Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease.

OBJECTIVE: To evaluate the clinical usefulness of tumor necrosis factor (TNF) inhibitors in patients with inflammatory eye disease that is resistant to conventional immunosuppressive therapies. METHODS: Sixteen patients (4 males and 12 females aged 7 to 78 years) who received etanercept (n = 14) or infliximab (n = 2) for either inflammatory eye disease or associated joint disease were studied retrospectively to determine the effect of these medications on their ocular inflammation. RESULTS: Nine cases of uveitis and 7 cases of scleritis were treated. Systemic diagnoses included rheumatoid arthritis (n = 8), juvenile rheumatoid arthritis (n = 3), ankylosing spondylitis (n = 1), and psoriatic spondylarthropathy (n = 1). Three patients had uveitis without associated systemic disease. Although 12 of 12 patients with active articular inflammation (100%) experienced improvement in joint disease, only 6 of 16 with ocular inflammation (38%) experienced improvement in eye disease. Five patients developed inflammatory eye disease for the first time while taking a TNF inhibitor. No patient discontinued treatment because of adverse drug effects. CONCLUSION: TNF inhibitors are well tolerated immunosuppressive medications that may benefit certain subgroups of patients with inflammatory eye disease, but they appear to be more effective in controlling associated inflammatory arthritis.     

Update on anti-tumor necrosis factor therapy in the spondyloarthropathies including psoriatic arthritis

PURPOSE OF REVIEW: The introduction of the macromolecule tumor necrosis factor inhibitors etanercept, infliximab, and adalimumab has proven very successful for patients with spondyloarthropathies. The greatest experience has accrued in ankylosing spondylitis and psoriatic arthritis. This paper reviews data from clinical trials with tumor necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis. RECENT FINDINGS: Treatment with tumor necrosis factor inhibitors has not only resulted in substantial improvement in the signs and symptoms of arthritis but has also improved functional status and quality of life in ankylosing spondylitis and psoriatic arthritis. Improvements in associated inflammatory features, such as enthesitis in psoriatic arthritis and uveitis in ankylosing spondylitis, have also been observed. Moreover, treatment has been shown to inhibit the progression of radiographic joint damage in psoriatic arthritis and to attenuate spinal inflammation in ankylosing spondylitis. The notable success of tumor necrosis factor inhibitors has not only changed the treatment paradigms for these conditions but has also stimulated studies aimed at improving diagnosis, prognostic stratification, and other aspects of clinical care. SUMMARY: The introduction of tumor necrosis factor inhibitors for patients with ankylosing spondylitis and psoriatic arthritis has had a tremendous impact on daily clinical care.     

Axial disease in psoriatic arthritis

The definition of axial disease in psoriatic arthritis has varied from isolated unilateral grade 2 sacroiliitis to criteria similar to those used for ankylosing spondylitis. Depending on the definition used, the prevalence of axial disease varies from 25% to 70% of patients with psoriatic arthritis. This article reviews the prevalence, clinical and radiologic features, pathogenesis, prognosis, and treatment of psoriatic spondylitis.     

Enteropathic arthritis

Enteropathic arthritis is a form of arthritis associated with the chronic inflammatory bowel diseases, ulcerative colitis, and Crohn's disease. This form of arthritis is classified as one of the group of seronegative spondyloarthropathies, which also includes psoriatic arthritis, reactive arthritis, and idiopathic ankylosing spondylitis. Joint involvement also occurs with other gastrointestinal diseases such as Whipple's disease, celiac disease, and following intestinal bypass surgery for morbid obesity. In these conditions, abnormal bowel permeability and immunologic and genetic influences are probably involved in the pathogenesis of the joint disease, although the exact mechanisms remain uncertain.     

Unusual cervical spine involvement in psoriatic arthritis: a case series

Cervical spine involvement in psoriatic arthritis is not uncommon and can often mimic symptoms and signs of ankylosing spondylitis. However, some specific features may help to differentiate between patients with psoriatic arthritis and ankylosing spondylitis. Here, we present a series of three patients with psoriatic arthritis and increasing cervical pain and loss of mobility. Each of the cases shows specific radiographic characteristics. These cases therefore illustrate different aspects of the involvement of the cervical spine in axial forms of psoriatic arthritis and highlight the importance of proper evaluation and management of axial disease in psoriatic arthritis.     

