Patient presentation: A 25-year-old man, on antiretroviral treatment for 12 years, presented with a generalised skin rash since the age of 11 years, and a 7-month history of a persistent scalp ulcer. He had no history of trauma, radiation or other chronic conditions. Despite an undetectable HIV viral load, he had failed to immune reconstitute (CD4 42 cells/µL). Physical examination revealed a generalised hypopigmented, papular skin rash resembling verruca plana and a 3 cm × 3 cm ulcer with rolled edges on the right parietal region of the scalp. There were no palpable lymph nodes in the head and neck areas. Biopsy of the ulcer revealed moderately differentiated SCC.
Management and outcome: Wide local excision of the lesion was done under local anaesthesia and histological analysis confirmed completely excised moderately differentiated SCC. Further examination four weeks later revealed two, smaller, histologically similar scalp lesions which were completely excised.
Conclusion: Patients with acquired EV require thorough, frequent examination for skin lesions with possible malignant transformation. Early identification of malignant transformation and treatment with surgical intervention is curative.
Background:
The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.
Methods:
We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).
Findings:
We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49).
Interpretation:
COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.
Funding:
UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by the activation of a cytokine storm derived from an excess release of cytokine (interleukin [IL]-6, interferon [IFN] I, C-X-C motif chemokine ligand [CXCL]10, tumor necrosis factor [TNF]-α, macrophage inflammatory protein [MIP]1) due to an uncontrolled immune activation. There has been a fivefold increase in the number of cases of pityriasis rosea during the SARS-CoV-2 pandemic. Using the keywords "pityriasis" and "COVID-19", we carried out a PubMed search, including all articles in the English language published until November 2021. We aimed to investigate the possible connection between SARS-CoV-2 and pityriasis rosea (PR). Pityriasis could be considered an immunological disease due to the involvement of cytokines and chemokines. Our analysis yielded 65 articles of which 53 were not considered; the others (n = 12) concerning the association between PR and COVID-19 were included in our study. We suggest two mechanisms underlying the involvement of the skin in viral infections: (i) viruses directly affecting the skin and/or inducing host immune response thus causing cutaneous manifestations; and (ii) viruses as a possible inducer of the reactivation of another virus. The first mechanism is probably related to a release of pro-inflammatory cytokine and infection-related biomarkers; in the second, several pathways could be involved in the reactivation of other latent viruses (human herpesviruses 6 and 7), such as a cytokine-cytokine receptor interaction, the Janus kinase-signal transducer and activator of transcription signaling pathway, and the IL-17 signaling pathway. We thus believe that a cytokine storm could be directly or indirectly responsible for a cutaneous manifestation. More investigations are needed to find specific pathways involved and thus confirm our speculations.
Although vaccination is widely accepted as an effective method of preventing and controlling the COVID‐19 pandemic, many people are concerned about possible cutaneous side effects which can delay or prevent them from being vaccinated. The objectives of this systematic review were to assess the global prevalence and clinical manifestations of cutaneous adverse reactions following COVID‐19 vaccination. PubMed and Scopus databases were searched for articles published from January 1, 2019, to December 31, 2021, and reference lists for each selected article were screened. Case reports, case series, observational studies, and randomized controlled trials that provided information on cutaneous adverse reactions following COVID‐19 vaccines were included. A total of 300 studies were included in a systematic review of which 32 studies with 946,366 participants were included in the meta‐analysis. The pooled prevalence of cutaneous manifestations following COVID‐19 vaccination was 3.8% (95% CI, 2.7%‐5.3%). COVID‐19 vaccines based on the mRNA platform had a higher prevalence than other platforms at 6.9% (95% CI, 3.8%‐12.3%). Various cutaneous manifestations have been reported from injection site reactions which were the most common (72.16%) to uncommon adverse reactions such as delayed inflammatory reactions to tissue filler (0.07%) and flares of pre‐existing dermatoses (0.07%). Severe cutaneous reactions such as anaphylaxis have also been reported, but in rare cases (0.05%). In conclusion, cutaneous adverse reactions are common, especially in those receiving mRNA vaccines. Most reactions are mild and are not contraindications to subsequent vaccination except for anaphylaxis, which rarely occurs. COVID‐19 vaccination may also be associated with flares of pre‐existing dermatoses and delayed inflammatory reactions to tissue filler. Patients with a history of allergies, pre‐existing skin conditions, or scheduled for filler injections should receive additional pre‐counseling and monitoring. A better understanding of potential side effects may strengthen public confidence in those wary of new vaccine technologies.
