RUBELLA ARTHRITIS—A Study of Twenty Cases

Twenty patients, five males and fifteen females, who had rubella arthritis were observed for periods ranging from one to ten years after recovery.Rubella arthritis in these patients was characterized by polyarthritis associated with fibrositis, myalgia, paresthesias and muscular weakness. All of the male patients but only one-third of the females had involvement of the knee joints. The small joints of the hands were the joints most commonly affected in women. Post-rubella arthritis rheumatic symptoms, especially fibrositis, persisted for many months in almost half of the females, not at all in the males.The leukocyte content of the blood tended to be low and the erythrocyte sedimentation rate accelerated in the few patients in which determinations were done.Latex tests were performed in 17 patients. Ten of the 17 were studied with the three-stage technique of Hall. Results of inhibition tests were positive in 80 per cent of the patients with rubella arthritis studied who were tested within 18 months after the onset of illness. None of the patients tested 18 months or more after rubella arthritis had positive reaction.     

The arthropathy of maintenance intermittent peritoneal dialysis.

Among 61 patients undergoing maintenance peritoneal dialysis for an average of 20 months, 13 (21%) had a history of attacks of acute arthritis and 19 (31%) were found to have tender and often swollen joints. Deposits of calcium pyrophosphate dihydrate crystals in articular cartilage were identified in four patients and inflammation probably induced by hydroxyapatite crystals was noted in one. Periarticular calcification was observed in 12 patients and subperiosteal resorption of the phalanges in 20. The average calcium X phosphorus product was significantly higher (P < 0.025) in patients with a history of attacks of acute arthritis or with inflamed joints (58 +/- 12) than in those without (50 +/- 12). In the 19 patients whose treatment was changed to continuous ambulatory peritoneal dialysis there was a significant decrease (P < 0.025) in the calcium X phosphorus product but not in the proportion of patients with attacks of acute arthritis or with inflamed joints. The results indicate that articular complications are frequent among patients undergoing maintenance peritoneal dialysis and may be more common than with long-term hemodialysis.     

Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study.

OBJECTIVE--To find out whether a 10-14 days'' course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics. DESIGN--Prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics. Patients were seen at three and six weeks and three, six, nine, 12, and 18 months after their first visit. SETTING--Departments of infectious diseases in three hospitals in Linköping, Malmö, and Stockholm, Sweden. PATIENTS--40 Consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks. INTERVENTIONS--20 Patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics. All patients received non-steroidal anti-inflammatory drugs, and four also received intra-articular steroid injections after at least six weeks'' observation. MAIN OUTCOME MEASURES--Arthritic symptoms assessed clinically and by using Ritchies'' index; blood measurements reflecting inflammatory activity; serum IgG, IgM, and IgA antibody titres; HLA tissue type. RESULTS--No difference was observed concerning duration of arthritis, grade of inflammation, and number of joints affected between patients treated and those not treated with antibiotics. Furthermore, there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin, IgG, and IgA concentrations. All values had returned to normal within three months. No patient developed chronic arthritis, but sustained slight arthralgia occurred in three patients. The HLA-B27 antigen was found in 23 (58%) of the patients, and its presence did not affect clinical outcome. The IgG, IgM, and IgA antibody responses were similar in patients treated with antibiotics and those not treated. CONCLUSION--Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection.     

Psoriatic arthritis in a fifth-century Judean Desert monastery

Psoriatic arthritis is a greatly underreported seronegative erosive arthropathy, due to the ambiguous lesions it leaves on bone in all but the most severe cases. For a confident diagnosis of psoriatic arthritis to be made, sacroiliac and intervertebral joint fusion must be present together with erosive lesions of the peripheral skeleton including most especially the terminal interphalangeal joints. In modern times it is only a small percentage of cases who experience such debilitating disease, which may explain who so few cases of psoriatic arthritis can confidently be identified from past populations. This report describes this pathological condition as observed in the comingled skeletal remains of nine males and one female from the tomb of Paulus in the Byzantine Monastery of Martyrius, in the Judean Desert. Visual study was complemented using radiographic techniques along with scanning electron microscopy. Two adult males show characteristic lesions of psoriatic arthritis, demonstrating the form known as arthritis mutilans. A third individual shows less widespread erosive lesions which may signify a pauciarticular example of psoriatic arthritis, as is true of most cases in modern times, or the remains may represent Reiter's disease. During the Byzantine period the earlier practise of expelling those with disfiguring diseases (biblical leprosy) evolved into a philanthropic, caring philosophy where the sick were housed and fed out of charity, often within monasteries. The presence of these cases of psoriatic arthritis within such a Judean Desert monastery confirms earlier suggestions that psoriasis was one of the diseases included by those in the ancient eastern Mediterranean under the umbrella term of biblical leprosy. © 1996 Wiley-Liss, Inc.     

