Dominique Monnet

How to diagnose spondyloarthritis early? Accuracy of peripheral enthesitis detection by power Doppler ultrasonography

Objective Early diagnosis of spondyloarthritis (SpA) is sometimes difficult owing to the lack of reliable diagnostic criteria. The objective of this study was to determine the diagnostic accuracy of detecting enthesitis by power Doppler ultrasonography (PDUS) in patients with suspected SpA. Methods A prospective single-centre cohort study was performed in patients with symptoms suggestive of SpA (inflammatory back pain, arthritis, enthesitis or dactylitis, HLAB27+ uveitis) who underwent clinical examination, pelvic x-ray, MRI of lumbar spine/sacroiliac joints, HLA-B typing and other tests judged useful for diagnosis. Blinded PDUS examination of seven sites of enthesitis was performed at baseline. The gold standard was the diagnosis made by the referring rheumatologist according to the development of symptoms and findings, blinded to PDUS results, during routine follow-up for up to 2 years. Results Between November 2002 and October 2004, 118 patients were included in the study. After 2 years a definite diagnosis was retained for 99 patients (51 SpA and 48 non-SpA). PDUS detection of at least one vascularised enthesis provided good predictive value for diagnosing SpA (sensitivity 76.5%; specificity 81.3%; positive likelihood ratio 4.1; OR 14.1; p<0.0001). Vascularised enthesitis detected by PDUS and Amors criteria were the only independent contributors to a diagnosis of SpA in multivariate logistic regression (c-index=0.87). Alternatively, CART analysis resulted in a highly sensitive and specific diagnostic tree by combining PDUS with Amors criteria. Conclusions PDUS appears to be a valuable first-line diagnostic tool to confirm a diagnosis of SpA.

Association between the IL-1 family gene cluster and spondyloarthritis

Objective Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spondyloarthritis. Particular attention was devoted to genotype–phenotype correlations. Methods Seven single-nucleotide polymorphisms (SNP) and a variable number tandem repeat located in the IL-1 gene cluster were genotyped in 185 independent spondyloarthritis trios. Family-based association test (FBAT) was computed using the FBAT software. Analysis was carried in spondyloarthritis as a whole and also in AS. A case–control replication study was performed for four of the SNP, in an independent sample of 414 spondyloarthritis and 264 controls. A combined analysis of both studies was performed. Results The SNP rs2856836 in IL1A was significantly associated with spondyloarthritis (p=0.009) and AS (p=0.010) in the family study. The case–control study revealed an association between another IL1A variant (rs1894399) and AS (p=0.035), and between IL1F10.3 (rs3811058) and spondyloarthritis (p=0.041). By combining family and case–control studies an association between AS and IL1A was confirmed (rs1894399, p=0.024), whereas non-AS was more significantly associated with IL1F10.3 (p=0.0043). Family-based and case–control studies revealed significant association between the two most frequent haplotypes combining the four SNP of the replication study and both spondyloarthritis (p=0.0054 and p=0.038) and AS phenotypes (p=0.018 and 0.0036). Conclusion This study is the first to demonstrate an association between several polymorphisms located in the IL-1 gene cluster and spondyloarthritis as a whole. The IL1A locus was strongly associated with AS phenotype, whereas IL1F10 was associated with non-AS.

HLA-A29 and Birdshot Chorioretinopathy

Birdshot chorioretinopathy primarily affects patients of European descent. At least 96%, if not all patients, are HLA-A29 carriers. HLA-A*29:01 and HLA-A*29:02, the two main subtypes of HLA-A29, differ only by a single mutation. In the general population HLA-A*29:02 is most frequent in whites, while HLA-A*29:01 is more frequent in Asians. The differential distribution of HLA-A*29:01 and HLA-A*29:02 has been actively debated as an explanation for the selective development of the disease in patients of European descent, but is no longer a valid argument. Another factor, probably not HLA linked, is either protective in Asians and in Africans or, conversely, triggers an autoimmune reactivity that is possibly present in whites and absent in Asians and in Africans. HLA-A*29:02 transgenic mice in which a spontaneous posterior uveitis is observed after 6 months of age provide further evidence that the HLA-A29 molecule plays a role in the pathogenesis of the disease.

