Javier Rueda-Gotor

Cardiovascular risk stratification in rheumatic diseases: carotid ultrasound is more sensitive than Coronary Artery Calcification Score to detect subclinical atherosclerosis in patients with rheumatoid arthritis

Objective To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography in detecting subclinical atherosclerosis in rheumatoid arthritis (RA). Methods A set of 104 consecutive RA patients without history of cardiovascular (CV) events were studied to determine CACS, carotid intima-media thickness (cIMT) and plaques. Systematic Coronary Risk Evaluation (SCORE) modified according to the EULAR recommendations (mSCORE) was also assessed. Results The mean disease duration was 10.8 years, 72.1% had rheumatoid factor and/or anti-CCP positivity and 16.4% extra-articular manifestations. Nine were excluded because they had type 2 diabetes mellitus or chronic kidney disease. CV risk was categorised in the remaining 95 RA patients according to the mSCORE as follows: low (n=21), moderate (n=60) and high/very high risk (n=14). Most patients with low mSCORE (16/21; 76.2%) had normal CACS (zero), and none of them CACS>100. However, a high number of patients with carotid plaques was disclosed in the groups with CACS 0 (23/40; 57.5%) or CACS 1–100 (29/38; 76.3%). 72 (75.8%) of the 95 patients fulfilled definitions for high/very high CV as they had an mSCORE ≥5% or mSCORE <5% plus one of the following findings: severe carotid ultrasonography findings (cIMT>0.9 mm and/or plaques) or CACS>100. A CACS>100 showed sensitivity similar to mSCORE (23.6% vs 19.4%). In contrast, the presence of severe carotid ultrasonography findings allowed identifying most patients who met definitions for high/very high CV risk (70/72; sensitivity 97.2% (95% CI 90.3 to 99.7)). Conclusions Carotid ultrasonography is more sensitive than CACS for the detection of subclinical atherosclerosis in RA.

Efficacy of Tocilizumab in Conventional Treatment–Refractory Adult-Onset Still's Disease: Multicenter Retrospective Open-Label Study of Thirty-Four Patients†

Adult‐onset Stills disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment.

Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center.

AbstractThe severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%).In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement.

SCORE and REGICOR function charts underestimate the cardiovascular risk in Spanish patients with rheumatoid arthritis.

IntroductionOur objective was to determine which one of the two function charts available in Spain to calculate cardiovascular (CV) risk, Systematic COronary Risk Evaluation (SCORE) or Framingham-REgistre GIroní del COR (REGICOR), should be used in patients with rheumatoid arthritis (RA).MethodsA series of RA patients seen over a one-year period without history of CV events were assessed. SCORE, REGICOR, modified (m)SCORE and mREGICOR according to the European League Against Rheumatism (EULAR) recommendations were applied. Carotid ultrasonography (US) was performed. Carotid intima-media thickness (cIMT) > 0.90 mm and/or carotid plaques were used as the gold standard test for severe subclinical atherosclerosis and high CV risk (US+). The area under the receiver operating curves (AUC) for the predicted risk for mSCORE and mREGICOR were calculated according to the presence of severe carotid US findings (US+).ResultsWe included 370 patients (80% women; mean age 58.9 ± 13.7 years); 36% had disease duration of 10 years or more; rheumatoid factor (RF) and/or anticyclic citrullinated peptide (anti-CCP) were positive in 68%; and 17% had extra-articular manifestations. The EULAR multiplier factor was used in 122 (33%) of the patients. The mSCORE was 2.16 ± 2.49% and the mREGICOR 4.36 ± 3.46%. Regarding US results, 196 (53%) patients were US+. The AUC mSCORE was 0.798 (CI 95%: 0.752 to 0.844) and AUC mREGICOR 0.741 (95% CI; 0.691 to 0.792). However, mSCORE and mREGICOR failed to identify 88% and 91% of US+ patients. More than 50% of patients with mSCORE ≥1% or mREGICOR >1% were US+.ConclusionsNeither of these two function charts was useful in estimating CV risk in Spanish RA patients.

