Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17343260 Decrease of proteinuria in a patient with adult-onset Still's disease and glomerulonephrit 2006 Nov We report the case of a 41-year-old man diagnosed with Still's disease. Multiple disease-modifying anti-rheumatic drug (DMARD) therapies failed to induce disease remission or to prevent progressive joint destruction. The man presented with active arthritis and classical Still's rash accompanied by fever. Anti-tumour necrosis factor-alpha (TNFalpha) therapy was planned but during the medical check-up prior to the biological therapy, renal insufficiency with marked proteinuria (PU) was discovered. With PU of 912 mg/24 h a renal biopsy was performed and a histopathological evaluation revealed the diagnosis of a residual mesangio-proliferative immunocomplex-based glomerulonephritis (GN). After excluding contraindications, infliximab therapy was initiated and a good response of the arthritis was documented after 6 weeks. A significant decrease in PU (279 mg/24 h) was noted after the third infliximab infusion. Because of an allergic reaction during the fifth dose, the infliximab was discontinued. During the time frame without anti-TNFalpha therapy, active joint disease reoccurred and the proteinuria increased significantly. Because of the active disease entanercept therapy was initiated. The arthritis diminished and the PU was reduced markedly within 4 weeks. In the follow-up period of 12 months a good response to therapy was sustained. As described by other investigators, the joint disease showed a rapid and sustained response to anti-TNFalpha therapy. The decrease in proteinuria during biological therapy was notable. It was concluded that the significant decrease in PU in this patient was achieved by eliminating the inflammatory activity of the underlying kidney disease.
17144498 [Electrophoretic analysis of lacrimal proteins--a diagnostic method in secondary Sjogren s 2006 PURPOSE: We analysed and compared electrophoretic tear proteins patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome. MATERIALS AND METHODS: Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate polyacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver. RESULTS: Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers. CONCLUSIONS: Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in auto-immune diseases.
17002793 Evidence for chronic, peripheral activation of neutrophils in polyarticular juvenile rheum 2006 Although strong epidemiologic evidence suggests an important role for adaptive immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis (JRA), there remain many aspects of the disease that suggest equally important contributions of the innate immune system. We used gene expression arrays and computer modeling to examine the function in neutrophils of 25 children with polyarticular JRA. Computer analysis identified 712 genes that were differentially expressed between patients and healthy controls. Computer-assisted analysis of the differentially expressed genes demonstrated functional connections linked to both interleukin (IL)-8- and interferon-gamma (IFN-gamma)-regulated processes. Of special note is that the gene expression fingerprint of children with active JRA remained essentially unchanged even after they had responded to therapy. This result differed markedly from our previously reported work, in which gene expression profiles in buffy coats of children with polyarticular JRA reverted to normal after disease control was achieved pharmacologically. These findings suggest that JRA neutrophils remain in an activated state even during disease quiescence. Computer modeling of array data further demonstrated disruption of gene regulatory networks in clusters of genes modulated by IFN-gamma and IL-8. These cytokines have previously been shown to independently regulate the frequency (IFN-gamma) and amplitude (IL-8) of the oscillations of key metabolites in neutrophils, including nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and superoxide ion. Using real-time, high-speed, single-cell photoimaging, we observed that 6/6 JRA patients displayed a characteristic defect in 12% to 23% of the neutrophils tested. Reagents known to induce only frequency fluctuations of NAD(P)H and superoxide ion induced both frequency and amplitude fluctuations in JRA neutrophils. This is a novel finding that was observed in children with both active (n = 4) and inactive (n = 2) JRA. A subpopulation of polyarticular JRA neutrophils are in a chronic, activated state, a state that persists when the disease is well controlled pharmacologically. Furthermore, polyarticular JRA neutrophils exhibit an intrinsic defect in the regulation of metabolic oscillations and superoxide ion production. Our data are consistent with the hypothesis that neutrophils play an essential role in the pathogenesis of polyarticular JRA.
