Recommendations for the management of comorbidity in hidradenitis suppurativa.

BACKGROUND: The association between hidradenitis suppurativa (HS) and some diseases is becoming relevant in recent years. Providing appropriate management of HS from an early stage requires to include prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat HS potentially related to the onset of a comorbidity. OBJECTIVE: To provide the dermatologist with an accurate, easily used tool that will inform the diagnosis of HS comorbidity, and to facilitate decision-making regarding the referral and treatment of patient with HS-associated comorbidity. METHODS: These recommendations have been developed by a working group composed of seven experts (three dermatologists, a cardiovascular specialist internist, a rheumatologist expert in spondyloarthritis, a gastroenterologist and a psychiatrist) and a team of three methodologist researchers. The expert group selected the HS comorbidities considered in these recommendations through a literature review. The recommendations on diagnostic criteria are based on the relevant clinical practice guidelines for each of the comorbidities and on the recommendations of the experts. The information regarding the repercussion of HS medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: The comorbidities considered in this guide are as follows: cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), inflammatory bowel disease, inflammatory joint disorders and psychological disorders (anxiety and depression). In addition, the association between HS and the consumption of alcohol and tobacco is included. The tables and figures are a precise, easy-to-use tool to systematize the diagnosis of comorbidity in patients with HS and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these recommendations will facilitate the dermatologist practice and benefit HS patients' health and quality of life.

Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis.

BACKGROUND: The CARD14 gene encodes a protein that enhances nuclear factor (NF)-κB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis. OBJECTIVES: To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis. METHODS: DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments. RESULTS: A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04). CONCLUSIONS: The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response.

Activating killer immunoglobulin-like receptors genes are associated with increased susceptibility to ankylosing spondylitis.

The aim of this study was to analyse the association of specific killer cell immunoglobulin-like receptors (KIR) genes and haplotypes with susceptibility to ankylosing spondylitis (AS) and its different clinical manifestations in a Spanish population. The presence or absence of all KIR genes was studied for their association with AS. A total of 176 patients with AS and 435 healthy control subjects were selected for this study based on clinical criteria. The commercial KIR-sequence-specific oligonucleotides (SSO) typing kit was used to investigate KIR typing. Frequencies of KIR2DS1 and KIR3DS1 genes were increased significantly in patients compared with healthy controls [52·8 versus 38·2%, PBonf < 0·01, odds ratio (OR) = 1·81 (1·28-2·59); 51·7 versus 37·5%, PBonf < 0·01, OR = 1·79 (1·25-2·54)]. Moreover, the frequency of activating genotypes in the AS patient group was significantly higher than in the healthy control group (P < 0·05). KIR2DS1 and KIR3DS1, in addition to human leucocyte antigen (HLA)-B27, may play an important role in the pathogenesis of AS. However, we show that the contribution of the KIR genes to AS susceptibility extends beyond the association with individual KIRs, with an imbalance between activating and inhibitory KIR genes seeming to influence the susceptibility to AS.

Recommendations for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists: a Delphi study.

Psoriatic arthritis, a chronic inflammatory musculoskeletal disease that is associated with psoriasis, causes joint erosions, accompanied by loss of function and quality-of-life. The clinical presentation is variable, with extreme phenotypes that can mimic rheumatoid arthritis or ankylosing spondylitis. Because psoriasis usually presents before psoriatic arthritis, the dermatologist plays a key role in early detection of the latter. As many treatments used in psoriasis are also used in psoriatic arthritis, treatment recommendations should take into consideration the type and severity of both conditions. This consensus paper presents guidelines for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists. The paper was drafted by a multidisciplinary group (6rheumatologists, 6dermatologists, and 2epidemiologists) using the Delphi method and contains recommendations, tables, and algorithms for the diagnosis, referral, and treatment of patients with psoriatic arthritis.

Erosive discovertebral lesion (Andersson lesion) as the first sign of disease in axial psoriatic arthritis.

