[Translated article] Validation of the Spanish Version of the PURE-4 Questionnaire for the Early Detection of Psoriatic Arthritis in Psoriatic Patients.

BACKGROUND AND OBJECTIVE: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity. METHODS: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire. RESULTS: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6). CONCLUSIONS: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit.

Validation of the Spanish Version of the PURE-4 Questionnaire for the Early Detection of Psoriatic Arthritis in Psoriatic Patients. / Validación de la versión española del cuestionario PURE-4 para la detección precoz de la artritis psoriásica en pacientes con psoriasis.

BACKGROUND AND OBJECTIVE: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity. METHODS: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire. RESULTS: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6). CONCLUSIONS: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit.

Results of a global, patient-based survey assessing the impact of psoriatic arthritis discussed in the context of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient's perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire. METHODS: An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted. RESULTS: This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains. CONCLUSION: These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

Gut microbiota dysbiosis in a cohort of patients with psoriasis.

BACKGROUND: There is increasing evidence of the key role that the gut microbiota plays in inflammatory diseases. OBJECTIVES: To identify differences in the faecal microbial composition of patients with psoriasis compared with healthy individuals in order to unravel the microbiota profiling in this autoimmune disease. METHODS: 16S rRNA gene sequencing and bioinformatic analyses were performed with the total DNA extracted from the faecal microbiota of 19 patients with psoriasis and 20 healthy individuals from the same geographic location. RESULTS: Gut microbiota composition of patients with psoriasis displayed a lower diversity and different relative abundance of certain bacterial taxa compared with healthy individuals. CONCLUSIONS: The gut microbiota profile of patients with psoriasis displayed a clear dysbiosis that can be targeted for microbiome-based therapeutic approaches. What's already known about this topic? Psoriasis is a chronic inflammatory immune-mediated skin disease, the aetiology of which remains unclear. The human microbiota is a complex microbial community that inhabits our body and has been related with the maintenance of a healthy status. Several studies have focused on the skin microbiome and its connection with psoriasis although less attention has been focused on the potential role of the gut microbiota in psoriatic disease. What does this study add? This study unravels the gut microbiome dysbiosis present in a cohort of patients with psoriasis, compared with a healthy control group from the same geographical location. This study shows a lower bacterial diversity and different relative abundance of certain bacterial taxa in patients with psoriasis. We gain knowledge and insight into the microbiome alterations in psoriatic disease, opening new avenues for therapeutic approaches to reshape the human microbiome towards a healthy status.

Psoriasis, psoriatic arthritis and type 2 diabetes mellitus: a systematic review and meta-analysis.

Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first author's last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty-four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random-effects analysis was determined to be 1·76 (95% CI 1·59-1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36-3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73-2·55) than the pooled OR. We perform meta-regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta-analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.

MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility.

OBJECTIVES: Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. METHODS: A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.

The effect of HLA-DR antigens on the susceptibility to, and clinical expression of psoriatic arthritis.

OBJECTIVE: To analyse the relative role of HLA-DR antigens in the susceptibility to, and clinical expression of psoriatic arthritis (PsA). PATIENTS AND METHODS: A retrospective cohort study of 120 patients with PsA who were assessed according to a standard protocol. Patients were classified in accordance with the predominant pattern observed in the last 5 years of disease evolution: polyarthritis (n = 33), oligoarthritis (n = 45), and spondylitis (n = 42). HLA-Cw gene typing was done by the polymerase chain reaction (PCR) sequence-specific oligonucleotide probes (PCR-SSOP) method, while HLA-DR and B27 typing were performed by serological methods. The distribution of HLA-DR and Cw antigens was also analysed in 50 patients with psoriasis alone. One hundred and seventy subjects from our general population served as controls. RESULTS: No definite association was found between HLA-DR alleles and the risk of psoriasis or PsA. HLA-DR4 was found to be under-represented in arthritic patients [probability (p) = 0.03]. HLA-DR7 showed association with oligoarthritis [odds ratio (OR) 6, 95% confidence interval (CI): 2-16, corrected probability (Pc) = 0.01], whereas HLA-DR8 appeared to be related to the risk of polyarthritis (OR 9.5, 95% CI: 2-42, Pc = 0.02). HLA-Cw*0602 conferred risk for psoriasis (Pc < 0.00001), but not for PsA. As expected, HLA-B27 appeared to be over-represented in patients with spondylitis (p = 0.03). CONCLUSIONS: This is the first report that associates HLA-DR8 with psoriatic polyarthritis. Although HLA-DR antigens have a marginal role in PsA or psoriasis susceptibility, they may be relevant to the modulation of the clinical expression of PsA. These HLA data add support to the classification of PsA into three disease subsets.

A polyarticular onset predicts erosive and deforming disease in psoriatic arthritis.

