Clément Prati

New Onset of Uveitis During Anti-Tumor Necrosis Factor Treatment for Rheumatic Diseases

UNLABELLED Uveitis may be associated with various inflammatory diseases. Previous reports suggested that tumor necrosis factor (TNF) blockers, especially anti-TNF monoclonal antibodies, may reduce the incidence of uveitis flares in some inflammatory diseases. Under these circumstances, de novo occurrence, ie, new onset of the first episode of uveitis under anti-TNF therapy, is uncommon. OBJECTIVES The aim of this study was to collect cases of new onset of uveitis under anti-TNF therapy, using a nationwide network, to describe these cases, and to gather with cases reported in the literature. METHODS All French rheumatologists, pediatric rheumatologists, and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were contacted in an attempt to declare the cases of new onset of uveitis, diagnosed by an ophthalmologist, in patients treated with TNF blockers. The analysis of the literature was performed through PubMed database and manual research. RESULTS Thirty-one cases were recorded, 19 men, mean age 43 (5-70) years, occurring in ankylosing spondylitis (19 cases), psoriatic arthritis (4 cases), rheumatoid arthritis (6 cases), juvenile idiopathic arthritis (2 cases). The TNF blocker at the time of uveitis was etanercept 23 times, adalimumab 3 times, infliximab 5 times, with a mean total duration of exposure to anti-TNF agents of 27 (4-96) months at uveitis occurrence. Most of the patients were good responders to TNF blockers at the time of uveitis onset. Analysis of the literature revealed 121 similar cases published in English. CONCLUSION Uveitis occurs de novo under anti-TNF therapy mainly in spondyloarthropathies, but also in rheumatoid arthritis and juvenile idiopathic arthritis patients and more frequently under etanercept.

Rituximab treatment for spondyloarthritis. A nationwide series: data from the AIR registry of the French Society of Rheumatology.

Objective. To evaluate the efficacy and safety of rituximab (RTX) in several subsets of spondyloarthritis (SpA) using the data of the AIR (Autoimmunity and Rituximab) registry. Methods. All patients receiving RTX for SpA, and prospectively included in the AIR registry from September 2005 to September 2010, were retrospectively analyzed. The response to treatment was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index for axial disease, joint count for peripheral disease, and C-reactive protein reduction. Results. Among the 595 patients included in the AIR registry, 26 patients with SpA from 13 centers were reported: ankylosing spondylitis (10), undifferentiated SpA (7), and psoriatic arthritis (9). Mean disease duration was 8.8 years (range 1−40). The extraarticular features found were psoriasis, 12 cases; uveitis, 4 cases; and Crohn’s disease, 3 cases. The mean number of disease-modifying antirheumatic drugs before RTX was 2.4; previous anti-tumor necrosis factor (TNF) agents were taken in 23 cases. The mean number of RTX courses was 1.5 (range 1−5), with a total of 35.6 patient-years. Efficacy was noted in 11/23 cases: 3 out of 3 anti-TNF-naive patients and 8 out of 20 anti-TNF nonresponder patients. No predictive factors of response could be identified, particularly in diagnosis subsets or clinical presentation (axial or peripheral). Conclusion. In this nationwide study of several subsets of SpA, RTX had only a moderate efficacy that was more marked in patients who were anti-TNF-naive.

Anakinra treatment of SAPHO syndrome: short-term results of an open study

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome comprises many features, but has no specific treatment.1 2 According to the target symptom (synovitis, skin, bone) non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), bisphosphonates3 and tumour necrosis factor (TNF) blockers4 may be proposed, but with variable results. Some patients do not exhibit improvement of symptoms despite use of several, sometimes combined, lines of treatment. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist has recently been described5 under the name DIRA. It associates sterile multifocal osteomyelitis, periostitis and pustulosis, which looks like SAPHO, with good response to anakinra, an interleukin 1 (IL-1) receptor antagonist. We describe the …