17507575 A child with primary Sjögren syndrome and a review of the literature. 2007 Oct Primary Sjögren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjögren syndrome antigen A, and anti-Sjögren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of pSS.
17468709 [Respiratory manifestations during the course of Sjogren's syndrome]. 2007 Apr INTRODUCTION: Sjogren's syndrome is a common auto-immune disease. BACKGROUND: Clinically significant pulmonary involvement affects approximately 10% of patients and may be the first manifestation of the disease, putting the respiratory physician in a position to suspect and confirm the diagnosis. Besides interstitial lung disease and bronchial disorders, cough is a common symptom of the disease and particularly difficult to treat. Lung cysts and amyloid deposits, sometimes associated with lymphoma, have recently been described. The development of a primary pulmonary lymphoma, usually from MALT, is a major complication of the disease. VIEWPOINT: Characterisation of the pathophysiology of pulmonary involvement in Sjogren's syndrome and the institution of specific treatment merits the interest of the respiratory physician. CONCLUSION: The respiratory physician should consider the diagnosis of Sjogren's syndrome in many different clinico-pathological situations.
18405175 Still's disease in patient with silicone breast implants: case report. 2008 Jan Still's disease is a systemic manifestation of juvenile arthritis that rarely occurs in adults and therefore is often forgotten in differential diagnosis of fever of unknown origin. The case presented here shows diagnostic difficulties in a patient with silicone breast implants and fever with Still disease. The cause-effect relationship between breast implants and Still disease is not certain, however, this possibility should be considered when a patient with fever resistant to antibiotics and with silicone implants is admitted to the hospital.
18955278 Tibetan Medicated-Bath Therapy may Improve Adjuvant Arthritis in Rat. 2009 Jun Tibetan medicated-bath therapy has been applied to patients with rheumatoid arthritis for centuries. However, the detailed action mechanism of Tibetan medicated-bath therapy on the morphology and function of joints remains unknown. We designed our investigation to evaluate the efficacy of Tibetan medicated-bath therapy on adjuvant arthritis (AA) of rats in comparison with water-bath and dexamethasone administration. AA was induced by intradermal injection of Mycobacterium butyricum suspended in sterile mineral oil. The control animals were similarly injected with sterile vehicle. Eight days after injection, rats were treated with fresh-water bath, Tibetan medicated-bath (40 degrees C, 15 min) or intramuscular injection with dexamethasone for 21 consecutive days after which we evaluated the severity of arthritis visually and microscopically and measured serum interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels. While arthritis did not significantly change after water-bath treatment, the Tibetan medicated-bath and dexamethasone groups showed diminished joint swelling and alleviation of, inflammatory cell infiltration and the destruction of bone and cartilage. Serum IL-6 and TNF-alpha levels significantly decreased. Our results demonstrated that Tibetan medicated-bath therapy exerted a reliable effect on rat adjuvant arthritis, which may be involved in the inflammatory cytokines, IL-6 and TNF-alpha. Our data provide evidence for clinical use of Tibetan-medicated bath therapy for arthritis patients.
16638139 Mental disorders in a population sample with musculoskeletal disorders. 2006 Apr 25 BACKGROUND: Studies using clinical and volunteer samples have reported an elevated prevalence of mood disorders in association with rheumatoid arthritis and osteoarthritis. Clinical studies using anxiety rating scales have reported inconsistent results, but studies using diagnostic instruments have reported that anxiety disorders may be even more strongly associated with arthritis than is depression. One study reported an association between lifetime substance use disorders and arthritis. METHODS: Data from iteration 1.2 of the Canadian Community Health Survey (CCHS) were used. This was a large-scale national Canadian health survey which administered the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects randomly selected from the national population. In the CCHS 1.2, subjects were asked whether they had been diagnosed by a health professional with arthritis or rheumatism. RESULTS: Subjects reporting arthritis or rheumatism had an elevated prevalence of mood, anxiety and substance use disorders. The strength of association resembled that seen in an omnibus category reporting any chronic condition, but was weaker than that seen with back pain or fibromyalgia. The effect of arthritis or rheumatism interacted with age, such that the odds ratios became smaller with increasing age. Mood and anxiety disorders, along with arthritis or rheumatism made an independent contribution to disability. CONCLUSION: Arthritis is associated with psychiatric morbidity in the general population, and this morbidity is seen across a variety of mental disorders. The strength of association is consistent with that seen in persons with other self-reported medical conditions.
