Miriam Teoli

Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab

Our understanding of the genetic basis of predisposition to psoriasis is increasing exponentially due to the progress of genetic studies. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics. We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the outcome of biologic therapy.

The Impact of Methodological Approaches for Presenting Long-Term Clinical Data on Estimates of Efficacy in Psoriasis Illustrated by Three-Year Treatment Data on Infliximab

Background: Psoriasis affects about 2–3% of the Caucasian population. Biologics such as infliximab, etanercept, adalimumab and ustekinumab are efficacious treatments of plaque-type psoriasis. Critical to monitoring drug efficacy and safety is availability of long-term data. Despite the chronic nature of psoriasis, to date limited long-term clinical data have been available, as challenges are inherent in conducting a long-term analysis. With increasing time, it is more likely that the number of patients discontinuing treatment will also increase, due to loss of efficacy, adverse events or loss to follow-up. Interpretation of these data becomes confounded when one must consider missing data. Several approaches to analysing long-term data exist, and each accounts for missing data differently. Objective: To demonstrate that the choice of a particular analysis method to account for missing data has great impact on the assessed response rate. Methods: We used data from an open-label study over 3 years of continuous treatment with infliximab in patients with plaque-type psoriasis. These data were analysed by three methods – last observation carried forward, observed values and non-responder imputation – to account for missing data. Results: The 3-year PASI 75 responses varied from 41 to 75%, depending on the method of analysis; this shows that the response rate can almost double when a more liberal analytical approach is used. Conclusions: While it is clear that the need for long-term data on biologics in psoriasis is great, considering the analysis undertaken is important when designing long-term studies and interpreting the resulting data. When analysis methods such as observed values only or last observation carried forward are used, the results of the more conservative non-responder imputation should also be presented to give a fair overview of the long-term efficacy of a treatment for plaque-type psoriasis.

Role of contrast-enhanced ultrasound in early diagnosis of psoriatic arthritis

Background: Radiographic examination (Rx) is still the best method to obtain an accurate diagnosis of psoriatic arthritis (PsA). Nevertheless, ultrasound (US) examination of the potentially involved joints has started to play a leading role. The sensitivity and specificity of a scan can be determined by contrast enhancement in the diagnosis of arthritis during PsA in comparison with basal US with MRI. Methods: Our study was made on 22 uninformed patients showing clinical suspicion of PsA. The patients were submitted to clinical evaluation, Rx, US with and without contrast enhancement and MRI. The parameters evaluated by basal US were effusion, synovial hypertrophy, positiveness to color power Doppler signals and bone erosion. Results: Contrast-enhanced US (CEUS) seems to amplify small alterations previously detected by US and, moreover, increases the diagnostic confidence in cases of suspected symptomatology with a negative diagnosis. Finally, CEUS appears to have a concordance of almost 100% with the results of MRI with contrast enhancement. Conclusion: US appears to be an effective method for detecting the alterations in bone outline and soft tissues, such as synovitis. Furthermore, US provides useful information concerning the evolution of vascularization and the dynamic behavior of tendons.

Methyl aminolaevulinate photodynamic therapy for the treatment of hidradenitis suppurativa and pilonidal cysts

Hidradenitis suppurativa (HS) and pilonidal cysts are chronic, inflammatory skin conditions involving apocrine gland‐bearing skin. Treatment is limited and unsatisfactory. Photodynamic therapy (PDT) has been reported to be safe and effective in the treatment of several off‐label skin conditions. We report the case of a 29‐year‐old man affected by HS and pilonidal cysts since the age of 21. In the past, the patient was treated with antibiotics, corticosteroids and retinoids, without significant clinical improvement. Treatment with methyl aminolaevulinate (MAL)‐PDT was started. A topical MAL cream (Metvix®) was applied to the affected areas with an occlusive dressing for 3 h and irradiated with a red light source. Therapy was repeated every 15 days for a total of nine applications. The patient completed a 6‐month follow‐up and achieved an almost complete clinical remission of the skin lesions (80%) and complete resolution of the itching and discomfort. This is the first case of HS associated with pilonidal cysts treated with MAL‐PDT. MAL‐PDT was effective and well tolerated in our patient. The costs of this therapy represent an important limitation, taking into account the high number of sessions that were performed compared with non‐melanoma skin cancers.

