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PMID	Title	PublicationDate	abstract
8835550	Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of	1995 Dec	OBJECTIVE: To compare 2 treatment strategies in a prospective 5 year study of patients with rheumatoid arthritis (RA): early treatment with slow acting antirheumatic drugs (SAARD) versus a "wait and see" attitude. METHODS: One hundred thirty-seven patients with RA of < 2 years' duration entered a double blind placebo controlled study: patients in the "early" (E) group were treated with auranofin within one year of diagnosis of RA, and SAARD treatment in the initially placebo treated group was delayed 8 months compared with the former group. [The results after 2 years clearly favored early treatment (Borg G, Allander E, Lund B, et al: J Rheumatol 1988; 15:1747-54)]. RESULTS: After a total observation period of 5 years in 75 representative patients, continued improvement in the E group was demonstrated, and differences between the 2 groups were maintained with regard to clinical variables, outcome measures, and radiographic evaluation. CONCLUSION: The results indicate the existence of a therapeutic window in RA within the first 2 years of the disease.
7942852	HLA-linked rheumatoid arthritis.	1994 Oct	Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the susceptibility allele frequency as 2.16%, and estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-half of familial RA, although it accounts for only approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically.
8323381	Serum osteocalcin and carboxyterminal propeptide of type I procollagen in rheumatoid arthr	1993 May	OBJECTIVES: Previous reports indicate that serum osteocalcin (serum bone GLA protein (S-BGP)) and carboxyterminal propeptide of type I procollagen (PICP) can be used as indicators of bone formation and turnover. The purpose of this study was to assess the activity of bone formation in patients with rheumatoid arthritis (RA) using S-BGP and S-PICP. The biochemical data were compared with data obtained from bone histomorphometry. METHODS: Concentrations of S-BGP and S-PICP were measured in 119 women with RA aged 30-66 years and 47 healthy female controls matched for age. Bone histomorphometry of iliac crest samples was performed in 107 patients with RA. RESULTS: Weak to moderate correlations between the serum markers and histological bone formation parameters were found. Concentrations of S-BGP and S-PICP were significantly decreased in patients with RA compared with the controls (S-BGP 7.2 (2.3) v 8.7 (2.1) micrograms/l; S-PICP 105 (32) v 117 (38) micrograms/l. The lowest values were found in patients with recent onset RA. CONCLUSIONS: These findings suggest that bone formation and bone remodelling are generally reduced in patients with RA.
8339135	The long-term use of D-penicillamine for treating rheumatoid arthritis: is continuous ther	1993 Jul	Patients with RA often fail to comply with their therapy. We investigated the extent of non-compliance with D-penicillamine therapy and also whether patients needed continuous treatment after they had shown a therapeutic response. We developed a simple urinary test, measuring cysteine-penicillamine mixed disulphide by a high performance liquid chromatography technique, as an indicator of compliance. Using this method we evaluated compliance in 59 consecutive RA patients attending rheumatology outpatients for monitoring of D-penicillamine therapy. Evidence of poor compliance was shown in 39%. There was no relationship between poor compliance and disease activity. A possible explanation for this paradox emerged from a therapeutic study of the efficacy of intermittent treatment in patients in partial clinical remission on long-term D-penicillamine. In 14 randomly selected patients the daily dose of D-penicillamine was reduced in frequency over 6 months from 250-750 mg daily to the same dose taken 1 week out of every 4. The patients were compared to matched controls who remained on continuous therapy. After 30 months both the intermittent and continuous therapy groups had similar clinical and laboratory scores for disease activity. Our results suggest that many patients may not comply with their prescribed D-penicillamine regime, but such variation in compliance may not be clinically important since intermittent treatment may sustain response in the longer term.
8296084	[New perspectives in the treatment of rheumatoid arthritis].	1993 Jul	The medical treatment of Rheumatoid Arthritis (RA), is currently going through deep changes, stimulated by the findings that the usual sequential fashion of administering different drugs does not stop the course of the disease and that erosions develop even in the first year. Combination therapy, including immunosuppressants, are advocated early in the course of RA. The use of potent and potentially dangerous drugs should be given to the patients who are more likely to develop a more severe disease. Clinical and laboratory markers of severity might guide the treatment of these patients.