18605365 Effects of purified micronized flavonoid fraction (Detralex) on prophylactic treatment of 2008 May BACKGROUND: In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a signicant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats. OBJECTIVES: To evaluate the effect of Detralex on methotrexate prophylactic treatment of adjuvant arthritis in rats. METHODS: Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day) and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations and whole body mineral density were evaluated as markers of inflammation and destructive changes associated with arthritis. RESULTS: Long-term prophylactic treatment with low dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, Detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of BMD in AA rats was significantly lower only in the group treated with the combination of Detralex+methotrexate. CONCLUSION: Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.
17023812 Multicentric reticulohistiocytosis presenting with destructive polyarthritis, laryngophary 2006 Oct Multicentric reticulohistiocytosis (MRH) is a rare multisystemic disease presenting with skin lesions and erosive polyarthritis and is often associated with malignancy. We describe a 60-year-old woman with diffuse papulonodular skin eruptions and progressive osteolytic bone damage over the bilateral hands, humeral head, and acromioclavicular joints within 2 years. Moreover, dysphagia and a hoarse voice occurred in this patient and an unusual huge mass-reticulohistiocytoma--developed over the left upper back. Tissue biopsy of the skin lesions, laryngeal nodules, and this large mass showed infiltration of numerous CD68(+) histiocytes and multinucleated giant cells with abundant eosinophilic ground-glass cytoplasm. Combination therapy with steroids and methotrexate improved her cutaneous, joint, and laryngopharyngeal symptoms. The large reticulohistiocytoma resolved with methylprednisolone pulse therapy. This polyarthritis, which can be confused with rheumatoid arthritis, can be diagnosed by careful immunohistochemical examination of biopsies. To prevent the irreversible disease process, early and aggressive therapy is necessary.
18178832 IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. 2008 Jan 15 IL-27 is the newest member of the cytokine family comprised of IL-12 and IL-23. IL-27 was originally described as a cytokine that along with IL-12 induces the differentiation of naive precursor T cells into Th1 effector cells. This activity has been called into question based on evidence in infectious disease and autoimmune models in which IL-27 is not absolutely required for the generation of IFN-gamma, and IL-27 plays a regulatory role in controlling inflammation. We have previously reported in proteoglycan-induced arthritis (PGIA), a model of rheumatoid arthritis, that severe arthritis is dependent on the production of IFN-gamma. In this study, we report that IL-27 was expressed in spleen and joint tissues of arthritic mice. We determined the involvement of IL-27 in PGIA by assessing the progression of arthritis in IL-27R-/- mice. Development of arthritis in IL-27R-/- mice was delayed and severity reduced in comparison with IL-27R+/+ littermate controls. Histology confirmed a reduction in joint cellularity, cartilage destruction, and bone erosion. Diminished arthritis was associated with fewer T cells producing IFN-gamma and decreased IFN-gamma secretion overtime. Moreover, the frequency of IL-4- and IL-17-expressing T cells and the production of IL-4 and IL-17 were similar in IL-27R-/- mice and controls. Our results indicate that IL-27 is critically involved in the induction of inflammation in PGIA. IL-27 functions by inducing the differentiation of IFN-gamma-producing T cells in vivo that are essential for the development of arthritis.
