Early diagnosis of rheumatoid arthritis

On the basis of own observations of courses the author adopts a definite attitude to the early symptomatology of the rheumatoid arthritis. During the first weeks of the rheumatoid arthritis the following symptoms are found: articular syndromes, more frequently in form of obstinate polyarthralgias, mono-oligoarthritis, accompanied by morning rigidity and accelerated BSR as well as impairment of the general condition. In the majority of the patients only the tentative diagnosis rheumatoid arthritis may be made. After a one to three months' course of the disease the diagnosis becomes more probable. It is above all based on constancy and symmetry, characteristic localisation of the articular process, morning rigidity, radiologically paraarticular loosening of the structure and morphological symptoms of an acute and subacute synovialitis. 6 to 12 months after the beginning of the disease a clinical picture forms which allows to make the diagnosis of a certain or classical rheumatoid arthritis in accordance with the criteria of the ARA. The occurrence of a high activity of multiple affection of the joints (permanent symmetrical polyarthritis including the small joints of the hands and feet), distinctive morning rigidity, high fever and much accelerated BSR, beginning with the first weeks of the disease, speaks for the possibility of the development of an arthrovisceral form of the course of rheumatoid arthritis.     

Difficulties in diagnosing pulmonary visceral forms of rheumatoid arthritis in tuberculous hospital

We describe the diagnostic workup and therapeutic management of patients with hepatolithiasis from the viewpoint of the interventional radiologist. The diagnosis is best established by direct cholangiography such as percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography. We consider percutaneous transhepatic stone removal a highly successful, minimally invasive, and safe procedure. Access can be gained to the biliary system in almost 100% of patients and complete stone clearance through percutaneous techniques, including stone fragmentation, removal of stones and fragments by baskets, and dilatation of underlying strictures in more than 90%. The role of these radiologic techniques is discussed vis-à-vis endoscopic and surgical alternatives.     

The concurrence of rheumatoid arthritis and limited systemic sclerosis: clinical and serologic characteristics of an overlap syndrome

OBJECTIVE: The characteristics of 3 patients with longstanding rheumatoid arthritis (RA) and consecutive evolution of limited cutaneous systemic sclerosis (IcSSc) were evaluated and compared with those of patients with IcSSc alone (n = 20) or with RA alone (n = 120). METHODS: Clinical features of the different patient populations were compared. Serologic analyses included tests for antinuclear antibodies (ANA) and ANA subsets, in particular anticentromere antibodies (ACA) and anti-heterogeneous nuclear RNP (hnRNP)-A2/RA33 (anti-A2/RA33). RESULTS: The 3 patients with RA developed IcSSc 11, 29, or 50 years after the onset of RA. Features of IcSSc were Raynaud's phenomenon, sclerodactyly, and telangiactasias in all 3 patients, and esophageal dysmotility in 1 patient. Rheumatoid factor (RF) and anti-A2/ RA33 were each found in 2 patients, and 1 of these patients was seropositive for both RF and anti-A2/RA33. ACA titers were positive in all cases. However, similar to the development of RA prior to IcSSc, the occurrence of autoantibodies typical of RA preceded the occurrence of ACA, at least in 2 of the patients. Using affinity-purified antibodies, cross-reactivities between anti-centromere protein A (CENP-A) and anti-CENP-B antibodies with anti-A2/RA33 antigens were seen in the 2 anti-A2/RA33-positive patients. Such cross-reactivities were not found in IcSSc patients without concomitant RA. Epitope mapping revealed that both autoantibody specificities recognized the known major epitopes: anti-CENP-B reacted with the C-terminal region and anti-A2/RA33 with the second RNA binding domain in the N-terminal region of hnRNP-A2. CONCLUSION: The RA-lcSSc overlap syndrome in these 3 patients with longstanding RA was characterized by an incomplete CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) syndrome. The study demonstrated the presence of autoantibodies typical of both diseases and cross-reactivity of ACA with hnRNP-A2/RA33 in the sera of these patients.     

The great toe as a clinical problem in rheumatoid arthritis

Two hundred consecutive in-patients with rheumatoid arthritis were examined for pain or deformity of the feet, and of the great toe in particular. Some abnormality occured in 196 feet and the deformities observed are presented. The symptoms that arise from these deformities are mainly derived from ill-fitting shoes, and the need for suitable foot-wear is emphasized. Two hitherto un-named entities are described namely Hallux tortus and chisel toe, since they give rise to their own shoe-fitting problems.     

