Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

The ATTRACT study: screening for the early identification of axial psoriatic arthritis in a cohort of Italian psoriatic patients.

OBJECTIVE: There is growing interest in the early identification of patients with axial psoriatic arthritis (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. METHODS: The dermatologist-centered screening (DCS) questionnaire was administrated by Dermatologists to consecutive patients fulfilling the inclusion criteria (1. age ≥ 18 years and 2. clinical diagnosis of psoriasis made by a dermatologist) to identify patients eligible (affirmative answers 1-3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic, and imaging data were collected from all referred patients. RESULTS: Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months, and 140 (53%) reporting back pain onset before the age of 45. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients.Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with Pso without PsA. CONCLUSION: The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA.

Brodalumab for the Treatment of Moderate-to-Severe Psoriasis: An Expert Delphi Consensus Statement.

Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against interleukin-17RA that has been approved for the treatment of moderate-to-severe psoriasis in Europe. We developed a Delphi consensus document focused on brodalumab for the treatment of moderate-to-severe psoriasis. Based on published literature and their clinical experience a steering committee drafted 17 statements covering 7 domains specific to the treatment of moderate-to-severe psoriasis with brodalumab. A panel of 32 Italian dermatologists indicated their level of agreement using a 5-point Likert scale (from 1 = "strongly disagree" to 5 = "strongly agree") using an online modified Delphi method. After the first round of voting (32 participants), positive consensus was reached for 15/17 (88.2%) of the proposed statements. Following a face-to-face virtual meeting, the steering committee decided that 5 statements would form "main principles" and 10 statements formed the final list. After a second round of voting, consensus was reached in 4/5 (80%) of the main principles and 8/10 (80%) for consensus statements. The final list of 5 main principles and 10 consensus statements identify key indications specific to the use of brodalumab in the treatment of moderate-to-severe psoriasis in Italy. These statements aid dermatologists in the management of patients with moderate-to-severe psoriasis.

Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

Certolizumab Pegol: A New Therapeutic Approach for Acrodermatitis Continua of Hallopeau.

Introduction: Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic, and recurrent form of pustular psoriasis (PP) localized to one or more digits. Due to the rarity of ACH, no clear treatment guidelines are currently available, making the therapeutic approach more complex. Case Presentation: We report the first case of a young woman with ACH who was successfully treated with certolizumab pegol (CZP). Discussion/Conclusion: PP and ACH are difficult to treat, and biologics may be an option more manageable than cyclosporine. CZP is the safest biologic therapy during pregnancy, so there is low risk in prescribing it in women with childbearing potential. However, continuing biological therapy during pregnancy always involves an assessment of the clinical benefits, which must outweigh the risks.

SARS-COV-2 Infection, Vaccination, and Immune-Mediated Diseases: Results of a Single-Center Retrospective Study.

Objectives: The relationship between infections or vaccine antigens and exacerbations or new onset of immune-mediated diseases (IMDs) has long been known. In this observational study, conducted during the COVID-19 pandemic, we evaluated the onset of clinical and laboratory immune manifestations related to COVID-19 or SARS-CoV-2 vaccination. Methods: Four groups of patients were evaluated: A) 584 COVID-19 inpatients hospitalized from March 2020 to June 2020 and from November 2020 to May 2021; B) 135 outpatients with previous SARS-CoV-2 infection, assessed within 6 months of recovery; C) outpatients with IMDs in remission and flared after SARS-COV-2 infection; D) outpatients with symptoms of probable immune-mediated origin after SARS-CoV-2 vaccination. Results: In cohort A we observed n. 28 (4.8%) arthralgia/myalgia, n. 2 (0.3%) arthritis, n. 3 (0.5%) pericarditis, n. 1 (0.2%) myocarditis, n. 11 (1.9%) thrombocytopenia or pancytopenia, and in the follow up cohort B we identified 9 (6.7%) cases of newly diagnosed IMDs after the recovery from COVID-19. In all cases, serological alterations were not observed.In cohort C we observed n.5 flares of pre-existing IMD after SARS-COV2 infection, and in the cohort D n. 13 IMD temporally close with SARS-CoV-2 vaccination in 8 healthy subjects (with clinical classifiable IMD-like presentation) and in 5 patients affected by an anamnestic IMD. Also in these latter cases, except in 2 healthy subjects, there were not found serological alterations specific of a classifiable IMD. Conclusions: This study suggests that the interplay between SARS-CoV-2 and the host may induce complex immune-mediated reactions, probably induced by the anti-spike antibodies, in healthy people and IMD patients without specific serological autoimmunity. Moreover, our data suggest that the anti-SARS-CoV-2 antibodies generated by the vaccination may cause in healthy subjects' clinical manifestations similar to well-definite IMDs. These findings support the hypothesis that SARS-Cov2 infection in COVID-19 induce an innate and adaptive immune response that may be both responsible of the symptoms correlated with the occurrence of the IMDs described in our study. And, in this context, the IMDs observed in healthy people in close temporal correlation with the vaccination suggest that the anti-Spike antibodies may play a key role in the induction of an abnormal and deregulated immune response.

