Juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis is a diverse group of diseases that includes systemic-onset, polyarticular, and pauciarticular types. Appreciation of the different types and their hallmarks is particularly important to accurate diagnosis, which is determined by exclusion of other known disease entities in children with chronic arthritis (more than three months' duration). Therapy should be directed at the arthritis per se (synovitis), at the extra-articular manifestations, and at the whole child. Salicylates provide the most satisfactory control of the arthritis per se and of the systemic manifestations in most cases. Iridocyclitis should be managed in consultation with an ophthalmologist. Patients should not be regarded as invalids or restricted needlessly. The prognosis for children with juvenile rheumatoid arthritis is good. In most patients, the disease remits without causing permanent joint damage.     

Approach to septic arthritis

Prompt diagnosis and treatment of infectious arthritis can help prevent significant morbidity and mortality. The acute onset of monoarticular joint pain, erythema, heat, and immobility should raise suspicion of sepsis. Constitutional symptoms such as fever, chills, and rigors are poorly sensitive for septic arthritis. In the absence of peripheral leukopenia or prosthetic joint replacement, synovial fluid white blood cell count in patients with septic arthritis is usually greater than 50,000 per mm3. Isolation of the causative agent through synovial fluid culture is not only definitive but also essential before selecting antibiotic therapy. Synovial fluid analysis is also useful to help distinguish crystal arthropathy from infectious arthritis, although the two occasionally coexist. Almost any microorganism can be pathogenic in septic arthritis; however, septic arthritis is caused by nongonococcal pathogens (most commonly Staphylococcus species) in more than 80 percent of patients. Gram stain results should guide initial antibiotic choice. Vancomycin can be used for gram-positive cocci, ceftriaxone for gram-negative cocci, and ceftazidime for gram-negative rods. If the Gram stain is negative, but there is strong clinical suspicion for bacterial arthritis, treatment with vancomycin plus ceftazidime or an aminoglycoside is appropriate. Evacuation of purulent material with arthrocentesis or surgical methods is necessary. Special consideration should be given to patients with prosthetic joint infection. In this population, the intraarticular cutoff values for infection may be as low as 1,100 white blood cells per mm3 with a neutrophil differential of greater than 64 percent.     

Suppressor cell-mediated neutropenia in Felty''s syndrome.

The mechanism of neutropenia in Felty's Syndrome (FS) was tested. The suppressor capacity of mononuclear cells from patients with FS on normal bone marrow granulopoiesis was tested by the in vitro colony forming unit in culture assay. Peripheral blood, bone marrow, and spleen cells from FS patients with marked neutropenia (less than 1,000 neutrophils/mm3) suppressed the colony forming unit in culture of normal bone marrow. Cells from rheumatoid arthritis patients without neutropenia, cells from patients with drug-induced neutropenia without rheumatoid arthritis, or plasma from FS patients failed to suppress the colony forming unit in culture. Though suppressor cells were predominantly thymus-derived (T) cells, monocytes were also effective in suppression. The suppressor efficiency of cells from the various compartments were spleen greater than bone marrow greater than peripheral blood. Splenectomy in FS transiently corrected the neutropenia and eliminated suppressor cell activity. Hyperactive suppressor cells may be responsible for the neutropenia in some patients with FS. Correction of neutropenia in these patients should be directed at modulating the suppressor cell subpopulation.     

Gout: current views. Stage oriented treatment

Gout is a common disease arising due to abnormal purin metabolism and excessive accumulation of uric acid in the blood (hyperuricemia) and manifesting with attacks of acute gouty arthritis. In long duration of gout uric acids accumulate in the bones and periarticular tissues as tophuses. Repeat attacks lead to development of chronic gouty arthritis. Purins restriction diet is an important component of gout treatment. Treatment of acute arthritis should be started early, in initial pains before the development of the attacks. Gouty arthritis in the presence of continuous hyperuricemia, tophyses and urolithiasis is treated with allopurinol. Its intake should be long and controlled by the blood level of uric acid. Balneotherapy is recommended for patients with chronic gouty arthritis associated with cardiovascular diseases, urolithiasis.     

Anti-CCP antibodies as an aid to prioritization of patients referred to the rheumatology clinic

Sir, As noted in your review article,¹ anti-cyclic citrullinatedpeptide antibodies (CCP) have been shown to be more sensitiveand specific for rheumatoid arthritis (RA) than the rheumatoidfactor (RF).² It is also well accepted that patients with earlyRA should be seen and treated as soon as     

Different HLA-D associations in adult and juvenile rheumatoid arthritis.