Severe uveitis in an HLA-B27-positive patient with ankylosing spondylitis

Background A 36-year-old male presented with bilateral, anterior, chronic uveitis, with cystoid macular edema. Decimal visual acuity was 0.25 in the right eye and 0.20 in the left eye. Ankylosing spondylitis had been diagnosed 13 years previously, with peripheral and axial involvement. He had no history of extra-articular manifestations of ankylosing spondylitis before this uveitis attack. Treatment with the anti-tumor necrosis factor agent etanercept was initiated 5 months before the attack of uveitis.Investigations Slit-lamp biomicroscopy, laser-flare photometry, optical coherence tomography, chest radiography, angiotensin-converting-enzyme test, mycobacterial culture from gastric lavage, serology tests for syphilis, brucellosis, toxoplasmosis, toxocarosis, antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, antimyeloperoxydase antibodies and antiproteinase 3 antibodies.Diagnosis Atypically severe HLA-B27-positive uveitis, in a patient with ankylosing spondylitis treated with etanercept.Management Intensive topical corticosteroid and cycloplegic treatment, subtenon triamcinolone acetonide injection, switch in treatment from etanercept to infliximab followed by discontinuation of tumor necrosis factor inhibitors, intravenous pulses of methylprednisolone followed by oral corticosteroids, and intravenous cyclophosphamide.

Longitudinal Cohort Study of Patients with Birdshot Chorioretinopathy. V. Quality of Life at Baseline

PURPOSE To describe results of a vision-specific quality-of-life (QOL) questionnaire at baseline examination of 80 subjects in a longitudinal cohort study of birdshot chorioretinopathy and to identify relationships between these results and measures of visual function. DESIGN Single-center, cross-sectional study. METHODS The National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) was administered to all subjects. NEI VFQ-25 composite scores were compared with best-corrected visual acuity (BCVA), symptoms, color confusion scores, and parameters from automated perimetry (mean deviation [MD], total deviation) for the better eye (with regard to the factor being studied) of each subject. Selected measures of visual function were compared with the 12 subscale scores. RESULTS The median composite score was 76.8 (range, 7.8 to 99.4). Worse composite scores were related to decreased BCVA (P = .030), but the correlation was weak, and subjects with normal BCVA (> or = 1.0) in both eyes had composite scores as low as 37.7. Lower composite scores were related to symptoms of blurry vision (P = .0097), nyctalopia (< .0001), poor contrast (P = .002), vibrating vision (P = .014), and poor peripheral vision (P = .007). Lower composite scores were related to worse MD (P = .005). Although nyctalopia and MD are related, each was associated with composites scores on multivariate analysis. Nyctalopia was associated with the largest number of subscales having decreased scores. CONCLUSIONS Birdshot chorioretinopathy has an impact on vision-specific QOL. BCVA alone does not explain decreased vision-specific QOL in our cohort; changes in automated perimetry and symptoms seem to be important contributors to alterations in QOL that are independent of BCVA changes.

Characteristics of Vogt-Koyanagi-Harada Disease in a French Cohort: Ethnicity, Systemic Manifestations, and HLA Genotype Data

Purpose: To assess in patients followed in a French referral center the clinical spectrum of Vogt-Koyanagi-Harada (VKH) disease and the HLA-DRB1*04 genotype. Methods: Patients previously diagnosed as having VKH disease were re-evaluated in a cross-sectional study using the VKH Committees revised criteria. High-resolution HLA-DRB1 genotyping was performed. Results: Eleven white patients satisfied ophthalmologic diagnostic criteria. All originated from Mediterranean countries. Nine and 3 patients had neurologic and/or cutaneous abnormalities, respectively. Among DRB1*04-positive patients, the HLA-DRB1*0405 subtype was 71%. Conclusion: These VKH patients predominantly had an incomplete form. The HLA-DRB1*0405 subtype allele was enriched in a group of Mediterranean stock.

Contrast sensitivity among patients with birdshot chorioretinopathy.

PURPOSE To assess contrast sensitivity in patients with birdshot chorioretinopathy; to identify relationships between contrast sensitivity, other measures of visual function, clinical findings, and quality of life. DESIGN Single-center, cross-sectional study. METHODS We measured contrast sensitivity in 63 patients (126 eyes) at four spatial frequencies (3, 6, 12, 18 cycles/degree [cpd]) using the CSV-1000E instrument (VectorVision, Greenville, Ohio, USA). Abnormal contrast sensitivity was defined as two standard deviations below the mean for population norms. Results at spatial frequency 12 cpd were compared to the following parameters in per-eye analyses: best-corrected visual acuity (BCVA); presence of eight specified symptoms; color vision; visual field parameters (foveal threshold, mean deviation); and optical coherence tomography parameters (central macular thickness, loss of the third highly reflective band). Results were compared to the National Eye Institute Visual Function Questionnaire (VFQ)-25 in per-patient analyses. Results were adjusted for age, disease duration, treatment, BCVA, and lens status. RESULTS Contrast sensitivity (spatial frequency 12 cpd) was abnormal in 99 eyes (92%), and was related to poor BCVA (P = .0004) and the symptom of poor contrast sensitivity (P = .025). Among 38 eyes with normal BCVA (> or =1.0), 31 eyes (82%) had abnormal contrast sensitivity. There was a positive correlation between contrast sensitivity in better eyes and the VFQ-25 composite scores (r = 0.51; P < .001). CONCLUSION Decreased contrast sensitivity is common in patients with birdshot chorioretinopathy and may occur in the absence of other visual changes. Contrast sensitivity may be a useful measure for clinical studies of birdshot chorioretinopathy and for monitoring patients with the disease.