Dimethyl Fumarate's Effectiveness and Safety in Psoriasis: A Real-Life Experience During the COVID-19 Pandemic.

INTRODUCTION: Dimethyl fumarate (DMF) is approved as oral systemic treatment for moderate-to-severe psoriasis. Scarce evidence is available for DMF treatment in psoriatic patients at the time of COVID-19 pandemic. The objective of this study was to assess the long-term effectiveness and safety of DMF monotherapy in moderate-to-severe psoriasis during the COVID-19 pandemic period. METHODS: This multicenter, retrospective study included patients with moderate-to-severe psoriasis who had received a 48-week DMF treatment during the COVID-19 pandemic. Selected outcomes were: variation of mean PASI, proportion of patients achieving PASI50 and PASI75, variation of mean PGA and face PGA, genital PGA, scalp PGA, mean itch VAS and mean DLQI. RESULTS: Forty-four patients were enrolled, and four patients became COVID-19 positive during the observation period but did not discontinue DMF therapy. DMF produced a significant improvement of signs and symptoms of psoriasis as expressed by mean PASI variation from 13.07 at baseline to 6.11 at week 48 (p < 0.0001), itch VAS from 3.22 at baseline to 1.18 at week 48 (p < 0.001), PGA from 2.84 at baseline to 1.30 at week 48 (p < 0.0001) and DLQI from 13.09 at baseline to 6.07 at week 48 (p < 0.0001). The percentage of patients who achieved PASI50 and PASI75 was 4.55% at week 4 and 59.09% at week 48 and 0% at week 4 and 22.73% at week 48, respectively. A clinical important decrease of mean PGA score was observed in all subgroups, face psoriasis, genital psoriasis and scalp psoriasis. Adverse events were predictable and manageable. CONCLUSIONS: DMF monotherapy is an effective and safe treatment option in moderate-to-severe psoriasis also in patients who develop SARS-CoV-2 infection.

Outcome following a short period of adalimumab dose escalation as rescue therapy in psoriatic patients.

BACKGROUND: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses. OBJECTIVES: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5). MATERIALS AND METHODS: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI> 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week. RESULTS: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis. CONCLUSION: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy.

Effects of a cream containing 5% hyaluronic acid mixed with a bacterial-wall-derived glycoprotein, glycyrretinic acid, piroctone olamine and climbazole on signs, symptoms and skin bacterial microbiota in subjects with seborrheic dermatitis of the face.

Objective: A new cream formulation containing hyaluronic acid 5%, complexed with a mix of a bacterial-wall-derived glycoprotein and peptide glycan complex (EDS), has been recently developed. We evaluated in a prospective, assessor-blinded, 6-week study the efficacy and tolerability of EDS in the treatment of facial seborrheic dermatitis (SD) and the effects on skin microbiota. Subjects and methods: Seventy-five subjects (mean age 46; 60 men) with moderate-severe SD of the face were enrolled. EDS cream was applied twice daily. The primary outcome was the evolution of the Investigator Global Assessment (IGA) score, evaluating erythema, scale/flaking, grade of seborrhea and itch. Superficial skin bacterial microbiome at baseline and after treatment was assessed, using the 16S rRNA gene methodology, in affected and non-affected face areas. Local tolerability was evaluated checking self-reported side effects at each visit. Results: Baseline IGA scores (mean±SD) was 10±3. The use of EDS reduced IGA score significantly by 70% at week 3 and by 88% at week 6. An increase in the abundance of Cutibacterium acnes genera associated with a significant drop of Staphylococcus genera presence was detected in affected areas. The ratio of relative abundance of genera Cutibacterium/Staphylococcus increased significantly after treatment in affected areas. The product was very well tolerated. Conclusion: Treatment with EDS applied twice daily for 6 consecutive weeks was associated with a reduction of the signs and symptoms of SD. Furthermore, after EDS cream treatment, a reequilibrating effect on facial skin microbiota was observed. The product was very well tolerated.

Omalizumab in Chronic Urticaria: An Italian Survey.

