DIAGNOSIS OF RHEUMATIC FEVER AND LIKE CONDITIONS—Evaluation of Certain of the Acute Phase Reactants in a Single Specimen of Blood

Certain of the acute phase reactant tests were performed on the same specimen of blood from persons with the following states: Normal, acute respiratory disease, streptococcosis, acute rheumatic fever, acute glomerulonephritis, acute rheumatoid arthritis, inactive rheumatic fever, lupus erythematosus, malignant disease, obesity, asthma, and allergic rhinitis. Of the tests performed, the mucoprotein-tyrosine and the antistreptolysin-0 titer when done together appeared to be the most discriminating. It is suggested that the performance of such tests on the same sample of blood might aid in differentiating mild acute rheumatic fever and acute rheumatoid arthritis from each other and also from other disease states.     

Role of infection in the pathogenesis of rheumatic diseases

Advanced immunological technology has revealed immunological abnormalities not only in some chronic and autoimmune connective tissue disorders but also in conditions like infective arthritis where infection apparently seems to play the only role. On the other hand role of infection in the pathogenesis of some connective tissue disorders has recently gained much importance from the observation of clinical, pathological and immunological similarities between these diseases and certain infectious diseases occurring in animal models. Meanwhile, knowledge gained into human leucocyte-A system and its association with certain diseases opens another angle in etiopathogenesis of certain rheumatic diseases. It has been postulated that adaptive mechanism of a microbe or the binding between the human leucocyte-A molecule and carbohydrate moiety of a microbe may set up an autoimmune reaction and in the presence of some triggering factors in the environment may lead on to disease manifestations. An attempt has been made to discuss the role of infection in the outcome of rheumatic diseases such as septic arthritis, polyarteritis nodosa, rheumatic fever, enteropathic arthritis, ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematoses in genetically susceptible individuals producing immunological abnormalities.     

感染与类风湿性关节炎

类风湿性关节炎(RA)等风湿性疾病的原因尚不明确(风湿热除外),目前研究发现RA的发病与遗传因素和环境因子(特别是病毒)有关。RA的发病与微生物感染密切相关,任何感染都可引起RA恶化,但迄今尚未确切地从病人血与滑液中找到活的微生物。多数学者认为微生物抗原在类风湿的发病中起始动作用。     

NONSPECIFIC ANTI-INFLAMMATORY AGENTS—Some Notes on Their Practical Application,Especially in Rheumatic Disorders

A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented.Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases.Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages.Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis.     

THE EFFECTS OF CORTISONE AND ADRENOCORTICOTROPIC HORMONE (ACTH) ON CERTAIN RHEUMATIC DISEASES

The adrenal cortical hormone, cortisone, and the pituitary adrenocorticotropic hormone (ACTH) possess potent antirheumatic properties. Their administration produces strikingly beneficial effects on a number of rheumatic diseases including rheumatoid arthritis, rheumatoid (ankylosing) spondylitis, acute rheumatic fever, disseminated lupus erythematosus, periarteritis nodosa, psoriatic arthritis, dermatomyositis, and gout. In general the effects of these substances are temporary and they cause suppression rather than cure of the disease processes. Improvement is maintained usually only by continuing administration, and on hormonal withdrawal prompt or fairly prompt relapse of the disease manifestations ensues. In addition to their antirheumatic effects cortisone and ACTH influence a wide variety of physiologic functions. Administration of them therefore may produce a number of metabolic and clinical changes, some of which are not advantageous from a therapeutic standpoint. Adverse side-reactions are more liable to occur when large doses of the hormones are given for prolonged periods; such reactions appear to be reversible and disappear when administration of the hormones is stopped. With cortisone, comparatively few untoward signs develop when smaller amounts are administered continuously even for periods of months.Greater clinical experience is needed before optimal doses and schedules of administration are finally determined. It appears that some severe cases, many moderately severe cases, and most moderate and mild cases of rheumatoid arthritis may be adequately controlled with smaller “maintenance” doses of cortisone ranging from 32 to 65 mg. a day, providing larger doses to suppress the disease manifestations are employed initially.Neither cortisone nor ACTH should be considered as a therapeutic agent for general use until more information regarding their physiologic activities and the consequences of prolonged or repeated administration of them are available. Until the potential dangers of these hormones can be determined precisely, the use of them should be considered as an investigative procedure.     

