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Background: Ixekizumab (anti-IL-17A) is a biological agent used for the treatment of moderate-to-severe psoriasis. Real-life data on the effectiveness and safety of ixekizumab are currently scarce. Objective: The objective of this study was to evaluate the effectiveness and safety of ixekizumab in a cohort of psoriatic and psoriatic arthritis patients. Methods: We conducted a retrospective study involving 201 patients affected by moderate-to-severe psoriasis and treated with ixekizumab at seven Italian University centers. Data analysis focused on 110 patients who started ixekizumab at baseline and completed at least 24 weeks of treatment. Results: Significant reduction of mean (± standard deviation) baseline Psoriasis Area Severity Index (PASI) score (14.3 ± 5.8) was detected at 4 weeks of ixekizumab therapy (4.9 ± 4.2, p < 0.001), with a further significant improvement at weeks 12 and 24 (1.9 ± 2.9 and 0.9 ± 1.6, respectively) (p < 0.001). Our analysis showed 90%, 72%, and 57% of patients achieving PASI 75, 90, and 100 responses (75%, 90%, and 100% reduction in PASI score), respectively, after 24 weeks’ therapy. For patients with arthritis (28%), a significant reduction in the mean (± standard deviation) baseline Disease Activity Score (DAS)-28 score (4.6 ± 5.1) was detected at week 4 (2.5 ± 3.9, p < 0.01), with a further significant improvement at weeks 12 and 24 (2.1 ± 1.2 and 1.4 ± 0.9, respectively) (p < 0.001). The bio-naïve group showed significantly higher PASI 90 and 100 response rates at week 12 than the bio-exposed one (p < 0.05). This trend in terms of PASI 100 response was also maintained at week 24 (p < 0.05). Furthermore, PASI 90 responses were significantly higher in anti-interleukin (IL)-17A-naïve patients at week 24 than in anti-IL-17A-experienced ones (p < 0.05). The dropout rate for adverse events (AEs) was as low as 2% (2/110), while AEs that did not cause treatment interruption were observed in 6% (7/110). Patients withdrawing from the study were defined as non-responders according to the non-responder imputation method. The retrospective design of the study does not allow missing data to be retrieved or homogeneous patient selection. Conclusions: The present study illustrates ixekizumab in real-world clinical practice, confirming its usefulness and safety in the management of psoriasis and psoriatic arthritis.

Oral lichen planus (OLP) lesions have an overall malignant transformation rate of 1.37%. In patients with chronic disease, the diagnosis of malignancy relies on histopathological examination guided by clinical suspicion. Narrow-band imaging (NBI) is a promising endoscopic technique which, using a filtered light with specific wavelengths, can highlight microvascular abnormalities associated with subclinical neoplastic changes of the upper aerodigestive tract epithelium. This study aimed to analyse the value of NBI in selecting patients for biopsy before the emergence of clinical changes, allowing early detection of oral malignancies arising from OLP. A prospective study was conducted, enrolling 32 consecutive patients with a histological diagnosis of OLP with no previous diagnosis of oral cancer or other oral inflammatory diseases. Patients with suspicious NBI lesions underwent biopsies, while other patients were included in the follow-up. Two patients were judged positive at NBI evaluation and squamous cell carcinoma was diagnosed after histological examination. None of the other patients developed clinical features of malignancies during follow-up. NBI evaluation may increase the accuracy of detection of subclinical neoplastic transformation in OLP lesions and further encourage clinicians to perform biopsies in selected cases.

