Sara Alonso

Age at disease onset: a key factor for understanding psoriatic disease

Psoriasis and PsA are immune-mediated diseases with a strong genetic component. More than 20 new loci have been recently linked to these diseases. However, interactions between these genes and the phenotypic traits of both diseases are poorly understood at present. Stratification of psoriatic disease according to the sex of the patients, genetic factors or age at onset has allowed in the last few years a better understanding of the principles governing the onset and progression of these processes. The age of onset of psoriasis has been used for decades as an appropriate descriptor to define two subpopulations of psoriatic patients (types I and II) whose clinical and immunogenetic characteristics have been very well differentiated. Moreover, in patients with PsA this distinction between type I and II psoriasis also seems equally operative. In patients with PsA expressing the HLA-C*06 antigen, the latency between the onset of psoriasis and onset of joint symptoms is longer than in those without this marker. It is also known that PsA tends to appear earlier in patients with HLA-B*27 positivity, and that these patients also show a shorter interval of time between the onset of cutaneous lesions and the onset of joint disease. This review highlights the growing importance of age at disease onset as a key stratification factor in worldwide clinical and genetic studies of psoriatic disease.

Entheseal ultrasound abnormalities in patients with SAPHO syndrome

This study was conducted to investigate the presence and characteristics of the ultrasound lesions that may be found in the entheses of patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. This cross-sectional study included 15 patients with SAPHO syndrome and 30 healthy controls matched for age, sex and body mass index. Subjects with regular sport activities as well as those with other rheumatic conditions were excluded from the study. Ultrasonography was used in both groups to study 14 entheses of the upper and lower extremities. Different elementary lesions representative of enthesis damage were defined. A total of 210 entheses in the study group and 420 in the control group were evaluated. Only one patient presented clinical enthesitis. In the study group, seven of the 15 patients (47%) showed morpho-structural entheseal alterations, versus only four of the 30 controls (13.3%; p < 0.001). The subjects with SAPHO showed ultrasound alterations in 32/210 entheses (15%), while the controls showed alterations in 20/420 entheses (4.8%), p < 0.001. The entheses with the largest number of morpho-structural alterations were those of the patellar and Achilles tendon. None of the controls showed power Doppler signal at enthesis or perienthesis level. Ultrasound evidence of enthesopathy seems to be a common feature in this series of patients with SAPHO syndrome.

Stratification by age of onset with 30 years as age limit is an effective means of identifying PSORS1-associated psoriasis in patients with psoriatic arthritis.

OBJECTIVES To determine which of the following is the best method to identify PSORS1-associated psoriasis in patients with psoriatic arthritis (PsA): age at disease onset or positive family history of disease. METHODS A total of 71 patients with PsA who met the CASPAR criteria were recruited on a randomized basis. The patients were stratified according to age at disease onset, with cutoff points at 25, 30, 35 and 40years of age. The alleles of locus Cw were analyzed by PCR-based methods, and their distribution was compared to that of 177 healthy blood donors. RESULTS HLA-Cw*0602-PSORS1- was associated with disease risk (56% vs. 18%) OR 5.8, 95%CI: 3.2-10.7, P=0.00001. A close relationship was established between this allele and onset of psoriasis under 30years of age (68% vs. 24%) OR 6.4, 95%CI: 2.3-18.2, P=0.0003. The relationship in turn lost significance above this age limit. An association was found between a family history of psoriasis and disease risk, though there was no specific cutoff point according to age at onset of the disease. Sixty-four percent of the subjects with positive family history were HLA-Cw*06 (+) compared to 44% of those without a family history, OR 2.3, 95% CI: 0.82-6.36, P=0.08. CONCLUSIONS In patients with PsA, the susceptibility effect of HLA-Cw*06 declines with increasing age of onset. Disease onset under or above 30years of age may contribute to differentiate type I vs. type II psoriasis in PsA populations, while the family history have a lesser contribution to such stratification.

Age at disease onset may help to further characterize the disease phenotype in psoriatic arthritis

OBJECTIVE To evaluate whether the age of disease presentation helps to better characterize the disease phenotype in PsA. METHODS Retrospective cohort study that included 205 consecutive patients fulfilling the CASPAR criteria for PsA. Study outcomes were assessed using univariate and multivariate analyses according to the age of onset of both skin and joint disease (cut off at 40years). RESULTS Early onset psoriasis (EOP) showed more extensive skin involvement (OR 2.3, P=0.011), axial pattern as disease onset (OR 4.6, P=0.009) and mixed pattern during evolution (OR 2.4, P=0.019), family history of both psoriasis (OR 3.1, P=0.003) and PsA (OR 4.0, P=0.021), higher prevalence of HLA-C*06 (OR 2.03, P=0.03) and HLA-B*27 (OR 2.7, P=0.02). Early onset arthritis (EOA) had more family history of PsA (OR 2.9, P=0.007), and HLA-B*27 positivity (OR 5.9, P<0.0001). Patients with late onset arthritis (LOA) were more likely to have DM (OR 4.0, P=0.009), hypertension (OR 2.5, P=0.004), dyslipidemia (OR 2.3, P=0.011), and obesity (OR 1.7, P=0.012). Late onset psoriasis (LOP) tended to have more obesity (OR 1.9, P=0.035), DM (OR 9.4, P<0.0001), hypertension (OR 4.1, P<0.0001), and ischemic heart disease during follow-up (OR 5.9, P=0.021). In multivariate analysis, LOP predicted DM development (OR 12.1, P=0.006). LOA was shown to be an independent risk factor for hypertension (OR 5.2, P=0.039). CONCLUSION Age at disease onset exerts a strong influence on several domains of disease phenotype in PsA. Therefore, this descriptor should be considered a good stratification option for epidemiological and genetic studies in PsA.