8810542	[An autopsy case of rheumatoid arthritis associated with proliferative endarteritis died o	1996 Jun	A 68-year-old male with a 2-year history of rheumatoid arthritis was hospitalized due to severe polyarthritis. Since level of rheumatoid factor was high, and subcutaneous nodules and cutaneous ulcers were present, the case was diagnosed as malignant rheumatoid arthritis (rheumatoid vasculitis). On 10th day after admission, severe dyspnea developed due to acute heart failure, followed by severe melaena. The patient did not respond to various treatments including steroid pulse therapy, and died 3 days later. Autopsy revealed widespread hemorrhagic infarction that was extended from the colon to the rectum. Proliferative endarteritis was recognized in mesenteric vessels, however neither necrosis nor inflammatory changes were observed. The melaena was caused by the interstinal infarction. The intestinal infarction was thought to be responsible for the circulatory disturbances due to heart failure in obstructive vessel lesion of mesenteric vessels.
8029382	[Differential stress management pattern of seropositive and seronegative polyarthritis pat	1994 May	46 seropositive female RA patients were compared to 28 seronegative female RA patients using the Stress Coping Questionnaire of Janke et al. (1985). In comparison to seropositive patients, seronegative patients exhibit a stress coping behaviour characterized by more self-pity but less substitutive gratification. They too show fewer attempts at controlling their reactions.
8535657	Overview of combination second-line or disease-modifying antirheumatic drug therapy in rhe	1995 Nov	This article discusses the use of combinations of disease-modifying antirheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA). Patients with RA have a disease that can be disabling and life threatening and current therapies do not prevent these complications. The need for more aggressive therapy is apparent. The rationale for combinations of DMARDs is explored and the efficacy and safety of reported combinations is summarized. The variables to be reviewed in selecting a combination of DMARDs are examined. Newer approaches employing multiple DMARDs will be considered.
8293010	[Association of rheumatoid arthritis and Kaposi disease. Apropos of a case arising after i	1993 Mar	A 66 year old Corsican HLA A2 and DR5-positive male with moderately active seropositive destructive rheumatoid arthritis developed Kaposi's sarcoma after intraarticular administration of corticosteroids. He had no history of oral corticosteroid therapy, organ transplantation, AIDS, or cancer. Chlorambucil proved ineffective but the outcome was spontaneously favorable following discontinuation of oral corticosteroid therapy initiated after the development of the skin lesions. Six previous reports of concomitant rheumatoid arthritis and Kaposi's sarcoma were found. All six cases occurred following systemic corticosteroid therapy. The high incidence of rheumatoid arthritis and the small number of patients with rheumatoid arthritis and Kaposi's sarcoma suggest that concomitant occurrence of the two conditions may be fortuitous. However, the responsibility of corticosteroid therapy, which preceded development of Kaposi's sarcoma in every case, cannot be ruled out.
8275575	Progressive pseudorheumatoid arthritis of childhood (PPAC) and normal adult height.	1993 Sep	Two brothers and a sister presented with spondyloepiphyseal dysplasia and progressive arthropathy. Stiffness and restricted mobility of several large joints had been present since childhood. Their adult height was normal, and skeletal radiography showed mild platyspondyly, abnormal epiphyses and severe osteoarthrosis with extensive synovial osteochondromatosis. This autosomal recessive type of spondyloepiphyseal dysplasia tarda must be distinguished from other forms of spondyloepiphyseal dysplasia, rheumatoid arthritis in childhood and osteoarthrosis in adults.
1405077	[Bronchoalveolar lavage fluid findings in rheumatoid arthritis].	1992 Apr	Findings of bronchoalveolar lavage fluid (BALF) were compared among three groups of patients: rheumatoid arthritis (RA) with or without interstitial lung disease (ILD), and collagen disease other than RA accompanied by ILD. Regardless of the presence or absence of associated ILD, the RA groups showed higher numbers of neutrophils in BALF with a mean number about 10 times that of the collagen disease group. In contrast, the percentages of lymphocytes in the RA groups were lower than that in the collagen disease group. Classification of alveolitis on the basis of BALF findings revealed neutrophil type (N) in 55% of the RA patients and lymphocyte type (L) in 25%. In the collagen disease group, N was found in 15.4%, and L in 38.5%. Regarding the lymphocyte subsets, many patients with RA accompanied by ILD had a CD 4/8 ratio of 1 or great. These findings suggest that highly characteristic neutrophil alveolitis is present in the pulmonary interstitium from the initial stage of RA.
1359635	Influence of acetylator status on sulphasalazine efficacy and toxicity in patients with rh	1992	The influence of acetylator status on the therapeutic efficacy and the toxicity of sulphasalazine (SASP) was assessed in 106 patients with rheumatoid arthritis (RA). Changes of indices of disease activity after 6 months, and progression of erosions after 2 years of SASP treatment were similar in fast and slow acetylators. Incidence and nature of withdrawals and side-effects, and requirement for intra-articular steroid injections or combination therapy due to poor response to SASP were almost identical in the two groups. A significant increase of the hepatic enzyme aspartate transaminase was noted mainly in slow acetylators, but was not associated with clinical disease. These results suggest that acetylator status does not relate significantly to either the efficacy or the toxicity of SASP in RA. It is possible that hepatic metabolism is affected by SASP, particularly in slow acetylators, but this does not lead to clinically identifiable problems.