Omalizumab is approved for use in chronic spontaneous urticaria (CSU); however, it is not approved for chronic inducible urticaria (CIndU). The aim of the present study was to assess the effectiveness of omalizumab in treating CSU and CIndU in Italy. This is a multicentre prospective observational real-life study involving patients with severe urticaria capable of undergoing omalizumab therapy. We enrolled 127 patients (59.1% females), ranging in age from 15 to 83 years, 69.3% had CSU alone, 26.8% had CSU and CIndU, and 3.9% had only CIndU (30.8% delayed pressure, 35.9% dermographic, 15.3% cholinergic, 12.8% cold, 5.1% aquagenic). After the first cycle of omalizumab (300 mg every 4 weeks for 24 weeks), 16 CSU patients and 10 patients (20.5%) with CIndU with or without CSU did not require a second cycle of omalizumab (300 mg every 4 weeks for 20 weeks). The patient with aquagenic urticaria achieved remission after the first cycle. None showed a lack of response to the second cycle of omalizumab. Omalizumab is a promising drug for both spontaneous and inducible chronic urticaria. Current evidence indicates that omalizumab may be approved also for CIndU.

Clinical outcomes and feasibility of the multidisciplinary management of patients with psoriatic arthritis: two-year clinical experience of a dermo-rheumatologic clinic.

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune arthritis, occurring in patients with psoriasis (Pso), that may affect the whole musculoskeletal system but also nails, eye, and gastrointestinal tract. Dermatologists and rheumatologists usually manage Pso and PsA separately, but early diagnosis and integrated management could achieve better outcomes of both skin and musculoskeletal manifestations, thus improving the health-related quality of life (HRQoL) of patients. In this work, we have described a model of integrated dermo-rheumatologic approach for the early diagnosis of PsA and to present the outcomes of the multidisciplinary management of PsA patients after 48 weeks of follow-up. Pso patients complaining musculoskeletal symptoms were enrolled in a DErmo-Rheumatologic Clinic (DERC) in order to screen, classify, and treat patients with PsA, employing an operative working procedure and a specific flowchart. The integrated dermatologic and rheumatologic management of PsA patients allowed a prompt establishment of the diagnosis and the best therapeutic approach in these patients, with a significant improvement of skin and articular diseases and, eventually, a consistent amelioration of HRQoL. Dermatologists and rheumatologists usually manage the "psoriatic disease" in separated outpatient clinics. In our study, we have demonstrated that a combined DERC, by means of a tight cooperation between the dermatologist and the rheumatologist, which use a specific working procedure and treatment flowchart, may achieve the optimal clinical management of these patients, with a consistent clinical remission of the disease and a significant amelioration of the HRQoL.

Correlation between immunohistochemical staining of CEACAM1 and clinicopathological findings in oral pre-neoplastic lesions and squamous cell carcinoma.

Squamous cell carcinoma of the oral cavity represents the sixth most common cancer worldwide and it is often preceded by pre-neoplastic lesions. Sometimes it is still difficult for pathologists to make objective differential diagnoses only on histological characteristics. Tumorigenesis is accompanied by altered expression of cell adhesion molecules, like carcinoembryonic antigen cell adhesion molecule (CEACAM)1. We wanted to investigative CEACAM1 in oral dysplastic lesions, carcinoma in situ (CIS) and oral squamous cell carcinoma (OSCC). We examined immunohistochemical CEACAM1 expression in 50 OSCC, 30 oral CIS and 40 pre-neoplastic lesions and assessed its correlation with clinical and pathological parameters. CEACAM1 was not expressed in normal mucosa, significantly expressed in CIS while it was negative in all the dysplastic lesions. In OSCC, high CEACAM1 expression was associated with tumor grade and inversely correlated with both overall and disease-specific 5-year survival. We showed that CEACAM1 expression is very dynamic: absent in dysplastic lesions, up-regulated in CIS and OSCC. We suggest that CEACAM1 could be a prognostic marker of OSCC and oral CIS. Our most important finding was that it could help pathologists diagnosing oral carcinoma in situ.

A validation study of the Simple Psoriatic Arthritis Screening (SiPAS) questionnaire to screen psoriasis patients for psoriatic arthritis.