Altogether 51 regular female consorts of men attending a venereal disease clinic for genital warts were examined using colposcopy, vaginal cytology and--when needed--surgical biopsy. Abnormal cytological smears were found in 18 out of 49 consorts (37%), which should be compared with 8 out of 124 (6%) matched female controls from a family planning clinic (p less than 0.001). Possibly premalignant lesions, i.e. atypical condylomata and/or frank dysplasia, were found in 14 (27%) out of 51 consorts. The prevalence of abnormal smears or biopsy-proven dysplasia was approximately the same in consorts with and without external warts. These findings call for close attention to the risk of development of cervical dysplasia in female consorts of men with genital warts.
This case report describes 2 umbilicated and ulcerated, skin-colored papules on the genitals, as well as a honey-colored crusted papule on the face.
The largest outbreak of monkeypox in history began in May, 2022, and has rapidly spread across the globe ever since. The purpose of this Review is to briefly describe human immune responses to orthopoxviruses; provide an overview of the vaccines available to combat this outbreak; and discuss the various clinical data and animal studies evaluating protective immunity to monkeypox elicited by vaccinia virus-based smallpox vaccines, address ongoing concerns regarding the outbreak, and provide suggestions for the appropriate use of vaccines as an outbreak control measure. Data showing clinical effectiveness (~85%) of smallpox vaccines against monkeypox come from surveillance studies conducted in central Africa in the 1980s and later during outbreaks in the same area. These data are supported by a large number of animal studies (primarily in non-human primates) with live virus challenge by various inoculation routes. These studies uniformly showed a high degree of protection and immunity against monkeypox virus following vaccination with various smallpox vaccines. Smallpox vaccines represent an effective countermeasure that can be used to control monkeypox outbreaks. However, smallpox vaccines do cause side-effects and the replication-competent, second-generation vaccines have contraindications. Third-generation vaccines, although safer for use in immunocompromised populations, require two doses, which is an impediment to rapid outbreak response. Lessons learned from the COVID-19 pandemic should be used to inform our collective response to this monkeypox outbreak and to future outbreaks.
The World Health Organization declared the global monkeypox outbreak a public health emergency of international concern in July 2022. In response, the American Academy of Dermatology and International League of Dermatological Societies expanded the existing COVID-19 Dermatology Registry to become the "AAD/ILDS Dermatology COVID-19, Monkeypox, and Emerging Infections Registry." The goal of the registry is to rapidly collate cases of monkeypox and other emerging infections and enable prompt dissemination of findings to front-line healthcare workers and other members of the medical community. The registry is now accepting reports of monkeypox cases and cutaneous reactions to monkeypox/smallpox vaccines. The success of this collaborative effort will depend on active case entry by the global dermatology community.
This Medical News article discusses recent European reports of asymptomatic monkeypox virus infections.
Given the current monkeypox virus (MPXV) outbreak in at‐risk men who have sex with men (MSM), clinicians should consider MPXV a differential diagnosis of syphilis, in any patient with a solitary painless genital nodule.
Open in new tabDownload slide
This case series describes the clinical resolution of systemic symptoms and lesions, along with any adverse events, in patients with monkeypox infection who were treated with tecovirimat on a compassionate use basis.
