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ID PMID Title PublicationDate abstract
20722046 Assessment of the natural history of forefoot bursae using ultrasonography in patients wit 2010 Dec OBJECTIVE: To determine the natural history and clinical significance of forefoot bursae over a 12-month period in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n=149) attending rheumatology outpatient clinics were assessed at baseline. A total of 120 participants, mean±SD age 60.7±12.1 years and mean±SD disease duration 12.99±10.4 years, completed the 12-month followup (98 women, 22 men, 93 rheumatoid factor positive, 24 rheumatoid factor negative, and 3 unknown). Musculoskeletal ultrasound (US) was used to identify forefoot bursae in all of the participants. Clinical markers of disease activity (well-being visual analog scale [VAS], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] level, and Disease Activity Score in 28 joints [DAS28]) and foot symptoms on the Leeds Foot Impact Scale (LFIS) Questionnaire were recorded on both occasions. RESULTS: Presence of US-detectable forefoot bursae was identified in 93.3% of returnee (n=120) participants (individual mean 3.7, range 0-11) at baseline. Significant associations were identified between bursae presence and patient-reported foot impact for impairment/footwear (LFISIF ; baseline: r=0.226, P=0.013 and 12 months: r=0.236, P=0.009) and activity limitation/participation restriction (LFISAP; baseline: r=0.254, P=0.005 and 12 months: r=0.235, P=0.010). After 12 months, 42.5% of participants had an increase in the number of US-detectable forefoot bursae and 45% of participants had a decrease. Changes in bursae number significantly correlated with changes in LFISIF (r=0.216, P=0.018) and LFISAP (r=0.193, P=0.036). No significant associations were identified between changes in bursae and changes in global well-being VAS, ESR, CRP level, or DAS28. CONCLUSION: The findings of this study suggest that forefoot bursae may regress or hypertrophy over time in patients with RA, and that these changes may be associated with self-reported foot impairment and activity restriction.
19288119 [Mayer S. Diamantberger (1864-1944). The first person to describe juvenile chronic arthrit 2009 May No evidence can be found in the medical textbooks from the beginning of the twentieth century that rheumatoid arthritis can also occur in children. Isolated cases were first published in the second half of the nineteenth century. In the Hôpital Rothschild in Paris several children with this disease were observed and nursed within a short period of time. M.S. Diamantberger, an assistant in this hospital, was intensively involved with these patients and analyzed all previously published cases. This was the theme of his dissertation which was first made public in 1890 and was published in 1891. Diamantberger proved for the first time that there are three totally different types of course in children and particularly mentioned the form affecting the internal organs and the eyes. Therefore he had described the so-called systemic form 6 years before Still and anticipated the oligarthritis accompanying inflammation of the eye. Diamantberger's work found wide acceptance in the French specialist literature. In 1988 this was reprinted in book form, nearly 100 years after the first publication. Nevertheless, only few clinicians in Germany have taken note of this and in the Anglo-American literature Diamantberger has remained unknown. Even today his name is not to be found neither in standard reference works on rheumatology nor in textbooks on pediatrics and the history of medicine. Another Parisian clinician, A. Chauffard, did not fare any better. He reported in 1896 on a systemic form of chronic polyarthritis in adults, the discovery of which is world-wide accredited to E. Bywaters in 1971. CONCLUSION: Many French authors were victims of the language barrier.
18815725 Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for J 2009 Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.