Background In Italy, the incidence of new cases of melanoma is roughly 10,000 cases per year, with an average rate of mortality of 5-6 per 100,000 population per year respectively. The objective of this retrospective study was to evaluate the epidemiological incidence of primitive melanoma, including the incidence of multiple melanomas occurring in the same patient. Furthermore, we studied all histological different types of melanoma focusing on the presence of an association nevus-melanoma. Methods A clinical epidemiologic retrospective study from January 2010 to March 2015 was recorded. For each lesion, mitotic rate, Breslow's index, ulceration, presence of regression, vascular and perineural invasion, lymphocytic infiltrate, microsatellitosis and presence of pre-existencing nevus were also studied. Results Five hundred eighty primitive cutaneous melanomas (CMs) were removed from 525 patients with an incidence of 18-20 new melanomas/100,000 habitants/year. Eighty percent of these were at stage T0-1. Among other melanomas, SSM was the predominant subtype (85% of cases). Only 18 cases had lymph node metastases and 13 (2%) lymph node and/or distant metastases (stage IV) at time of diagnosis. Mitotic figures were present in 25% of cases (143 cases out of 580) without significant gender differences. Conclusions The incidence of new melanomas founded is close to the CM's incidence in US population in 2016 with a high percentage of superficial melanomas highlighting the importance of prevention campaigns. The presence of melanoma on a preexisting nevus in only 16% of cases allow to conclude that this association is overestimated in literature. On the contrary the high incidence of a second melanoma in the 7% of cases in a relatively short period of survey leads to the conclusion that this data is underestimated.

Hepatotropic viral infections are a relevant global health problem and present multiple extrahepatic manifestations in addition to hepatic disease. Along with generic cutaneous symptoms correlated to the cholestatic liver disease that may arise during the infection, some cutaneous manifestations of hepatotropic viral infections are characteristic, enabling to suspect the underlying infection. This review will present the principal cutaneous manifestations of hepatotropic virus infection. Cutaneous manifestations are rare in HAV infections: these include urticaria, panniculitis, scarlatiniform eruption, evanescent skin rash, maculopapular prolonged rash, serum sickness-like illness rash, cutaneous vasculitis, cryoglobulinemia. The commonest cutaneous manifestation associated to HBV infection is serum sickness-like syndrome. Polyarteritis nodosa (PAN) is among the most common and serious cutaneous manifestations of HBV infection. In children, HBV infection may acutely manifest as papular acrodermatitis of childhood (Gianotti-Crosti Syndrome), with non-pruritic, non-coalescing, round papules. Patients with chronic HBV infection may also develop mixed cryoglobulinemia, that is, inter alia, the most documented extrahepatic manifestation of HCV infection. Cutaneous lichen planus has been associated to HBV and HCV infection. As for oral lichen planus, the association with HBV and HCV is more debated. Interestingly, patients with oral lichen planus with HCV have a higher risk of developing oral squamous cell carcinoma. Dermatologists should be aware of the possible cutaneous manifestations associated to viral hepatitis.

Dear EditorThere are differing opinions on the use of biologic drugs for psoriasis during the COVID-19 outbreak [1–3]. We would like to share our experience at the biggest hospital in our region wh...

Autoimmune skin diseases can occur in pregnancy, and the treatment is often required to control both maternal disease and fetal outcomes. Moreover, the control of mother's diseases and fetal health is a challenge for dermatologists because of the teratogenic effects of many drugs. So it is important to know exactly which drugs can be administrated in the different stages of pregnancy. Authors reviewing the literature and relying on daily dermatological experience agree that during pregnancy effective drug treatment of autoimmune diseases is possible with reasonable safety for the fetus/child and lactation. During pregnancy and lactation patients with autoimmune disorders should be evaluated carefully, and the benefit-risk of continued therapy should be reassessed. The points to consider presented in this review show that, despite limitations, effective drug treatment of autoimmune diseases is possible with reasonable safety for the fetus/child during pregnancy and lactation. Prior to conception it is necessary to explain to the patients what the risks of pregnancy are. It is preferred to avoid a pregnancy in active disease and replace treatment with an allowed therapy. During pregnancy it is necessary to avoid treatment with mycophenolate mofetil, cyclophosphamide and methotrexate. In some very particular cases, as life saver drug, cyclosporine and rituximab can be used. Finally, some drugs can be used monitoring the patient, in particular, systemic corticosteroid at low dosage, dapsone, azathioprine, iloprost and sildenafil.