Bullous dermatomyositis: A marker of poor prognosis and aggressive internal malignancy?

infected lesiotis and the persistence of HPV seems to be related to this reduction or to LC altered function (14). In a recent review ( I ) it was des^cribed that HPV does not infect or replicates in APCs located in the epithelium, resulting in failure ofHPV presentation to the immune system. Another possibility is that LCs. although able to bind and internalize HPV. are not activated by these events and they do not induce a response. This indicates that LC may be a target used by HPV as an immune escape mechanism (15). The increased number of hypertrophie FXIIla-tDD in HPV vulvar lesions suggests that this group of cells might play a role in the pathogenesis of HPV infection. Considering that FXlIIa+ DD are capable of antigen presenting, the present study leads tis to suggest that FXllla-i DDwouldbcable to engulf the viral antigens and to promote their presentation to the immune system.

Hydroxyurea associated with concomitant occurrence of diffuse longitudinal melanonychia and multiple squamous cell carcinomas in an elderly subject

BACKGROUND Hydroxyurea is a cytostatic agent used to treat myeloproliferative disorders and long-term treatment is associated with mucocutaneous adverse events and nail hyperpigmentation. OBJECTIVE The purpose of this study was to report the concomitant occurrence of multiple squamous cell carcinomas and diffuse nail hyperpigmentation associated with hydroxyurea treatment, and to describe a successful therapeutic approach using imiquimod 5%. CASE SUMMARY We report the case of an 81-year-old white man (weight, 82 kg; height, 173 cm; photodamaged type II skin) affected with cirrhosis of the liver, chronic idiopathic myelofibrosis, and a 3-year history of longitudinal melanonychia and periungual hyperpigmentation. His current medication regimen was hydroxyurea (500 mg BID), iron (525 mg QD), and folic acid (15 mg QD) for the myeloproliferative disease and the associated anemia; spironolactone (25 mg BID) and furosemide (20 mg BID) for the complications of cirrhosis; allopurinol (100 mg QD) to treat gout; and theophylline (250 mg QD) for chronic bronchitis. The patient presented with several actinic keratoses, squamous cell carcinomas, and multiple keratoacanthomas, one of which was pigmented. Both the longitudinal melanonychia and the multiple skin cancers first appeared after approximately 6 months of hydroxyurea treatment. A correlation between dose and manifestation was investigated but none was found. Based on the Naranjo algorithm, the adverse reaction observed was probably related to the hydroxyurea treatment (score = 6); however, the hydroxyurea chemotherapy could not be discontinued because of the myeloproliferative disorder. Complete remission was observed after 6 to 10 weeks of imiquimod 5% (10 mg/cm of skin cancer) treatment. The patient completed a 10-month follow-up, maintaining a complete resolution of the treated skin lesions; however, the development of a painful hand ulcer, possibly associated with the hydroxyurea, and new skin cancers were observed at the last follow-up visit. CONCLUSIONS We report this case of the concomitant appearance of multiple skin cancers and nail changes associated with hydroxyurea use. The progressive appearance of squamous epitheliomas and other cutaneous adverse events, such as the ulcer, suggests that alternative chemotherapies should be considered for the treatment of myeloproliferative diseases.