19227188 [Nationwide survey for autoantibodies and proposal of a new method for standardization of 2009 Jan There exist inter-laboratory differences in measurements of rheumatoid factor (RF) and antinuclear antibodies (ANA), leading to a misdiagnosis of rheumatoid arthritis (RA) and other collagen diseases. This study was carried out to bring the positivity of RF and ANA of different reagents into accord by standardizing their data. The titer and cutoff value was inconsistent among the 17 different kits. We found a possibility in standardization of RF by a new concept in cooperation with Japanese Committee for Clinical Laboratory Standards (JCCLS). Sera from 1300 healthy subjects and 79 RA patients were measured for RF by 17 different RF kits, and sera with a little deviation among the kits were selected. Panels for detection of RF positive rate in healthy subjects were made from the pooled sera. The cutoff value in 5% positive in the panel was defined tentatively as 15 IU/ml. The 100 IU/ml was also able to become in general accord by adjusting the individual data using pooled RF-positive reference sera. The nationwide survey of immunofluorescence ANA (IF-ANA) was performed in 41 laboratories using 6 pooled sera. The reported titer was fairly different among laboratories, and a striking discrepancy was found for low-titer samples. When the titer was corrected by simultaneously measured reference serum, inconsistency of ANA titer among different laboratories was mostly compensated. Here, we propose a new method for standardization of RF and also try to standardize the positivity of RF and IF-ANA by providing pooled reference sera.
20979749 [Significance of arthroscopy in the diagnosis of unilateral knee arthritis]. 2010 Jun 15 OBJECTIVE: To investigate the role of arthroscopy in the diagnosis of unilateral knee arthritis of unknown causes. METHODS: During December 2005 to February 2008,74 patients of unilateral knee arthritis of unknown origins were treated with arthroscopy. And magnetic resonance imaging (MRI) scans were performed for all of them before knee arthroscopy. The diagnosis was made by the synovial appearance in gross examination in arthroscopy combined with synovial pathology, synovial fluid analysis and clinical manifestations. RESULTS: Among these patients, 71 cases were definitely diagnosed and 3 cases had unknown causes. Thirty-nine cases (52.9%) were of rheumatoid arthritis (RA), 7 (9.5%) of seronegative spondyloarthropathy (SPA), 7 patients (9.5%) of septic arthritis, 6 patients (8.1%) of RA coexisting gout arthritis, 5 patients (6.5%) of gout arthritis, 5 patients (6.5%) of tuberculosis of knee joint, 1 patient (1.3%) of pigmented villonodular synovitis and 1 patient (1.3%) of multicentric reticulohistiocytosis. CONCLUSION: Arthroscopy provides valuable diagnostic information in unilateral knee arthritis of unknown causes. RA is the major cause of unilateral knee arthritis of unknown causes. Synovial appearance in gross examination in arthroscopy, synovial pathology and crystals are helpful to make a diagnosis.
20483039 Ultrasound imaging for the rheumatologist XXVI. Sonographic assessment of the knee in pati 2010 Mar Psoriatic arthritis (PsA) is an arthropathy associated to psoriasis, which is part of the spondyloarthropathy family, and which may present with various forms, from mono-oligoarthritis to symmetric polyarthritis mimicking rheumatoid arthritis. In longstanding disease, the symmetric polyarthritis is the most common pattern of PsA, involving small joint of hands, feet, wrists, ankles and, very frequently, knees. Other common features are represented by the inflammation of enthesis and tendons. Ultrasound (US) examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 10-14 MHz. One-hundred and sixty-six knee joints were investigated in a total of 83 patients. Prior to US assessment, all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (detected by palpation and/or active or passive mobilisation of the knee), and knee swelling. Sixty-two (74.7%) knee joints were found clinically involved, while at least one US finding indicative of joint inflammation was obtained in 70 (84.3%) knee joints. In the 59% of the patients we noticed synovial hypertrophy. Enthesitis was present in 39.7% of the subjects studied. This study demonstrated that US detected a higher number of inflamed knee joints and enthesis with respect to clinical assessment in PsA patients.
19505409 Successful treatment with etanercept of a patient with psoriatic arthritis after adalimuma 2009 Apr Inhibitors of tumor necrosis factor (TNF) alpha (infliximab, etanercept, adalimumab) are nowadays widely used for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), not responding to conventional therapies. Anti-TNF alpha drugs have demonstrated great efficacy in slowing the disease, however, to date, concern still remains regarding acute and long-term toxicity related to TNF block. Increase in liver tests may be observed during treatment with anti-TNF agents, more often related to concomitant drugs (i.e. NSAIDS, methotrexate) or to reactivation of chronic HBV or HCV infections. However, liver damage directly induced by the drug has been described in patients treated with infliximab or adalimumab. To our knowledge, no cases of liver injury closely related to etanercept have been reported so far. We report the case of a patient with PsA who presented liver dysfunction during adalimumab, subsequently successfully treated with etanercept.
