Clinical and genetic characteristics of ankylosing spondylitis patients with peripheral arthritis at disease onset.

OBJECTIVES: The aim of this study was to assess the clinical and genetic characteristics associated with the presence of peripheral arthritis (PA) at disease onset in patients with ankylosing spondylitis (AS). METHODS: 456 Spanish AS patients, diagnosed according to the modified New York Criteria, who had at least ten years of follow-up since initial disease onset were selected from the National Spondyloarthropathies Registry (REGISPONSER). 18.9% of AS patients initially presented PA. Clinical variables and 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes were analysed. SNP genotyping was performed using the Illumina GoldenGate genotyping platform. Association tests for allele frequencies and for categorical clinical variables were performed by the χ2 test and with the unpaired t-test for continuous variables. p-values of <0.05 were considered statistically significant. RESULTS: AS patients with PA showed an earlier age of disease onset (p=0.021), longer disease duration (p=0.020) and longer duration of AS symptoms from onset (p=0.034) than AS patients without PA. We found significant associations with the presence of PA at disease onset in 14 SNPs located in 10 genes: HLA-DQB2 (rs2857210 and rs9276615), HLA-DOB (rs2857151, rs2621332 and rs1383261), JAK2 (rs7857730), IL-23R (rs11209008 and rs10489630), CYP1B1 (rs1056836), NELL1 (rs8176786), KL (rs564481), and MEFV (rs224204), IL-2RB (rs743777) and IL-1A (rs1800587). CONCLUSIONS: Both clinical and genetic factors are associated with the presence of PA at disease onset in Spanish AS patients. The results suggest that this subset of AS patients with PA at disease onset might have differentiation factors involved in disease pathogenesis.

Fibromyalgia and non-celiac gluten sensitivity: a description with remission of fibromyalgia.

Fibromyalgia (FM) syndrome is a disabling clinical condition of unknown cause, and only symptomatic treatment with limited benefit is available. Gluten sensitivity that does not fulfill the diagnostic criteria for celiac disease (CD) is increasingly recognized as a frequent and treatable condition with a wide spectrum of manifestations that overlap with the manifestations of FM, including chronic musculoskeletal pain, asthenia, and irritable bowel syndrome. The aim of this report was to describe 20 selected patients with FM without CD who improved when placed on a gluten-free diet. An anti-transglutaminase assay, duodenal biopsy, and HLA typing were performed in all cases. CD was ruled out by negative anti-transglutaminase assay results and absence of villous atrophy in the duodenal biopsy. All patients had intraepithelial lymphocytosis without villous atrophy. Clinical response was defined as achieving at least one of the following scenarios: remission of FM pain criteria, return to work, return to normal life, or the discontinuation of opioids. The mean follow-up period was 16 months (range 5-31). This observation supports the hypothesis that non-celiac gluten sensitivity may be an underlying cause of FM syndrome.

Non-celiac gluten sensitivity and chronic refractory low back pain with spondyloarthritis features.

OBJECTIVE: To propose the hypothesis that non-celiac gluten sensitivity is associated with chronic low-back pain related to spondyloarthritis, and a gluten free diet has a therapeutic benefit in a subgroup of patients. Gut involvement is a well-known association of spondyloarthritis but limited to a few disorders such as inflammatory bowel disease. Currently the therapeutic implication of this association is pharmacologic treatment for inflammation with immunosupresive drugs for both diseases. Here is a case series of patients with chronic low-back pain, spondyloarthritis related features, and response to gluten free diet despite celiac disease being ruled out. METHODS: Retrospective case report of 110 patients from a tertiary hospital rheumatology clinic specialized in chronic pain and gluten sensitivity. These are patients with refractory low-back pain and spondyloarthritis features who followed a gluten free diet despite celiac disease being ruled out. Demanding improvement was defined based on the achievement of at least one of the following objectives: asymptomatic status, remission of chronic low-back pain, returning to normal life, returning to work, changing from confinement to bed/wheelchair to being able to walk, returning to self-sufficiency for hygiene and personal care, discontinuation of opioids. RESULTS: Average age at low-back onset pain was 30. Average disease duration was 15 years. 87 (79%) of the patients experienced improvement. 69 (62%) of the patients achieved demanding improvement. Average duration of gluten-free diet in patients with demanding improvement was 60 months. 56 out of 69 patients with demanding improvement ingested gluten. Of these 56 patients, 54 experienced clinical worsening and were considered as having non-celiac gluten sensitivity. Oral aphthae and having a relative with celiac disease were associated with demanding improvement. Out of 28 patients retrospectively classified as having axial spondyloarthritis, 23 had demanding improvement. Out of 16 patients with uveitis, 13 had demanding improvement. Out of 83 patients with fibromyalgia, 48 had demanding improvement. CONCLUSION: These observational data support the proposed hypothesis and offer information regarding possible clinical predictors of response to diet.

Zoledronic Acid Treatment in Primary Bone Marrow Edema Syndrome.

Primary bone marrow edema syndrome (BMES) is characterized by the combination of joint pain and distinctive magnetic resonance imaging changes. It has been suggested that the use of bisphosphonate drugs reduce symptom severity. Our objective was to review cases of patients diagnosed with BMES in the last 7 years who had been treated with zoledronic acid. Access to a pharmaceutical database was gained in order to obtain a list of zoledronic acid prescriptions. Based on clinical and MRI criteria for BMES, patients were selected. Baseline pain intensity was evaluated on a scale of 0 to 3 and was also assessed after 3 and 12 months. Functional recovery was evaluated by noting if a patient had returned to carrying out his or her normal daily activities. Out of 633 patients, 17 cases of BMES were identified (8 men), with a median age of 54 ± 14.1 years. The most frequently affected joint was the ankle (9), followed by the hip. Sixteen patients presented with moderate to severe pain initially. Of those patients, 13 had no pain after 12 months. Zoledronic acid is a option in the management of BMES, since 75% of patients treated with it presented with a complete response.

Non-celiac gluten sensitivity and rheumatic diseases.

Celiac disease is an autoimmune systemic disease having among its clinical manifestations frequent symptoms common to rheumatologic diseases such as musculoskeletal pain, asthenia, and cognitive fatigue. It is associated with other autoimmune diseases like Sjögren disease. It is a well-characterized disease with specific diagnostic tests. Non-celiac gluten sensitivity is an emerging entity with symptoms similar to celiac disease, but without specific diagnostic tests. The concept of non-celiac gluten sensitivity and its diagnostic problems are reviewed, and the hypothesis of its association with fibromyalgia, spondyloarthritis, and autoimmune conditions is proposed. Clinical observations supporting the hypothesis are described, highlighting the benefit of treating non-celiac gluten sensitivity.