Liver in Leprosy: Histological and Biochemical Findings

The histological findings and their correlation with biochemical functions of the liver in 240 leprosy patients are presented. In 21% with tuberculoid leprosy and in 62% with lepromatous leprosy leprous granulomata were found in the liver. A significant prevalence of granulomatous lesions in the liver among patients with tuberculoid and borderline-tuberculoid leprosy of less than one year''s duration suggests that bacillaemia occurs early in all forms of leprosy.There was a direct correlation between bacterial index and the presence of acid-fast bacilli in the liver. Of 50 patients with negative skin smears seven had acid-fast bacilli at liver biopsy. From none of these liver homogenates were acid-fast bacilli grown on culture in Löwenstein-Jensen medium.The alterations in liver functions were more consistently seen when acid-fast bacilli were associated with the presence of leprous granulomatous lesions. The acid-fast bacilli were found to persist even after one to five years of specific antileprosy therapy and after the bacilli in the skin had cleared up. This may explain the relatively frequent recrudescence or relapse of the bacillated types of leprosy when specific antileprosy therapy is stopped soon after bacterial negativity is attained on skin smears.     

Cytology of testicular changes in leprosy

OBJECTIVE: To study the changes in testicular aspirates and semen of patients with leprosy. STUDY DESIGN: A prospective study of 56 patients in the reproductive-age group, with no record of treatment for leprosy. Both Ridley-Jopling and WHO classification systems were used. Skin and/or nerve biopsies were performed for documentation of the diagnosis. Semen analysis and fine needle aspirates of the testes were performed. Smears from the testicular aspirates were stained with May-Grünwald-Giemsa and Ziehl-Neelsen stain. RESULTS: Five patients were unable to produce an ejaculate. Abnormal semen analysis and/or testicular aspirates were seen in 24 (42.8%) patients. Eleven had oligospermia and eight azoospermia. Abnormalities in testicular aspirates ranged from hypospermatogenesis (4) through maturation arrest (1) and atrophy (11). Two patients had hydrocoele, and two had associated microfilariae. Three patients with multibacillary leprosy had type 2 reaction. Mycobacterium lepre was demonstrable in testicular aspirates from all patients with multibacillary and in three with paucibacillary leprosy. CONCLUSION: Abnormal semen analysis and/or testicular aspirates occur in a very high percentage of patients with leprosy. While this is expected for multibacillary disease, the high incidence in the paucibacillary form was surprising. With the rapid elimination of leprosy, fertility-related disability might emerge as a major problem in these people.     

Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of febrile peritonitis, pleuritis and synovitis. Arthritis is a common and important feature of FMF. The clinical spectrum of arthritis in 71 FMF patients was retrospectively investigated. Mutations in the familial Mediterranean (MEFV) gene were screened. Unlike the previous reports on arthritis of FMF, most of the FMF patients (59%) in this study had symmetric two-joint arthritis whereas monoarticular, oligoarticular and polyarticular arthritis was presented in 20, 8 and 10% of the patients, respectively. Knees were affected in 45 (63%) patients, ankles in 30 (42%), elbows in 11 (15%), wrists in 12 (17%), hips in 12 (17%), small joints of the hands 7 (10%), small joints of the feet 2 (3%) and sacroiliac in 1 (1%). Destruction of the hip was observed in 2 (3%) patients and required hip replacement. Amyloidosis developed in 2 (3%) of our patients. Mutations in the MEFV gene were identified in 50 (71%) patients and the most dominant mutation detected was M694V (64%). Since FMF can be diagnosed by a simple DNA mutation analysis, all arthritis patients of certain origins (Arabs, Turks, Armenians and Jews) should be tested for FMF in order to prevent the complications (amyloidosis and protracted arthritis) by introducing colchicine which is the treatment of choice for FMF.     