20525844 Application of the DAREA/DAPSA score for assessment of disease activity in psoriatic arthr 2010 Aug BACKGROUND AND OBJECTIVES: Instruments for measuring disease activity in psoriatic arthritis (PsA) are not yet firmly established, and most of the currently employed ones have been derived for rheumatoid arthritis. Some of these instruments are based on 28 joint counts, which do not capture joints frequently affected in PsA. Therefore, the reliability and validity of DAREA (for 'Disease Activity index for REactive Arthritis'), which was originally developed for reactive arthritis and employs a 66/68 joint count, was tested in patients with PsA. METHODS: Trial data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial were analysed. Results were then independently validated using an observational data set. DAREA was compared to other composite indices regarding correlations with core set variables, sensitivity to change and criterion validity. RESULTS: Good correlation of the DAREA with single items of disease activity, other composite scores (r=0.6-0.9) and physical function (Health Assessment Questionnaire; r=0.5) was found. Likewise, DAREA was at least as sensitive to change as the other indices and more so in patients with distal interphalangeal joint involvement. Additionally, DAREA correlated well with radiographic changes. CONCLUSION: The analyses of this study provide evidence of the utility and validity of the DAREA for PsA disease activity assessment. A second name should therefore be assigned to this score: DAPSA (for 'Disease Activity index for PSoriatic Arthritis').
19399560 Reconstructing the rheumatoid wrist: a utility analysis comparing total wrist fusion and t 2010 Mar Rheumatologists and hand surgeons have historically demonstrated strikingly divergent attitudes toward the benefits of surgical intervention, either total wrist fusion or total wrist arthroplasty, for the rheumatoid wrist. A utility analysis was conducted to compare a national random sample of hand surgeons and rheumatologists regarding their opinions about surgical management of severe rheumatoid wrist disease. A web-based trade-off utility survey was developed, and participants were presented with survey scenarios comparing well-controlled rheumatoid arthritis with operative and non-operative management. Utility values were calculated for each scenario, and a decision analytic model was constructed. Utility values for rheumatologists and hand surgeons did not differ significantly for any scenario. Total wrist arthroplasty was associated with the highest expected gain in quality-adjusted life-years for each subgroup. This decision analytic model demonstrates similar opinions between two subspecialties that have historically demonstrated divergent attitudes towards rheumatoid hand surgery.
19784790 Different expression levels of TNF receptors on the rheumatoid synovial macrophages derive 2009 Jul TNFalpha plays a crucial role in the pathogenesis of rheumatoid arthritis. It is very important to examine the expression of the TNF receptors, the ligand of TNFalpha. In this study, we developed a triple-color flow cytometric analysis using CD45 and CD14 monoclonal antibodies to simply detect the expression of the TNF receptors on the heterogeneous rheumatoid synovial cells. Using this system, we detected a higher population of macrophages and a greater TNF receptor expression on the synovial macrophages derived from a synovectomy in comparison to the findings obtained from knee joint replacement surgery.
