Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

BACKGROUND: IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. METHODS: Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. RESULTS: After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). CONCLUSION: We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Stenotrophomonas maltophilia skin infection in an immunocompetent patient: Primary cutaneous CD30+ T-cell lymphoproliferative disorder or pseudolymphoma?

Cutaneous pseudolymphomas are a wide group of diseases mimicking cutaneous lymphoma. They comprise several skin conditions with different etiopathogenesis, clinical-pathological features, and prognosis, which may occur in the absence of an identifiable trigger factor or after administration of medications or vaccinations, tattoos, infections, or arthropod bites. They present with different manifestations: from solitary to regionally clustered lesions, up to generalized distribution and, in rare cases, erythroderma. They persist variably, from weeks to years, and resolve spontaneously or after antibiotics, but may recur in some cases. CD30+ T-cell pseudolymphomas are characterized by the presence of large, activated lymphoid cells, generally in response to viral infections, arthropod assault reactions, and drug eruptions. Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacillus responsible for opportunistic infections in immunocompromised patients. Infection of intact skin in immunocompetent patients is particularly rare. Here, we report a case of a man presenting an isolated nodule histopathologically mimicking a primary cutaneous CD30+ T-cell lymphoproliferative disorder.

Effectiveness of ixekizumab for the treatment of moderate-to-severe plaque psoriasis with involvement of difficult-to-treat areas: A 52-week multicenter retrospective study.

Biological drugs have dramatically changed the approach to treating moderate-to-severe plaque psoriasis, achieving excellent skin clearance and safety outcomes. However, the management of difficult-to-treat areas (e.g., scalp, palms/soles, nails, and genitalia) still represents a challenge in psoriasis treatment. Data in the literature on difficult-to-treat sites are limited and, frequently, no specific analysis is performed during clinical trials. We conducted a 52-week, retrospective study to evaluate the effectiveness of ixekizumab in 120 patients with moderate-to-severe plaque psoriasis of at least one difficult-to-treat area (scalp, palmoplantar surfaces, nails, and genitalia). Ninety-nine patients had scalp psoriasis, 35 had involvement of the palms or soles, 27 were affected by genital psoriasis, and 22 patients reported involvement of the nails. After 1 year of treatment, 96% of patients with scalp involvement, 95.6% of patients with palmoplantar psoriasis, 95.2% of patients with genital psoriasis, and 85% of patients with nail involvement achieved a site-specific Physician's Global Assessment of 0 or 1 (clear or almost clear). No serious adverse events were observed during the study. Our study supports the effectiveness of ixekizumab in plaque psoriasis involving difficult-to-treat sites.

Immunogenicity of three doses of anti-SARS-CoV-2 BNT162b2 vaccine in psoriasis patients treated with biologics.

Introduction: Psoriasis has not been directly linked to a poor prognosis for COVID-19, yet immunomodulatory agents used for its management may lead to increased vulnerability to the dangerous complications of SARS-CoV-2 infection, as well as impair the effectiveness of the recently introduced vaccines. The three-dose antibody response trend and the safety of BNT162b2 mRNA vaccine in psoriasis patients treated with biologic drugs have remained under-researched. Materials and methods: Forty-five psoriatic patients on biologic treatment were enrolled to evaluate their humoral response to three doses of BNT162b2. IgG titers anti-SARS-CoV-2 spike protein were evaluated at baseline (day 0, first dose), after 3 weeks (second dose), four weeks post-second dose, at the time of the third dose administration and 4 weeks post-third dose. Seropositivity was defined as IgG ≥15 antibody-binding units (BAU)/mL. Data on vaccine safety were also collected by interview at each visit. Results: A statistically significant increase in antibody titers was observed after each dose of vaccine compared with baseline, with no significant differences between patients and controls. Methotrexate used in combination with biologics has been shown to negatively influence the antibody response to the vaccine. On the contrary, increasing body mass index (BMI) positively influenced the antibody response. No adverse effects were reported, and no relapses of psoriasis were observed in the weeks following vaccine administration in our study population. Conclusions: Our data are largely consistent with the recent literature on this topic confirming the substantial efficacy and safety of BNT162b2 mRNA vaccine on psoriatic patients treated with biologics of different types and support the recommendation to perform additional doses in this specific subgroup of patients.

Efficacy and safety of N-acetyl-GED-0507-34-LEVO gel in patients with moderate-to severe facial acne vulgaris: a phase IIb randomized double-blind, vehicle-controlled trial.