Dropped head syndrome in a patient with scleromyositis.

Dropped head syndrome (DHS) occurs in patients with severe weakness of the neck extensor muscles, of diverse origin, but most frequently because of neuromuscular diseases. Exceptionally, DHS may be the first manifestation of a systemic autoimmune disease. This report describes the case of a patient with DHS as a presenting sign of scleromyositis. We analyze the clinical features of the case and discuss the most important aspects of its pathogenesis and differential diagnosis.

HLA-DR17 is associated with enthesitis in psoriatic arthritis

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 6 mai 2011

Adverse effects of bisphosphonates

Abstract Aminobisphosphonates are drugs that have been used successfully in the treatment of osteoporosis for more than 20 years. Although main registry studies found a scarcity of relevant adverse events, in recent years and as a result of pharmacovigilance, different complications have been reported, some potentially serious. This has raised questions on the safety of these drugs, especially in high doses, like those used in oncology and long-term treatment, as needed in patients with osteoporosis. In this review, based on the analysis of relevant scientific evidence from clinical trials, case series, cohort studies and databases published to date, we summarize the clinical and epidemiological characteristics of the adverse effects of these drugs.

The Region Centromeric to HLA-C Is a Key Region for Understanding the Phenotypic Variability of Psoriatic Arthritis.

With the aim of clarifying the role of several polymorphisms around the HLA-C locus in the clinical expression of PsA, the distribution of several polymorphic markers and genes located around the HLA-C locus was analyzed in a well-established cohort of 110 patients with PsA, 50 patients with psoriasis alone, and 110 healthy controls. The frequency of these genes was also analyzed by PsA articular models, based on three main subgroups: oligoarthritis, polyarthritis, and spondylitis. Distal interphalangeal joint (DIP) involvement was associated with the presence of MICB-CA20 (OR 6.0, 95% CI: 1.58–22.69, P = 0.005). HLA-DRB∗07 was associated with oligoarticular forms of PsA (OR 4.1, 95% CI: 1.8–9.3, P = 0.0007). The spondylitic forms overexpressed the antigen HLA-B∗27 (OR 5.7, 95% CI: 2.4–13.6, P = 0.0001). MICA-A5.1 showed association with polyarthritis (OR 3.7, 95% CI: 1.5–8.8, P = 0.006). Genes telomeric to HLA-C were overexpressed in psoriasis but not in PsA subphenotypes. This study shows that the region centromeric to HLA-C is a key region that expresses not only disease risk genes but also genes that help explain the phenotypic variability of PsA.

Paniculitis mesentérica en un paciente con espondilitis anquilosante

Mesenteric panniculitis is an inflammatory, chronic, and idiopathic disease that mainly affects the adipose tissue of the mesentery of the small intestine. It is considered as the inflammatory stage of a sclerosing mesenteritis, which can evolve into a third stage called retractable mesenteritis where fibrosis predominates.1 Two cases have been described where mesenteric panniculitis extends into the retroperitoneum and evolves into retroperitoneal fibrosis.2 Retroperitoneal fibrosis is a histologically benign entity. Most cases are idiopathic, but they have been associated with malignancies, drugs, prior surgery and infections as well as autoimmune diseases such as ankylosing spondylitis, and are considered by some as a manifestation of extra-articular disease.3 We report the case of a 65-year-old man with ankylosing spondylitis of 17 years of evolution and repeat bilateral uveitis. His spondylitis had a progressive course, which was not being controlled with anti-inflammatory drugs, so we decided to start treatment with etanercept, which was not effective. In the last eight months he presented gradual diarrhea and abdominal pain, so his case was studied by the Department of Gastroenterology, who performed a colonoscopy discarding inflammatory bowel disease. One day before admission to the General Surgery department he presented acute abdominal pain and bilious vomiting. On examination, the abdomen was distended without signs of peritoneal irritation. He had leukocytosis with elevated acute phase reactants and Xrays showed dilation of the small bowel. We proceeded to perform abdominal CT (Fig. 1) observing the “fat ring sign” characteristic of mesenteric panniculitis, which consists of the observation of surrounding heterogeneous mesenteric masses4 displacing the bowel. Faced with an episode of intestinal obstruction, fluid therapy was instituted with bowel rest, with resolution of the problem. He was subsequently followed as an outpatient; we repeated the Mantoux and Quantiferon tests, which were negative. A year later, he remains gastrointestinally asymptomatic. In the literature review we found only one other published case of an association between ankylosing spondylitis and mesenteric panniculitis, which was initially misdiagnosed as Crohn’s disease. In this case the diagnosis was made through imaging, which was highly suggestive of this entity, consistent with the patient’s progress. For this reason, there was no histologic confirmation.