Spondylarthropathies and anti-TNFalpha drugs

PURPOSE: Spondylarthropathies are a heterogeneous group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondylarthropathies. These diseases are characterised by inflammation in the spine, sacroiliac joints, entheses, peripheral joints, and a strong association with HLA-B27; they may cause severe destruction and/or ankylosis in a minority of patients. Conventional treatment includes non steroidal anti-inflammatory drugs, corticosteroid injections, and DMARDs such as sulfasalazine in patients with peripheral arthritis. TNFalpha appears as an important actor in the pathogenesis of spondylarthropathies. METHOD AND RESULTS: Among the anti-TNFalpha drugs, etanercept and infliximab have proved to be effective in the symptomatic treatment of ankylosing spondylitis and psoriatic arthritis. A clinical relapse was observed within a few weeks after treatment discontinuation in a majority of patients. Potential beneficial effects on the destructive and/or ankylosing evolution remains to be confirmed. CONCLUSIONS: Patients with active, severe and refractory spondylarthropathies are potential candidates for treatment with anti-TNFalpha drugs. Taking into account not only the efficacy but also the side effects, with rare but potentially severe complications such as tuberculosis or other opportunistic infections, and the relatively high cost of these drugs, preliminary criteria for the initiation, monitoring and discontinuation of these drugs in the treatment of spondylarthropathies were proposed. Long-term follow-up in large populations of patients with spondylarthropathies is necessary to better define the benefit/risk/cost ratio of anti-TNFalpha drugs.     

Imaging of psoriatic arthritis

Imaging of psoriatic arthritis (PsA) is important for two reasons: the differential diagnosis from other arthritides and the assessment of structural damage that can be inhibited by the new drugs such as the anti-TNFalpha agents. Plain film radiographic findings of peripheral arthritis have been important in elaborating the concept of PsA as a separate disease entity. Characteristic aspects of psoriatic peripheral arthritis help the differentiation from rheumatoid arthritis. High-resolution ultrasonography (US), US combined with power Doppler (PDUS) and magnetic resonance imaging (MRI) can be used to image joint synovitis of PsA. Radiologic features of spondylitis associated with psoriasis are similar to spondylitis associated with reactive arthritis and differ from those of primary ankylosing spondylitis (AS) and the spondylitis associated with inflammatory bowel disease. MRI is very sensitive for the early diagnosis of sacroiliitis. There have been no MRI studies on the spine of patients with PsA. In primary AS bone oedema in the vertebral bodies is an indicator of active disease and can ameliorate during anti-TNFalpha therapy. Historically, plain film radiography have played a pivotal role in defining enthesitis lesions of SpA. However, entheseal bone changes appear late. US and MRI have proved to be a highly sensitive and non invasive tools. Recent US and MRI studies on both finger and toe dactylitis have established that dactylitis is due to flexor tenosynovitis and marked adjacent soft tissue swelling with a variable degree of small joint synovitis. There is no evidence of enthesitis of the insertion of the flexor digitorum tendons and of the attachment of the capsule of the digit joints.     

Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis

OBJECTIVE: To evaluate the cardiovascular risk profile of spondylarthropathy patients, particularly ankylosing spondylitis and psoriatic arthritis. METHODS: A Pubmed literature search was performed to collect English-language articles for this clinically orientated review. Studies were selected if they included (cardiovascular) mortality and morbidity and/or data about cardiovascular risk factors in spondylarthropathies. RESULTS: Ankylosing spondylitis as well as psoriatic arthritis appear to be associated with an increased cardiovascular mortality and morbidity. Several factors, ie, smoking, altered lipid profile, hypertension, increased fibrinogen level, enhanced number of platelets, and hypercoagulability might explain the enhanced cardiovascular risk. Moreover, a decline in physical activity, the presence of HLA-B27, and inflammation may play a role. Finally, undertreatment of cardiovascular morbidity also may contribute to the higher cardiovascular risk. CONCLUSIONS: The available data indicate an increased cardiovascular risk in spondylarthropathy patients, particularly those with ankylosing spondylitis and psoriatic arthritis. RELEVANCE: Rheumatologists should be aware of the enhanced cardiovascular risk in patients with ankylosing spondylitis and psoriatic arthritis. If modifiable cardiovascular risk factors are identified, treatment could ultimately result in a lower cardiovascular morbidity and mortality.     

