Yao syndrome: a novel systemic autoinflammatory disease with cutaneous manifestations.

Yao syndrome (YAOS) is a novel systemic autoinflammatory disease linked to the nucleotide-binding oligomerization domain (NOD2) gene. It is characterized by periodic fevers, gastrointestinal (GI) symptoms, arthritis, and dermatitis, among other symptoms. A sparse literature exists on this disease, and little is known about its dermatological manifestations. A review of available literature was performed to characterize the cutaneous manifestations of Yao syndrome. Cutaneous manifestations were documented in 85.7% of patients, with common characteristic descriptions of erythematous patches and plaques involving the face, trunk, abdomen, and extremities. Based on our review of treatment modalities employed for Yao syndrome, prednisone is an appropriate initial approach, with oral sulfasalazine and other disease-modifying antirheumatic drugs serving as appropriate secondary options. YAOS should be considered in the differential diagnosis of patients presenting with a dermatitic rash, especially in the context of concurrent articular symptoms, periodic fever, and GI symptoms.

Paradoxical Psoriasis: An Updated Review of Clinical Features, Pathogenesis, and Treatment Options.

The definition of paradoxical psoriasis (PP) encompasses 2 main scenarios, namely, (i) new-onset psoriasis in patients treated for a different disease and (ii) worsening as well as phenotypical change of pre-existing psoriasis. Originally restricted to the appearance of an untoward psoriasiform reaction under TNF inhibitors, the term has gained new meaning, with the progressive observation of psoriasis-like eruptions also with other medications. Although the conceptual framework of PP has expanded, a molecular and clinicotherapeutic classification is still lacking. In addition, a certain degree of confusion surrounds the correct terminology to indicate these eruptions. In this paper, evidence on the epidemiology, clinical features, pathogenesis, and treatment of PP is reviewed, providing a perspective on possible pathogenesis-driven therapeutic approaches.

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Anti-Herpes zoster vaccination in patients with dermatologic diseases: a position statement from the Italian SIDeMaST group of sexually transmitted, infectious and tropical diseases.

Herpes zoster (HZ) is a condition caused by the reactivation of varicella-zoster virus (VZV), the virus responsible for chickepox, which is the clinical manifestation of the primary infection. Congenital or acquired immune system deficiencies, as well as the physiological decline in immune response occurring in the elderly, known as immune senescence, can allow VZV reactivation and, consequently, HZ. One out of 3 people develops HZ during their lifetime. Moreover, thirty percent of the affected subjects develop post-herpetic neuralgia, the most frequent complication after HZ skin rash. Patients with dermatological conditions characterized by alteration of the immune system, such as systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous diseases, and cutaneous lymphomas, are at higher risk of developing HZ and post-herpetic neuralgia, even when their disease is in remission. In the present work, we described the currently available vaccinations against HZ and provided recommendations for the vaccination against HZ in patients with dermatological diseases.

Hidradenitis Suppurativa-Related Autoinflammatory Syndromes: An Updated Review on the Clinics, Genetics, and Treatment of Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PASH), Pyogenic Arthritis, Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PAPASH), Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO), and Rarer Forms.

Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder of the terminal hair follicle, which can present in sporadic, familial, or syndromic form. A classification has been proposed for the latter, distinguishing cases associated with a known genetic condition, with follicular keratinization disorders or with autoinflammatory diseases. This review focuses on the clinical and genetic features of those entities (ie, pyoderma gangrenosum [PG], acne and HS; PG, acne, pyogenic arthritis and HS; psoriatic arthritis, PG, acne and HS; synovitis, acne, pustulosis, hyperostosis, osteitis; and so forth) for which the collective term HS-related autoinflammatory syndromes is proposed.

Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study.

BACKGROUND: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

Biologics for Hidradenitis suppurativa: evolution of the treatment paradigm.

INTRODUCTION: Hidradenitis suppurativa (HS) is an autoinflammatory skin disease with a high unmet need for effective medical management. Clinically, it is characterized by inflammatory nodules that may progress into abscesses, draining tunnels and extensive scarring, mainly affecting apocrine gland-bearing areas. AREAS COVERED: Treatment options include topical and systemic medications and a variety of surgical procedures. The anti-TNF-α antibody adalimumab and the anti-IL-17 secukinumab are the only two approved biologics for HS, showing moderate efficacy. HS research is a rapidly growing field, with a wide range of agents leveraging distinct mechanisms of action currently under development. Drugs targeting the IL-17 and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are the most advanced in both ongoing and completed Phase 3 studies, promising deeper levels of response. Use of other, off-label biologics is also discussed. EXPERT OPINION: A therapeutic algorithm is proposed based on comorbidities and existing evidence. Patient-tailored combinations between biologics and other biologics or small molecules will hopefully allow clinicians to target most events in HS pathophysiology in a complementary way while obtaining a meaningful effect on their devastating manifestations.

The Bowel-Associated Arthritis-Dermatosis Syndrome (BADAS): A Systematic Review.

Bowel-associated arthritis-dermatosis syndrome (BADAS) is a rare neutrophilic dermatosis that was first described in 1971 in patients who underwent bypass surgery for obesity. Over the years, the number of reported cases associated with medical gastroenterological conditions, particularly inflammatory bowel disease (IBD), has progressively increased. To date, there are no systematic reviews in the literature on BADAS. The design of an a priori protocol was based on PRISMA guidelines, and a search of PubMed and Scopus databases was conducted for articles published between 1971 and 2023 related to the topic. Fifty-one articles including 113 patients with BADAS were analyzed in this systematic review. Bariatric surgery and IBD were the most frequently reported causes of BADAS, accounting for 63.7% and 24.7% of all cases, respectively. A total of 85% of cases displayed the typical dermatological presentation, including urticarial maculopapular lesions centered by a vesicopustule, with the majority of lesions located on the upper limbs (73.5%). Polyarthralgia or localized arthritis were always present. Atypical presentations included cellulitis-like, erythema-nodosum-like, Sweet-syndrome-like and pyoderma-gangrenosum-like manifestations. Gastrointestinal symptoms were frequently observed in IBD-related cases (67.9%). The histopathology showed a neutrophilic infiltrate (96.6%). The most commonly used treatment regimens consisted of systemic corticosteroids, metronidazole and tetracyclines, either alone or in combination. A relapsing-remitting course was observed in 52.1% of patients. In conclusion, BADAS is a neutrophilic dermatosis that presents with a wide variety of cutaneous manifestations, both typical and atypical. Gastrointestinal symptoms are frequently observed, particularly in cases related to IBD. The histopathology is clear but not specific compared with other neutrophilic dermatoses. The diagnosis can be challenging, but the relapsing-remitting course and the strong association with polyarthralgia and gastrointestinal disease can aid in the diagnosis.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases.

Lymphomatoid papulosis (LyP) is a benign condition, listed among primary cutaneous CD30+ lymphoproliferative disorders. Its typical picture consists of relapsing-remitting papular lesions and it can be encountered in the course of a hematologic disease, at times representing its first manifestation. Hypereosinophilic syndromes are a heterogeneous group of disorders characterized by persistent peripheral blood hypereosinophilia that may lead to life-threatening organ damage. Among eosinophilic disorders, the subtype identified as myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions has aroused particular interest due to its excellent response to tyrosine kinase inhibitors, including imatinib. Here, we described the case of two 33-year-old men presenting with LyP and myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement who achieved complete clinical and molecular remission of both conditions a few months after starting imatinib.