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

BACKGROUND: 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. OBJECTIVES: The aim of our study was to analyse the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C gene deletions) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between Psoriasis Area and Severity Index (PASI) 75 response at week 12 and HLA-Cw6 status. METHODS: Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment. RESULTS: We observed increased response to ustekinumab in Cw6-positive (Cw6POS) patients [PASI 75 at week 12: 96·4% in Cw6POS vs. 65·2% in Cw6-negative (Cw6NEG) patients; P = 0·008]. In addition, we show that HLA-Cw6POS patients responded faster to ustekinumab, 89·3% of them reaching PASI 50 at week 4, after a single injection (vs. 60·9% of HLA-Cw6NEG patients). The superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96·35% Cw6POS vs. 72·7% Cw6NEG; odds ratio 9·8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C gene deletions did not show any significant association with response to ustekinumab. CONCLUSIONS: Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.

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 percent of psoriatic patients. Recently, it has been demonstrated that tumor necrosis factor alpha (TNF-alpha) 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-alpha, 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.

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.

Preoperative advantages of HF sonography of pilonidal sinus.

AIM AND METHODS: Pilonidal sinus is a not infrequent disease, probably due to a disontogenetic origin. Histologically, there is a pseudocystic formation in the subcutaneous adipose tissue, containing some hair bulbs. It usually presents a recurring inflammatory course. The pathologic formation does not normally have thick wall, being made up of thin epidermal epithelium, without internal vascularisation and with frequent subcutaneous fistulae. Even though the clinical diagnosis is rather easy, surgery may prove, on the contrary, a demanding task, with a high incidence of recurrence and complications. An adequate knowledge of the condition and its development, with a precise definition of the margins of the lesions, may simplify the surgery, reducing the chance of recurrence or complications. The use of echography in the diagnosis of this disease, in our cohort of 72 patients, has always provided valuable information. In particular, 13 and 18 MHz linear probes and 20 MHz mechanical array have been used, and the latter in particular for the evaluation of fistolous cavities/passageways under the skin. Results. In all our cases, echography has demonstrated pseudocystic formations, without real walls, with fairly high levels of internal echoes, compared to the hair follicles, or, more rarely, true macrocalcifications with one or more cavities/passageways near the skin, without internal vascularisation, according to the histological findings. Echographic data are rapidly obtained, and can prove useful for surgeons for a a better management of patients. Conclusion. We consider diagnostic echography, using high frequency probes, useful for the anatomical definition of this disease, as well as to enable better surgical management.

Mogamulizumab and bexarotene are a promising association for the treatment of advanced cutaneous T-cell lymphomas: a case series.

BACKGROUND: Treatment choices for patients with advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) who have failed first-line systemic therapies can be challenging, as several options are available. However, most evidence is based on observational and early phase studies due to the rarity of the disease. Mogamulizumab has recently been approved for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy; it has a good tolerability profile prompting its use in combination with other agents. This article aims at describing the role of the concomitant use of bexarotene with mogamulizumab in this setting. CASES PRESENTATION: To add information in the field, we describe our experience with four patients with MF/SS who failed first- and second-line treatments and started the combination mogamulizumab in addition to bexarotene. The combination of bexarotene with mogamulizumab in patients with advanced MF/SS after the failure of bexarotene alone obtained a response in all the four patients observed. The response was maintained longer than expected. CONCLUSIONS: The combination is promising and deserves further study.

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.

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.

Percutaneous vesiculodeferentography in the diagnosis of male infertility: A review of our results and the data reported in the literature.

Vesiculodeferentography was used in the past to evaluate suspected cases of obstruction of the seminal ducts. Over the years, numerous attempts have been made to improve the technique used to perform this examination and to render it less invasive. Its use is currently indicated in selected cases, where it is combined with functional studies like seminal tract washout and followed by immediate interventions to correct the alterations revealed. Vesiculodeferentography includes collection of the contents of the seminal vesicles, which can later be used in vitro assisted fertilization procedures.

SommarioLa vesciculodeferentografia, esame utilizzato in passato nei casi di sospette ostruzioni delle vie seminali, è stato negli anni oggetto di numerosi studi allo scopo di migliorarne la tecnica di esecuzione e renderla meno invasiva. Attualmente è indicata solo in casi selezionati, in associazione a un'indagine funzionale quale il Seminal Tract Washout e prevedendo un contemporaneo ­ o in via subordinata, successivo ­ atto terapeutico.Ovviamente, peraltro, la procedura ­ ipso facto ­ prevede il prelievo di materiale dalla seminale e ciò può consentire una successiva procedura di fecondazione assistita in vitro.