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.

Treating psoriasis with etanercept in italian clinical practice: prescribing practices and duration of remission following discontinuation.

BACKGROUND: conventional antipsoriatic therapies are often administered until remission, with treatment resumed in the case of relapse, in order to reduce the likelihood of cumulative, dose-dependent toxicities. Biological agents have been safely used in continuous therapy. OBJECTIVE: to assess the use of etanercept for psoriasis in clinical practice in Italy. METHODS: this was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis (with a Psoriasis Area and Severity Index [PASI] score >or=10) treated with etanercept. The study comprised a treatment and subsequent discontinuation period. Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008. Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction >or=50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached >or=10 or the patient had a clinical relapse. Data were collected retrospectively up to June 2008 and prospectively between July 2008 and January 2009. Patients received etanercept during the treatment period, followed by no etanercept treatment (other psoriasis treatment permitted) during the discontinuation period, and etanercept again during re-treatment. The main outcome measures were: PASI scores (type A responders: PASI reduction >or=75% [PASI75]; type B responders: PASI50 and PASI final score <10), Dermatology Life Quality Index (DLQI) scores and body surface area (BSA) involvement. Time from discontinuation to re-treatment was evaluated. Use of other antipsoriatic medications was recorded throughout. RESULTS: eighty-five patients were evaluable for the treatment period. Overall, 55 (64.7%) of these patients were prescribed etanercept 50 mg twice weekly. The mean treatment duration was approximately 25 weeks. In total, 79 patients (92.9%) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis. Overall, 68/85 (80%) were type A responders. During the treatment period, 7/85 (8.2%) patients received other antipsoriatic therapies. Improvements in mean DLQI score (-71.5%) and mean BSA involvement (-79.2%) were also observed. Etanercept was well tolerated. During the discontinuation period, 40/77 (51.9%) patients used other antipsoriatic medications (group 1) and 37/77 (48.1%) did not (group 2). The mean duration of discontinuation was significantly longer in group 1 (174 days) than in group 2 (117 days, log-rank test: p = 0.0013). CONCLUSION: in clinical practice, the duration of discontinuation from etanercept was in accordance with previously reported data, and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not. High rates of PASI50 and PASI75 response were obtained with etanercept, and these rates were higher than those observed in controlled clinical studies. Etanercept treatment was flexible, effective and well tolerated, and was associated with improved quality of life.

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.

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

BACKGROUND: Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. METHODS: Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). RESULTS: Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. CONCLUSIONS: The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

The transitioning from conventional therapy to biological treatment in psoriatic patients: STRATOS, a project of Marche Region.

BACKGROUND: STRATOS is the acronym of the "STRuctured Approach to the Treatment of psOriatic patientS". The optimization of the psoriasis's therapeutic management is one of the most important goals for dermatologists. According to Mrowietz's consensus report, the transitioning from conventional therapy to biological therapy is mainly due to the lack/loss of efficacy and/or for safety reasons. The aim of the manuscript was to describe the principal results obtained by the Dermatologic Clinic of Polytechnic University of Marche Region and the Units of Dermatology of the Marche Region applying, in our regional reality, Mrowietz's protocol for the daily management of patients with moderate-to-severe plaque. METHODS: Forty-seven patients with moderate to severe chronic plaque psoriasis have been monitored during the six-months study period. RESULTS: Psoriatic patients with diabetes showed further concomitant comorbidities compared to non-diabetics, as hypertension and hypercholesterolemia. Moreover, based on WHO classification, overweight was diagnosed in female patients, whereas obesity was prevalent in male patients. This aspect confirms the strict link between the multifaceted aspects of psoriatic patient which is primarily related to the persistent low-grade inflammation. In our psoriatic group, 10% of monitored patients were affected by Crohn disease or ulcerative colitis. CONCLUSIONS: The Mrowietz's transitioning protocol is a useful, reliable and feasible tool to manage the therapeutic iter of psoriatic patients in an Italian clinical setting also at regional level.

Predictive value of biologic parameters for primary chemotherapy in operable breast cancer.

Primary chemotherapy represents an ideal model to evaluate the relationships between treatments and the prognostic and predictive parameters provided by the new technologies. First- and second-generation trials have shown that primary chemotherapy significantly improves the rate of breast conservation without increasing the risk of ipsilateral recurrence and while assuring survival rates comparable with those achieved with postoperative chemotherapy. Moreover, patients who exhibited a pathologic complete response (pCR) showed better progression-free survival and overall survival. The third-generation trials were aimed at improving the percentage of pCR, identifying and validating gene and protein biomarkers of chemotherapy sensitivity, and better defining the individual risk of relapse. Several parameters, such as index of proliferation and apoptosis, expression of proteins (eg, p53 and Bcl-2), and hormone receptor and epidermal growth factor family receptors, have been related to response to primary chemotherapy. Negative hormone receptors and greater proliferative activity seem to be the only parameters more consistently associated with greater chemotherapy sensitivity. However, the strength of this association is not sufficient to differentiate patients at different degrees of risk and does not allow for an individualized therapeutic choice. Newer technologies offer the possibility of evaluating thousands of genes and identifying clusters of gene expression associated with significantly different risks of relapse and patterns of sensitivity/resistance to specific drugs. The primary chemotherapy model is the ideal clinical setting in which to validate the relationship between tumor molecular profiling and treatment outcomes and to design tailored therapies based on observed effects on individual tumors.