The lag time between onset of symptoms and diagnosis of rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) may be biologically reversible if treated in the first several months, yet it is unknown whether patients are diagnosed that early. We investigated the lag time between symptom onset and diagnosis of RA in a population with excellent access to rheumatology care. METHODS: Using review of medical records, we evaluated all patients newly diagnosed as having RA from 1987 through 1990, at a health maintenance organization in central Massachusetts. Total lag time from symptom onset to first definite diagnosis was divided into medical encounter lag time (from symptom onset to first medical encounter) and diagnosis lag time (from first medical encounter to diagnosis). RESULTS: The median total lag time was 36 weeks (range 4 weeks to > 10 years). The median medical encounter lag time was 4 weeks (not all patients included in the analysis). The median diagnosis lag time was 18 weeks. Diagnosis lag time was shorter for patients with progressive disease and positive rheumatoid factor on the initial test. Of 25 patients with symmetric arthritis and positive rheumatoid factor, only 5 (20%) were diagnosed within 2 months, and 10 (40%) were diagnosed more than 6 months after symptom onset. CONCLUSION: RA diagnosis is usually delayed for several months after symptoms begin, in large part because of delay in diagnosis by the physician. Thus, the goal of initiating treatment extremely early may be unrealistic for most patients.     

Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance

In summary, angiogenesis, the formation of new blood vessels, is important in leukocyte extravasation and thus the pathogenesis of RA. The outcome of neovascularization highly depends on the imbalance between angiogenic and angiostatic mediators produced in the rheumatoid synovium. Therefore, angiogenesis research is important for the understanding of the pathogenesis of inflammatory arthritis. In addition, existing and potential angiostatic drugs may be useful for future therapy of RA.     

Possibilities and limits of the morphological diagnosis of rheumatoid arthritis]

For the morphological diagnostics of rheumatoid arthritis only the judgment of the synovial membrane is of practical importance. Based on the experience gleaned on more than 2,000 synovectomy preparations the following evidence concerning the possibilities and the limits of the morphological diagnostics and the judgment of activity can be enunciated. 1. A certain histological diagnosis of the rheumatoid arthritis is possible only when rheumatoid granulomas or their equivalents are proved. 2. A probability diagnosis results from a definite combination of symptoms of proliferative and exsudative reactions of the synovial membrane. Especially the absence of proliferative signs decreases the degree of probability of the diagnostic evidence. 3. Seropositive and seronegative cases do not reveal any differences in histological respect. The possibility of the class-specific determination of rheumatoid factors by means of an immunofluorescence test and the fact the seronegative cases showed IgM and IgM rheumatoid factors, when this test was used, demands an examination of this evidence. 4. As to the synovial membranes of large joints in the same membrane so distinctive local differences of the findings may exist that thus the value of the needle biopsy is restricted. Only positive findings may be evaluated diagnostically. 5. Apart from a diagnosis the histological findings of the synovial membrane also allow a judgment of the local activity. The basis activity and the actual activity are differentiated. The basis activity is regarded as an expression of the immunological activity, the actual activity as an expression of the inflammatory activity. There are no unambiguous relations to the total clinical activity. Differences in the behaviour of the activity between seropositive and seronegative cases are not to be proved. A revision of this evidence under the aspect of the class-specific proof of the rheumatoid factor is necessary.     

Correlations between clinical facets of outcome in rheumatoid arthritis

8 subjects with a variety of orthopedic implants were examined by the security staff at an international airport using arch and hand-held metal detectors. None of the subjects caused activation of the alarm on the arch, although the presence of metal was registered in 2 at a level below the alarm threshold. The hand-held detectors alarmed over the larger superficial implants. A substantial tissue screening effect was noted.     

The characteristics of the clinical course in individual types of radiation-induced cataracts

Twenty-eight patients exposed to acute and chronic ionizing radiation were followed up. Radiation cataracts were diagnosed in 22 eyes. Localizations of changes in the lens after ionizing and solar radiation are similar. Opacities are localized under the posterior lenticular capsule, round the nucleus, and under the anterior capsule and do not depend on the type of radiation. Opacities caused by solar radiation are notably smaller and look as numerous small dots. Study of cataracts of different origin and assessment of the efficacies of different anticataract drugs were carried out for evaluating the progress of different types of cataracts (cellular, extracellular, and capsular forms).     

The value of synovial biopsies in the diagnosis of rheumatoid arthritis and in estimating local inflammatory activity

Fifty surgically removed synivial membranes from large joints of patients with rheumatoid arthritis were examined histologically from 10 different areas. The diagnostic reliability and the histologically graded basic and actual activity were estimated. All 3 parameters differed considerably within the individual synovial membrane. To assess the diagnostic value of synovial needle biopsies the results were compared with those of simulated biopsy cylinders. The morphological results gained from the biopsy cylinders were much poorer, showing that needle biopsies are limited diagnostic value.     