Emerging role of anti-tumor necrosis factor therapy in rheumatic diseases

Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine that has been implicated in a variety of rheumatic and inflammatory diseases. New understanding of the importance of TNF-alpha in the pathophysiology of rheumatoid arthritis and Crohn's disease led to the development of a new class of targeted anti-TNF therapies. Anti-TNF-alpha agents including etanercept (a fusion protein of the p75 TNF receptor and IgG1) and infliximab (a chimeric monoclonal antibody specific for TNF-alpha) have been approved for the treatment of rheumatoid arthritis. In addition, infliximab has been approved in the treatment of patients with active or fistulating Crohn's disease. A new appreciation of the importance of TNF-alpha in other rheumatic and inflammatory diseases has led to a broadening of the application of anti-TNF agents. Both etanercept and infliximab have been used in open-label and randomized studies in patients with psoriatic arthritis. Although larger randomized trials are needed to confirm early results, both these anti-TNF-alpha agents, etanercept and infliximab, have demonstrated activity in improving the signs and symptoms of psoriatic arthritis and psoriasis. Infliximab has also been shown to be effective in patients with other rheumatic diseases, including ankylosing spondylitis, and may be effective in adult-onset Still's disease, polymyositis, and Beh?et's disease. Further investigations will fully elucidate the role of infliximab in these and other rheumatic diseases.     

Arthritis in Flemish paintings (1400-1700).

A close examination of the hands of people depicted in paintings of the Flemish school showed that in five paintings there were figures with hand lesions resembling those of rhematoid arthritis. Although none of the deformities or swellings are indisputable examples of rheumatoid arthritis, they do at least suggest that the painters must have been confronted with rheumatoid-like lesions in their models. In two other paintings there were signs of rheumatic fever and of temporal arteritis. No arthritic lesions were found in the works of painters of the Italian Renaissance, probably because they are less detailed. The finding of rheumatoid deformities in the Flemish paintings does, however, question the general belief that rheumatoid arthritis is a condition that has arisen relatively recently.     

Molecular heterogeneity among north Indian isolates of Group A Streptococcus

AIM: To monitor molecular heterogeneity among the clinical isolates of group A Streptococcus (GAS) from north India by Vir and emm typing. METHODS AND RESULTS: GAS isolates, 31 from pharyngitis and nine from rheumatic fever (RF)/rheumatic heart disease (RHD) patients were differentiated into 16 Vir types (VT). These isolates were further discriminated into 23 emm types. Most of emm types were Vir type specific, except few (7.5%), which revealed different Vir types within same emm type. The most prevalent emm type found was emm 49 (15%) followed by 7.5% of emm 69, emm 71 and emm 75 which were different from emm type distribution reported from south India. CONCLUSIONS: Analysis of data revealed 40% heterogeneity by Vir typing and 57.5% by emm typing among GAS isolates which is significant in view of small number of isolates studied. SIGNIFICANCE OF IMPACT OF THE STUDY: The molecular study for the first time demonstrates different emm types prevalent and circulating in northern region of India and such data may help in selection of types for vaccine development.     

Radiological aspects of collagen diseases

The collagen diseases, an ill-defined group of clinical entities, have as their basis a generalized alteration of the connective tissue, especially of its extracellular components. They include periarteritis nodosa, disseminated lupus erythematosus, dermatomyositis, scleroderma, rheumatic fever and rheumatoid arthritis. The radiological findings in a series of cases of these diseases were reviewed. In 28 cases of periarteritis, 20 cases showed some abnormal findings in the thorax. These included pleural effusions, pulmonary changes, pericardial effusions and cardiac enlargement. In 32 cases of disseminated lupus erythematosus, thoracic findings were noted in 21. They resembled the changes found in periarteritis. In some 25 cases of scleroderma, diverse radiological findings were noted. These included "cystic" changes in the lungs (one case) and pulmonary "hives." In the intestinal tract esophageal and small bowel alterations were found, both ectatic and stenotic. In the soft tissues of the "pressure areas" variable degrees of calcification were observed. Dermatomyositis is the rarest of the collagen disease group; only one autopsy-proven case is available for study. Chest x-rays taken a year before death showed slight cardiac enlargement. The lungs were clear. In acute rheumatic fever, x-ray examination may disclose pericardial or pleural effusion, and so-called rheumatic pneumonitis; the latter has no specific diagnostic features. Soft tissue swellings may develop around some of the joints. In rheumatoid arthritis, joint changes are numerous and fairly characteristic, and are followed in many cases by fibrous or bony ankylosis and deformities of considerable degree. Awareness of the commoner radiological changes in this entire group of diseases should result in earlier establishment of diagnosis, especially in the more obscure examples.     