HLA-D typing was performed in 126 patients with juvenile rheumatoid arthritis. HLA-DW4, the antigen found in previous studies to characterize adult rheumatoid arthritis, had a significantly lower frequency in children with arthritis than in normal controls (P less than 0.04). By contrast, in children the antigens HLA-DW7 (P less than 0.03) and HLA-DW8 (P less than 0.01) were increased compared to controls. The antigen TMo, detected with homozygous typing cells from a child with juvenile rheumatoid arthritis, was found to be related to the cross-reactive specificities HLA-DW7 and DW11. 46% of the patients with persistent pauciarticular arthritis of childhood typed for the antigen TMo, compared to only 1% of normal controls. Thus the relative risk for persistent pauciarticular arthritis in relation to the presence of TMo was 67.7 (P less than 0.0001). These results provide evidence of fundamental differences between adult rheumatoid arthritis and arthritis of childhood. The latter group appears to include a population distinguishable clinically and characterized in these studies by the HLA-D determinant TMo.     

Chronic musculoskeletal pain in children: part II. Rheumatic causes

Primary care physicians should have a working knowledge of rheumatic diseases of childhood that manifest primarily as musculoskeletal pain. Children with juvenile rheumatoid arthritis can present with painless joint inflammation and may have normal results on rheumatologic tests. Significant morbidity may result from associated painless uveitis, and children with juvenile rheumatoid arthritis should be screened by an ophthalmologist. The spondyloarthropathies (including juvenile ankylosing spondylitis and reactive arthritis) often cause enthesitis, and patients typically have positive results on a human leukocyte antigen B27 test and negative results on an antinuclear antibody test. Patients with acute rheumatic fever present with migratory arthritis two to three weeks after having untreated group A beta-hemolytic streptococcal pharyngitis. Henoch-Schbnlein purpura may manifest as arthritis before the classic purpuric rash appears. Systemic lupus erythematosus is rare in childhood but may cause significant morbidity and mortality if not treated early. Nonsteroidal anti-inflammatory drugs and physical therapy may be useful early interventions if a rheumatic illness is suspected. Family physicians should refer children when the diagnosis is in question or subspecialty treatment is required. Part I of this series discusses an approach to diagnosis with judicious use of laboratory and radiologic testing.     

Joint replacement. The primary care physician's role.

Ideally, primary care physicians can successfully manage cases of arthritis in a manner that obviates the need for reconstructive surgery. However, that is not always possible. When surgical intervention is believed to be of potential benefit, the primary care physician needs to enlist the help of a surgeon and other health professionals to determine the best approach. Primary care physicians should take an active role in preoperative planning, perioperative management, and rehabilitation. The unique characteristics of the patient's specific type of arthritis and use of medications must be carefully considered. This approach should optimize the chances for a successful outcome.     

Total joint arthroplasty. The wrist.

Total wrist arthroplasty, which has been performed in 101 patients, has proved to be a satisfactory procedure for the relief of pain and provision of mobility in the deformed wrist involved with rheumatoid arthritis. This procedure should not be performed after traumatic conditions in patients who expect to make heavy use of the wrist. Early cases were associated with technical problems in the development of the concept, but at present the procedure is reliable and is most often preferred to arthrodesis inpatients with rheumatoid arthritis.     

Rheumatoid arthritis. Practical use of medications

The treatment of rheumatoid arthritis is undergoing steady change as new medications are approved and new regimens are attempted. Once the diagnosis is ensured, therapy should include appropriate rest, physical and occupational therapy, involvement of the family or a supportive caregiver, and, most important, participation of the patient. If the disease is not terribly aggressive, therapy with nonsteroidal anti-inflammatory drugs is appropriate initially. If no response is obtained within 2 to 3 weeks, a new dose or different nonsteroidal agent is recommended. In many patients, aspirin, particularly if enteric-coated, is successful and very cost-effective. Disease-modifying antirheumatic drugs (DMARDs) are sometimes being used earlier in disease than previously. Hydroxychloroquine sulfate (Plaquenil Sulfate), auranofin (Ridaura), or sulfasalazine (Azulfidine, S.A.S.-500) is sometimes effective for early rheumatoid arthritis. For patients with more aggressive disease, intramuscular gold is the drug of first choice, and it is the only one that has been shown to decrease the rate of formation of new erosions. Significant toxic reactions occur in 30% to 40% of patients, however. D-penicillamine (Cuprimine, Depen) and azathioprine (Imuran) can be used if intramuscular gold is unsuccessful. Methotrexate (Rheumatrex Dose Pack) is the newest DMARD approved for treatment of rheumatoid arthritis. Its onset of action is rapid, and it is an effective anti-inflammatory agent. Its toxicity in patients with rheumatoid arthritis is not yet fully understood, however. Combination therapy with DMARDs is in its infancy, but such treatment is likely to become more prevalent in the future.     