BACKGROUND: Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-γ (PPARγ) modulator N-acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne-inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process. OBJECTIVES: To evaluate the efficacy and safety of NAC-GED (5% and 2%) in patients with moderate-to-severe facial acne vulgaris. METHODS: This double-blind phase II randomized controlled clinical trial was conducted at 36 sites in Germany, Italy and Poland. Patients aged 12-30 years with facial acne, an Investigator Global Assessment (IGA) score of 3-4, and an inflammatory and noninflammatory lesion count of 20-100 were randomized to topical application of the study drug (2% or 5%) or placebo (vehicle), once daily for 12 weeks. The co-primary efficacy endpoints were percentage change from baseline in total lesion count (TLC) and IGA success at week 12; the safety endpoints were adverse events (AEs) and serious AEs. This study was registered with EudraCT (2018-003307-19). RESULTS: Between Q1 in 2019 and Q1 in 2020 450 patients [n = 418 (92·9%) IGA 3; n = 32 (7·1%) IGA 4] were randomly assigned to NAC-GED 5% (n = 150), NAC-GED 2% (n = 150) or vehicle (n = 150). The percentage change in TLC reduction was statistically significantly higher in both the NAC-GED 5% [-57·1%, 95% confidence interval (CI) -60·8 to -53·4; P < 0·001] and NAC-GED 2% (-44·7%, 95% CI -49·1 to -40·1; P < 0·001) groups compared with vehicle (-33·9%, 95% CI -37·6 to -30·2). A higher proportion of patients treated with NAC-GED 5% experienced IGA success (45%, 95% CI 38-53) vs. the vehicle group (24%, 95% CI 18-31; P < 0·001). The IGA success rate was 33% in the NAC-GED 2% group (P = not significant vs. vehicle). The percentage of patients who had one or more AEs was 19%, 16% and 19% in the NAC-GED 5%, NAC-GED 2% and vehicle groups, respectively. CONCLUSIONS: The topical application of NAC-GED 5% reduced TLC, increased the IGA success rate and was safe for use in patients with acne vulgaris. Thus, NAC-GED, a new PPARγ modulator, showed an effective clinical response. What is already known about this topic? Acne vulgaris, one of the most common dermatological diseases, affects more than 85% of adolescents. There is a medical need for innovative and safe treatment of acne vulgaris. The peroxisome proliferator-activated receptor-γ (PPARγ) is involved in lipid metabolism and specifically in cell differentiation, sebum production and the inflammatory reaction. What does this study add? N-acetyl-GED-0507-34-LEVO (NAC-GED 5%), a PPARγ modulator, significantly improves acne manifestations in patients with moderate-to-severe acne and is safe and well tolerated. The results suggest that the PPARγ receptor is a novel therapeutic target for acne. The results provide a basis for a large phase III trial to assess the effectiveness and safety profile of NAC-GED in combating a disease that afflicts 80-90% of adolescents.

Psoriasis in Tigray, Ethiopia: Focusing on available treatments.

Psoriasis has been reported to be rare in people with skin of color. However, the actual prevalence is probably underestimated by the lack of wide epidemiological studies. The aim of the study is to present our experience in Tigray, Ethiopia, focusing on the issues related to diagnosis, clinical features and therapies. A total of 1288 people affected by psoriasis were visited and 954 were included in a retrospective analysis through the review of medical records of patients attending at three Dermatologic Centers in Ethiopia from 2005 to 2016. The most common clinical form is plaque psoriasis (62.9%), followed by guttate (13.9%), pustular (9.5%), inverse (7.5%), and erythrodermic (6.1%) ones. The prevalence of psoriatic arthritis is 17%. It is often diagnosed late resulting in particularly deforming and debilitating disease. Patients with severe psoriasis often require hospitalization due to the reduced availability of effective treatments and appropriate skin care, resulting in a prolonged recurrence rate or decreased disease-free interval. In poorer rural areas, patients use some traditional African plants such as Kigelia africana which have been shown to have partial benefits in the treatment of psoriasis. Unfortunately, the only available conventional therapies are topical steroids, salicylic acid, methotrexate, and the sun. More studies concerning the appropriate management of people with psoriasis in low income countries, including standardization of indigenous therapies and a reduction of costs of conventional drugs, could help the care of people with psoriasis.

Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

Diffuse (Generalized) Plane Xanthoma Misdiagnosed as Carotenoderma: Usefulness of Reflectance Confocal Microscopy.

Diffuse (generalized) plane xanthoma is a rare normolipemic xanthomatosis, frequently associated with multiple myeloma and monoclonal gammopathy. Its clinical presentation is well described, and in most cases, clinical suspicion is immediate. Rarely, it can clinically present with a diffuse and uniform yellowish discoloration, and in this context, several investigations are required to identify the correct diagnosis. We describe a case characterized by progressive diffuse yellow-orange discoloration lasting about 3 years and classified as carotenoderma in which reflectance confocal microscopy addressed the diagnosis and drove the correct selection of the biopsy site. Definitive diagnosis of diffuse (generalized) plane xanthoma was confirmed later by histological examination.

Glandular Schwannoma: An Uncommon Variant of Schwannoma with Controversial Histogenesis.

