IntroductionIxekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real-life studies. Nevertheless, long-term real-world experiences are still lacking, with little data up to 4 years of treatment.ObjectivesTo analyse survival, effectiveness and safety of ixekizumab in a real-life cohort of patients affected by moderate-to-severe psoriasis or psoriatic arthritis up to 260 weeks (5 years).MethodsWe included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and <= 3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response.ResultsDS was 65.5% at 260 weeks, with being a super-responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and <= 3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87-0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84-0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88-0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83-0.99, p = 0.027), and PASI <= 3 (OR 0.86, CI 0.76-0.97, p = 0.018) at 104 weeks. No severe adverse events were observed.ConclusionsIxekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long-term response.

Interleukin-17 (IL-17) is central in the pathogenesis of psoriasis (1). Brodalumab was approved in Europe in 2017, and its blockade of IL-17 receptor A provides, in clinical trials, quick onset of action and long-term maintenance of treatment response with a favorable safety profile (2,3). Data regarding real-life use are limited (4–6). We retrospectively assessed efficacy and safety of brodalumab in moderate to severe psoriasis patients attending the Dermatology Clinic of the Turin University Hospital for up to 48weeks. Patients received subcutaneous brodalumab 210mg every 2weeks after the administration of 210mg every week for the first 3weeks. Disease severity at baseline was measured by the Psoriasis Area Severity Index (PASI); PASI improvement of 90% (PASI90) and 100% (PASI100) was recorded at 12, 24, and 48weeks. DLQI response rates were collected at baseline and after 48weeks of treatment. Among 1635 patients on biologics attending our clinic, 202 received brodalumab (Table 1). At week 12, 125 (68%) and 97 (53%) patients achieved PASI90 and PASI100, respectively. At week 24, 93 patients (77%) and 111 (65%) achieved PASI90 and PASI100, respectively. At week 48, 32 patients (78%) achieved PASI90 response, while 39 (64%) had complete clearance. Between baseline and week 48, DLQI improved from a mean of 13.8 to 1.3 (p< .001) and PASI improved from 23.3 to 2.2 (p< .001) respectively). Obesity did not seem to reduce the efficacy or time to onset of action of brodalumab since no difference in efficacy was observed between patients with a BMI above or below 30. No significant differences in efficacy were detected at the different time points between patients with and without joint involvement (Figure 1). Bio-naïve patients improved faster than bio-experienced patients in the first weeks of treatment and at every time point. At week 12, the mean PASI in the bio-naïve population was lower than in the bio-experienced (1.56 vs 2.47; p1⁄4 .045), and more patients achieved PASI 90 and PASI <3 (76% vs 56%; p1⁄4 .004 and 86% vs 69%; p1⁄4 .005). At week 24, more bio-naïve patients than bio-experienced patients achieved PASI90 (84% vs 67%, p1⁄4 .021). Forty-nine patients reported side effects, the most frequent of which were arthralgia (15 patients) in patients without joint involvement at baseline and asthenia (10 patients). Two patients discontinued treatment due to reported side effects, one due to joint pain and one due to a major dental abscess resistant to multiple antibiotic therapies. Brodalumab rapidly improves psoriasis in the first few weeks of treatment, particularly in bio-naïve patients, which is in line with the results of registration studies and previous real-life experience (3,5,6). Performance in bio-experienced patients is also good, as previously reported (5,6). Although not approved in the treatment of psoriatic arthritis, joint involvement does not appear to affect the response to therapy.