OBJECTIVES: To present two cases of Andersson lesion (AL) as the form of onset of psoriatic arthritis (PsA), to review the form of onset of axial disease in PsA in our area, and to study the prevalence of AL in this series. PATIENTS AND METHODS: Two patients with psoriasis and recent-onset inflammatory back pain (IBP) with no known arthritis are presented. A final diagnosis of AL based on magnetic resonance imaging (MRI) findings was made. The medical records of 120 consecutive patients with axial PsA were reviewed and the most relevant features at disease onset analysed. RESULTS: Including the two cases presented, an AL prevalence of 5.7% was found in this series. The most common onset forms of axial PsA were: oligoarthritis (30%), IBP (21.7%), enthesitis (17.5%), polyarthritis (16%), gluteal pain (8.3%), dactylitis (3.3%), and distal interphalangeal (DIP) involvement (3.3%). Compared to women, men more frequently showed enthesitis (25% vs. 9%, p = 0.03) and IBP (31% vs. 10.7%, p = 0.007) as onset forms whereas a polyarticular onset was predominant in women (25% vs. 8%, p = 0.01). The polyarticular onset was predictive of radiological damage in the cervical column during follow-up [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.82-6.83, p = 0.01]. Enthesitis (23.6% vs. 8.3%, p = 0.02) and IBP (29.7% vs. 10.4%) were the predominant onset forms in patients with age at disease onset ≤ 40 years and polyarthritis (27% vs. 8.3%, p = 0.009) was predominant in those with disease onset > 40 years. CONCLUSIONS: AL is an uncommon finding in axial PsA and its appearance at disease onset is exceptional. MRI is a key tool in its early recognition.

Linguistic and Cultural Adaptation to Spanish of the Screening Tool Psoriatic Arthritis UnclutteRed Screening Evaluation (PURE4). / Adaptación lingüística y cultural al español del cuestionario Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4).

BACKGROUND AND OBJECTIVE: The 4-item Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) questionnaire is a useful tool for identifying patients with suspected psoriatic arthritis before referring them to a rheumatology department for confirmation. The original English version has good discriminant validity (sensitivity, 85.7%; specificity, 83.6%). We aimed to produce an adapted Spanish version of the PURE-4 for validation and use in Spain. MATERIAL AND METHOD: We applied the method recommended by the International Society for Pharmacoeconomic and Outcome Research for the cultural adaptation of patient-centered measurement tools. The phases in the processes involved forward translation, reconciliation, back translation review, harmonization, cognitive debriefing and review, and proofreading. RESULTS: We obtained the permission of the author of the original questionnaire. Two native-speaking translators translated the questionnaire into Spanish. Small changes, mainly in the way the items were expressed, were then made in order to reconcile the 2 translations. The questionnaire was then back translated to English and revised to achieve a version equivalent to the original. A Spanish translation derived from the revision was tested for understandability in 7 patients, and the final Spanish version was then produced. During the translation phases, the project manager and a scientific committee made up of a dermatologist and a rheumatologist reviewed the different versions. Team members exchanged information throughout the process, providing for harmonization and the quality control that guaranteed conceptual equivalence. CONCLUSIONS: This adaptation of the PURE-4 questionnaire for use in Spain has been the first step toward using it in routine clinical practice. The standardized method we used ensures that the Spanish and the original versions are equivalent.

Dermatologists' Role in the Early Diagnosis of Psoriatic Arthritis: Expert Recommendations. / El papel del dermatólogo en el diagnóstico precoz de la artritis psoriásica: recomendaciones de un grupo de expertos.

Psoriatic arthritis is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Because skin involvement usually precedes joint involvement, dermatologists play a key role in early detection. Early diagnosis is important for reducing the risk of irreversible structural damage, attenuating the deterioration of physical function, and improving patients' quality of life. This consensus statement was drafted by a group of 9 dermatologists and 1 rheumatologist to provide simple recommendations to help dermatologists screen for psoriatic arthritis in patients with psoriasis. The experts offer consensus-based guidelines that draw on a review of available scientific evidence and on experience acquired in routine clinical practice.

Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome and psoriatic arthritis exhibit a different immunogenetic profile.