Vasculopathy and disordered angiogenesis in selected rheumatic diseases: rheumatoid arthritis and systemic sclerosis

Angiogenesis is important in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes rheumatoid arthritis and systemic sclerosis. Rheumatoid arthritis is the rheumatic disease in which the role of angiogenesis has been studied most extensively. However, whereas rheumatoid arthritis is characterized by excessive angiogenesis, the situation is not as clear cut in other rheumatic diseases. For example, systemic sclerosis is characterized by reduced capillary density with insufficient angiogenic responses. Results with angiogenesis inhibitors are controversial, and there is--in parallel--a wide range of upregulated angiogenic factors such as vascular endothelial growth factor. Dysregulation of angiogenesis in systemic sclerosis is accompanied by other pathogenic processes, including fibrosis, autoimmunity and vasculopathy. Animal models with at least partial features of the vasculopathy observed in systemic sclerosis include wound healing models, graft versus host disease models and, in particular, the University of California at Davis line 200 chicken model of systemic sclerosis.     

Molecular mimicry--hypothesis or reality?

A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter''s syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.     

Rheumatic fever in Southern California; problems related to diagnosis

Rheumatic fever occurs in native of Southern California and is a cause of death. The incidence of streptococcosis in Los Angeles is approximately equal to that in three other major cities in the United States where rheumatic fever is known to occur commonly. Manifestations of rheumatic fever may range from mild to severe. It is suggested that a greater percentage of patients in Southern California have symptoms of rheumatic fever that are more mild. Differentiation between prolonged, uncomplicated streptococcosis and rheumatic fever is a major problem. The judicious use of a battery of tests, acute phase reactants, on the same blood sample will frequently help to establish the diagnosis in borderline situations so common to Southern California.     

Ethnic differences in mortality from acute rheumatic fever and chronic rheumatic heart disease in New Mexico, 1958-1982.

To examine time trends and differences in mortality rates from acute rheumatic fever and chronic rheumatic heart disease in New Mexico''s Hispanic, American Indian, and non-Hispanic white populations, we analyzed vital records data for 1958 through 1982. Age-adjusted mortality rates for acute rheumatic fever were low and showed no consistent temporal trends among the three ethnic groups over the study period. Age-adjusted and age-specific mortality rates for chronic rheumatic heart disease in Hispanic and non-Hispanic whites decreased over the 25-year period, although rates were higher among Hispanics than among non-Hispanics during most of the time period. In American Indians, age-adjusted mortality rates for chronic rheumatic heart disease increased between 1968 and 1977 to twice the non-Indian mortality rates during the same period. Despite this increase in mortality from chronic rheumatic heart disease among New Mexico''s American Indians from 1968 to 1977, the New Mexico data generally reflect national trends of decreasing mortality from chronic rheumatic heart disease.     

Surgery in the treatment of rheumatoid arthritis and ankylosing spondylitis

The pain, deformities and disabilities resulting from rheumatoid arthritis and ankylosing spondylitis must be treated by a team composed of physician, physical medicine expert, orthopaedic surgeon, and, in certain cases, deep X-ray therapist working simultaneously.The principle of "rest" in order to relieve pain has to be combined with methods designed to preserve and restore function. The multiple joint deformities in these cases may necessitate a long programme of reconstructive or functional treatment, which entails whole-hearted co-operation on the part of the patient in intensive post-operative exercise regime.PROCEDURES ADVOCATED FOR THE UPPER LIMB INCLUDE EXCISION OF THE ACROMION PROCESS TOGETHER WITH THE SUBACROMIAL BURSA TO ALLOW FREE MOVEMENT BETWEEN THE CENTRAL TENDON OF THE DELTOID AND THE TENDINOUS SHOULDER CUFF: arthrodesis of the shoulder in cases where there is more severe joint destruction: in certain cases of elbow-joint arthritis, excision of the radial head and sub-total synovectomy may preserve joint function and avoid or delay the necessity for arthroplasty which can be carried out in two ways: (a) similar to the formal joint excision, or (b) re-shaping the lower end of the humerus and upper end of the ulna lining these surfaces with fascia. The former method is preferable in cases of rheumatoid arthritis. To overcome wrist-joint deformity and restore pronation and supination excision of the lower end of the ulna together with radiocarpal fusion in position for optimum function is advocated. Finger and toe joints may be corrected by resection of the bone ends and capsulectomy.In the lower limbs bilateral involvement of the hip-joint is best treated by vitallium mould arthroplasty which may be carried out in four ways: (1) Routine arthroplasty; (2) Modified Whitman procedure; (3) Modified Colonna operation; and (4) The proximal shaft or intertrochanteric arthroplasty. It is essential in these operations to have knowledge of the operative technique, the use of special hip gouges and reamers, and detailed post-operative supervision.For dorsal kyphosis of the spine, spinal osteotomy at the lumbar level provides excellent correction but is an operation demanding care and skill in its execution.The author's remarks are based on experience gained when working with Dr. M. N. Smith-Petersen at the Massachusetts General Hospital, Boston, U.S.A.     