A new side effect of BCG immunotherapy — BCG-induced arthritis in man

Summary Ten of 159 patients showed arthritic symptoms during the course of BCG immunotherapy for advanced cancer. The arthritic symptoms occurring after BCG injections had the following characteristics: (1) The incidence of arthritis was closely correlated with the host immunologic responsiveness to BCG; (2) These symptoms usually occurred 1–5 months after the first BCG injection (7/10); (3) The arthritic symptoms usually started with morning stiffness (9/10), which was followed by acute inflammatory signs in the affected joints. They gradually subsided in response to treatment with nonsteroid antiinflammatory drugs, but were not completely cured while the effectiveness of BCG continued; (4) The symptoms were aggravated by additional BCG injections (8/10). (5) This form of arthritis could be differentiated from rheumatoid arthritis, tuberculous, or purulent arthritis by its clinical course and by roentgenograms of the affected joints. It is thought to be induced by the adjuvant effect of BCG, and is a new side effect of BCG immunotherapy.     

Rheumatoid Disease in Children

Data relative to 102 patients seen between 1940 and 1960 with infantile rheumatoid arthritis were analyzed. The systemic nature of the disease and variable early clinical picture make early diagnosis very difficult. Only 20% had articular symptoms at the onset. The youngest was aged 6 months and there was a greater incidence of onset in the first two years of life. Particular attention was paid to the site of original joint involvement as compared with the subsequent final joint pathology. Spindle fingers or swollen proximal interphalangeal joints appear late in the disease but are usually diagnostic of infantile rheumatoid arthritis. Diagnosis is essentially a clinical one; laboratory tests are of little diagnostic value. Prognosis is related to the age of onset, on institution of therapy, and systemic manifestations. Of these patients 50% were functionally normal at the time of follow-up, 25% had mild residual disability and 25% were severely crippled.     

Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis

Tumour necrosis factor (TNF)-alpha plays a key role in the pathogenesis of rheumatoid arthritis (RA). It binds to two receptors, namely TNF receptor (TNFR)I and TNFRII. Several studies have suggested an association between TNFRII 196R/R genotype and RA. The objective of the present study was to evaluate the predictive value of the TNFRII 196R allele for RA diagnosis and prognosis in a cohort of patients with very early arthritis. We followed up a total of 278 patients recruited from the community, who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for less than 6 months, and who had not received disease-modifying antirheumatic drugs or steroid therapy. At 2 years, patients were classified according to the American College of Rheumatology criteria. All patients were genotyped with respect to TNFRII 196M/R polymorphism. Radiographs of hands and feet (read according to the modified Sharp method) and the Health Assessment Questionnaire were used to quantify structural and functional severity. The cohort of 278 patients was found to include 156 and 122 RA and non-RA patients, respectively. The TNFRII 196R allele was found to be associated with RA (P = 0.002). However, progression of radiographic severity and Health Assessment Questionnaire scores over 1 year did not differ between carriers of the 196R allele and noncarriers. Our findings suggest that the TNFRII 196R allele may be associated with RA diagnosis but that it does not predict early radiographic progression or functional severity in patients with very early, unclassified arthritis.     

Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai

Background

Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.

Methodology/Principal Findings

Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.

Conclusions/Significance

One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.     

Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity

A cross-sectional clinical trial in which the serum anti-phenolic glycolipid (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients with leprosy as an adjunct early leprosy diagnostic marker was conducted. The families of 83 patients underwent clinical examination and serum anti-PGL1 measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28 were contacts of borderline (BB) leprosy, 54 were contacts of borderline tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of indeterminate (I) leprosy. Consanguinity with the patients was determined for 232 (72.5%) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC had collateral consanguinity. Fifty-eight contacts (18.1%) tested positive for anti-PGL1 antibodies. The number of seropositive contacts based on the clinical forms of the index case was 17 (29.3%) for LL, 15 (25.9%) for BL, one (1.7%) for BB, 14 (24.1%) for BT, three (5.2%) for TT and eight (13.7%) for I. At the one year follow-up, two (3.4%) of these seropositive contacts had developed BT leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM antibody may be useful for evaluating antigen exposure and as a tool for an early leprosy diagnosis in HHC.     