OBJECTIVES: To validate in a multicentric cohort of patients a self-administered PsA screening tool, called Simple Psoriatic Arthritis Screening (SiPAS) questionnaire, to screen psoriasis patients for signs and symptoms of PsA. METHODS: The SiPAS questionnaire was validated in a multicentric Italian cohort of psoriasis patients referred to two rheumatological centres. RESULTS: A total of 202 psoriasis patients were screened with SiPAS in the validation study. Sixty-two psoriasis patients (30.7%) were diagnosed with PsA. The five screening questions (1. Have you ever had a finger or a toe and/or another joint swollen and painful without any apparent reason?; 2. Occasionally, has an entire finger or toe become swollen, making it look like a 'sausage'?; 3. Do you wake up at night because of low back pain?; 4. Have you had pain in your heels?; 5. Has a doctor ever diagnosed you with psoriatic arthritis?) with a dichotomous response, demonstrated high sensitivity and specificity for predicting PsA. Likelihood ratios for individual parameters varied between 2.06 and 4.75. Using the Bayesian Analysis, the presence of three of five items answered as "yes" showed respectively a sensibility and a specificity of 79% and 87%, with a positive likelihood ratio of 6.14. CONCLUSIONS: The SiPAS questionnaire is able to quickly screen psoriasis patients for PsA. A SiPAS score ≥3 is an indication for referral to a rheumatologist. The SiPAS needs further validation.

In vitro activity of the protegrin IB-367 alone and in combination compared with conventional antifungal agents against dermatophytes.

The occurrence of resistance or side effects in patients receiving antifungal agents leads to failure in the treatment of mycosis. The aim of this experimental study was to investigate the in vitro effects of IB-367 alone and in combination with three standard antifungal drugs, fluconazole (FLU), itraconazole (ITRA) and terbinafine (TERB), against 20 clinical isolates of dermatophytes belonging to three species. Minimum inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), synergy test, time-kill curves, fungal biomass (FB) and hyphal damage using 2,3-bis-(2-methoxy-4-nitro-5-sulfenylamino carbonil)-2H-tetrazolium hydroxide assay (XTT) were performed to study the efficacy of IB-367. In this study, we observed that TERB and ITRA had MICs lower values for all the strains compared to IB-367 and FLU. Synergy was found in 35%, 30% and 25% of IB-367/FLU, IB-367/ITRA and IB-367/TERB interactions respectively. IB-367 exerted a fungicidal activity against Trichophyton mentagrophytes, T. rubrum and Microsporum canis at concentrations starting from 1x MIC. At a concentration of 5x MIC, IB-367 showed the highest rates of hyphae damage for M. canis 53% and T. mentagrophytes 50%; against the same isolates it caused a reduction of 1 log of the total viable count cell hyphae damage. We propose IB-367 as a promising candidate for the future design of antifungal drugs.

Prognostic value of CD44 expression in penile squamous cell carcinoma: a pilot study.

BACKGROUND: Several studies have reported on the prognostic value of molecular markers for metastasis risk and survival in penile squamous cell carcinoma (SCC) patients. The usefulness of CD44 expression as such a marker has been studied in different tumors, but not in penile SCC. Our aim was to determine whether CD44 expression may serve as a prognostic marker for lymph node metastasis and survival in penile SCC patients. METHODS: CD44 immunoistochemical expression was investigated in tissue specimens from 39 patients with penile SCC. CD44 cell positivity, staining intensity and distribution were analyzed and correlated with tumor stage, grade, lymph node status and disease-specific survival. RESULTS: CD44 expression was detected in epithelial cells of both intratumoral and normal tissues with different intensities and staining distributions. In normal tissues CD44 protein was mainly detected in cell membranes, whereas in the tumor compartments it was found in both the cell membranes and the cytoplasm. The intensities and percentages of CD44 expressing cells did not correlate with tumor stage and/or grade. Seventy-three percent of the patients with lymph node metastasis showed high intensities of CD44 staining, as compared to 44% of the patients without lymph node metastasis (P = 0.03). Lymph node-positive patients showed both cytoplasmic and membranous CD44 expression. High CD44 expression was found to be significantly correlated with a decreased 5 year overall survival (P = 0.01). CONCLUSIONS: CD44 levels and patterns of expression can be considered as markers for penile SCC aggressiveness and, in addition, may serve as predictive markers for lymph node metastasis, also in patients with clinically negative lymph nodes. CD44 expression may provide prognostic information for penile SCC patients, next to classical clinical-pathological factors.

D2-40 immunoreactivity in penile squamous cell carcinoma: a marker of aggressiveness.