Genetic susceptibility to acute rheumatic fever: a systematic review and meta-analysis of twin studies

Background

Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a systematic review and meta-analysis of twin studies of concordance of acute rheumatic fever in order to derive quantitative estimates of the size of the genetic effect.

Methods

We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumatic heart disease in monozygotic versus dizygotic twins that used accepted diagnostic criteria for acute rheumatic fever and zygosity without age, gender or language restrictions. Twin similarity was measured by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was calculated by combining raw data from each study. ORs from separate studies were combined by random-effects meta-analysis to evaluate association between zygosity status and concordance. Heritability was estimated by fitting a variance components model to the data.

Results

435 twin pairs from six independent studies met the inclusion criteria. The pooled probandwise concordance risk for acute rheumatic fever was 44% in monozygotic twins and 12% in dizygotic twins, and the association between zygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P<0.001), with no significant study heterogeneity (P = 0.768). The estimated heritability across all the studies was 60%.

Conclusions

Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genome scanning may provide a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease.     

Medical History: Arthritis in Saxon and mediaeval skeletons

Examination of 400 Saxon, Romano-British, and mediaeval skeletons from seven archaeological excavations in the west of England showed an unexpectedly high incidence of osteoarthritis and osteophytosis. Three skeletons had evidence of an erosive peripheral arthritis—one with probable gout, one probable psoriatic arthropathy, and one with possible rheumatoid arthritis. The pattern and types of rheumatic disease, and the resultant disability, were apparently different. An exuberant form of large joint osteoarthritis was common and rheumatoid arthritis and similar diseases rare.     

RHEUMATIC FEVER IN COLLEGE STUDENTS

The results of three independent surveys concerned with rheumatic fever and heart disease in students at the University of California were assembled and found to be in close agreement. A full 2 per cent of all students believed they had had rheumatic fever; and several times that proportion gave a history of one of the rheumatic manifestations. Only 0.25 per cent had demonstrable rheumatic heart disease and 0.1 per cent had congenital heart disease.Physiologic murmurs may occur in 3 per cent or more of students entering college.Penicillin prophylaxis is important in persons with rheumatic heart disease, but it is important not to put a label of rheumatic heart disease on persons who think they have had rheumatic fever but who have no demonstrable heart disease. Long term penicillin prophylaxis or other long term prophylactic procedures directed against rheumatic fever are not indicated unless the diagnostic criteria for rheumatic fever are clearly met or unless rheumatic heart involvement is definitely present.     

Antilymphocyte antibodies in various human diseases as a factor of reduced functional activity of T-suppressors

A total of 157 sera from adults and children with rheumatoid arthritis, rheumatic fever, myocarditis, neurodermite, bronchial asthma, wound infections, second degree obesity without symptoms of diabetes were examined. 60% of sera contained high concentrations of antibodies possessing cytotoxicity against thymus cells, but not against bone marrow cells. Sera of healthy children and adults contained no cytotoxic antibodies. Sera cytotoxic against mouse thymus cells inhibited the suppressing activity of mouse splenocytes in experiments on syngeneic transfer, reducing the ability of human lymphocytes to form T-RFC. The latter phenomenon is associated with the decline in the number of T-theophyllin-sensitive lymphocytes, known as T-suppressors.     

Antilymphocytic antibodies in human diseases as a factor decreasing the functional activity of T-suppressors

157 sera from adults and children with rheumatoid arthritis, rheumatic fever, myocarditis, neurodermatitis, bronchial asthma, wound infections, second degree obesity without symptoms of diabetes were examined. 60% of sera contained high concentrations of antibodies possessing cytotoxicity against thymus cells, but not against bone marrow cells. Sera of healthy children and adults contained no cytotoxic antibodies. Sera cytotoxic against mouse thymus cells inhibited the suppressing activity of mouse splenocytes in experiments on syngeneic transfer, reducing the ability of human lymphocytes to form T-RFC. The latter phenomenon is associated with the decline in the number of T-theophylline-sensitive lymphocytes, known as T-suppressors.