In recent years, dermatologic manifestations in oncohematologic patients have become more common. The aim of our study was to determine the incidence and heterogeneity of skin manifestations in patients followed at our Hematology Department. This observational monocentrical study was conducted on 60 patients. We divided the observed conditions in exanthematous, purpuric, vesicular-bullous, papulonodular, urticarial, and eczematous manifestations. Moreover, all lesions were classified according to pathogenesis, in (a) specific skin manifestations, caused by neoplastic skin infiltration; (b) immune-mediated manifestations, based on immunological mechanisms; and (c) skin lesions due to immunodeficiency. Altogether, 73 clinical manifestations were reported. Specific manifestations (a) were detected in 15.1% of the cases, mainly with papulonodular appearance. Immune-mediated manifestations (b) were found in 37 cases (50.7%), particularly with eczematous or exanthematous appearance, and leukemia was the malignancy most frequently reported in these patients. Eventually, lesions due to immunosuppression (c) were reported in 34.2% of the cases. They were represented by infections and cutaneous malignancies, and usually manifested with papulonodular lesions. Skin lesions in oncohematologic patients are a common event. A multidisciplinary approach based on the collaboration between the hematologist and the dermatologist is crucial to achieve a proper diagnosis, and correctly manage these manifestations.

PSOdisk is a 10-item visual instrument, aimed at assessing the burden of disease in patients with psoriasis. To compare PSOdisk with a scientifically validated questionnaire, the Dermatology Life Quality Index (DLQI), and asses both tools in relation to Psoriasis Severity Index (PASI) and patient acceptance. Fifty patients with cutaneous psoriasis and/or arthritic psoriasis were recruited. Correlation analysis between PSOdisk and DLQI was performed using Pearson’s product-moment correlation coefficient. A multivariate linear regression was carried out to investigate the effect of PASI on PSOdisk and DLQI scores. In addition, we evaluated completion times as well as patient satisfaction for both PSOdisk and DLQI. PSOdisk and DLQI mean scores were 22.04 ± 20.56 and 3.35 ± 4.52, respectively. The mean value for PASI was 5.98 ± 5.89 and for age was 55.88 ± 14.09 years. The mean value of Cronbach’s coefficient alpha was 0.88 for PSOdisk and 0.90 for DLQI, suggesting good reliability. A significant correlation was found between PSOdisk and PASI, and a statistically significant correlation between DLQI and PASI. Multivariate linear regression analysis demonstrated a statistically significant effect of PASI on both the DLQI score and PSOdisk score. PSOdisk demonstrates good correlation with DLQI and PASI, good patient satisfaction, and requires a short completion time.

Although psoriasis is predominantly a chronic inflammatory skin disorder, it has been known to be associated with cardiovascular disease. Patients with psoriasis, particularly with moderate to severe forms, present an increased rate of cardiovascular mortality, myocardial infarction and stroke. However the pathophysiology of the relationship between psoriasis and cardiovascular risk and comorbidities has not yet completely known. Chronic inflammation may be considered a solid link between psoriasis and related cardiovascular events. Several cytokines and inflammatory cells play a pivotal role in the development of psoriatic lesions, resulting in angiogenesis and endothelial dysfunction. Furthermore, the imbalance between oxidative stress and antioxidant mechanisms in psoriatic patients may contribute to explain the pathogenesis of increased reactive oxygen species and the formation of atherosclerotic plaque. Other mechanistic pathways which may be involved in this relationship include cardiovascular effects of medications, a common genetic background and a higher prevalence of cardiovascular risk factors, which are often under-diagnosed and under-treated in psoriatic patients. Indeed, the early detection of specific markers of cardiovascular impairment, such as N-terminal pro B-type natriuretic peptide, homocysteine and YKL-40, may enable psoriatic patients at higher cardiovascular risk to be identified as soon as possible. This review examines the increased cardiovascular risk profile and high prevalence of cardiovascular disease associated with psoriasis, focusing on pathogenic links between psoriasis and atherosclerosis, serological markers of cardiovascular involvement and the implications of antipsoriatic therapies on cardiovascular risk and proposes a flow chart, that every dermatologist should follow to screen psoriatic patients.