Evaluation of related with age of IFN-gamma levels of treated leprosy patients and their healthy relatives compared with a control group

OBJECTIVE: This study was to search how change with age of IFN-gamma (IFN-gamma) levels of leprosy patients who had received or still undergoing treatment, their healthy close relatives and healthy people. METHOD: From a total of 39 patients, 28 had received leprosy treatment and recovered with some defects [17 Lepromatous Leprosy(LL), 7 Borderline Lepromatous (BL), 3 Borderlien Tuberculoid (BT), 1 Tuberculoid form (TT)] and 11 (9 LL, 2 BL) were undergoing therapy in a hospital at that moment. Close relatives of the patients included 39 people living with treated patients in the same house and the control group consisted of 39 healthy people. Human IFN-gamma kits were used as a solid phase sandwich ELISA method. RESULTS: The IFN-gamma values of treated leprosy patients, therapy receiving patients, relatives group's and control group's were detected as 11-20 pg/mL, 11-18 pg/mL, 12-145 pg/mL and 12-65 pg/mL respectively. CONCLUSION: According to the statistical evaluation of these three groups, IFN-gamma levels of patients were detected lower than other two groups. According to the age, if IFN-gamma levels were compared, it was detected that significant relationship between relatives groups and interferon gamma levels.     

Ultrasonography of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis: a comparison with magnetic resonance imaging, conventional radiography and clinical examination

Signs of inflammation and destruction in the finger joints are the principal features of rheumatoid arthritis (RA). There are few studies assessing the sensitivity and specificity of ultrasonography in detecting these signs. The objective of the present study was to investigate whether ultrasonography can provide information on signs of inflammation and destruction in RA finger joints that are not available with conventional radiography and clinical examination, and comparable to the information provided by magnetic resonance imaging (MRI). The second to fifth metacarpophalangeal and proximal interphalangeal joints of 40 RA patients and 20 control persons were assessed with ultrasonography, clinical examination, radiography and MRI. With MRI as the reference method, the sensitivity, specificity and accuracy of ultrasonography in detecting bone erosions in the finger joints were 0.59, 0.98 and 0.96, respectively; they were 0.42, 0.99 and 0.95 for radiography. The sensitivity, specificity and accuracy of ultrasonography, with signs of inflammation on T1-weighted MRI sequences as the reference method, were 0.70, 0.78 and 0.76, respectively; they were 0.40, 0.85 and 0.72 for the clinical examination. With MRI as the reference method, ultrasonography had higher sensitivity and accuracy in detecting signs of inflammation and destruction in RA finger joints than did clinical and radiographic examinations, without loss of specificity. This study shows that ultrasonography has the potential to improve assessment of patients with RA.     

Diagnostic utility of musculoskeletal ultrasound in patients with suspected arthritis – a probabilistic approach

Introduction

This study aimed to assess the utility of musculoskeletal ultrasound (MSUS) in patients with joint symptoms using a probabilistic approach.

Methods

One hundred and three patients without prior rheumatologic diagnosis and referred to our clinic for evaluation of inflammatory arthritis were included. Patients were assessed clinically including joint examination, laboratory testing including acute-phase reactants, rheumatoid factor (RF) and anti citrulinated protein antibody (ACPA), and radiographs of hands and feet if clinically indicated. A diagnostic assessment was then performed by the responsible rheumatologist where the probability of a) any inflammatory arthritis and b) rheumatoid arthritis was given on a 5-point scale ranging from 0 to 20% up to 80 to 100% probability. Subsequently, an ultrasound examination of the wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP) joints 2 to 5 in both hands, metatarsophalangeal (MTP) joints 2 to 5 in both feet and any symptomatic joints was performed and the results presented to the same rheumatologist. The latter then assessed the diagnostic probabilities again, using the same scale.