Journal of the European Academy of Dermatology and VenereologyVolume 36, Issue 10 p. e838-e841 Letter to the Editor Risankizumab shows faster response in bio naïve than in bio-experienced psoriatic patients L. Mastorino, Corresponding Author L. Mastorino [email protected] orcid.org/0000-0001-7386-3219 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalyCorrespondence: L. Mastorino. E-mail: [email protected]Search for more papers by this authorF. Castelli, F. Castelli Section of Dermatology, Koelliker Hospital, Turin, ItalySearch for more papers by this authorE. Stroppiana, E. Stroppiana Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorA. Verrone, A. Verrone Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorM. Ortoncelli, M. Ortoncelli Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorS. Susca, S. Susca Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorS. Boskovic, S. Boskovic Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorS.G. Passerini, S.G. Passerini Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorN. Macagno, N. Macagno orcid.org/0000-0002-0097-2139 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorC. Cariti, C. Cariti Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorM. Licciardello, M. Licciardello Section of Dermatology, Koelliker Hospital, Turin, ItalySearch for more papers by this authorC. Solaroli, C. Solaroli Section of Dermatology, Koelliker Hospital, Turin, ItalySearch for more papers by this authorG. Pertusi, G. Pertusi Outpatient Clinic, Section of Dermatology, ASL VC, Vercelli, ItalySearch for more papers by this authorM.G. Aragone, M.G. Aragone Outpatient Clinic, Section of Dermatology, ASL AL, Alessandria, ItalySearch for more papers by this authorG. Baggini, G. Baggini Outpatient Clinic, Section of Dermatology, ASL AL, Alessandria, ItalySearch for more papers by this authorC. Addese, C. Addese Outpatient Clinic, Section of Dermatology, ASLTO4, Ivrea, ItalySearch for more papers by this authorC. Leporati, C. Leporati Outpatient Clinic, Section of Dermatology, ASLTO4, Ivrea, ItalySearch for more papers by this authorR. Peila, R. Peila Outpatient Clinic, Section of Dermatology, ASLTO4, Ivrea, ItalySearch for more papers by this authorM.T. Giura, M.T. Giura Surgery Department, Section of Dermatology, Cardinal Massaia Hospital, ASL AT, Asti, ItalySearch for more papers by this authorG. Rossotto, G. Rossotto Surgery Department, Section of Dermatology, Cardinal Massaia Hospital, ASL AT, Asti, ItalySearch for more papers by this authorP. Pella, P. Pella Oncology Department, Section of Dermatology, Degli Infermi Hospital, ASL BI, Biella, ItalySearch for more papers by this authorL. Mocci, L. Mocci Section of Dermatology, AO AL Santi Antonio e Biagio e Cesare Arrigo, Alessandria, ItalySearch for more papers by this authorG. Merlo, G. Merlo Section of Dermatology, AO AL Santi Antonio e Biagio e Cesare Arrigo, Alessandria, ItalySearch for more papers by this authorR. Tiberio, R. Tiberio Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorF. Graziola, F. Graziola Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorP. Quaglino, P. Quaglino orcid.org/0000-0003-4185-9586 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy Share last authorship.Search for more papers by this authorP. Dapavo, P. Dapavo Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy Share last authorship.Search for more papers by this authorS. Ribero, S. Ribero orcid.org/0000-0002-0098-1406 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy Share last authorship.Search for more papers by this author L. Mastorino, Corresponding Author L. Mastorino [email protected] orcid.org/0000-0001-7386-3219 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalyCorrespondence: L. Mastorino. E-mail: [email protected]Search for more papers by this authorF. Castelli, F. Castelli Section of Dermatology, Koelliker Hospital, Turin, ItalySearch for more papers by this authorE. Stroppiana, E. Stroppiana Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorA. Verrone, A. Verrone Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorM. Ortoncelli, M. Ortoncelli Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorS. Susca, S. Susca Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorS. Boskovic, S. Boskovic Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorS.G. Passerini, S.G. Passerini Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorN. Macagno, N. Macagno orcid.org/0000-0002-0097-2139 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorC. Cariti, C. Cariti Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, ItalySearch for more papers by this authorM. Licciardello, M. Licciardello Section of Dermatology, Koelliker Hospital, Turin, ItalySearch for more papers by this authorC. Solaroli, C. Solaroli Section of Dermatology, Koelliker Hospital, Turin, ItalySearch for more papers by this authorG. Pertusi, G. Pertusi Outpatient Clinic, Section of Dermatology, ASL VC, Vercelli, ItalySearch for more papers by this authorM.G. Aragone, M.G. Aragone Outpatient Clinic, Section of Dermatology, ASL AL, Alessandria, ItalySearch for more papers by this authorG. Baggini, G. Baggini Outpatient Clinic, Section of Dermatology, ASL AL, Alessandria, ItalySearch for more papers by this authorC. Addese, C. Addese Outpatient Clinic, Section of Dermatology, ASLTO4, Ivrea, ItalySearch for more papers by this authorC. Leporati, C. Leporati Outpatient Clinic, Section of Dermatology, ASLTO4, Ivrea, ItalySearch for more papers by this authorR. Peila, R. Peila Outpatient Clinic, Section of Dermatology, ASLTO4, Ivrea, ItalySearch for more papers by this authorM.T. Giura, M.T. Giura Surgery Department, Section of Dermatology, Cardinal Massaia Hospital, ASL AT, Asti, ItalySearch for more papers by this authorG. Rossotto, G. Rossotto Surgery Department, Section of Dermatology, Cardinal Massaia Hospital, ASL AT, Asti, ItalySearch for more papers by this authorP. Pella, P. Pella Oncology Department, Section of Dermatology, Degli Infermi Hospital, ASL BI, Biella, ItalySearch for more papers by this authorL. Mocci, L. Mocci Section of Dermatology, AO AL Santi Antonio e Biagio e Cesare Arrigo, Alessandria, ItalySearch for more papers by this authorG. Merlo, G. Merlo Section of Dermatology, AO AL Santi Antonio e Biagio e Cesare Arrigo, Alessandria, ItalySearch for more papers by this authorR. Tiberio, R. Tiberio Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorF. Graziola, F. Graziola Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorP. Quaglino, P. Quaglino orcid.org/0000-0003-4185-9586 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy Share last authorship.Search for more papers by this authorP. Dapavo, P. Dapavo Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy Share last authorship.Search for more papers by this authorS. Ribero, S. Ribero orcid.org/0000-0002-0098-1406 Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy Share last authorship.Search for more papers by this author First published: 10 June 2022 https://doi.org/10.1111/jdv.18314Citations: 5 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1Mastorino L, Sara S, Megna M et al. Risankizumab shows high efficacy and Maintenance in improvement of response until week 52. Dermatol Ther 2022; 14: e15378. Google Scholar 2Gordon KB, Strober B, Lebwohl M et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet 2018; 392: 650–661. 10.1016/S0140-6736(18)31713-6 CASPubMedWeb of Science®Google Scholar 3Warren RB, Blauvelt A, Poulin Y et al. Efficacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, open-label, efficacy-assessor-blinded clinical trial. Br J Dermatol 2021; 184: 50–59. 10.1111/bjd.19341 CASPubMedWeb of Science®Google Scholar 4Gkalpakiotis S, Cetkovska P, Arenberger P et al. Risankizumab for the treatment of moderate-to-severe psoriasis: real-life multicenter experience from The Czech Republic. 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BACKGROUND Studies specifically conducted to assess gender differences in genital lichen sclerosus (GLS) are not available. This multicenter study aimed to identify possible gender-related differences on GLS clinical features, history and course, through collecting data from a large mixed-sex sample of patients. METHODS This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was specifically collected: clinical features and severity of symptoms related to GLS, extragenital involvement, previous therapies, diagnostic suspicion at referral, type of referring physicians, development of genital squamous-cell carcinoma (SCC). RESULTS Females complained of symptoms more frequent and severe than men; pallor and scarring-sclerosis-atrophy were the most frequent features without gender differences; itching- related signs were more frequent in females than in males as well as extragenital involvement; prior to receiving a definitive diagnosis, females received treatment more frequently than males; 40% of patients were referred with a misdiagnosis; the highest rate of correct suspected diagnosis at referral came from dermatologists than from other physicians; duration of the disease was found to predispose to SCC development. CONCLUSIONS Our findings highlighted several gender differences on clinical presentation and symptom profile of GLS. In spite of some characteristic features, misdiagnosis at referrals was frequent.