Drug-induced bullous pemphigoid (DIBP) has been reported to be an autoimmune bullous disease induced or precipitated by several drugs, immunopathologically similar to classic bullous pemphigoid. Several medications may not only cause DIBP, including diuretics, antiarrythmics-antihypertensives, and recently antitumor necrosis factor agents, other drugs as chloroquine, but also rarely by antibiotics as amoxicillin and penicillin. The authors present the third case of DIBP induced by quinolones and the second case of localized DIBP triggered by oral ciprofloxacin. A DIBP can be suspected in old patients when they add or change some drugs in their normal medication regimen.

Background Psoriasis is an inflammatory disease, that is increasingly being considered as a systemic disorder. Among associated comorbidities, metabolic syndrome plays an important role. The effects of biological therapies on metabolic syndrome is controversial. Methods Thirty-one psoriatic patients with metabolic syndrome, eligible to treatment with anti-TNFα agents, were enrolled. Metabolic parameters were measured during 4 subsequent visits, one every 40 to 60 days. PASI, BSA and DLQI assessed the severity of psoriasis and the impact on quality of life. Results We include 31 patients, 18 treated with etanercept and 13 with adalimumab. Metabolic parameters evaluated at V4 in both groups showed different trends in the blood glucose values: a slight decrease in adalimumab group, an increase in etanercept group, with an almost significant comparison test (P=0.073). Similarly, the lipid profile revealed an opposing trend, with an increase in triglycerides in adalimumab patients, and a decrease in the other group, without statistically significant differences. No statistically significant difference was recorded in HDL cholesterol. An improvement in systolic and diastolic pressure was appreciated in both groups, although not significantly. The waist circumference slightly decreased in both groups. PASI 75 score was reached in 60% of the patients. In addition, BSA and DLQI improved. Conclusions Our study showed a slight improvement of metabolic parameters, at times with a trend toward significance. Additional long-term studies and a larger number of patients are needed to more clearly define the association between psoriasis and cardiovascular disease and understand the effect of biological therapies on metabolic parameters.

Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), α6β4 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p = 0.006), and between Col VII positivity and Setterfield severity score (p = 0.020).

Granuloma annulare (GA) is a chronic, benign, and usually self-limiting cutaneous inflammatory disease, typically characterized by small, localized, skin-coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50-70% of localized GA cases are self-limiting and show spontaneous resolution after 1-2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low-dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA.

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Summary Papular elastolytic giant cell granuloma is an unusual variant of annular elastolytic giant cell granuloma. Its rarity makes the assessment of the real efficacy of any treatment difficult, as spontaneous remission is possible. We report a case whose interest, besides the rarity of the occurrence, rests in the pure papular expression of the clinical features, the association with a monoclonal gammopathy and the apparent efficacy of topical tacrolimus.