Guess what! Pseudomonas aeruginosa sepsis.

A 62-year-old woman affected by end-stage renal disease secondary to Waldenstrom's disease was admitted to place a central venous catheter for hemodialysis purposes. During the admission, she gradually developed a number of necrotic ulcerative and fluctuant nodular skin lesions on the submammary flexures, groins and limbs accompanied by high fever and chills. Yellow-green purulent material could be drained from the site of introduction of the jugular catheter. Skin biopsies were taken from the edge of an inguinal necrotic-ulcerative lesion and from a fluctuant nodular lesion of the thigh, where pus was drained and cultured.

Renal safety and efficacy of i.v. bisphosphonates in patients with skeletal metastases treated for up to 10 Years.

INTRODUCTION: Bisphosphonates (BPs) delay the onset or reduce the incidence of skeletal complications in patients with bone metastases. However, there are few data on the renal safety and activity of i.v. BPs beyond 2 years of administration. MATERIALS AND METHODS: We retrospectively analyzed serum creatinine (SCr) levels and skeletal-related events (SREs) in cancer patients receiving i.v. BPs for >or= 24 months. All patients received 90 mg pamidronate every 3-4 weeks. Pre- and post-treatment SCr levels and the peak levels attained were recorded. A notable SCr increase was defined as: an increase >0.5 mg/dl for patients with baseline SCr <1.4 mg/dl; an increase >1 mg/dl for patients with baseline SCr >1.4 mg/dl; or doubling over baseline. The following parameters were also analyzed: the proportion of patients with at least one SRE, the distribution of each type of SRE, the time to first SRE, and the skeletal morbidity rate (SMR). RESULTS: Fifty-seven patients with bone metastases resulting from breast cancer (BC) (n = 48), multiple myeloma (n = 7), renal cell carcinoma (n = 1), and prostate cancer (n = 1) were evaluated. The median age at the start of treatment was 57 years (range, 27-81); 25% of the patients were >70 years old. Forty-three patients received pamidronate then switched to zoledronic acid. The median overall duration of BP administration was 34 months (range, 24+ to 131+), with a median duration of zoledronic acid therapy of 25 months (range, 2-40). Twenty-seven of 48 BC patients received different chemotherapy regimens (median number of lines, 2; range, 1-6). The median SCr levels were: baseline, 0.82 mg/dl (range, 0.4-1.4); time of analysis, 0.89 mg/dl (0.4-2); highest level, 1.0 mg/dl (0.5-2). A notable SCr increase was observed in seven patients (12.2%; all grade 1). Twenty-six patients (45.6%) experienced SREs after starting BP treatment. The median time to first SRE was 911 days (95% confidence interval, 731; 1,023). The SMR was 0.20 events per year. Ten patients ceased treatment because of: an SCr level of 2 mg/dl (n = 1) physician decision (n = 6) and jaw osteonecrosis (n = 3). Ten patients died of progressive disease. CONCLUSION: i.v. BPs are safe and active during prolonged treatment administration, and renal function is maintained in patients receiving multiple cytotoxic therapies. Jaw osteonecrosis occurred in 5% of the study population, and its causal relationship with BP treatment requires further observation and study.

Videocapillaroscopic findings in the microcirculation of the psoriatic plaque.

BACKGROUND: Videocapillaroscopy (VCP) is a method to study the morphology and dynamics of microcirculation, but information about capillaroscopic features of the psoriatic plaque is limited. OBJECTIVE: To investigate the distribution, morphology and density of capillaries in lesional and perilesional skin of the psoriatic plaque. METHODS: VCP of a well-delimited plaque of the trunk, arms or legs in 15 consecutive patients with untreated, chronic plaque psoriasis was performed. RESULTS: In the lesional skin, capillaries were tortuous and dilated, homogeneously appearing as 'bushy'. In the perilesional skin, capillary loops seemed to be on a parallel course with respect to the skin surface, with their apex directed towards the marginal zone. The number of capillary loops per area unit was statistically increased in perilesional compared to lesional skin. CONCLUSION: According to the morphology, distribution and density of capillary loops, two different angiogenetic patterns were found in lesional and perilesional skin.