Spondyloarthropathy and rheumatoid arthritis in Alaskan Yupik Eskimos

In a Yupik Eskimo population, the prevalence, incidence and clinical features of rheumatoid arthritis (RA) were similar to those described for the United States population in general. More frequent than RA were seronegative spondyloarthropathic disorders, many of which could not be classified by existing disease criteria. Of the adult patients with spondyloarthropathy only half could be classified as having Reiter's syndrome (RS), ankylosing spondylitis (AS) or psoriatic spondylitis. The remaining patients had many signs and symptoms consistent with spondyloarthropathy, but they either did not meet the diagnostic criteria for any specific disease or had features pathognomonic of more than one. The clinical manifestations of the patients who did not meet standard disease definitions are summarized and compared to those of the patients with RS, AS and psoriatic spondylitis. Because of the many shared features, we believe that these as yet unclassified disease states belong with AS and RS in a single spondyloarthropathic disease spectrum and should be defined and recognized as such.     

Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease

Objective

To evaluate the clinical usefulness of tumor necrosis factor (TNF) inhibitors in patients with inflammatory eye disease that is resistant to conventional immunosuppressive therapies.

Methods

Sixteen patients (4 males and 12 females aged 7 to 78 years) who received etanercept (n = 14) or infliximab (n = 2) for either inflammatory eye disease or associated joint disease were studied retrospectively to determine the effect of these medications on their ocular inflammation.

Results

Nine cases of uveitis and 7 cases of scleritis were treated. Systemic diagnoses included rheumatoid arthritis (n = 8), juvenile rheumatoid arthritis (n = 3), ankylosing spondylitis (n = 1), and psoriatic spondylarthropathy (n = 1). Three patients had uveitis without associated systemic disease. Although 12 of 12 patients with active articular inflammation (100%) experienced improvement in joint disease, only 6 of 16 with ocular inflammation (38%) experienced improvement in eye disease. Five patients developed inflammatory eye disease for the first time while taking a TNF inhibitor. No patient discontinued treatment because of adverse drug effects.

Conclusion

TNF inhibitors are well tolerated immunosuppressive medications that may benefit certain subgroups of patients with inflammatory eye disease, but they appear to be more effective in controlling associated inflammatory arthritis.

     

Eye inflammation in psoriatic arthritis.

In a study of 112 patients (49 men, 63 women) with psoriatic arthritis, ocular inflammation was noted in 35 (31.2%). Conjunctivitis was the most common lesion, being found in 19.6% (10 males, 12 females). Iritis occurred in 7.1% (5 men, 3 women), episcleritis in 1.8% (1 man, 1 woman), and keratoconjunctivitis sicca in 2.7% (3 women). 20 patients (10 men, 10 women) had radiological sacroiliitis and 11 of these (7 men, 4 women) had ankylosing spondylitis according to the New York criteria. Eye lesions were noted in 7 of the patients with sacroiliitis, 3 having iritis (15%) and 4 (20%) conjunctivitis. 2 patients with spondylitis had iritis (18%) and 1 (9%) conjunctivitis. It is concluded that inflammatory eye lesions are a frequent accompaniment to psoriatic arthritis. This is taken as further evidence for the concept of the seronegative spondyloarthritides.     

Familial occurrence of systemic sclerosis, rheumatoid arthritis and other immunological disorders: report of two kindreds with study of HLA antigens and review of the literature

We report two Caucasian families with systemic sclerosis and other connective tissue and immunological disorders, including rheumatoid arthritis, discoid lupus erythematosus, psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, asthma, Sj?gren's syndrome, Raynaud's phenomenon and thyroid disease. In one of these families, two sisters are affected with systemic sclerosis. Clinical, serological, and HLA haplotype results are reported, along with a review of the medical literature on familial occurrence of systemic sclerosis.     