20012976 [Epidemiology of primary Sjörgren's syndrome]. 2010 Feb According to the classification criteria of the American-European Consensus Group (AECG), the prevalence of primary Sjögren's syndrome (pSS) of about 0.2% in the adult population and a yearly incidence of 4/100.000 in the general population are far lower than previously assumed. Moreover, the repeatedly reported male/female ratio of 1:9 seems to lie more in the range of 1:20. Male pSS patients show fewer immunological, histopathological or sialographic findings and organ involvement. Information on age at disease onset has also changed over the last decade. Recent studies indicate an onset age of approximately 45 years as compared to 56 in earlier studies of the last decade. Patients with an early disease onset are more frequently positive for rheumatoid factor (RF) and/or anti-Ro/SS-A. These patients also seem to have a higher risk of developing hypocomplementemia or lymphadenopathy. As compared to earlier cohorts, the introduction of the rather specific AECG criteria will probably result in the participation of fewer men, younger patients in general and of more seriously ill patients in future cohorts. The change in the spectrum of pSS patients obviously reflects the altered classification criteria since the AECG criteria require anti-Ro/La positivity and therefore exclude a high number of patients with other immunological markers who also show severe sicca symptoms and organ involvements. About 5%-10% of pSS patients in rheumatological care suffer from severe extraglandular manifestations, which generally occur soon after disease onset. In particular, palpable purpura, hypocomplementemia, cryoglobulinemia and lymphoma are associated with increased mortality. In Germany, approximately one tenth of Sjögren syndrome patients receive specialized rheumatological care. There is still insufficient knowledge about the vast majority of pSS patients who are not treated by rheumatologists. These patients, as well as all those who, according to the AECG criteria, are not classified as having pSS either due to anti-Ro/La negativity or having secondary Sjögren's syndrome, probably add up to at least 0.4% of the adult population which, at present, suffers from considerable immunopathologic sicca symptoms.
20838859 Lactobacillus casei reduces the inflammatory joint damage associated with collagen-induced 2011 Apr This study evaluated the therapeutic efficacy of Lactobacillus casei in treating rheumatoid arthritis using collagen-induced arthritis (CIA) animal model. Healthy female Wistar rats (weight-180-200 g) were included in this study. Oral administration of L. casei was started on the same day. Indomethacin was used as standard reference drug. Serum level of IL-6, α-TNF, and IL-10 were observed. Four-point arthritis indexes were also assessed at the end of week for 28th day. L. casei-treated rats had shown normal histopathology without any synovial infiltration, pannus formation, cartilage, and bone destruction. Arthritis score was also lower for the group treated with L. casei. Oral administration of L. casei significantly decreased the pro-inflammatory cytokines. Present study suggests that L. casei has potent antiarthritic effect in CIA model. Inhibition of COX-2 via inhibiting the pro-inflammatory cytokines is an understanding of the complex interactions involved in these pathways.
19360377 Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inh 2009 Oct OBJECTIVE: To seek a mechanism linking tobacco smoking with the increased incidence and severity of rheumatoid arthritis, deduced from many retrospective surveys, by studying arthritis/fibrosis development in rats. METHODS: Rats (>300) received low levels of sodium/potassium thiocyanate (10 or 25 mmol/l) in their drinking water to raise their blood thiocyanate levels, mimicking the elevated levels of blood, salivary and urinary thiocyanate found in smokers. RESULTS: Thiocyanate supplements increased the severity of experimental arthritis induced by tailbase injection of (1) Freund's complete adjuvants (mycobacteria plus various adjuvant-active oils), (2) collagen type-II with Freund's incomplete adjuvant (no mycobacteria), (3) the synthetic lipid amine, avridine in an oil and (4) the natural hydrocarbons squalene (C(30)H(50)) and pristane (C(19)H(40)). This pro-arthritic effect was independent of sex, rat strain or changing diet and housing facilities. Thiocyanate supplements also amplified the acute/persisting inflammatory responses to paw injections of pristane, zymosan and microcrystalline hydroxyapatite. Iodide salts also mimicked some of these effects of thiocyanate. CONCLUSION: Thiocyanate, a detoxication product of HCN present in tobacco smoke, increased (or even induced) inflammatory responses to several agents causing arthritis or fibrotic inflammation in rats. It, therefore, can act as a co-arthritigen, or 'virulence factor' and could be a therapeutic target to reduce arthritis expression and morbidity.