1363000	[Therapeutic maintenance and tolerance of sulfasalazine in rheumatoid polyarthritis. Retro	1992 Oct	This retrospective study evaluated treatment with sulfasalazine (SAS) in a mean dosage of 2.1 g/day in 95 patients with rheumatoid arthritis (RA) who were followed-up for 3 months to 4 years. Mean disease duration was 7 years; 79 patients had previously received at least one disease-modifying drug. Four per cent of patients were lost to follow-up. Mean duration of treatment was 15 months (3 weeks-50 months). Treatment continuation rates were 57% at one year, 40% at two years, and 26% at three years. Reasons for discontinuation of SAS included adverse effects (n = 24), inefficacy (n = 33), and death unrelated to SAS therapy (n = 2). In four patients, SAS was discontinued within three months of the first dose because of a severe adverse effect (diffuse erythematous rash, diffuse bullous rash, hepatitis with jaundice, agranulocytosis). SAS-induced biologic markers for lupus were seen in one patient. Furthermore, 12% of evaluable patients developed antinuclear antibodies during SAS therapy. The SAS treatment continuation rate was higher (p = 0.05) among patients under 40 years of age (n = 18) than among older patients. This difference was due to a correlation between age and tolerance with less SAS-induced side effects in patients under 40 years of age (p = 0.03). The SAS treatment continuation rate was unrelated to the duration of rheumatoid arthritis or number of previous maintenance treatments. This study suggests that rheumatoid arthritis patients under 40 years of age exhibit better tolerance to SAS therapy.
7562775	Pancytopenia related eosinophilia in rheumatoid arthritis: a specific methotrexate phenome	1995 Jul	Methotrexate (MTX) induced pancytopenia has been reported in about 3% of patients with rheumatoid arthritis (RA) receiving low dose MTX. We describe 4 additional patients with RA (2M, 2F; mean age 65 yrs; mean duration of RA 9 yrs) who developed pancytopenia while receiving low dose MTX. Risk factors identified for the development of pancytopenia in our patients included impaired renal function, hypoalbuminemia, advanced age, low folate level, concurrent use of multiple comedication, nonsteroidal antiinflammatory drugs, and cotrimoxazole). Remarkably, pancytopenia related eosinophilia was observed in blood and bone marrow after restoring the intracellular folate level by folinic acid. The range of eosinophils was 22-56% of the number of peripheral white blood cells (mean nadir 33%). The peak level of eosinophilic granulocytes was reached after a mean of 6 days in hospital (range 4-8), whereas the peak of neutrophils was reached after a mean of 11 days (range 9-13 days). The duration of the eosinophilic response was 11 days. As eosinophilia has not been observed in other drug induced pancytopenias in patients with RA this could be a specific MTX induced phenomenon.
8386246	Neurologic involvement in patients with rheumatoid arthritis with atlantoaxial subluxation	1993 Feb	Anterior subluxation of the atlantoaxial joint (AAS) is a frequent and potentially serious complication of rheumatoid arthritis (RA). The results of neurological evaluation, obtained in 30 patients with RA with AAS, and of somatosensory evoked potentials (SEP) studies, accomplished in 25 of these patients, were compared with the findings observed in 20 patients with RA without AAS, all of whom underwent neurological evaluation and SEP studies. Abnormal plantar responses were found only in patients with RA with AAS. There were more frequent SEP abnormalities in patients with RA with AAS than in patients without AAS, namely increased latencies of the N13 potentials evoked by stimulation of the median and radial nerves, which correspond to conduction delays at the cervical spinal cord level. A sensitivity of 56% and a specificity of 90% for SEP studies in the diagnosis of AAS in patients with RA were found. On the other hand, the observation that the mean values for the latencies of the N11 and N13 potentials evoked by stimulation of the radial nerves were significantly higher in patients with RA with AAS compared to patients with RA without AAS may suggest the existence of a frequent subclinical involvement of the cervical spinal cord caused by AAS.
8835576	Temporal association between the use of methotrexate and development of leukemia in 2 pati	1995 Dec	To date only a single case of leukemia coincident with the use of methotrexate (MTX) in rheumatoid arthritis (RA) has been reported. We report 2 additional patients with RA, each of whom developed leukemia after receiving short term low dose MTX. Whether these cases represent an adverse effect of MTX treatment has yet to be determined.