The ZC3HC1 rs11556924 polymorphism is associated with increased carotid intima-media thickness in patients with rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a complex polygenic disease associated with chronic inflammation, accelerated atherosclerosis and increased cardiovascular (CV) mortality. A recent meta-analysis has described the ZC3HC1 rs11556924 polymorphism as one of the most important signals associated with coronary artery disease (CAD) in non-rheumatic Caucasian individuals. In this study we evaluated the potential association of this gene polymorphism with subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in RA patients.MethodsThis study included 502 RA patients from Northern Spain. The ZC3HC1 rs11556924 polymorphism was genotyped with TaqMan single-nucleotide polymorphism (SNP) genotyping assays (C__31283062_10) in a 7900HT real-time polymerase chain reaction (PCR) system. cIMT was also assessed in these patients by carotid ultrasonography (US) technology.ResultsRA patients carrying the TT genotype had significantly higher cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.76 ± 0.18 mm and mean ± SD: 0.71 ± 0.16 mm respectively; P = 0.03) even after adjusting the results for sex, age at the time of US study, follow-up time and traditional CV risk factors (P = 0.04) evidencing that the effect conferred by ZC3HC1 rs11556924 polymorphism is independent of the traditional CV risk factors.ConclusionOur results indicate that ZC3HC1 rs11556924 polymorphism is associated with subclinical atherosclerosis in RA.

Urticarial vasculitis in northern Spain: clinical study of 21 cases.

AbstractUrticarial vasculitis (UV) is a subset of cutaneous vasculitis (CV), characterized clinically by urticarial skin lesions of more than 24 hours’ duration and histologically by leukocytoclastic vasculitis. We assessed the frequency, clinical features, treatment, and outcome of a series of patients with UV. We conducted a retrospective study of patients with UV included in a large series of unselected patients with CV from a university hospital. Of 766 patients with CV, UV was diagnosed in 21 (2.7%; 9 male and 12 female patients; median age, 35 yr; range, 1–78 yr; interquartile range, 5–54 yr). Eight of the 21 cases were aged younger than 20 years old. Potential precipitating factors were upper respiratory tract infections and drugs (penicillin) (n = 4; in all cases in patients aged <20 yr), human immunodeficiency virus (HIV) infection (n = 1), and malignancy (n = 1). Besides urticarial lesions, other features such as palpable purpura (n = 7), arthralgia and/or arthritis (n = 13), abdominal pain (n = 2), nephropathy (n = 2), and peripheral neuropathy (n = 1) were observed. Hypocomplementemia (low C4) with low C1q was disclosed in 2 patients. Other abnormal laboratory findings were leukocytosis (n = 7), increased erythrocyte sedimentation rate (n = 6), anemia (n = 4), and antinuclear antibody positivity (n = 2). Treatment included corticosteroids (n = 12), antihistaminic drugs (n = 6), chloroquine (n = 4), nonsteroidal antiinflammatory drugs (n = 3), colchicine (n = 2), and azathioprine (n = 1). After a median follow-up of 10 months (interquartile range, 2–38 mo) recurrences were observed in 4 patients. Apart from 1 patient who died because of an underlying malignancy, the outcome was good with full recovery in the remaining patients. In conclusion, our results indicate that UV is rare but not exceptional. In children UV is often preceded by an upper respiratory tract infection. Urticarial lesions and joint manifestations are the most frequent clinical manifestation. Low complement serum levels are observed in a minority of cases. The prognosis is generally good, but depends on the underlying disease.

Single-organ cutaneous small-vessel vasculitis according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides: a study of 60 patients from a series of 766 cutaneous vasculitis cases

OBJECTIVE Cutaneous vasculitis (CV) encompasses a wide group of entities characterized by inflammation of skin blood vessels. The term single-organ vasculitis was recently coined by the 2012 Chapel Hill Consensus Conference (CHCC) to define vasculitis affecting a single organ. To our knowledge there are no published reports on single-organ cutaneous small vessel vasculitis (SoCSVV). Our aim was to characterize this entity from a wide series of patients with CV. METHODS We analysed cases of SoCSVV from a series of 766 patients with CV from a single university referral centre. According to 2012 CHCC, the following conditions were required to define SoCSVV: (i) skin biopsy showing characteristic leucocytoclastic vasculitis and (ii) vasculitis limited to skin. RESULTS We included 60 patients (26 women and 34 men) with a mean age of 56 years. The main precipitating factors for SoCSVV were drugs [26 patients (52%)] and previous infection [17 patients (34%)]. The main clinical manifestations were palpable purpura (81.7%) and fever (18.3%). The most frequent laboratory findings were leucocytosis and elevated ESR. Nearly one-quarter of patients with SoCSVV required pharmacological therapy. Corticosteroids (15%) and NSAIDs (13.3%) were the main agents prescribed. After a median follow-up of 4 months, complete recovery was observed in all the patients, although relapses occurred in 8% of patients. CONCLUSION SoCSVV defined according to the 2012 CHCC may be considered a benign disease usually associated with drugs and/or a previous infection.

