A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: Skin lesion morphology, clinical course, and scarring.

BACKGROUND: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. OBJECTIVE: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. METHODS: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. RESULTS: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. LIMITATIONS: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. DISCUSSION: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.

Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases.

BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.

Inconsistent Collection and Reporting of Gender Minority Data in HIV and Sexually Transmitted Infection Surveillance Across the United States in 2015.

OBJECTIVES: To describe collection and reporting of gender data, including for transgender individuals and other gender minorities, in HIV and sexually transmitted infection (STI) surveillance in the United States. METHODS: We performed a cross-sectional study of the top 50 US jurisdictions in 2015 for incident infections of HIV, gonorrhea, chlamydia, or primary and secondary syphilis. For each jurisdiction, we described gender-reporting options on HIV and STI data collection forms (also called confidential morbidity report forms) and data surveillance reports, which present aggregate data at either the county or the state level. RESULTS: Seventy-one jurisdictions were among the top 50 for at least 1 infection, and we included them. Gender minority categories appeared on 60 of 71 (85%) HIV confidential morbidity report forms and 33 of 70 (47%) STI confidential morbidity report forms, and in 22 of 71 (31%) HIV surveillance reports and 8 of 71 (11%) STI surveillance reports. CONCLUSIONS: Collection and reporting of gender data were suboptimal and inconsistent. Gender minority data were collected more often than reported, suggesting barriers to reporting. Health departments should standardize collection and reporting of gender data in HIV and STI surveillance to better inform prevention and control efforts.

Psoriasis patients are enriched for genetic variants that protect against HIV-1 disease.

An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis.

An open-label study of anakinra for the treatment of moderate to severe hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by sterile abscesses and fistulae predominantly affecting the axillae and groin. Various biologic agents have been attempted for HS, but there is still no definitive treatment. OBJECTIVES: We sought to evaluate the efficacy, safety, and tolerability of anakinra in the treatment of moderate to severe HS. METHODS: Six patients with moderate to severe HS were enrolled in an open-label study with all patients receiving active treatment for 8 weeks with an additional 8 weeks of follow-up off therapy. RESULTS: The 5 patients who completed the 8-week therapy showed a significant mean decrease in their modified Sartorius score of 34.8 points. The physician and patient global assessment of overall activity showed significant reductions between baseline and 8 weeks of therapy: 45.8 points and 35.6 points, respectively. The Dermatology Life Quality Index showed a significant reduction after 8 weeks of treatment with anakinra. Functional T-cell analysis revealed that patients had increased percentages of CD3(+) T cells in lesional skin compared with nonlesional skin before therapy. LIMITATIONS: The limited number of patients and lack of control group are limitations. CONCLUSIONS: Anakinra demonstrated decreased HS disease activity by both objective and subjective measures.

Skin cancer risk in people living with HIV: a call for action.

A diagnosis of HIV poses secondary medical risks to patients, ranging from infections to neoplastic conditions. Regarding skin cancer, these risks extend beyond the well known association with Kaposi sarcoma and include Merkel cell carcinoma, squamous cell carcinoma, and high-risk melanomas. Despite evidence of these risks, knowledge and awareness remain low, among care providers for people living with HIV, individual patients, and even some specialists in dermatology. Crucially, medical organisations do not adequately address this concern, as there is an absence of treatment guidelines for the screening and management of skin cancer for people living with HIV. To continue providing high-quality care for this population, the increased risk of multiple high-risk skin cancers needs to be appropriately recognised by both providers and patients. Accordingly, we call for renewed emphasis on patient education and implementation of improved organisational guidelines for skin cancer screening protocols.

Ulcerative erythematous papules and plaques on the face and lower legs of a man living with HIV: a clinicopathological challenge.

A 44-year-old male presented with a 2-month history of erythematous ulcerative papules and plaques on the scalp, face, and bilateral lower legs. He had a 5-year history of well-controlled HIV on antiretroviral therapy and recurrent syphilis infections. His face had violaceous plaques, while bilateral ankles and calves had ulcerative lesions with necrotic centers and purple borders. The morphologies clinically mimicked pyoderma gangrenosum on the lower extremities and cutaneous lymphoma on the face. Biopsy and reactive rapid plasma reagin confirmed a diagnosis of lues maligna, and the patient was successfully treated with penicillin G benzathine.

Skewed distribution of natural killer cells in psoriasis skin lesions.

Psoriasis is a hyper-proliferative disease of the skin in which immunological mechanisms play a direct pathogenetic role. There have been limited studies of natural killer (NK) cells in psoriasis. The aim of this study was to examine the phenotype of NK cells in skin biopsies and peripheral blood mononuclear cells from patients with psoriasis and healthy controls. CD56(+) CD16(-) and CD56(+) CD16(+) NK cells were isolated from lesional skin, unaffected skin and PBMC of psoriasis patients, and normal skin and PBMC from healthy controls. The expression of CD57, NKG2A and NKG2C was assessed by flow cytometry. NK cells in psoriasis skin lesions were skewed in their expression of CD57, a marker of NK cell maturity, with CD57 expression significantly reduced and NKG2A expression increased on NK cells in lesional and unaffected skin compared to controls. These data suggest that in this patient cohort, NK cells could be isolated from psoriasis lesions and exhibit an immature phenotype.

Melanoma death prevention: moving away from the sun.