Aortic involvement in giant cell arteritis: Current data

Aortitis due to giant cell arteritis (GCA) is rare but probably underestimated given the frequent paucity of symptoms. Thus, early studies relied on the occurrence of complications to estimate the prevalence of GCA aortitis. With this method, aortitis was a feature in 3 to 18% of GCA patients. Since then, the introduction of modern imaging techniques has established that aortitis is more common than previously thought. Aortitis should be considered in patients with atypical clinical presentations of GCA consisting, for instance, in isolated laboratory evidence of systemic inflammation or a relapse during treatment. Aortitis may be difficult to diagnose, as temporal artery biopsy has limited sensitivity in patients with predominant large-vessel involvement. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are both highly effective for the early diagnosis of aortitis. Case-series evaluating PET in patients with GCA found evidence of aortitis in over half the cases, with predominant involvement of the thoracic aorta. To date, no evidence is available about the potential usefulness of PET or MRI in monitoring patients with GCA aortitis over time. Involvement of the aorta and other large arteries does not change the treatment strategy, which rests on corticosteroid therapy. Administration of a corticosteroid-sparing drug should be considered, most notably when a relapse occurs. Aortitis is associated with an increased risk of aneurysm of the thoracic aorta. Consequently, all GCA patients should be monitored for aneurysm at regular intervals, even after treatment discontinuation. The recommended strategy is an annual evaluation including a chest radiograph, echocardiogram, and abdominal Doppler sonogram; these imaging studies can be replaced by contrast-enhanced computed tomography of the chest and abdomen.

Paradoxical effects of anti-TNF-α agents in inflammatory diseases.

Anti-TNF agents represent a major breakthrough in the management of inflammatory diseases. Among the side effects of these agents are the so-called paradoxical effects described in this review. They represent new onset or exacerbation of a condition (symptom/disease), usually improved with TNF blockers. These paradoxical effects are mainly psoriasiform skin reactions, uveitis and granulomatous diseases (such as sarcoidosis and Crohns disease). Infrequent and probably underreported, they should be discussed from the viewpoint of spontaneous features of the underlying disease (e.g., uveitis or psoriasis in a case of spondyloarthritis). The causal mechanism of occurrence is still a matter of debate, but may implicate an imbalance of cytokines toward interferons, chemokines and probably IL-17. These reactions may raise differential diagnosis problems. Symptoms resolve, most of the time, due to the discontinuation of the anti-TNF agent or sometimes a switch to another TNF blocker; but in some cases, it is a class effect that could lead to the withdrawal of all anti-TNF agents.

Scleritis: A Paradoxical Effect of Etanercept? Etanercept-associated Inflammatory Eye Disease

Objective. To describe 3 cases of scleritis associated with etanercept use for rheumatoid arthritis (RA) and to review the literature related to inflammatory eye diseases associated with the use of etanercept. Methods. Three cases of severe scleritis during etanercept therapy were analyzed. A systematic review of the literature in PubMed, Embase, and the Cochrane Library was performed, from 1962 to July 2010. Results. Three patients with seropositive RA developed scleritis 7–28 months after initiation of etanercept, for the first time during their long-lasting disease. In all patients the underlying disease had responded well to anti-tumor necrosis factor therapy. Ocular inflammation went into remission after discontinuation of etanercept, and no other relapses were observed. One patient experienced a dechallenge-rechallenge phenomenon (improvement in symptoms following discontinuation of the agent, then reappearance or worsening of symptoms on reexposure to the agent). Forty-two cases of inflammatory eye diseases believed to be associated with the use of etanercept have been reported in the literature: 33 uveitis, 8 scleritis, 1 orbital myositis, concerning 16 patients with RA, 10 with juvenile idiopathic arthritis, 14 with ankylosing spondylitis, and 2 with psoriatic spondyloarthropathy. Dechallenge was performed in 28 patients, leading to resolution of symptoms. Rechallenge was done in 6 cases, with clear exacerbation. Conclusion. Ocular inflammation is paradoxically a potential adverse effect of etanercept, even in previously uninvolved eyes.