Schwannomas are benign, encapsulated nerve sheath tumors arising from Schwann cells; several histologic variants of schwannoma have been described, including the exceedingly rare glandular schwannoma (GS). The histogenesis of the glands in GS (as well as in other peripheral nerve sheath tumors with a glandular component) remains unclear; no consensus exists as to whether glands should be interpreted as metaplastic elements or entrapped reactive glands. We report a case of GS with detailed immunohistochemical analysis of the epithelial component. We believe that our findings raise further questions regarding the histogenesis of glands in GS, casting doubts on the traditional distinction between true metaplasia and glandular entrapment. Further research is warranted in this regard.

Italian Guidelines in diagnosis and treatment of alopecia areata.

Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations.

Treatment of severe psoriasis with ixekizumab in a liver transplant recipient with concomitant hepatitis B virus infection.

Treatment of severe psoriasis (PsO) in organ transplant (OT) patients is difficult. In fact, systemic drugs used for PsO therapy can be detrimental to transplanted organs and/or can increase the risk of serious infections in subjects already taking antireject medicines. Current guidelines fail to give indications on how to manage PsO OT subjects. Moreover, only a few cases of patients with the above-cited characteristics treated with systemic therapies have been published so far. Here, we report our experience concerning a liver transplant patient successfully treated with ixekizumab for his psoriasis throughout 1 year.

Uncommon Histopathological Variants of Malignant Melanoma. Part 2.

Despite new horizons opened by recent advances in molecular pathology, histological evaluation still remains the diagnostic gold standard regarding cutaneous melanocytic neoplasms. Several histological variants of melanoma have been described, and their knowledge is crucial for accurate diagnosis and classification of cases with unusual clinico-pathological features. Uncommon histological variants of melanoma have been described based on a broad constellation of features, including architectural pattern, stromal alterations, cytological attributes, and other morphological properties. This review is aimed at providing an extensive discussion of unusual but distinctive histopathological variants of melanoma.

Papular Mycosis Fungoides Is a Distinctive Variant of Early-stage Mycosis Fungoides: Extended Retrospective Study With Long-term Follow-up.

Papular mycosis fungoides (PMF) is a rare variant of mycosis fungoides (MF). The exact nosology and prognosis of PMF are still unclear. We retrospectively identified cases of PMF from the files of the Department of Dermatology of the Medical University of Graz, Austria, and checked the follow-up data. The patients comprised 13 men and 5 women (median age: 57.5 y; range 13 to 77 y). In 4 patients, an initial clinicopathologic diagnosis of atypical pityriasis lichenoides was made; these cases were subsequently reclassified as PMF due to the onset of conventional patches of MF during follow-up. Follow-up data of our cases showed that 2 patients died of disease progression 50 and 199 months after the first presentation, respectively. Two patients are alive with progressive disease after 215 and 300 months, respectively. Ten patients are alive with stable disease (median: 70 mo). Four patients were in complete remission at last follow-up visit (median: 215 mo; 2 of them died of unrelated causes). Our data confirm that PMF represents a clinicopathologic variant of early MF with prognosis similar to conventional presentations of the disease. Familiarity with PMF and distinction from other cutaneous papular lymphoid proliferations is necessary for a precise diagnosis and management of these patients.

Alveolar Soft-Part Sarcoma of the Tongue.

Alveolar soft-part sarcoma is a rare neoplasm of unknown histogenesis that accounts for less than 1% of all soft-tissue sarcomas. The tumor is highly vascularized with small vascular spaces separating nests of cells, and from cytogenetic point of view, is characterized by chromosome rearrangement der(17)t(X:17)(p11:q25) that results in the ASPL-TFE3 translocation. It can occur at any age, but it is most common between 15 and 35 years of age. The prognosis is poor, despite the relatively slow growth of the tumor. We present here an atypical case of alveolar soft-part sarcoma in which the age of the patient, the location, and the histopathologic characteristics of the lesion represented a diagnostic challenge.

Ultrasound assessment of enthesis thickness in psoriasis and psoriatic arthritis: A cross-sectional study.

BACKGROUND: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. AIMS: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. METHODS: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. RESULTS: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. LIMITATIONS: The small sample of patients studied is a limiting factor in this study. CONCLUSIONS: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis.

Uncommon Histopathological Variants of Malignant Melanoma: Part 1.

Despite new horizons opened by recent advances in molecular pathology, histological evaluation still remains the diagnostic gold standard regarding cutaneous melanocytic neoplasms. Several histological variants of melanoma have been described, and their knowledge is crucial for accurate diagnosis and classification of cases with unusual clinicopathological features. Uncommon histological variants of melanoma have been described based on a broad constellation of features, including architectural pattern, stromal alterations, cytological attributes, and other morphological properties. This review is aimed at providing an extensive discussion of unusual but distinctive histopathological variants of melanoma.