Cost of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and systemic lupus erythematosus in Germany

OBJECTIVE: To estimate and compare the direct and indirect costs of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE), and to evaluate the effect of sex, disease duration and functional status on the various cost domains. METHODS: Data of outpatients, aged 18-65, with rheumatoid arthritis (n = 4351), ankylosing spondylitis (n = 827), PsA (n = 908) or SLE (n = 844), who were enrolled in the national database of the German collaborative arthritis centres in 2002, were analysed. Data on healthcare consumption, out-of-pocket expenses and productivity losses were derived from doctors and patients. For the calculation of indirect costs, the human capital approach (HCA) and the friction cost approach (FCA) were applied. RESULTS: Mean direct costs amounted to 4737 euros a year in rheumatoid arthritis, 3676 euros in ankylosing spondylitis, 3156 euros in PsA and 3191 euros in SLE. By using the HCA, total costs were calculated at 15,637 euros in rheumatoid arthritis, 13,513 euros in ankylosing spondylitis, 11,075 euros in PsA and 14,411 euros in SLE, whereas with the FCA the numbers were 7899 euros, 7204 euros, 5570 euros and 6518 euros, respectively. Costs increased with disease duration and were strongly dependent on functional status. In patients with the highest disability (<50% of full function), the total costs on applying the HCA were 34,915 euros in rheumatoid arthritis, 29,647 euros in alkylosing spondylitis, 37,440 euros in PsA and 32,296 euros in SLE. CONCLUSION: The costs of illness are high in all four diseases, with a strong effect of functional status on total costs. Indirect costs differ by the factor 3, based on whether the HCA or the FCA is used.     

Spondyloarthropathies in sub-Saharan Africa

HLA-B27 is virtually absent in most of the sub-Saharan Africa populations, and ankylosing spondylitis is rare; only a few patients have been reported from central and southern Africa. HLA-B27 was present in only one of 17 patients (6%). The disease shows clinical features that are similar to those observed in white HLA-B27-negative patients with ankylosing spondylitis; ie, the disease onset is later compared with HLAB27-positive patients, the patients rarely get acute anterior uveitis as one of the extra-articular manifestations, and familial occurrence of ankylosing spondylitis is rarely observed. There is a virtual absence of ankylosing spondylitis even in the west African countries of Gambia and Senegal, where 3% to 6% of the general population has HLA-B27. The epidemic of HIV infection in sub-Saharan Africa in recent years, however, has been associated with a dramatic upsurge in the prevalence of spondyloarthropathies other than ankylosing spondylitis, primarily reactive arthritis and undifferentiated forms of the disease, and less often psoriatic arthritis. HLA-B27, because of its rarity and virtual lack of association with the observed cases of spondyloarthropathy in this population, cannot be used as an aid to diagnosis of spondyloarthropathy in black Africans. Conversely, HIV infection is increasingly showing such a strong association with reactive arthritis, psoriatic arthritis, and undifferentiated spondyloarthropathies in sub-Saharan African populations that any patient with acute or chronic inflammatory arthritis may need to be tested for possible HIV infection. More research is needed on the evaluation of risk and protective factors in sub-Saharan African populations to better delineate the relative importance of genetic and environmental factors in the pathogenesis of spondyloarthropathies.     