19059799 Exposition to anti-TNF drugs during pregnancy: outcome of 15 cases and review of the liter 2009 Jan OBJECTIVE: To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy METHODS: French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. RESULTS: Spondylarthropathies (n=8), rheumatoid arthritis (n=4), juvenile idiopathic arthritis (n=2), and psoriatic arthritis (n=1) were treated by infliximab (n=3), adalimumab (n=2), or etanercept (n=10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. CONCLUSION: The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth.
18698189 Quality improvement in pediatric rheumatology: what do we need to do? 2008 Sep PURPOSE OF REVIEW: Quality improvement is a mandate for all individuals and institutions in medicine. Quality improvement has spread to the specialty certifying boards, resident education accreditation, licensure boards, and hospital medical staff offices. This review summarizes the thrust of quality improvement, provides justification for the conduct of quality improvement work, and reviews the progress in development of quality measures in rheumatology to date. RECENT FINDINGS: The American College of Rheumatology, quality of care, and quality measure committees have developed quality indicators for rheumatoid arthritis, gout, osteoporosis, and drug safety. Pediatric rheumatology is charged with developing quality measures for juvenile idiopathic arthritis; thus, there is a commitment to improve the processes and patient outcomes. Quality improvement science has progressed over the last decade and employs methodology that utilizes small number and rapid improvement cycles. Examples of this quality improvement methodology are elaborated in this review. SUMMARY: The review summarizes the history and current mandates for quality improvement in the medical community, progress made in the development of quality measures for adult rheumatologic conditions, and preliminary quality measures for juvenile idiopathic arthritis, and cites examples of quality improvement in progress in the pediatric rheumatology.
17368783 [Clinical diagnosis of Lyme borreliosis in case of joint and muscular presentations]. 2007 Jul The diagnosis of Lyme borreliosis in case of joint and muscular presentations is generally suggested by epidemiological factors. However, as a rule, laboratory testing is required to confirm the diagnosis. When considering the epidemiology of Lyme borreliosis in France, the only areas free of ticks infected by Borrelia burgdorgeri sl, are those close to the Mediterranean sea or at high altitude. The risk is greatest in the Alsace region. Exposure is particularly high among forest workers and people who use the countryside for their leisure activities. The likelihood of infection following a tick bite is difficult to assess; indeed, the bite site may remain unnoticed. A medical history of erythema migrans, if untreated, is a major diagnostic clue, although the association appears to be less consistent in France than in the US. Lyme arthritis generally arises apparently spontaneously. It is characteristically mono- or oligo-articular, asymmetrical, predominantly affects the knee, and has an intermittent course. Synovial cysts and enthesitis are common. Myositis is rare, polymorphic, and has been linked to other symptoms in the same localizations. Minor arthralgia and myalgia frequently occur, principally early in the course of the infection. It was suggested that sequels of the disease include so-called fibromyalgic syndromes. The principal differential diagnosis as far as arthritis is concerned, is made on spondylarthropathy and chronic juvenile arthritis. Rheumatoid arthritis is another pathology, although Lyme arthritis does sometimes evolve to chronicity.
16522230 [Levels of serum interleukin-15 and the expression of T-helper lymphocyte subsets in perip 2006 Feb OBJECTIVE: To study the changes of serum interleukin-15 (IL-15) levels and the expression of CD4(+)T (T-helper lymphocyte) subsets CD4(+)CD45RA(+) and CD4(+)CD45RO(+) in peripheral blood of children with juvenile rheumatoid arthritis (JRA). METHODS: The serum concentration of IL-15 was detected using ELISA in 39 children with JRA. The expressions of CD4(+)CD45RA(+)T and CD4(+)CD45RO(+)T in peripheral blood were detected by flow cytometry in 24 out of the 39 patients with JRA. Twenty-six age and sex-matched healthy children were used as the Control group. RESULTS: The mean serum IL-15 level in JRA patients was significantly higher than that in controls (1.37 +/- 0.98 pg/mL vs 0.96 +/- 0.41 pg/mL, P <0.05). Among the 39 JRA patients, the serum IL-15 level in 17 patients with systemic JRA increased remarkably (P < 0.01), but not in patients with the other two types of JRA, the oligoarthritis and polyarthritis (n=13, n=9, respectively), compared with that in controls. The mean serum IL-15 level of the JRA patients was significantly reduced after conventional treatment (P < 0.01). The serum IL-15 level in JRA patients positively correlated with white blood cell count (r=0.347, P <0.05) and C reactive protein (r=0.452, P < 0.01) but not with the erythrocyte sedimentation rate. The patients with high serum IL-15 levels (> or = medium level 1.73 pg/mL) had higher expression of CD4(+)CD45RO(+)T than those with low serum IL-15 levels (< medium level) (16.29 +/- 5.46% vs 11.75 +/- 3.15 %, P < 0.05). CONCLUSIONS: The serum IL-15 levels in JRA patients increased significantly. An increased IL-15 level can transform CD45RA into CD45RO in peripheral blood of patients with JRA, and then result in T lymphocyte activation and mediate the immunopathological impairment. IL-15 may be used a marker for the evaluation of severity of JRA.