Evaluation of Clinical and Ultrasonographic Parameters in Psoriatic Arthritis Patients Treated with Adalimumab: A Retrospective Study

Objectives. The aim of this study was to evaluate clinical and US-PD parameters in PsA during adalimumab treatment. Methods. A retrospective study has been conducted in forty patients affected by moderate-to-severe peripheral PsA. Clinical, laboratory, and US-PD evaluations were performed at baseline, after 4, 12, and 24 weeks of treatment. They included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), Health Assessment Questionnaire (HAQ) modified for Spondyloarthritis, Psoriasis Area Severity Index (PASI) score, the 28-joint Disease Activity Score (DAS 28), and US-PD assessment. US-PD findings were scored according to a semiquantitative scale (ranging 0–3) for synovial proliferation (SP), joint effusion (SE), bone erosions (BE), and PD. Results. Data obtained for clinical, laboratory findings and US-PD evaluation showed statistical significant improvement in all the measures performed except for BE. A significant parallel decrease in SE, SP, and PD values were demonstrated. Conclusion. This study demonstrated that US-PD is a valid technique in monitoring the response to adalimumab in moderate-to-severe PsA.

Remission of psoriatic arthritis after etanercept discontinuation: analysis of patients' clinical characteristics leading to disease relapse.

Psoriatic arthritis is a chronic, inflammatory, disabling arthritis affecting up to 30% of psoriatic patients. Recently, it has been demonstrated that tumor necrosis factor alpha (TNF-α) plays a pivotal role in inducing and maintaining joint damage and that molecules that block this cytokine are effective in the treatment of psoriatic arthritis. Etanercept is a recombinant fusion protein acting as a competitive inhibitor of TNF-α, and numerous clinical trials have demonstrated its efficacy in determining psoriatic arthritis remission. However, specific criteria defining psoriatic arthritis remission have not been delineated and few data describing the length of the remission after etanercept discontinuation are available. The aim of this observational, retrospective study was to assess post-remission efficacy maintenance and relapse characteristics after etanercept interruption in patients with moderate-to-severe peripheral psoriatic arthritis (PsA) and cutaneous involvement.

Golimumab in Patients Affected by Moderate to Severe Psoriatic Arthritis: An Open-Label Study in Thirty-Two Patients Previously Treated with Other Biologics

Background: Clinical trials have demonstrated the efficacy of golimumab (GLB) in improving the signs and symptoms of psoriatic arthritis (PsA). Objective: The aim of this study was to evaluate the efficacy of GLB in monotherapy in patients affected by PsA with cutaneous involvement unresponsive to other anti-tumor necrosis factor-α (TNF-α) agents. Methods: This study included 32 patients treated with GLB as monotherapy, at a dosage of 50 mg, subcutaneously, every 4 weeks. Patients were divided into 3 groups (A, B, and C) according to their number of previous anti-TNF-α treatments (1, 2, or 3). Clinical and laboratory evaluations were performed at weeks 0, 12, and 24. Results: All patients showed significant improvement of their clinical, inflammatory, and quality of life indexes. Conclusion: Data suggest that GLB can be successful and safe in patients affected by PsA with skin involvement previously treated with other anti-TNF-α agents.

Patients with Moderate to Severe Plaque Psoriasis: One Year after the European Medicines Agency Recommendation of Efalizumab Suspension

Background: In February 19, 2009, the European Medicines Agency (EMA) had recommended the suspension of the marketing authorization for efalizumab after the occurrence of cases of progressive multifocal leukoencephalopathy. Objective: To explore the efficacy of alternative therapies for psoriasis and the health status of patients who discontinued efalizumab. Methods: An observational study was performed on 101 patients. After the EMA communication, efalizumab was discontinued in the following 2–3 months. In agreement with the patients, we decided to either prescribe other treatments or none at all. Results: After 1 year, 11 patients are still not treated, 63 patients are treated with biologics, and 9 patients are treated with systemic conventional therapies. Conclusion: In order to prevent rebound or relapse, various approaches are available, including cyclosporine, methotrexate and biologic therapies. Interestingly, in 11 out of 31 patients who did not receive any systemic drug, psoriasis is still under control, suggesting a long-term effect of efalizumab.