OBJECTIVES: To analyse the factors predicting erosive-deforming arthropathy in patients with psoriatic arthritis (PsA). METHODS: A prospective cohort study was undertaken with 71 patients diagnosed as having PsA (44 men and 27 women, mean age 47 (SD 12) years). At the recruitment period patients had disease without evidence of radiological damage. Patients were studied and followed up according to a standard protocol from January 1991 to June 2001. Erosive and deforming disease was defined by the presence of erosions, joint space narrowing, subluxation, and/or ankylosis of peripheral joints. Univariate and multivariate analyses were performed to evaluate factors predicting erosive and deforming disease. RESULTS: At the end of the study 32 of 71 (45%) patients had developed erosive and deforming disease. Among them, 18 of 32 (56%) had a polyarticular onset, two of 32 (6%) showed a distal interphalangeal joint disease onset, six of 32 (19%) presented with oligoarthritis, and six of 32 (19%) presented with axial disease as the form of disease onset (p=0.001). Mean time to detect erosions or joint space narrowing was 20 (SD 4) months. Men showed fewer erosions than women (p=0.05). Patients who carried the HLA-B27 antigen showed less erosive disease than patients who lacked it (p=0.05). Patients with erosive and deforming disease had poorer functional performance than those without it as measured with the Health Assessment Questionnaire (HAQ) and the American College of Rheumatology (ACR) criteria (p<0.05 with both measurements). In multivariate analysis, only a polyarticular onset remained as an indicator of erosive and deforming disease (odds ratio (OR) 37, 95% confidence interval (95% CI) 3.6 to 88, p=0.025). CONCLUSIONS: A polyarticular onset (five or more swollen joints) of PsA was the unique independent risk factor which predicted the appearance of erosive and deforming disease over time. These data may be useful for clinicians treating patients with PsA, as it may guide treatment towards a more aggressive and earlier intervention.

Periarticular calcinosis associated with anti-Jo-1 antibodies sine myositis. Expanding the clinical spectrum of the antisynthetase syndrome.

We describe a 58-year-old woman who developed interstitial lung disease (ILD), polyarthritis, and anti-Jo-1 antibodies, with no clinical evidence of myositis. Despite successful treatment with corticosteroid and azathioprine for her arthritis and pulmonary condition, she developed deforming arthropathy of the hands, with periarticular calcinosis. The association of anti-Jo-1 antibodies, ILD, and periarticular calcinosis with subluxing arthropathy sine myositis is rare, with few cases reported. This report expands the clinical spectrum of the antisynthetase syndrome, which is broader than previously reported.

[Atypical manifestations of Whipple's disease]. / Manifestaciones atípicas de la enfermedad de Whipple.

We report 2 new cases of Whipple's disease (WD) with especial characteristics. In one case, an asymptomatic leukocytosis was the first manifestation, and after therapy the patient developed a gastric adenocarcinoma. In the second, the clinic suspect we led to try antibiotic treatment in absent of histological manifestations. The clinical, analytical and histological characteristics of both patients are described. We propose that WD should be listed in the differential diagnosis of unknown leukocytosis. Moreover, we indicate the possibility to try empirical antibiotic therapy in long-term cases without histological confirmation. Finally, we suggest a possible role of WD in the development of cancer.

Manifestaciones atípicas de la enfermedad de Whipple / Atipic manifestations of Whipple's disease

Presentamos 2 casos de enfermedad de Whipple (EW) de larga evolución con características especiales. En un caso, la presentación inicial fue una leucocitosis asintomática, hecho que no hemos encontrado publicado previamente, y que en su evolución desarrolló un adenocarcinoma gástrico. En el 2° caso, la sospecha clínica nos llevó a realizar tratamiento antibiótico empírico pese a la negatividad de los hallazgos histológicos. Se describen las características clínicas, analíticas e histológicas de ambos pacientes. Proponemos incluir a la EW dentro del diagnóstico diferencial de las leucocitosis de origen desconocido. Señalamos además la posibilidad de realizar tratamiento antibiótico empírico en aquellos casos de larga evolución con deterioro progresivo, aún sin confirmación histólogica. Finalmente planteamos que la cronicidad del proceso pueda influir en el desarrollo de neoplasias. (AU)

[Silent axial arthropathy in inflammatory bowel disease. Clinical, radiological and genetic characteristics]. / Artropatía axial silente en la enfermedad inflamatoria intestinal. Características clínicas, radiológicas y genéticas.

OBJECTIVES: To evaluate the prevalence, clinical and radiological characteristics, association with HLA B27 in a subgroup of patients with inflammatory bowel disease (IBD) and subclinical sacroileitis. The sensitivity of the diagnostic criteria for spondyloarthropathy in this group of patients is evaluated. MATERIALS AND METHODS: All patients with inflammatory bowel disease attending an outpatient gastroenterology unit from January 1994 to June 1994 were recruited. A total of 62 patients with IBD and without clinical evidence of axial involvement were included in the study. The demographic, clinical, and radiological characteristics were collected. The radiological examination included PA and lateral views for the dorso-lumbar, and three views (Ferguson, right and left oblique views) for the sacroiliac joints. Films were interpreted by three independent readers. The HLA B27 allele distribution was analyzed in the 62 patients and in 80 healthy controls. The modified New York criteria, Amor criteria, and European Spondyloarthropathy Study Group criteria were evaluated. Patients were prospectively followed for two years with the same initial protocol. The statistical management of data was performed with the information program SPSS/PC. RESULTS: Fifteen cases of silent sacroileitis were detected, and most of them were grade 2 unilateral sacroileitis. There was no correlation between sacroileitis and IBP type, extradigestive symptoms, disease duration, sex, or peripheral arthritis. The frequency of HLA B27 in the sacroileitis group was 20% (p < 0.05). During the two-year follow-up period none of these cases has changed from diagnostic category. The sensitivity of diagnostic the criteria for spondyloarthropathy was low in these patients (40%-53%). CONCLUSIONS: A high frequency of asymptomatic sacroileitis in patients with IBD was detected. We propose the term Silent Axial Arthropathy to define this category of patients and, as with other authors, we consider this is a third form of rheumatic syndrome in IBD, different from the classical forms of peripheral arthritis and ankylosing spondylitis.

Diaphysitis in tumoral calcinosis syndrome.

Diaphysitis is uncommon in children. We describe a case of diaphyseal inflammation in several bones with high levels of phosphorus in an 8-year-old boy who later developed subcutaneous masses of tumoral calcinosis. This report serves as a review of this puzzling problem in clinical diagnosis.