16226476 Calcaneal osteomyelitis due to fistulization of an ulcerated rheumatoid nodule. 2006 Jan Calcaneal osteomyelitis is uncommon and difficult to treat. Cases due to fistulization of an infected rheumatoid nodule are exceedingly rare. PATIENT: A 65-year-old patient with nodular rheumatoid arthritis (RA) experienced osteomyelitis of the left calcaneus due to inoculation from a fistula draining an ulcerated rheumatoid nodule. Pseudomonas aeruginosa and Enterobacter cloacae were recovered. The conventional treatment of calcaneal osteomyelitis relies on antibiotics and calcanectomy or foot amputation. We used two appropriate antibiotics and monthly intravenous injections of 90 mg of pamidronate. RESULT: One year into treatment, the patient was free of pain and the skin wound was fully healed. On a follow-up computed tomography (CT) scan, the fistulous tract was seen to be closed and the large calcaneal defect almost completely filled with new bone. CONCLUSION: Combining two antibiotics and pamidronate may be a viable alternative to excision surgery or amputation in some patients with bone infection carrying a risk of fracture.
17049776 Suppression of the onset and progression of collagen-induced arthritis in rats by QFGJS, a 2007 Mar 1 QFGJS is an herbal preparation, and its pronounced effectiveness in treating adjuvant-induced arthritis (AIA) has been previously demonstrated. We herein aimed to confirm its anti-arthritic effect on collagen-induced arthritis (CIA) in rats. CIA was established in female Wistar rats with intradermal injection of type II bovine collagen at the base of the tail of animals. CIA rats were treated daily with oral administration of different doses of QFGJS beginning on the day of the induction of arthritis (day 0, the prophylactic treatment) or on the day after the onset of arthritis (day 13, the therapeutic treatment) until day 30. The results showed that prophylactic treatment with QFGJS significantly suppressed the onset of arthritis, and therapeutic treatment with QFGJS markedly reduced paw swelling and ESR levels even in the established CIA. Radiologic and histopathologic changes in the arthritic joints were also significantly reduced in the QFGJS-treated versus vehicle-treated rats. Moreover, the serum levels of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were markedly lowered in the QFGJS-treated rats. Hence, our studies demonstrate the quality, safety, and effectiveness of QFGJS as an anti-arthritic agent, which makes QFGJS a strong candidate for further clinical trials on rheumatoid arthritis (RA) patients.