A New HLA Extended Haplotype Containing the A*2910 Allele in Birdshot Retinochoroidopathy: Susceptibility Narrowed to the HLA Molecule Itself

PURPOSE Birdshot retinochoroidopathy (BSRC) is a rare posterior uveitis characterized by distinctive, multiple, hypopigmented choroidal and retinal lesions. Most, if not all, patients are white and share the major histocompatibility antigen HLA-A29. Furthermore, the A*2902 subtype is closely associated with BSRC, and only a very few patients share the A*2901 subtype. Surprisingly, although A*2901 and A*2902 differ only by a single mutation (D102H), studies of microsatellites located near HLA-A have shown that two strong A*2901 and A*2902 extended haplotypes are observed in patients and control subjects. The present study analyzes the HLA-A extended haplotype of two patients who were HLA-A*2910 carriers. METHODS Among 180 patients who fulfilled internationally defined criteria for the diagnosis of BSRC and who were HLA-A29 subtyped, two patients were found to be HLA-A*2910 carriers. These patients were tested for the microsatellite alleles MOGa, -b, -c, and -e (of the myelin oligodendrocyte glycoprotein [MOG] gene) and D6S265, D6S510, RF, C5_4_5, and D6S105. RESULTS Although A*2902 and A*2910 differed by only a single mutation, (E177K) a new A*2910 extended haplotype was found to be distinct from the A*2901 and A*2902 extended haplotypes previously described in patients and control subjects. Among all studied microsatellite markers, no allele was shared by these extended haplotypes. CONCLUSIONS These results suggest that susceptibility to BSRC is linked to the histocompatibility HLA-A29 molecule itself, although the development of the disease also involves inherited or probably acquired factors not linked to the major histocompatibility complex.

Extraocular manifestations of birdshot chorioretinopathy in 118 French patients

INTRODUCTION Published studies on birdshot chorioretinopathy (BCR) did not provide definitive information on possibly associated extraocular manifestations. METHODS Single-center cross-sectional analysis of extraocular manifestations in a cohort of patients with BCR. RESULTS Since 2002, 118 patients (45 men, 73 women) were enrolled. Their mean age was 51.5 years at diagnosis. The most common features of their medical histories were: hypertension (32 patients), drug allergy (19), sinusitis (17), thyroid disease (12), otitis media (11), asthma (11); diabetes (10); cancer (8); psoriasis (5); monoclonal gammopathies (3). At the time of disease onset, arthralgias were noted in 23, ENT manifestations in 26, Raynauds phenomenon in 6, headaches in 10, psoriasis in 3 others. Between diagnosis and cross-sectional evaluation visits, only the frequency of hypertension has increased significantly (11 additional patients). DISCUSSION AND CONCLUSIONS No predominant extraocular manifestation of BCR was identified in our patients. Their ongoing follow-up may yet discern whether BCR is definitively eye-restricted.

Thrombotic Microangiopathy and Purtscher-like Retinopathy as a Rare Presentation of Juvenile Dermatomyositis

Juvenile dermatomyositis is a rare systemic vasculopathy that may sometimes present with acute complications. We report here the case of a 7-year-old boy with severe dermatomyositis associated with thrombocytopenia and blurry vision. The presence of schistocytosis and the secondary occurrence of hemolytic anemia were consistent with a diagnosis of thrombotic thrombocytopenic purpura (TTP). Further investigations demonstrated the association of TTP with muscular microangiopathy and Purtscher-like retinopathy. Retinal and hematologic involvements dramatically improved after the initiation of plasma exchange in emergency. This report emphasizes that early recognition of TTP and prompt plasmapheresis are important in a child with severe juvenile dermatomyositis associated with thrombocytopenia.