Bullous pemphigoid may occur in extremely variegated manners, misleading even experienced dermatologists. Indeed the type and/or distribution of lesions may be unusual. Furthermore, there may be an atypical demographic profile of patients, a different clinical course and a different responsiveness to therapy. Up to 20% of the cases the onset is characterized by a non-bullous phase, lasting weeks, months or in particular cases remaining the only manifestation of the disease. During this early phase lesions are generally pruritic erythematous, eczematous or urticarial; however, lesions may also resemble polycyclic, targetoid, nodular or lichenoid lesions. These atypical lesions may also coexist with typical bullae. Other atypical presentations include a vesicular eruption and an erythroderma. Manifestations in children differ from adult forms, presenting an exclusive genital involvement in 50% of cases or a preponderant involvement of the face, the palms and the soles. Rarely bullous pemphigoid is confined to certain body areas, due to particular triggering factors or to a lower disease activity. Therefore, the need to formulate universally recognized diagnostic criteria is increasingly evident, especially for atypical bullous pemphigoid. Direct immunofluorescence of perilesional skin and detection of circulating autoantibodies are mandatory in the diagnosis, especially when the clinical presentation is doubtful.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increase in blood platelets and dominated by a predisposition to vascular events. Cutaneous manifestations can complicate its course. itching has been the most common symptom reported; however, the percentage has ranged from 3% to 46%, depending on the survey. Erythromelalgia is found in 6% of cases, and livedo reticularis, minor bleeding, acrocyanosis, and Raynaud's phenomenon are rare manifestations. It is important to recognize and treat these events, because they can affect patients' quality of life and could worsen the prognosis. In addition to skin involvement as a possible sign of ET, the treatment of ET can be associated with cutaneous complications. Hydroxycarbamide, interferon-alfa, and anagrelide can induce different skin lesions. Hydroxycarbamide has been associated with major complications, including painful leg ulcers and actinic keratoses. Minor events include alopecia and hyperpigmentation. Xerosis, pruritus, and photosensitivity are some of the complications reported by patients treated with interferon-alfa. Anagrelide has proved to be associated with fewer dermatologic effects, only detected in single cases. Knowledge of the ET cutaneous manifestations, together with the clinical examination findings, can result in an earlier diagnosis and the start of effective treatment.

Anti-TNFα drugs have strongly changed the way in which we deal with moderate and severe psoriasis. However, it is debatable whether biological drugs could increase the risk of developing cancer. The correlation between anti-TNFα drugs and lymphomas is well-known and is reported in all the technical details of biologic drugs. However, the association between anti-TNFα agents and solid tumors is still controversial. The authors report a case of bilateral salivary gland tumor in a psoriatic patient treated with several immunosuppressive therapies including anti-TNFα inhibitors.

Introduction La cryptococcose est une infection induite par une levure encapsulee, le Cryptococcus neoformans, un mycete dimorphique saprophyte du milieu externe (sol, fiente pigeon), qui se developpe a l’occasion d’un deficit immunitaire. La clinique est souvent polymorphe : lesions acneiformes, purpura, vesicules, nodules, abces, granulomes, ulceres et pustules. Observation Les auteurs decrivent le cas d’un homme de 68 ans, qui consultait dans le service d’hematologie pour une leucemie lymphocytaire chronique refractaire a la therapie, qui presentait un nodule erythemateux-violace, apparu un mois auparavant sur le dos de la main droite. Cette lesion n’avait pas repondu a une corticotherapie topique et a une therapie antibiotique (trimethoprime-sulfamethoxazole). L’examen histologique a confirme la suspicion clinique de cryptococcose demontrant des cryptocoques a la coloration par Alcian Blue-PAS. La presence de lesions viscerales a ete exclue par des examens morphologiques. Apres un cycle de deux semaines de fluconazole (300 mg/j) suivi d’un cycle d’itraconazole (200 mg/j pendant 2 mois), le patient est completement gueri. Discussion La cryptococcose cutanee est generalement une localisation secondaire d’une primo-infection pulmonaire a diffusion hematogene. Les auteurs tiennent a souligner que, bien que l’infection cutanee primaire, induite par voie transcutanee, soit rare, le diagnostic de cryptococcose doit etre considere devant tout nodule chez un patient immunodeprime, notamment si present dans les zones decouvertes du corps.

Tumour necrosis factor (TNF) antagonists are generally well tolerated, but carry the risk of side effects. In patients with psoriasis, the potential risks with anti-TNF agents may be overestimated because the most commonly reported adverse events are based on studies in patients with rheumatoid arthritis or inflammatory bowel disease. Whereas patients with psoriasis typically receive monotherapy, these patients are treated with biological-based combination therapies. Furthermore, patients with psoriasis have distinctive and different comorbidities, which could play a role in the development of different adverse events. However, the potential risks of the use of biological agents should always be taken into consideration. © 2010 Adis Data Information BV. All rights reserved.

The tumor necrosis factor-α ( TNF-α ) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-α is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-α gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-α inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility ( P =0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters ( P -values ranging from 0.016 to 2.908 × 10 −12 ). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.

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.