The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the brink. Among several factors that contribute to an increased risk of COVID-19 and progression to exacerbated manifestations, host genetic landscape is increasingly being recognized as a critical determinant of susceptibility/resistance to infection and a prognosticator of clinical outcomes in infected individuals. Recently, several case-control association studies investigated the influence of human gene variants on COVID-19 susceptibility and severity to identify the culpable mutations. However, a comprehensive synthesis of the recent advances in COVID-19 host genetics research was lacking, and the inconsistent findings of the association studies required reliable evaluation of the strength of association with greater statistical power. In this study, we embarked on a systematic search of all possible reports of genetic association with COVID-19 till April 07, 2022, and performed meta-analyses of all the genetic polymorphisms that were examined in at least three studies. After identifying a total of 84 studies that investigated the association of 130 polymorphisms in 61 genes, we performed meta-analyses of all the eligible studies. Seven genetic polymorphisms involving 15550 cases and 444007 controls were explored for association with COVID-19 susceptibility, of which, ACE1 I/D rs4646994/rs1799752, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 showed increased risk of infection. Meta-analyses of 11 gene variants involving 6702 patients with severe COVID-19 and 8640 infected individuals with non-severe manifestations revealed statistically significant association of ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 with COVID-19 severity. Overall, our study presents a synthesis of evidence on all the genetic determinants implicated in COVID-19 to date, and provides evidence of correlation between the above polymorphisms with COVID-19 susceptibility and severity.
To date, a total of seven human coronaviruses (HCoVs) have been identified, all of which are important respiratory pathogens. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global pandemic causing millions of infections and deaths. Here, we summarize the discovery and fundamental virology of HCoVs, discuss their zoonotic transmission and highlight the weak species barrier of SARS-CoV-2. We also discuss the possible origins of SARS-CoV-2 variants of concern identified to date and discuss the experimental challenges in characterizing mutations of interest and propose methods to circumvent them. As the COVID-19 treatment and prevention landscape rapidly evolves, we summarize current therapeutics and vaccines, and their implications on SARS-CoV-2 variants. Finally, we explore how interspecies transmission of SARS-CoV-2 may drive the emergence of novel strains, how disease severity may evolve and how COVID-19 will likely continue to burden healthcare systems globally.
Background: Since May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ form earlier reports.
Methods: We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak.
Results: In total, 185 patients were included. Most cases started with primarily localised homogeneous papules, not pustules, in the probable area of inoculation, whichcould be cutaneous or mucous, including single lesions. Generalised small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalised phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalised, none died. Smallpox vaccination and well-controlled HIV disease were not associated with markers of severity. Contact during sex is the most likely mechanism of transmission. In this outbreak, cases have been described in males having sex with males and are strongly associated with high-risk sexual behaviours. Seventy-six percent of the patients had other sexually transmitted diseases upon screening.
Conclusions: The clinical findings in this outbreak differ from previous findings and highly suggest contact transmission and initiation at the entry site. The characterisation of the epidemiology of this outbreak has implications for control.
Purpose of review:
Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature T-cell malignancy that arises in approximately 5% of carriers of human T-lymphotropic virus type 1 (HTLV-1), but this risk is not random among carriers. We describe recent advance in pathogenesis, risk factors and for early detection of ATL.
Recent findings:
Unraveling ATL molecular genetics has shed light on pathogenesis and provides insights into novel therapeutic targets. Moreover, an important step in improving outcomes is identifying asymptomatic carriers who are at high risk of progression to ATL, which has traditionally relied on quantifying the proviral load (PVL). This can be done by quantifying oligoclonality- and in particular the expanded clone- with molecular and flow cytometric techniques, that can be applied to a clinical setting. Studies using these methods have shown that carriers with oligoclonal populations are at an increased risk of transformation, beyond that that predicted by PVL alone.
Summary:
There is an urgent unmet need for developing novel therapies in ATL in order to improve survival. Recent advances in the molecular and epigenetic landscape of ATL, and the early detection of disease offer the potential to intervene early, before disease becomes aggressive, and to offer tailored therapeutic strategies.
The current monkeypox outbreak reawakens the concern that poxviridae have high potential of zoonotic spillover and for causing pandemic.¹ Much fieldwork and research has been done by healthcare and public health workers in Africa during previous human outbreaks, and their knowledge should inform our global response to the current outbreak. However, unusual clinical presentations now have potential implications in recognizing disease. Infections from poxviridae such as monkeypox have common cutaneous signs that occur early, may be related to periods of transmissibility, and can leave scarring. Therefore, dermatologists will play a key role in recognizing and diagnosing infections, and in educating and preparing front-line healthcare workers for early detection of new cases and clusters of monkeypox.
Background:
Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre.
Methods:
In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak.
Findings:
Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes.
Interpretation:
Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing.
Funding:
None.