BackgroundLimited data are available on risk factors associated with lichen sclerosus and no data are available on gender differences in genital lichen sclerosus (GLS).ObjectiveThis multicentre study aimed at identifying potential risk factors for GLS, through data collection from a large, mixed-sex sample of patients comparing gender-related differences in relation to data from the general population.MethodsThis was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was collected: demographic data, anthropometric measures, comorbidities, family history of LS, clinical features and symptoms related to GLS.ResultsOverweight and obesity, blood hypertension, hypothyroidism and an educational attainment equal or above upper secondary school level were more frequent among the study patients than among the general Italian population. Moreover, a family history of GLS was reported more frequently than expected among GLS patients. These factors were similar in males and females. The disease tended to occur later in females than in males.ConclusionsOur findings suggest that metabolic factors, and possibly a sedentary lifestyle, may play a role in GLS pathogenesis in genetically predisposed patients, and that risk profile is similar in males and females despite some difference in the onset of symptoms.

Background: Mycosis fungoides (MF) is rare in young patients. Its clinical behavior is still uncertain, as some reports have suggested that it has a more aggressive course than does the adult-onset type. Aim: To ascertain if early-onset MF represents a heterogeneous group of cutaneous T cell lymphomas. Materials and Methods: Clinical, immunohistopathological and follow-up data of early-onset (<20 years of age) MF cases reported in the literature (n = 42) plus 7 described herein were compared with those of a cohort of adult-onset MF patients (n = 252) diagnosed at our institution since 1975. Results: The majority of the 49 early-onset MF patients had patch-plaque stage disease at diagnosis. Ten had hypopigmented lesions. The predominant phenotype was CD3+ CD4+CD7–CD8–. Seven patients had a stage progression, 6 with extracutaneous involvement. Five- and 10-year survival rates were 93 and 74%, respectively. Conclusions: No statistically significant differences were found in the disease course between early- and adult-onset MF.