21794569 [Polyarticular septic arthritis: analysis of 19 cases]. 2009 Feb OBJECTIVE: Polyarticular septic arthritis accounts for 15% of all septic arthritis, but there are few references in the literature. We describe characteristics of patients with polyarticular septic arthritis in a rheumatology service. PATIENTS AND METHOD: Retrospective analysis of patients with septic arthritis involving more than one joint. Only patients with positive culture of synovial fluid were included. Clinical, analytical and radiological variables are reviewed. RESULTS: 19 patients (14 male) had a polyarticular infection. Mean age was 55 years. Mean time from onset to diagnosis was 6 days. The knee was the most commonly involved joint, followed by ankle. The mean number of joints involved per patient was 3. Risk factors included diabetes, chronic renal or hepatic disease, gout and rheumatoid arthritis. Most commonly isolated agents were S. aureus (47%) and S. agalactiae (21%). Blood cultures were positive in 52,6% and 15.8% had septic shock. Scintygraphic bone scan showed a polyarticular uptake. Mean duration of antibiotic therapy was 46±27 days. Clinical outcome was good in 52,6%, complicated in 26%, and mortality rate was 15.8% (3 cases). Joint debridement was performed in 21%. CONCLUSIONS: Multiple joint involvement does not exclude the diagnosis of septic arthritis. Inflammatory arthritis is an important risk factor. S. aureus in the main infectious agent. The morbidity and mortality of this condition are important, so we need to maintain a high index of suspicion for the condition.
21136365 [Adult-onset of Still's disease with atypical articular and skin manifestations]. 2010 Dec BACKGROUND: Adult-onset Still's disease (ASD) is an uncommon clinical entity. It is a diagnosis of exclusion, characterized by a clinical triad of intermittent fever spikes, evanescent rash, and either arthralgia or arthritis. Destructive arthritis more commonly affects the hips, wrists, tarsal joints and cervical spine. AIM: To report an unusual case of ASD with severe distal interphalangeal destructive arthritis and finger skin vesiculopustules. OBSERVATION: A 19 years old girl was followed for 2 year-history of ASD with polycyclic articular involvement. She noted, since 2 months, rapid appearance of painful tumefaction in the distal interphalangeal joints (DIP) with maculopustular eruption distributed exclusively on the hands, in front, only of DIP and few proximal interphalangeal joints (PIP). Further more, she complained of polyarticular active disease. Hands and wrists X-ray showed narrowed distal-interphalangeal joint space of only DIP joints. RMN imaging revealed in addition carpal, metacarpal and PIP articular inflammatory damage. The infectious investigation remained negative. A surgical skin and DIP biopsy specimens showed disseminated micro-abscesses with polynuclear leukocyte dermal infiltration. There was no signs of osteitis. Bacterial and fungal cultures from the pus failed to reveal any causative organisms. Skin lesions gradually disappeared in response to conventional ASD therapy after intensification. Hence, the diagnosis of distal destructive arthritis of ASD associated with atypical neutrophilic dermatosis (Sweet's syndrome) was made. CONCLUSION: ASD is rare, heterogeneous, with unpredictable evolution. The distal destructive arthritis represents a possible complication. The presence of pustules as atypical cutaneous features of Sweet's syndrome may be seen in severe forms of ASD and clinicians must be alert to the possibility of a misdiagnosis in these cases.
19180009 Primary Sjögren's syndrome mimicking lymphoma in a pediatric patient. A rare and possibly 2009 Feb A 12-year-old girl presented at the Oncoemato-logic Department with an acute onset of generalized lymphadenopathy. Lymphoproliferative disorders were highly suspected. Biopsied cervical and inguinal lymph node disclosed neither malignant cells nor monoclonal proliferation of lymphocytes. Revaluating the diagnosis, anamnestic data revealed multiple episodes of bilateral parotid swelling since age one, without systemic symptoms. Laboratory investigations, parotid ecography, Schirmer test revealed Sjogren's syndrome without associated disease. Sjogren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition.