This evidence-backed editorial addresses the limitations of solely primary prevention campaigns and outlines the proven efficacy of early detection/secondary prevention strategies with respect to melanoma. It synthesizes experience from several outreach efforts that have resulted in sustained improvements in knowledge and self-skin examination behaviors. Data demonstrate that educational campaigns emphasizing increased knowledge about melanoma and self-screening practices correlate with thinner tumors. The editorial also confronts the lack of data around skin cancer screening per the US Preventative Services Task Force. It explains how we might address the issue to obtain solid evidence to back a recommendation for screening of high-risk populations in the future. Cost-efficacy of skin cancer screening is also addressed. Lastly, lessons learned from other cancers, particularly breast cancer, with respect to successful educational campaign creation and development of an effective cause marketing campaign for advocacy are discussed. Hypothetical ideas for a screening algorithm and for educational/media campaigns are presented with the hope of triggering thoughtful discussion and forward momentum.

Autoinflammation: From monogenic syndromes to common skin diseases.

Autoinflammation is characterized by aberrant regulation of the innate immune system and often manifests as periodic fevers and systemic inflammation involving multiple organs, including the skin. Mutations leading to abnormal behavior or activity of the interleukin 1 beta (IL-1ß)-processing inflammasome complex have been found in several rare autoinflammatory syndromes, for which anticytokine therapy such as IL-1 or tumor necrosis factor-alfa inhibition may be effective. It is becoming clear that features of autoinflammation also affect common dermatoses, some of which were previously thought to be solely autoimmune in origin (eg, vitiligo, systemic lupus erythematosus). Recognizing the pathogenetic role of autoinflammation can open up new avenues for the targeted treatment of complex, inflammatory dermatoses.

Syphilis: recommendations for dermatologists on a resurgent epidemic.

Despite reaching historical lows in the early 2000s, cases of both primary and secondary syphilis and congenital syphilis have increased dramatically in the U.S. over the last decade. In the U.S., the current syphilis epidemic is disproportionately impacting communities that have been historically underserved in medicine. These include men who have sex with men, especially those infected with HIV; people of color; and reproductive-age women with poor access to prenatal care. With syphilis now being more commonly diagnosed in non-STI than STI clinics in all genders, and since primary and secondary syphilis and congenital syphilis present with characteristic mucocutaneous manifestations, dermatologists are in a position to help reduce the advance of this preventable epidemic, by actively considering this diagnosis and incorporating syphilis screening into their practice. Herein, we delineate strategies by which dermatologists can contribute to this critical effort in their roles as clinicians, public health advocates, and researchers. In particular, we discuss the rapidly changing demographics of syphilis, nuances in serologic testing and treatment, strategies to increase public healthcare access and equity in these underserved populations, and research gaps in this field.

Mpox-A Rapidly Evolving Disease.

The 2022 mpox outbreak has rapidly emerged onto the global medical scene while the world continues to grapple with the COVID-19 pandemic. Unlike COVID-19, however, most patients with mpox present with skin findings, the evolving clinical presentation of which may be mistaken for other common skin diseases, particularly sexually transmitted infections. This Special Communication provides an overview of the evolution of mpox skin findings from its initial description in humans in 1970 to the present-day multinational outbreak.

Biologic Therapies in HIV/AIDS Patients with Inflammatory Diseases: A Systematic Review of the Literature.

Biologic therapies have been increasingly developed and used for the treatment of severe inflammatory diseases. However, the safety and efficacy profile of biologic drugs in patients with HIV is not well established as this patient population is historically excluded from clinical trials. We review the available evidence of biologic use in people with HIV. We conducted a systematic review of the literature up to June 29, 2022 and included studies that treated patients with HIV who have inflammatory disease using biologic drugs. Clinical data regarding safety and efficacy were abstracted into tables. One hundred twelve studies were included, and 179 patients were included in our study. Nearly all classes of biologics drugs had a favorable safety profile with minimal or minor adverse events. Anti-CD-20 inhibitors and TNF-alpha inhibitors were associated with opportunistic infections. Transient increase in HIV viral load was noted with use of some agents such as TNF-alpha inhibitors. The quality of evidence is low, restricted to case reports and retrospective reviews. However, the safety profile of biologics observed in these patients with HIV was overall favorable.

Use of canakinumab in the cryopyrin-associated periodic syndrome.

BACKGROUND: The cryopyrin-associated periodic syndrome (CAPS) is a rare inherited inflammatory disease associated with overproduction of interleukin-1. Canakinumab is a human anti-interleukin-1beta monoclonal antibody. METHODS: We performed a three-part, 48-week, double-blind, placebo-controlled, randomized withdrawal study of canakinumab in patients with CAPS. In part 1, 35 patients received 150 mg of canakinumab subcutaneously. Those with a complete response to treatment entered part 2 and were randomly assigned to receive either 150 mg of canakinumab or placebo every 8 weeks for up to 24 weeks. After the completion of part 2 or at the time of relapse, whichever occurred first, patients proceeded to part 3 and received at least two more doses of canakinumab. We evaluated therapeutic responses using disease-activity scores and analysis of levels of C-reactive protein (CRP) and serum amyloid A protein (SAA). RESULTS: In part 1 of the study, 34 of the 35 patients (97%) had a complete response to canakinumab. Of these patients, 31 entered part 2, and all 15 patients receiving canakinumab remained in remission. Disease flares occurred in 13 of the 16 patients (81%) receiving placebo (P<0.001). At the end of part 2, median CRP and SAA values were normal (<10 mg per liter for both measures) in patients receiving canakinumab but were elevated in those receiving placebo (P<0.001 and P=0.002, respectively). Of the 31 patients, 28 (90%) completed part 3 in remission. In part 2, the incidence of suspected infections was greater in the canakinumab group than in the placebo group (P=0.03). Two serious adverse events occurred during treatment with canakinumab: one case of urosepsis and an episode of vertigo. CONCLUSIONS: Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS. (ClinicalTrials.gov number, NCT00465985.)