Drug-associated Cutaneous Vasculitis: Study of 239 Patients from a Single Referral Center

Objective. The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides defined drug-associated immune complex vasculitis as a distinct entity included within the category of vasculitis associated with probable etiology. In the present study we assessed the clinical spectrum of patients with drug-associated cutaneous vasculitis (DACV). Methods. Case records were reviewed of patients with DACV treated at a tertiary referral hospital over a 36-year period. A diagnosis of DACV was considered if the drug was taken within a week before the onset of the disease. Results. From a series of 773 unselected cutaneous vasculitis cases, 239 patients (30.9%; 133 men and 106 women; mean age 36 yrs) were diagnosed with DACV. Antibiotics (n = 149; 62.3%), mainly β-lactams and nonsteroidal antiinflammatory drugs (NSAID; n = 24; 10%) were the most common drugs. Besides skin lesions (100%), the most common clinical features were joint (51%) and gastrointestinal (38.1%) manifestations, nephropathy (34.7%), and fever (23.8%). The most remarkable laboratory data were increased erythrocyte sedimentation rate (40.2%), presence of serum cryoglobulins (26%), leukocytosis (24.7%), positive antinuclear antibodies (21.1%), anemia (18.8%), and positive rheumatoid factor (17.5%). Despite drug discontinuation and bed rest, 108 patients (45.2%) required medical treatment, mainly corticosteroids (n = 71) or immunosuppressive drugs (n = 7). After a median followup of 5 months, relapses occurred in 18.4% of patients, and persistent microhematuria or renal insufficiency in 3.3% and 5%, respectively. Conclusion. DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.

Successful effect of tocilizumab in anti-TNF-α-induced palmoplantar pustulosis in rheumatoid arthritis

Anti-tumour necrosis factor-alpha (TNF-α) agents are effective drugs used in several chronic inflammatory diseases such as rheumatoid arthritis (RA). Psoriasiform lesions, including palmoplantar pustulosis, have been described following anti-TNF-α therapy. These lesions often resolve with topical therapy with or without discontinuation of these drugs. However, in some cases, psoriasiform lesions may persist despite anti-TNF-α withdrawal. We report on two RA patients treated with adalimumab (ADA) who developed palmoplantar pustular despite dermatological treatment and ADA discontinuation. Tocilizumab (TCZ) therapy was initiated because of persistence of skin lesions and flare of the disease. Following treatment with this drug, complete resolution of the dermatological lesions and induction of remission of RA was achieved. To the best of our knowledge, management of palmoplantar pustulosis due to TNF-α agents with TCZ leading to both improvement of the disease and resolution of the cutaneous lesions has not previously been reported.

Antitumour necrosis factor α treatment reduces retinol-binding protein 4 serum levels in non-diabetic ankylosing spondylitis patients

Increased cardiovascular (CV) mortality due to accelerated atherosclerosis occurs in ankylosing spondylitis (AS) patients.1 ,2 Beneficial effects of antitumour necrosis factor (anti-TNF)-α agents on disease activity and endothelial cell activation were reported in AS.3 ,4 Dramatic reduction of insulin resistance (IR) and improvement of insulin sensitivity after infliximab administration were also described in non-diabetic AS patients.5 We aimed to assess, for the first time, whether infliximab administration in AS patients may alter levels of retinol-binding protein 4 (RBP-4), a protein released from adipocytes, considered as an emerging cardiometabolic risk factor, which correlates with IR in individuals with obesity, impaired glucose tolerance or type 2 diabetes, and in non-obese subjects with or without family history of type 2 diabetes.6–⇓8 RBP-4 serum levels were measured by ELISA (Phoenix Pharmaceuticals, EK-028-28) in 30 consecutive non-diabetic and mostly non-obese AS patients without history of CV events before and after an infliximab infusion. Local institutional committee approval and patients’ informed consent were obtained. Information on blood sample determinations in this cohort was previously reported.9 Infliximab was given as an intravenous infusion in saline solution over 120 min.5 Measurements were made in …