D2-40 immunohistochemical expression was investigated in tissue specimens from 39 patients with squamous cell carcinoma of the penis who underwent partial or total penectomy between 1987 and 2008. Patient age, tumor size, and grade; D2-40-positive lymphatic vessel density in intratumoral, peritumoral, and normal tissue; cell positivity for D2-40 in intratumoral and normal tissue; and D2-40 staining intensity and distribution were analyzed and correlated with disease-specific survival. Analysis of D2-40-positive lymphatics disclosed that mean lymphatic vessel density was greater in peritumoral tissue than in intratumoral and normal tissue and lower in patients with lymph node metastasis than in those without lymph node metastasis. The receiver operating characteristic curve showed that an intratumoral lymphatic vessel density greater than 2.0 had 83.3% sensitivity and 78% specificity in predicting lymph node metastasis. Analysis of cell immunoreactivity showed cytoplasmic D2-40 positivity in intratumoral and normal tissue in 89.7% and 65.5% of patients, respectively. A strong correlation emerged between grade of cell differentiation and D2-40 immunoreactivity in intratumoral tissue; in particular, 88.9% of tumors with weak podoplanin expression were G1, whereas strong cellular immunoreactivity was detected in 83.3% of G3 patients (P = .003; χ(2) test). A significant correlation was also noted between pattern of reactivity and tumor grade because the basal layer was positive in patients with undifferentiated tumors (100% of G3) and in 72.2% of G1 tumors (P = .021; χ(2) test). D2-40 seems to be a useful marker for the development of node metastasis in squamous cell carcinoma of the penis, although validation in larger series is required to confirm its predictive value.

A patient with psoriasis and vitiligo treated with etanercept.

Psoriasis is a chronic, immune-mediated, inflammatory dermatosis whose aetiopathogenesis remains unclear, although tumour necrosis factor alpha (TNFalpha) appears to play a crucial role. The biological potential of TNFalpha inhibitors, such as etanercept, which reduce the inflammatory cascade, has radically changed the therapeutic management of patients with psoriasis and other immunomediated inflammatory diseases, associated with TNFalpha. The pathogenesis of the selective destruction of melanocytes in vitiligo is not fully understood, although there is growing evidence that several T helper type 1 cytokines, particularly TNFalpha, may be involved in the depigmentation process. A patient is described who presented with both psoriasis and vitiligo, and was treated with etanercept. After 24 weeks of therapy, the patient's psoriasis had improved markedly and the patient noted a mild improvement of vitiligo, with a reduction in macules and repigmentation in the scapular region.

Lesional skin chemokine CTACK/CCL27 expression in mycosis fungoides and disease control by IFN-alpha and PUVA therapy.

Recruitment of neoplastic T cells to skin is a critical step in the pathogenesis of mycosis fungoides (MF) lesions. Cutaneous T-cell attracting chemokine (CTACK)/CCL27 attracts memory T cells to skin, resulting in increased cutaneous expression. The interactions between neoplastic cells and skin immune system require further elucidation. CTACK/CCL27 expression and density of dendritic cells (DC), CD8+ and CD4+ lymphocytes were investigated in skin lesions of 52 early-stage MF patients treated by interferon (IFN)-alpha in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA). Skin lesion biopsies obtained at diagnosis and after treatment were studied by immunohistochemistry. Initial CTACK/CCL27 expression was abnormal/suprabasal in 36 patients. Normal/basal CTACK/CCL27 expression tended to correlate with a high DC density and low CD4+ cell density in the neoplastic infiltrate. Treatment induced a significant increase in CTACK/CCL27 expression (chi(2) test: P=0.004). Overall, 33 patients relapsed [median event-free survival (EFS), 46 months] during follow-up (median, 92.5 months, range, 43-165). Normal/basal CTACK/CCL27 expression at the end of treatment correlated with lower rates of recurrence and a longer median EFS (111 months vs. 39 months with suprabasal expression; log rank test: P=0.031). CTACK/CCL27 overexpression in early-stage MF might thus be related to a balance between neoplastic cells and immunomodulant DC. Normal CTACK/CCL27 expression after treatment designates a subset of patients with favorable disease behavior. The mechanisms underpinning CTACK/CCL27 overexpression after therapy in the remaining patients, who are at greater risk of recurrence, warrant further investigation.

Lichen striatus in adults and pimecrolimus: open, off-label clinical study.

BACKGROUND: Lichen striatus is a well-known, acquired, self-healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side-effects, particularly cutaneous atrophy. OBJECTIVE: To report the results of an open, off-label study on the use of pimecrolimus 1% in the treatment of diffuse, nonresponsive forms of lichen striatus. METHODS: Three adult patients suffering from relapsing or disseminated and itchy lichen striatus received topical application of pimecrolimus 1% cream (Elidel, Novartis Pharma, Basle, Switzerland) twice daily for 6 weeks, or until complete disappearance of the cutaneous lesions. RESULTS: All patients experienced rapid healing of the dermatosis, without any recurrence for at least 14 months. CONCLUSION: Our preliminary results show that pimecrolimus may represent a useful therapeutic alternative for lichen striatus, although further studies on a larger number of cases are needed to confirm its safety and efficacy in the treatment of this condition.