Development of multiple primary melanomas is a rare but well recognized disease, with an estimated incidence ranging from 1.75% to 8.5% in several series. The clinical, histological and epidemiological characteristics of 49 patients, identified from 2470 with histologically confirmed melanoma, are described in this study. Thirty-five of these patients had two primary melanomas, 11 had three melanomas and three had four, five and six melanomas, respectively. Diagnosis was concurrent in 22 patients (45%); in the remaining cases the median time interval between the first and second melanoma was 22.6 months and the longest interval was 21.5 years. The mean Breslow's thickness decreased significantly (P < 0.001) from the first melanoma to the second and third lesion. The multiple melanoma patients had a higher percentage of subjects over 70 years of age or with lentigo maligna melanoma than single melanoma patients. The mean follow-up time was 12 years (range 4 23 years). The 5-year survival rate from first melanoma excision (83%) does not differ from that of patients with a single melanoma. In conclusion, the presence of multiple primary melanomas does not appear to be a negative prognostic factor; our data show the importance of close follow-up in melanoma patients in order to detect not only metastases, but also subsequent primaries in their earliest phases.

The efficacy of systemic polychemotherapy in the treatment of primary cutaneous B-cell lymphomas (CBCL) or T-cell lymphomas (CTCL) is still controversial. A series of 81 patients (46 primary CBCL and 35 CTCL) were treated with COP or CHOP regimens. In primary CBCL, the overall objective response rate (RR) was 98 %, with an 89 % CR rate and a 33 % relapse-rate. Five-year disease-free survival was 70 %, 5-year survival 97 %. Patients with leg or widespread lesions showed a higher relapse-rate (55 % vs 26 %) than those with trunk or head lesions. The overall objective RR was 40 % in CTCL patients, with a 23 % CR rate; median response duration was 5.7 months, median survival 19 months. The results confirm both the good prognosis of primary CBCL and the efficacy of polichemotherapy. CHOP regimen is to be preferred to COP in as much as it reduces relapse rates. Conversely, there are no indications for the use of COP/CHOP regimens as first-line chemotherapy in CTCL patients.

Seven patients with chronic plaque psoriasis were treated with topical calcipotriol for 8 to 24 weeks; the lesions improved in 5 patients. Immunohistochemistry was performed on frozen sections, to evaluate the expression of adhesion molecules and extracellular matrix components before and after therapy. Changes in expression and topography of beta1 and beta4 integrins were found on psoriatic lesions before therapy and a reduction in the expression of tenascin was detected as well. Moreover, several activation markers such as ICAM-1, HLA-DR, CD26 were focally positive, with a diffuse cytoplasmic reactivity, in basal and suprabasal layers in untreated lesions. In the 5 patients in whom lesions regressed after topical calcipotriol treatment, we observed a histological normalization of the epidermis and the inflammatory infiltrate was reduced. Moreover, not only was there a normalization in the expression and topography of adhesion molecules, but also the integrin pattern observed after therapy was superimposable to that of normal skin.

17th Colloquium of the International Society of Dermatopathology (ISD) and Swiss Group of Dermatopathology (SGDP) of the Swiss Society of Dermatology and Venerology

CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas; the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis; azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR beta-chain gene.

Background: Response of cutaneous T-cell lymphoma (CTCL) to systemic chemotherapy is unsatisfactory: despite an initially high response rate (RR), duration is always short-lived. Objective: To investigate the capability of a third-generation regimen including idarubicin in improving RR and response duration in CTCL patients. Methods: Twenty-five patients with advanced CTCL (stages IIB and IV) were treated with a 12-week polychemotherapeutic regimen (VICOP-B), which foresees the use of idarubicin in association with etoposide, cyclophosphamide, vincristine, prednisone and bleomycin. Results: The overall objective RR was 80% (36% complete response). The mycosis fungoides (MF) RR was 84%, with a median duration of 8.7 months. The pleomorphic-lymphoma RR was higher (100%), but the corresponding response duration was shorter (median: 3 months). No responses were documented in Sézary syndrome. Conclusion: VICOP-B regimen is effective and feasible as first-line chemotherapy in advanced MF, with or without extracutaneous involvement.

CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using immunohistochemical techniques. A sporadic focal CD26 positivity was found in normal skin, whereas increased expression of CD26 was observed both in cutaneous T-cell lymphomas and in inflammatory skin diseases, e.g. psoriasis, lichen planus and spongiotic dermatitis, in the basal and spinous layers. CD26 keratinocyte staining was not specific for a single disease, but seems to be associated with the presence of a reactive or neoplastic infiltrate in the epidermis. We propose that the CD26 molecule may function as a keratinocyte activation antigen.