20441604 Systemic lupus erythematosus and its ABCs (APRIL/BLyS complexes). 2010 BLyS and APRIL are closely related members of the TNF ligand superfamily. These cytokines individually may contribute importantly to the development and maintenance of systemic lupus erythematosus (SLE). Dillon and colleagues demonstrate that in contrast to most members of the TNF ligand superfamily, which form only homotrimers, BLyS and APRIL can complex as heterotrimers. These complexes have in vitro biological activity, and circulating levels of BLyS/APRIL heterotrimers are frequently elevated in SLE, but not rheumatoid arthritis, patients. Although the mechanism and regulation of heterotrimer formation, the interconversion (if any) between homotrimers and heterotrimers, and, indeed, the normal physiologic role for such heterotrimers remain unknown, their preferential overexpression in SLE, but not in rheumatoid arthritis, raises the possibility that such heterotrimers may be playing a contributory role in SLE.
20080915 Chronic conditions and health problems in rheumatic diseases: comparisons with rheumatoid 2010 Feb OBJECTIVES: To describe and compare the prevalence of lifetime and current self-reported comorbidity and associated quality of life in 4 rheumatic diseases, and to investigate comorbid conditions in light of the overlap between the index condition and comorbid conditions (CC), and in the context of symptom-type diagnoses. METHODS: We studied comorbidity in 11,704 patients with fibromyalgia (FM), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and noninflammatory rheumatic disorders (NIRD). Patients completed semiannual self-reports relating to 22 present and past illnesses and completed the EuroQol (EQ-5D) utility index. RESULTS: CC were most common in FM, followed by SLE. FM comorbidity was dominated by depression, mental illness, and symptom-type comorbidity (e.g., gastrointestinal and genitourinary disorders). In SLE, there were substantial increases in hypertension, depression, cataract, fractures, and cardiovascular and cerebrovascular, neurologic, lung, gall bladder and endocrine disorders compared with RA. Any current CC reduced the EQ-5D utility by 0.08 to 0.16 units. The lowest EQ-5D score was noted for current psychiatric illness (0.55) and current depression (0.60). CONCLUSION: Four patterns of comorbidity emerged: that associated with aging; that associated with aging but enhanced by the index condition, as in SLE and cardiovascular disease; comorbidity that is part of the symptoms complex of the index condition; and CC that represent lifetime traits or manifestations of the underlying illness. Depression was the most strongly associated correlate of EQ-5D quality of life, and current depression was present in about 15% of patients with RA or NIRD and 34% to 39% of those with SLE and FM.
19616611 The B cell, arthritis, and the sympathetic nervous system. 2010 Feb The pathogenesis of rheumatoid arthritis (RA) is still an unresolved puzzle. Many factors and inflammatory cells play together to initiate a chronic inflammatory process that, if untreated, leads to complete destruction of involved joints. Recent success in treating severe forms of RA with B cell-depleting or -modifying agents revived the concept that the B cell might play a pivotal role in the pathogenesis of some forms of arthritis. However, the rather unspecific treatment approach affecting all B cells, no matter if autoreactive or not, leads to potential harmful side-effects, e.g., severe infections. Therefore, finding regulatory systems that more specifically modulate B cell function is important to improve current treatment options. One such regulatory system is the sympathetic nervous system (SNS), which is known to modulate B cell function, but also profoundly influences arthritis development and severity. This review develops the hypothesis that the SNS via modulating B cell function influences arthritis development and progression. For this purpose data is presented that shows (1) how the SNS influences B cell function, (2) how the SNS influences arthritis development and severity, and (3) how B cells are involved in the disease process with an emphasis on possible contact points for SNS neuromodulation.
20185892 Cutaneous sarcoidosis occurring during anti-TNF-alpha treatment: report of two cases. 2010 We report two cases of cutaneous granuloma induced by anti-TNF-alpha therapy: a 47-year-old man suffering from psoriatic arthritis treated with infliximab and a 56-year-old woman treated with adalimumab for polyarticular juvenile rheumatoid arthritis. The biospies confirmed the diagnosis of a 'sarcoidosis-like' reaction. No systemic involvement was observed. Such cases of noninfectious granulomatous diseases occurring during anti-TNF-alpha therapy are becoming increasingly frequent.