BACKGROUND AND OBJECTIVES: Patients with psoriatic arthritis (PsA) as well as those with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome share some common features, and in fact, for many authors the SAPHO concept fits well into the broader concept of PsA. However, some clinical features are unique to the SAPHO syndrome, and in the other hand, these patients do not show the known association between the HLA-B27 antigen and the spondyloarthropathies. To date, there are no studies comparing the immunogenetic profile of these two conditions, so the main objective of the present report was to analyse whether or not both entities may share the same genetic basis. PATIENTS AND METHODS: All patients with SAPHO syndrome (n=25) seen in a single university hospital from 1985 to 2005 were recruited and followed up in standardised manner in order to study their main characteristics and HLA profile. The HLA-Cw6, DR and B27 antigen distribution of these cases was compared to that of 50 patients with psoriasis vulgaris, 120 with PsA, and 170 healthy blood donors. PsA patients were classified in accordance with their predominant pattern observed in the last 5 years of disease evolution. Odds ratios (OR) values were calculated to measure the strength of the association between HLA antigens and disease, while the statistical significance of the association was assessed with a two-tailed Fisher's exact test. P<0.05 values were considered significant. RESULTS: No association was found between HLA-Cw6, B27, or DR antigens, and SAPHO syndrome. HLA-Cw6 was strongly associated with psoriasis, OR 12 (95% CI: 5.6-26, p<0.0001) and PsA, OR 10 (95% CI: 5.4-19.5, p<0.0001), however this antigen was equally distributed among the three articular categories of PsA. HLA-DR4 was found under-represented in PsA patients compared to controls, OR 0.4 (95% CI: 0.2-0.7, p=0.002). HLA-DR7 correlated well with psoriatic oligoarthritis, OR 9.6 (95% CI: 2.9-28, p<0.0001), HLA-DR8 was found associated with polyarthritis, OR 6.7 (95% CI: 2-25, p=0.002), while HLA-B27 was over-represented in psoriatic spondylitis, OR 10 (95% CI: 3.3-25, p<0.0001). CONCLUSIONS: Psoriasis/PsA and SAP-HO syndrome show a different immunogenetic background, however the genetic basis of SAPHO syndrome remains unknown.

Association of IL1Β (-511 A/C) and IL6 (-174 G > C) polymorphisms with higher disease activity and clinical pattern of psoriatic arthritis.

The objective of this study is to analyze whether IL1ß (-511G > A) and IL6 (-174 G > C) polymorphisms are associated with inflammatory activity, radiographic damage or clinical pattern of psoriatic arthritis (PsA). One hundred twenty-five patients classified as PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included. Patients were stratified according to their clinical pattern at inclusion as peripheral, axial, or mixed involvement. Disease activity in peripheral or mixed forms was measured using the number of swollen and tender joints, pain analog visual scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score 28 (DAS28). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used for axial and mixed forms, as were pain visual analog scale, ESR and CRP. Radiographic damage was evaluated using a modified Sharp score and modified stoke ankylosing spondylitis spinal score (SASSSm). The polymorphisms for the promoter region of IL1ß (-511 G/A) and IL-6 (-174 G/C) were analyzed. The G allele of IL1B (-511G/A) polymorphism was associated with higher peripheral joint disease activity (OR 3.13; p < 0.0004; CI 95 % 1.43-6.82, p (corrected) <0.008), while the G allele of the IL6 (174G > C) polymorphism presented a strong trend to be associated with peripheral forms (70.86 %) (OR 1.89; p < 0.03; CI 95 % 1.06-3.39, p-corrected 0.05). In addition, this allele showed a lower association with HLA-B27 (15.78 %) compared with C allele (28.57 %) (OR 0.469; p = 0.02; CI 95 % 0.238-0.923, p-corrected 0.03). This study suggests that the G allele polymorphism of IL1B (-511 A/C) is associated with higher peripheral joint disease activity. On the other hand, the IL6 (-174 G/C) polymorphism showed a strong trend to be associated with the peripheral pattern of PsA.

Musculoskeletal infections in intravenous drug addicts: report of 34 cases with analysis of microbiological aspects and pathogenic mechanisms.

OBJECTIVE: To analyse characteristics of musculoskeletal infections in Spanish intravenous (i.v.) drug addicts. METHODS: A retrospective analysis of 34 medical records was carried out and the aetiologic agent was confirmed in all cases. RESULTS: The mean age was 26 years and the sex ratio was 25M/9F. Twenty-four patients were HIV-positive and 10 HIV-negative. There were no differences between the 2 subgroups. Septic arthritis, seen in 27 cases (79%), was the most common type of infection. Axial involvement was present in 23 cases (67%). The organisms isolated included Staphylococcus aureus (25 cases), Candida albicans (3 cases), Mycobacterium tuberculosis (2 cases), and Neisseria gonorrhoeae, Salmonella typhi, Staphylococcus epidermidis and Streptococcus pyogenes in one case each. Candida albicans affected the sternocostal joints. Laboratory data showed non-specific findings. The outcome was mostly good and only one patient died. CONCLUSION: Human immunodeficiency virus does not affect characteristics of musculoskeletal infections in i.v. drug addicts. Staphylococcus aureus is the most frequently isolated pathogen in this population.

Vertebral osteomyelitis in northern Spain. Report of 62 cases.