Biologic therapies in the spondyloarthritis: new opportunities,new challenges

Therapeutic options for patients suffering from the more severe forms of spondyloarthritis have been rather limited in the last decades. There is now accumulating evidence that antitumor necrosis factor therapy is highly effective in spondyloarthritis, especially in ankylosing spondylitis and psoriatic arthritis. Based on the data recently published on more than 500 patients with ankylosing spondylitis and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis. The antitumor necrosis factor-alpha agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis in the United States and partly in Europe. The situation in spondyloarthritis is different from that of rheumatoid arthritis because there is an unmet medical need, especially in ankylosing spondylitis: no therapies with disease-modifying antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, tumor necrosis factor blockers may even be considered a first-line treatment in a patient with active ankylosing spondylitis and psoriatic arthritis whose condition is not sufficiently controlled with nonsteroidal antiinflammatory drugs in the case of axial disease, and sulfasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg was required, and intervals between 6 and 12 weeks were necessary to suppress disease activity constantly-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are no studies yet on adalimumab (standard rheumatoid arthritis dose, 20-40 mg subcutaneously every 1-2 weeks) in spondyloarthritis. Infliximab was very recently approved for AS in Europe. The efficacy of etanercept was first demonstrated in psoriatic arthritis, and it is now approved for this indication. A double-blind study has also been performed in ankylosing spondylitis, with similarly clear efficacy. There is preliminary evidence that both agents do also work in other spondyloarthritis, such as undifferentiated spondyloarthritis. Ideally, both agents will be approved soon for the short-term treatment of severe, uncontrolled spondyloarthritis. In parallel, studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term antitumor necrosis factor therapy and whether radiologic progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can be largely prevented by appropriate screening. At it stands now, the benefits of antitumor necrosis factor therapy in ankylosing spondylitis seem to outweigh these shortcomings.     

Psoriatic arthritis and chronic lymphoedema: treatment efficacy by adalimumab

Lymphoedema is a rare complication of psoriatic arthritis (PsA) and inflammatory joint disease, with no response noted to disease-modifying drugs. However, reports are emerging of a beneficial effect on lymphoedema in patients treated with tumor necrosis factor-alpha antagonists for PsA (Etanercept), rheumatoid arthritis (Etanercept) and ankylosing spondylitis (Infliximab). We describe a psoriatic arthritis patient whose lymphoedema greatly improved following commencement of adalimumab.     

Quantification of radiological damage in inflammatory arthritis: rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Quantification of radiological damage in inflammatory arthritis is important. It has proven its value in clinical trials, but its use in clinical practice is becoming more important as well. Scoring methods for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are available. These differ in the joints and features assessed. This results in differences in the scoring range, but also in the method of performance. The various methods for the three diseases are detailed in this chapter. Most information is available for rheumatoid and for this disease the relationship between radiological damage and long-term outcome is summarised.     

Psoriatic arthritis: a systematic review

Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra-articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non-steroidal anti-inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti-tumor necrosis factor-α drugs to control symptoms and to slow or arrest radiological disease progression.     

Relationship of psoriatic arthritis with the other spondyloarthropathies

PURPOSE OF REVIEW: The seronegative spondyloarthropathies are a group of disorders sharing common clinical features, the hallmark of which is sacroiliitis. Despite the 40 years since psoriatic arthritis was recognized, controversy still exists about which patients to include within this disease group and the relation of psoriatic arthritis with the other spondyloarthropathies. RECENT FINDINGS: Early disease can present difficulties because it is inappropriate to use criteria developed on established cases in early arthritis, in which many cases may be initially undifferentiated. The taxonomy of juvenile spondyloarthropathy remains a contentious issue, and further modifications of the Durban criteria have been suggested. The predictive value of the European Spondyloarthropathy Study Group criteria for spondyloarthropathy varies with the prevalence of the disease in the population under consideration, as has been demonstrated in ambulatory practice in France and Spain. It appears that physicians differ in their interpretation of the individual features, particularly of such clinical items as asymmetry and predominantly lower limb involvement. The combination of dactylitis of a toe, heel pain, and oligoarthritis appears to be strongly suggestive of psoriatic arthritis. However, solitary heel pain can be problematic, and ultrasonographic entheseal erosion at the calcaneum has been shown equally in rheumatoid arthritis and psoriatic arthritis. MRI may be more sensitive and quantitatively discriminative in psoriatic arthritis. Spinal involvement in psoriatic arthritis can be asymptomatic, as in classical ankylosing spondylitis. Importantly, psoriatic spondylitis has been observed in the absence of sacroiliitis. SUMMARY: Clinicians generally agree that psoriatic arthritis constitutes a discreet subset within the spondyloarthropathy group, but the demarcation continues to be the subject of clinical research. The matter is confounded by the lack of agreed classification criteria for psoriatic arthritis; although in both adult and juvenile disease criteria for spondyloarthropathy exist, the place of psoriatic arthritis within this larger group requires further definition.