Theoretical background of effect mechanism by extracorporeal immunomodulation.

Therapeutic plasmapheresis has usually been applied to diseases with unknown causes. Clear analysis of the mechanism of the effect that apheresis has on diseases derived from unknown causes has not been completed. The effect of leukocytapheresis on ulcerative colitis (UC) or rheumatoid arthritis (RA) also lacks clear analysis, but removal of 10(10) adhesive cells resulted in the suppression of both acute and chronic inflammatory reactions. The number of cells removed was not unreasonable for efficacy. A quite acceptable explanation is that the cells activated in the inflammatory lesions are more adhesive than nonactivated cells. However, only a few minutes of contact with the surface of the device can activate blood immune cells. All of the apheresis therapies, not only leukocytapheresis, should be evaluated for their efficacies, excluding the effects of contact activation. According to results presently available, the suppressive effect of leukocytapheresis on RA or UC is through to depend upon the removal of activated inflammation related cells that might transfer inflammatory signals. It may be that those cells removed are bound because of cell stimulation caused by microorganisms or foreign bodies.     

Treatment of early rheumatoid arthritis in developing countries. Biologics or disease-modifying anti-rheumatic drugs?

Biologics are highly effective in the treatment of rheumatoid arthritis (RA), but they are very expensive. The costs of biologics should limit their usage in patients with RA, especially in the developing countries. Therefore, it is necessary to develop suitable strategies for treating RA patients in these countries. In this article, the efficacy, toxicity, and cost-effectiveness of conventional DMARDs and biologics will be investigated. The therapeutic strategies for treating early RA will also be proposed.     

Hemochromatosis: diagnosis and treatment.

What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis.

Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1beta and/or TNFalpha. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO(-)(2) as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO(-)(2) than those from patients with rheumatoid arthritis. In addition, IL-1beta was more potent than TNFalpha in inducing nitric oxide in both arthritides, and TNFalpha alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.     

Selective cyclooxygenase-2 inhibitors for the treatment of arthritis.

The purpose of this paper is to review the rationale for a new class of nonsteroidal anti-inflammatory drugs (NSAIDs) known as selective cyclooxygenase (COX)-2 inhibitors and to present preliminary clinical data on 2 COX-2 inhibitors that are approved for use in the United States. The primary mechanism of NSAIDs in the treatment of inflammation is the inhibition of COX, which exists in 2 forms. COX-I appears to regulate many normal physiologic functions, and COX-2 mediates the inflammatory response. Theoretically, an NSAID that inhibits COX-2 selectively should decrease inflammation but not influence normal physiologic functions and thus should cause fewer gastrointestinal side effects. Preliminary data suggest that celecoxib, a highly selective COX-2 inhibitor, is superior to placebo and similar to traditional NSAIDs in the short-term treatment of pain due to osteoarthritis, although it has been associated with adverse effects such as headache, change in bowel habits, abdominal discomfort, and dizziness. Celecoxib also has been shown to be as effective as traditional NSAIDs in the treatment of rheumatoid arthritis, but it may cause fewer adverse effects, including endoscopically documented ulcers. Celecoxib is metabolized in the liver by the cytochrome P-450 isozyme CYP2C9, and thus serious drug interactions are possible. In the treatment of osteoarthritis, rofecoxib has been shown to be as effective as traditional NSAIDs and may cause fewer endoscopically documented ulcers, but its complete adverse-effect profile is not known. Until the selective COX-2 inhibitors are widely used and more clinical as well as pharmacoeconomic studies are published, the exact role of COX-2 therapy cannot be determined. words: cyclooxygenase, celecoxib, rofecoxib, rheumatoid arthritis, osteoarthritis.     

Physical activity barriers and program preferences among indigent internal medicine patients with arthritis.