Psoriasis Onset with Tocilizumab Treatment for Rheumatoid Arthritis

To the Editor: Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the interleukin 6 (IL-6) receptor, approved in the treatment of rheumatoid arthritis (RA), with potential use in other inflammatory diseases1. We describe a case of psoriasis onset during TCZ treatment in a patient with RA. A white woman, born in 1955, for 20 years had erosive RA, negative for anticitrullinated protein antibodies. Her condition did not respond to several disease-modifying … Address correspondence to Prof. D. Wendling, University Hospital J. Minjoz – Rheumatology, Boulevard Fleming, Besancon 25030, France. E-mail: dwendling{at}chu-besancon.fr

Mortality in spondylarthritis

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that can lead to chronic pain in axial and peripheral joints and to functional impairments after several years. Excess mortality has been reported in patients with AS. We reviewed recent studies of patients with AS who were treated and monitored according to the improved methods developed in the past few years, without radiation therapy. Our results do not support excess mortality in these patients. Long-term follow-up data from patients enrolled in biologics registries will provide additional information. Cardiovascular disease is the leading cause of death in patients with AS, as in the general population. However, the cardiovascular mortality rate may be slightly increased in patients with AS, probably as a result of dyslipidemia and early endothelial dysfunction. Similarly, and as expected, there is excess mortality related to the spinal disease itself and to renal and gastrointestinal disease. More surprisingly, alcohol abuse and injury or suicide cause excess mortality compared to the general population. In the absence of radiation or radium-224 therapy, and regardless of the other treatments used, the evidence does not support an increased rate of lymphoma or other malignancies compared to the general population. In this review, we discuss the causes and rates of mortality in patients with AS.

Spondyloarthropathy and chronic B hepatitis. Effect of anti-TNF therapy

UNLABELLED Several cases of TNF antagonist-related reactivation of hepatitis B have been reported. Here, we describe 4 cases in patients with spondyloarthropathies. Long-term monitoring of the hepatitis B virus (HBV) load is in order in HBV-positive patients treated with TNF antagonists. CASE REPORTS There were 3 men and 1 woman, aged 30-40 years. Follow-up ranged from 1 to 5 years. In 2 patients, the HBV infection was not discovered until the pre-TNF antagonist therapy workup. A viral load increase was noted after a TNF antagonist was added to methotrexate in 2 patients, whose viral load values returned to baseline after the introduction of the antiviral agent lamivudine. Lamivudine was started at the same time as the TNF antagonist in the other 2 patients, whose viral loads remained undetectable. Escape phenomenon requiring a switch to another antiviral agent was required in 1 patient after more than 4 years of treatment with 3 TNF antagonists. CONCLUSION These 4 case reports illustrate the challenges raised by latent HBV infection in patients who require TNF antagonist therapy. They support routine HBV testing before treatment initiation, followed in HBV-positive patients by viral load monitoring. Antiviral therapy can be used preventively and should be given if the viral load increases under TNF antagonist therapy. In patients on antiviral therapy, viral load monitoring should be continued, given the risk of escape phenomenon after several years.

Early diagnosis and management are crucial in spondyloarthritis

Spondyloarthritis raises considerable diagnostic challenges. The mean time from symptom onset to the definitive diagnosis was 8 years in classical studies. This diagnostic delay has a deleterious impact not only for the patient, but also potentially on the course of the disease and therefore on its social and economic costs. In addition, delays in diagnosis translate into delays in management. The main reason for diagnostic delays is that early classification criteria sets include marked radiographic changes, which require time to develop. New criteria are now available that should allow earlier patient classification and that recognize the existence of non-radiographic forms of spondyloarthritis. Results from prospective cohort studies of early spondyloarthritis, on the one hand, and continuing medical education efforts aimed at informing all healthcare professionals of changes in concepts, on the other, should prove effective in decreasing the time to diagnosis, thereby optimizing patient management.