Epidemiological and clinical aspects relating to the variability of rheumatoid arthritis

OBJECTIVE: To review epidemiological studies dealing with the temporal and geographic variability in the occurrence of rheumatoid arthritis (RA) and clinical studies that address the variability of severity and manifestations among populations. METHODS: An extensive search of the literature, including a Medline search, was completed. Studies addressing the origin, history, and trends in the occurrence of RA were reviewed first. Next, studies of the prevalence and incidence of RA in different populations were reviewed, and occurrence rates compared. Standardization was attempted by tabulating adult prevalence rates of studies using equivalent sets of criteria. Studies comparing RA patients from two populations were sought next. Finally, studies dealing with explanations of the presumed variability were reviewed. RESULTS: Temporal variability is indicated by paleopathological evidence that RA has existed in the New World since 4000 BC, whereas there is no evidence that it occurred in Europe before the 17th century, or in Africa before the 20th century. Epidemiological studies show a possible trend of decreasing incidence of RA in the United States and Western Europe, whereas reports from Africa note a rising incidence. In white populations of Europe and America, prevalence is approximately 1%, and incidence is 0.03%. Significantly higher rates are found in some North American Indians, and significantly lower rates in some Asian and African populations, even when the different population structures are taken into account. In the latter populations, different patterns of occurrence from those observed in whites emerge, such as greater female preponderance and a much younger peak age at onset. Direct standardized comparisons of two diverse populations of RA patients showed some differences in expression, severity, or manifestations of RA between populations. CONCLUSION: The occurrence and manifestations of RA are temporally and geographically variable.     

Radionuclide diagnosis of local inflammation in patients with rheumatoid arthritis

Radionuclide scintigraphy with osteotropic radiopharmaceuticals labelled 99Tc proved highly sensitive in assessment of local inflammation. Osteoscintigraphy allows detection of preclinical and pre-x-ray lesions in the joints in RA and assessment of the treatment efficacy. Characteristic signs of the radionuclide distribution and accumulation can serve as a prompt in differential diagnosis of RA, DOA, reactive and gouty arthritis.     

The correlation of indium-111 joint scans with clinical synovitis in rheumatoid arthritis

OBJECTIVE: An inflammatory compartment radionuclide such as Indium-111 chloride (111InCl3) may offer advantages over bone seeking radionuclides in the assessment of active rheumatoid synovitis. As an iron analog, 111InCl3 binds iron complexing proteins including transferrin. Active rheumatoid synovitis is a transferrin receptor rich compartment, reflecting profound cellular activation and proliferation. We investigated 111InCl3 scanning for the detection of active rheumatoid arthritis (RA). METHODS: Nine patients satisfying ACR criteria for definite or probable RA were scanned twice at a 28-day interval. Patients were undergoing multiple medication changes with resultant fluctuating disease activity. Blinded readings were performed by an experienced nuclear medicine physician and correlated with simultaneous clinical examinations by a single rheumatologist. Sixteen assessed joint areas/patient and a total of 144 joint areas were available for analysis. RESULTS: Scintigraphy correlated with swollen and tender joint scores at both timepoints. Specificity was highest with stringent scoring. Sensitivity was lowest for small joints with lower 111InCl3 uptake relative to background. A receiver operator curve (ROC), generated to analyze the diagnostic value of varying 111InCl3 scan stringency, demonstrated utilization of the most accurate portion of the ROC curve by the reader. CONCLUSION: 111InCl3 joint scintigraphy correlates with clinically detectable rheumatoid synovitis, supporting the hypothesis that transferrin receptor levels reflect rheumatoid disease activity.     

The prognosis of rheumatoid arthritis

Although DNA replication is a very accurate process, a small number of new mutations are generated at every cell division. The generation of a new mutation during the formation of an ovum or sperm cell can cause an early miscarriage or birth defect. The generation of new mutations during embryogenesis can cause a variety of localized birth defects. The molecular delineation of these errors in somatic and gonadal cells has clarified the basis of some birth defects, and has both refined and complicated genetic counselling for a number of paediatric conditions. The processes responsible for these new mutations are present in all cells. For this reason new mutations accumulate in all cells throughout life and contribute to the ageing process. Thus the molecular events that cause many miscarriages and birth defects are the same as those that ultimately lead to death.     

Effects of stress management on clinical outcomes in rheumatoid arthritis

An intriguing feature of early zygote development in Chlamydomonas reinhardtii is the active elimination of chloroplast DNA from the mating-type minus parent due presumably to the action of a zygote-specific nuclease. Meiotic progeny thus inherit chloroplast DNA almost exclusively from the mating-type plus parent. The plus-linked nuclear mutation mat3 prevents this selective destruction of minus chloroplast DNA and generates progeny that display a biparental inheritance pattern. Here we show that the mat3 mutation creates additional phenotypes not previously described: the cells are much smaller than wild type and they possess substantially reduced amounts of both mitochondrial and chloroplast DNA. We propose that the primary defect of the mat3 mutation is a disruption of cell-size control and that the inhibition of the uniparental transmission of chloroplast genomes is a secondary consequence of the reduced amount of chloroplast DNA in the mat3 parent.