The study purpose was to determine, among indigent arthritis patients, physical activity barriers, program preference frequencies and demographic associations. A structured interview of 223 indigent, internal medicine clinic patients with self-reported arthritis was administered in a cross-sectional study design. The two most frequently reported barriers included bad health (52%) and pain (51%). The majority preferred to exercise alone (54%), close to home (76%), and in the early morning/evening (83%). The preferred method of receiving exercise information was by video or audio tape. Frequency of reported barriers was significantly associated with age, ethnicity, and gender; specific program preferences were significantly associated with age and gender only. Exercise programs for indigent patients with arthritis should be home-based with flexible scheduling. Educational material should include both video and audio tape formats. Future interventions should consider barriers related to poor health and pain while remaining responsive to age, gender, and ethnic differences. Nurses can play a pivotal role in such interventions.     

Chlorbutin, azathioprine, D-penicillamine and levamisole (decaris) in the treatment of patients with rheumatoid arthritis. IV. Comparative evaluation of their effects on systemic (extra-articular) manifestations of the disease

The authors studied and compared the action of chlorbutin, azathioprin, of large and mean doses of D-penicillamine and levamisole with that of nonsteroidal antiinflammatory drugs (NAID) on rheumatoid arthritis systemic manifestations in 186 patients treated with these drugs for more than 3 months. It was shown that the basic drug compared very favourably with NAID. The cytostatics and levamisole were discovered to be highly efficacious. The authors believe that if the patients are afflicted with alveolitis and rheumatoid nephropathy, this should be regarded as indication for use of chlorbutin and levamisole.     

Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: a literature review

The aim of this study was to review the research literature on pain and quality of life (QoL) and the relationship between these variables among people aged 75 years and above with rheumatoid arthritis and/or osteoarthritis. A Medline and CINAHL search was carried out using MeSH terms rheumatoid arthritis, osteoarthritis, QoL and pain in various combinations. Seventeen articles were identified that met the requirements for methodological quality and inclusion criteria. No study focused only on respondents aged 75 years or over. The studies had varying representation of this age group. Pain was common in both groups and was found to increase with age and disease duration among those with rheumatoid arthritis but not among those with osteoarthritis. Increased pain could lead to depression. Pain, functional limitation and increased age were found to decrease QoL among those with rheumatoid arthritis and osteoarthritis alike. Social support was found to buffer against negative effects on QoL among those with osteoarthritis while no moderating effects were found in rheumatoid arthritis. Increased age was found to relate to pain (rheumatoid arthritis) and decrease QoL (both rheumatoid arthritis and osteoarthritis). It is, however, hard to draw any firm conclusions about older people's pain and QoL because of the lack of studies including respondents aged 75 years or over. Thus, research about pain and QoL, especially focusing on the old and the very elderly with rheumatoid arthritis/osteoarthritis, is needed. It also seems justified to say that nursing care should especially focus on older people and that these people should be assessed for their level of pain, functional limitations and QoL especially in the case of having rheumatoid arthritis and/or osteoarthritis.     

Complications of cervical arthritis.

Cervical arthritis can result in clinically important complications through a variety of mechanisms. The potentially most serious complication is spinal cord or nerve root compression, caused by either degenerative osteophytes or one or more of several subluxation patterns prevalent in inflammatory joint diseases. Disabling pain arising directly from the affected joints is more difficult to document but probably occurs often in the upper cervical spine, particularly in patients with rheumatoid arthritis. Limitation of head and neck mobility, with or without pain, commonly develops in inflammatory arthropathies, especially ankylosing spondylitis and juvenile rheumatoid arthritis. In the absence of neurologic signs or symptoms, most cases of symptomatic cervical arthritis should be diagnosed and treated conservatively.     

Oral steroids in rheumatoid arthritis. Helpful but not remittive

Although low-dose oral corticosteroid therapy cannot be considered remittive, it has earned a place in the therapeutic armamentarium for rheumatoid arthritis. Major clinical trials of a group using corticosteroid compared with a control group have not been done since the 1950s. One of these three large trials showed some slowing of the destructive joint changes of rheumatoid arthritis with use of low doses of corticosteroid. However, these agents have well-known side effects, especially when used long-term. Elderly patients or those who have features of the disease that indicate progression (eg, multiple joint involvement, elevated ESR, early evidence of erosion on x-ray films) are likely to benefit from carefully controlled doses of a corticosteroid. Because these drugs diminish bone formation and arthritis itself accelerates osteoporosis, supplemental calcium and vitamin D are useful adjuncts. A remittive agent and aspirin-like drug should be prescribed along with the corticosteroid. Abrupt withdrawal of even a very low dose of corticosteroids in rheumatoid arthritis patients causes a flare.