OBJECTIVE: The records of 62 patients with clinical and radiographic evidence of vertebral osteomyelitis and positive bacteriological diagnosis, seen between 1979 and 1996, were reviewed in order to gather data on the epidemiology and the clinical pattern displayed by patients with this condition in northern Spain. RESULTS: Staphylococcus aureus (15 cases), Mycobacterium tuberculosis (15 cases) and Brucella melitensis (13 cases) were the microorganisms most frequently found in our patient series. After improvement of the sanitary and hygienic control of food products, the role of Brucella melitensis is decreasing as a causative agent (only 3 cases in the last 6 years). Staphylococcus epidermidis, present in 4 cases (6.6%), should be suspected in elderly patients with previous intravenous cannulations (3 of 4 cases). The most frequent risk factors were alcoholism (7 cases), chronic hepatic disease (7 cases), diabetes (6 cases) and previous surgery (6 cases). Delay in diagnosis was high (the mean number of days between the onset of symptoms and diagnosis was 125). The lumbar region was the most commonly affected site. Neurologic involvement was present in 10 patients on admission (16%). ESR was > 50 mm/hr in a high number of cases. Blood cultures were found to be the most valuable routine test. Plain x-rays were normal in 10 patients (16%); in 6 of them Staphylococcus aureus was the responsible organism. Other imaging modalities showed a high sensitivity. Surgical drainage was necessary in 12 individuals (in 7 due to Mycobacterium tuberculosis). Outcome was good in the majority of cases: only 2 patients with associated endocarditis died. Neurologic sequelae were present in another 3 patients. CONCLUSION: Vertebral osteomyelitis can be caused by a variety of pathogens. Therefore, bacteriological studies are necessary to establish the etiologic diagnosis and determine the specific antimicrobial treatment required.

Absence of pulmonary fibrosis in patients with psoriatic arthritis treated with weekly low-dose methotrexate.

OBJECTIVES: To analyse pulmonary toxicity in psoriatic arthritis patients treated with weekly low-dose methotrexate. METHODS: A transversal study was carried out to analyse the findings on chest x-rays and high resolution computed tomography, and the results of pulmonary function tests in 27 Caucasian psoriatic arthritis patients treated with weekly low-dose methotrexate. None of them had previous recognized interstitial lung disease. RESULTS: The median age of the patient cohort was 50 years (range 24-70 years) and the sex ratio was 20M/7F. 17 patients had previously used other disease-modifying antirheumatic drugs. The mean weekly dose of methotrexate was 8.46 mg (range 5-15 mg), the average treatment period was 52 months (range 3-240 months), and the median cumulative dose was 2241 mg (range 300-6520 mg). High resolution computed tomography failed to show alveolar or interstitial involvement in any patient. Diffusing lung capacity for carbon monoxide was mildly altered only in 2 cases. Pulmonary function tests did not show differences between patients with and without recognized risk factors for developing methotrexate-associated lung toxicity identified in rheumatoid arthritis patients (old age, diabetes, hypoalbuminemia, previous use of disease modifying antirheumatic drugs). CONCLUSION: In this cohort of 27 psoriatic arthritis patients methotrexate was not associated with pulmonary fibrosis evaluated by means of sensitive imaging findings and pulmonary function tests.

Successful treatment with low-dose weekly methotrexate in a case of undifferentiated spondyloarthropathy coexisting with cutaneous polyarteritis nodosa.

A case of a 56-year-old woman diagnosed with HLA-B27-positive undifferentiated spondyloarthropathy who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa is presented. The rarity of this association and the dramatic response of both conditions to low-dose weekly methotrexate are emphasised.

Subclinical sacroiliitis in inflammatory bowel disease: a clinical and follow-up study.

The aim of this study was to evaluate the clinical features, evolution and reliability of spondyloarthropathy criteria in a subset of patients with subclinical sacroiliitis and inflammatory bowel disease (IBD). All patients with IBD (n 62) attending a gastroenterology clinic from a referral centre were included to assess the prevalence of articular involvement. Patients were evaluated according to a specific protocol designed for the study, which included epidemiological and clinical variables, physical examination and radiological assessment. Only those with subclinical sacroiliitis were followed prospectively for 4 years. This group was visited every 6 months with the same initial protocol. Sacroiliac joints were studied using frontal and oblique X-ray views and graded according to New York criteria. HLA B27 typing was performed by serological methods in all patients and in 80 healthy controls. The reliability of Amor and ESSG criteria for spondyloarthropathy was evaluated. Fifteen patients (24%) presented with isolated subclinical sacroiliitis. In this group a higher frequency of peripheral arthritis and erythema nodosum was observed (p = NS compared to those without sacroiliitis). Most cases (60%) were grade II unilateral sacroiliitis. Three patients were HLA B27+ (p>0.05 compared to healthy controls). The resultant sensitivity of Amor's and ESSG criteria ranged from 40% to 46%. An unexpectedly high freuqency (9.5%) of psoriasis was observed in the whole group. There is a high prevalence of isolated subclinical sacroiliitis in IBD. This may represent a forme fruste of enteropathic ankylosing spondylitis, a stunted form of axial involvement because of therapy, or a third category of rheumatic disease associated with IBD. It may also represent a common characteristic of spondyloarthropathies, rather than a specific finding of IBD. The recently developed spondyloarthropathy criteria are not particularly helpful for the diagnosis of this milder form of spondyloarthropathy.