16911769 Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel t 2006 Conventional treatments for autoimmune diseases have relied heavily on nonspecific immune suppressants, which possess a variety of adverse effects without inhibiting the autoimmune process in a specific manner. In the present study we demonstrate the effectiveness of antigen-specific, maturation-resistant, tolerogenic dendritic cells (DC) in suppressing collagen-induced arthritis, a murine model of rheumatoid arthritis. Treatment of DC progenitors with the NF-kappaB inhibiting agent LF 15-0195 (LF) resulted in a population of tolerogenic DC that are characterized by low expression of MHC class II, CD40, and CD86 molecules, as well as by poor allostimulatory capacity in a mixed leukocyte reaction. Administering LF-treated DC pulsed with keyhole limpet hemocyanin antigen to naïve mice resulted hyporesponsiveness specific for this antigen. Furthermore, administration of LF-treated DC to mice with collagen-induced arthritis resulted in an improved clinical score, in an inhibited antigen-specific T-cell response, and in reduced antibody response to the collagen. The efficacy of LF-treated DC in preventing arthritis was substantiated by histological examination, which revealed a significant decrease in inflammatory cell infiltration in the joints. In conclusion, we demonstrate that in vitro-generated antigen-specific immature DC may have important potential as a tolerogenic vaccine for the treatment of autoimmune arthritis.
16583464 Evaluation of the comparative efficacy and tolerability of rofecoxib and naproxen in child 2006 May OBJECTIVE: To compare the safety and efficacy of rofecoxib* to naproxen for the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was a 12-week, multicenter, randomized, double-blind, double-dummy, active comparator-controlled, non-inferiority study with a prespecified 52-week open-label active comparator-controlled extension. Children (ages 2-11 yrs) and adolescents (ages 12-17 yrs) received lower-dose (LD)-rofecoxib [0.3 mg/kg/day up to 12.5 mg/day (base study only)]; or higher-dose (HD)-rofecoxib (0.6 mg/kg/day up to 25 mg/day) or naproxen 15 mg/kg/day as oral suspensions. Adolescents received daily rofecoxib (LD) 12.5 (base study only) or (HD) 25 mg, or naproxen 15 mg/kg/day (maximum 1,000 mg/day) as tablets. The primary endpoint was the time-weighted average proportion of patients meeting the American College of Rheumatology Pediatric-30 (ACR Pedi 30) response criteria. A prespecified bound for the 95% confidence interval for the ratio of the percentage of ACR Pedi 30 responders was used to assess non-inferiority of treatment response between groups. Safety was assessed throughout the study. RESULTS: A total of 310 patients ages 2-17 years (181 (3/4) age 11) were randomized to receive LD-rofecoxib (N=109), HD-rofecoxib (N=100), or naproxen (N=101). The ACR Pedi 30 response rates following 12 weeks of treatment were 46.2%, 54.5%, and 55.1%, respectively. The relative rates of response compared to naproxen were 0.81 (95% CI 0.61, 1.07) and 0.98 (95% CI 0.76, 1.26) for LD- and HD-rofecoxib, respectively. Both rofecoxib doses were not inferior to naproxen. Patients (N=227) entering the extension received HD-rofecoxib or naproxen with efficacy maintained during the extension. All treatments were generally well tolerated throughout the study. CONCLUSION: Daily treatment of JRA patients with rofecoxib up to 12.5 or 25 mg was well tolerated, providing sustained clinical effectiveness comparable to naproxen 15 mg/kg. *On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.
16213770 Chronic inflammatory joint disease revealing borderline leprosy. 2006 May Musculoskeletal symptoms are not infrequent in leprosy and, when inaugural, may be difficult to differentiate from other conditions, most notably rheumatoid arthritis. We report the case of a 24 year-old man with a 5 year history of intermittent inflammatory arthritis and fever. Physical findings and radiographs were normal initially. Several years later, he had severe wasting of the hand muscles, stocking-glove sensory loss, burn scars on the hands, and plantar ulcers. Electrophysiological test results indicated sensory-motor neuropathy with predominant demyelination. Laboratory tests showed inflammation without immunological abnormalities. A prominent endoneurial inflammatory infiltrate composed of mononuclear cells was seen on a nerve biopsy specimen, suggesting leprosy. A family study then revealed that the patient's aunt had been diagnosed with leprosy. Dapsone, clofazimine, and rifampin were given. The joint manifestations and laboratory tests for inflammation improved. However, no changes were noted in the neurological symptoms.