8197843	Periarticular bone in rheumatoid arthritis versus arthrosis. Histomorphometry in 103 hip b	1994 Apr	Histomorphologic differences of the periarticular bone in rheumatoid arthritis (RA) and osteoarthrosis (OA) may be of importance for long-term prosthetic fixation. We have evaluated bone specimens, obtained during total hip replacement from an acetabular and a femoral biopsy site, in 42 RA-hips and 61 OA-hips. In both groups the bone turnover was increased in the acetabulum compared to that in the femur. In the acetabulums the total trabecular bone volume was equal, but osteoid volume, osteoid surface, resorptive surface, and the appositional rate were increased in RA. On the femoral side, only the osteoid volume was higher in RA. The increased bone turnover with a greater amount of unmineralized tissue, as well as resorptive activity in the acetabulum, may be of importance for the higher rate of acetabular component migration and loosening after total hip replacement in RA.
8184199	[The involvement of the sacroiliac joints in rheumatoid arthritis. A retrospective radiogr	1994 Mar	The frequency and type of involvement of the sacroiliac joints in rheumatoid arthritis (RA) is a controversial issue. In this study we compared sacroiliac plain radiographs of 120 RA patients and 106 age and sex-matched primary osteoarthritis (OA) patients. Nobody had a history of low back pain. On the basis of the radiologist's report, sacroiliac alterations were found in 24 (20.0%) RA patients (subchondral sclerosis in 20, joint space narrowing in 2, bone erosions in 1 and bone ankylosis in 1) and in 13 (12.3%) OA patients (subchondral sclerosis in all). Neither the frequency nor the radiographic pattern of alterations were significantly different between the two groups. We conclude that radiographic changes of the sacroiliac joints in RA are mostly of degenerative nature not differing from those found in a OA control population.
8091148	Double blind radiological assessment of continuous oral pamidronic acid in patients with r	1994	Continuous oral pamidronate (APD), 1000 mg/day, was administered to 14 patients with rheumatoid arthritis. A control group of 13 patients with similar conditions received placebo under a double blind randomized study design. Periarticular erosion scores were significantly higher in the control group after 12 months treatment. This was attributed to a deterioration in this group rather than to an improvement in the APD treated one. By contrast, intraarticular narrowing score was not influenced by APD. Tolerance to oral APD was acceptable in all patients.
1536716	Are intestinal bacteria involved in the etiology of rheumatoid arthritis? Review article.	1992 Jan	Observations in bowel-related joint diseases give support to this hypothesis. In Crohn's disease and ulcerative colitis, the bowel wall inflammation is complicated in about 20% of the patients by joint inflammation. Bowel infection by Salmonella, Shigella and Yersinia can provoke joint inflammation and supports an etiological link between bowel bacteria and arthritis. The arthropathic properties of the most abundant group of intestinal bacteria, i.e. the obligate anaerobic bacteria, were studied in an animal model. Cell wall fragments (CWF), with peptidoglycan as the major component, from some Eubacterium and Bifidobacterium species induced a severe chronic polyarthritis in Lewis rats after a single intraperitoneal injection. Eubacterium was found in numbers of 10(8)-10(9) per gram in stools of healthy subjects and rheumatoid arthritis (RA) patients. CWF of isolated strains of E. aerofaciens were arthropathic. Soluble peptidoglycan polysaccharide complexes (PG-PS) originating from the obligate anaerobic flora were purified from human intestinal contents. PG-PS from ileostomy fluid that proved to be less processed by intestinal enzymes induced chronic arthritis in rats after a single administration in oil in the base of the tail. It was concluded that the human intestinal bowel contains soluble bacterial cell wall products that are arthropathic in an animal model. Peptidoglycan (PG) or its subunits was reported to be present in mammalian tissues. Immunohistochemical studies from our group showed the presence of intestinal PG-PS in sections of normal rat spleen. Bacterial cell wall or PG-induced joint inflammation in rats is proven to be absolutely dependent on functional T cells. T-cell lines were isolated from the lymph nodes of rats with an E. aerofaciens CWF arthritis. A helper T-cell line B13 was in vivo arthritogenic in knee or ankle joints upon intravenous injection in rats and proliferated in vitro on syngeneic spleen cells alone, but was additionally stimulated by intestinal PG-PS and E. aerofaciens CWF. It was postulated that the arthritogenic T cells that seem to be autoreactive are, in fact, recognizing bacterial PG-PS on antigen-presenting cells (APC). It is generally accepted that RA is a T-cell-dependent process and that therefore the reaction is directed at small peptides bound by the major histocompatibility complex of APC. The only peptides present in arthritis inducing intestinal PG-PS and in CWF are PG peptides interlinking the sugar chains. We feel that the immunoreaction against PG peptides plays a pivotal role in experimental and human arthritis of an unknown etiology.