Results

The rheumatologists’ certainty for presence/absence of inflammatory arthritis and rheumatoid arthritis was increased significantly following ultrasound performance. The proportion of patient for whom diagnostic certainty for inflammatory arthritis was maximal was 33.0% before and 71.8% after musculoskeletal ultrasound (P <0.001). With regard to a diagnosis of RA, the proportions were 31.1% pre-test and 61.2% post-test (P <0.001). MSUS findings agreed with the final diagnosis in 95% of patients.

Conclusion

Musculoskeletal ultrasound, when added to routine rheumatologic investigation, greatly increases the diagnostic certainty in patients referred for the evaluation of inflammatory arthritis. The changes from pre-test to post-test probability quantify the diagnostic utility of musculoskeletal ultrasound in probabilistic terms.     

Factors Contributing to the Delay in Diagnosis and Continued Transmission of Leprosy in Brazil – An Explorative,Quantitative, Questionnaire Based Study

BackgroundLeprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil.

Methodology/ Principal Findings

This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010).

Conclusions/ Significance

This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable.     

Low-field magnetic resonance imaging study on carpal arthritis in systemic sclerosis - low-grade erosive arthritis of carpal bones is an unexpected and frequent disease manifestation

Introduction

The aim of the present study was to assess the prevalence and characteristics of subclinical arthritis of carpal and metacarpophalangeal joints in patients with systemic sclerosis (SSc).

Methods

Low-field (0.2 T) magnetic resonance imaging (MRI) was performed in consecutive patients with SSc attending our center between January 2010 and March 2011. Results were assessed in a standardized manner using the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) and standardized assessments of all hand joints. Patients with arthritis due to overlap syndromes were excluded.

Results

Of 38 inpatients and eight outpatients who were screened for inclusion, 30 patients participated in the study and 26 patients could be evaluated. Erosions, bone marrow edema, synovitis, and joint effusions were found in 87%, 37%, 68%, and 58%, respectively, and 24% of patients had additional tenovaginitis. Arthritis affected only a low number of joints per analyzed hand. All bones and joints could be affected, but synovitis and bone marrow edema occurred predominantly in the proximal row of carpal bones, most frequently affecting the lunate bone. The extent of inflammatory changes measured with the RAMRIS correlated significantly with the functional status assessed with the validated German functional score questionnaire Funktionsfragebogen Hannover.

Conclusion

Low-grade arthritic changes on low-field MRI are frequent in patients with pure SSc. The features of arthritis in SSc differ from rheumatoid arthritis. The distribution, the MRI pattern and the predilection for the lunate bone raise the hypothesis that arthritis in SSc may be caused not only by immunological inflammation but also by ischemic mechanisms.     

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.     

The M20 IL-1 inhibitor prevents onset of adjuvant arthritis

Cytokines, specifically IL-1 and TNF, have been implicated as important mediators of joint destruction in rheumatoid arthritis (RA). Elevated levels of IL-1 in the joint fluid of patients with RA have been reported, as well as the presence of IL-1 inhibitory activity. We have reported the characterization of an inhibitor derived from a myelomonocytic cell line cloned in our laboratory which is specific for IL-1. This IL-1 inhibitor is protein in nature which specifically inhibits activityin vitro andin vivo. Previous studies showed that the inhibitor reduced acute inflammatory reactions associated with IL-1 (fever, leukocytosis, local foot pad swelling, lymph node enlargement and acute phase reactants). Thus it was of interest to study whether the M20 IL-1 inhibitor could modify adjuvant-induced chronic inflammation in rats, which is often used as a model for human RA. Administration of complete Freund's adjuvant (CFA) into Lewis rats, resulted in a severe adjuvant arthritis (AA) which reached peak severity after 14 days. Daily administration of IL-1 inhibitor, beginning after injection of CFA, abolished the appearance of AA. The parameters investigated were: joint swelling (the increase in diameter of joints), peri-articular erythema, limping of the rats and histological examination. The effect of the M20 IL-1 inhibitor was shown to be dose dependent and the IL-1 inhibitor alone had no adverse effects. These results indicate that the M20 IL-1 inhibitor may have a role in the treatment of AA and may be used to reduce pathological processes in joint inflammation.