Haematogenous vertebral osteomyelitis in the elderly.

The aim of our study was to analyse the characteristics of haematogenous vertebral osteomyelitis (HVO) in the elderly. A retrospective comparative analysis of the medical records of 72 patients (38 younger than 63 years, group 1, and 34 aged 63 years and over, group 2) with haematogenous vertebral osteomyelitis of confirmed aetiology was carried out. Intravenous drug addiction and infection with the human immunodeficiency virus were seen in 4/38 (10%) and 5/38 (13%) patients from group 1 and 0/34 patients (0%) from group 2 (P = 0.05 and 0.035, respectively). Seven of 34 elderly (20%) and 0/38 (0%) young individuals had recently had surgery (P = 0.0036). Escherichia coli was isolated in 7/34 elderly (20%) and 0/38 (0%) young patients (P = 0.0036). The remaining studied data did not reach statistical significance. Recent surgery is a risk factor for developing HVO in the elderly, the urinary tract being the source of the pathogen in a large number of elderly patients with spinal infection.

Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A retrospective study.

The aim of this study was to analyse retrospectively the prevalence and the clinical features of clinically asymptomatic axial involvement in patients with psoriasis and axial radiological features of spondyloarthropathy (PsSpA). We performed a cross-sectional study based on the clinical records of 70 patients, 44 men and 26 women, with a mean age of 48.7+/-14.2 years. PsSpA was defined by the presence of radiographic sacroiliitis (SI) greater than or equal to grade 2, and/or any other typical radiological sign of spondylitis in patients with psoriasis. When the radiological signs were present in the absence of inflammatory back pain and/or buttock pain, patients were grouped as having asymptomatic axial disease. HLA-B27 was determined by serological methods in the 70 patients and in 82 healthy controls from our general population. Fourteen patients (20%), 11 with radiological SI, two with facet joint erosion-fusion and one with aseptic discitis, showed no evidence of symptomatic spinal disease. Twenty-nine patients (41%) showed cervical spine disease (CSD), but only 17 of them (58.6%) had pain and rigidity at this level, whereas 12 (41.4%) did not show clinical symptoms. CSD was associated with duration of arthritis (P = 0.043) and peripheral erosions (P = 0.037). HLA-B27 correlated well with bilateral SI (P = 0.002) and PsSpA (P<0.0004, RR 6.4), but showed no association with unilateral SI nor with syndesmophytes or asymptomatic disease. Univariate analysis demonstrated associations between symptomatic disease and longer duration of arthritis (P = 0.041) and higher IgM values (P = 0.05). There is a high prevalence of asymptomatic involvement in patients with PsSpA The significance of these asymptomatic changes is not known, but they probably represent a common characteristic of spondyloarthropathies rather than a specific feature associated with psoriasis.

Comparative analysis of psoriatic spondyloarthropathy between men and women.

This study analyzed gender-related differences in a cohort of patients with psoriatic spondyloarthropathy (SpA) We performed a retrospective cross-sectional study of 100 patients (mean age 48 +/- 14 years; 63 men, 37 women), diagnosed as having psoriatic SpA on the basis of ESSG criteria. All patients were studied according to a standard protocol, and HLA-B27 and Cw status were analyzed in the study population and their frequencies compared to that of 177 healthy blood donors. The clinical features of PsSpA were compared between men and women by univariate analyses. Twenty-three patients showed isolated axial disease (M:F ratio 3.6:1), 36 had polyaxial disease (M:F ratio 1:1), and 41 showed oligoaxial pattern (M:F ratio 1.7:1). HLA-B27 was correlated with male sex (P=0.002) and isolated axial disease (P=0.016). Univariate analysis showed female sex to be correlated with lower complement levels (P < 0.05), erosive disease (P = 0.05), higher swelling joint count (P = 0.002), and higher scores on the Health Assessment Questionnaire-Specific for SpA (P < 0.05). The HLA-B27 antigen seems to be a defined genetic risk factor only in men with psoriatic SpA. The extent of the spondylitic process is quite similar between the two, although women show poorer functional performance and more aggressive peripheral disease.