Relapsing polychondritis (RP) is a chronic multisystemic disease characterized by recurrent episodes of cartilage inflammation throughout the body. The lower respiratory tract is involved in 20% to 50% of patients and results in significant morbidity. Effective medical therapies and airway interventions are available in experienced centers; however, no single treatment is curative, and the prognosis of RP with airway disease remains overall guarded.

OBJECTIVE:To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP).METHODS:Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008.RESULTS:RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention.CONCLUSION:In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

PURPOSE:To retrospectively determine the prevalence of expiratory computed tomographic (CT) abnormalities, including malacia and air trapping, in patients with relapsing polychondritis and to retrospectively determine the frequency with which expiratory abnormalities are accompanied by inspiratory abnormalities on CT scans.MATERIALS AND METHODS:Institutional review board approval was obtained, and informed consent was not required for this retrospective HIPAA-compliant study. A computerized hospital information system was used to identify all patients with clinically diagnosed or biopsy-proved relapsing polychondritis who were referred for CT airway imaging during a 17-month period. The study cohort comprised 18 patients (15 women, three men; mean age, 47 years; age range, 20-71 years). Multidetector helical CT was performed in all patients by using a standard protocol, which included end-inspiratory and dynamic expiratory volumetric imaging. Two observers who were blinded to the original scan interpretations simultaneously reviewed CT scans. Findings were recorded in consensus. Dynamic expiratory CT scans were assessed for malacia that involved the trachea and main bronchi (reduction in cross-sectional area of more than 50%) and for air trapping (failure of lung parenchyma to increase in attenuation during expiration). Air trapping was visually classified according to pattern and extent (lobular, segmental, lobar, or whole lung). Inspiratory CT scans were evaluated for tracheal and bronchial stenosis (>25% luminal diameter narrowing compared with a corresponding uninvolved segment), wall thickening (>2 mm), and calcification.RESULTS:Expiratory CT abnormalities were present in 17 (94%) of 18 patients and included malacia in 13 patients (72%) and air trapping in 17 patients (94%). Inspiratory CT abnormalities were found in eight (47%) of 17 patients who had expiratory CT abnormalities. Calcification of the airway walls was present in seven (39%) of 18 patients. All patients who had inspiratory CT abnormalities demonstrated expiratory CT abnormalities.CONCLUSION:Expiratory CT abnormalities were present in the majority of patients with relapsing polychondritis who were referred for airway imaging, yet only half of these patients demonstrated abnormalities on routine inspiratory CT scans. Thus, dynamic expiratory CT should be a standard component of imaging assessment in patients with relapsing polychondritis.

PURPOSE: Relapsing polychondritis (RP) is a rare systemic inflammatory disease affecting cartilaginous structures. The most severe complications involve the tracheobronchial tree and the cardinal symptoms include dyspnea and cough. Life-threatening upper airway obstruction occurs when critical narrowing occurs. Due to rarity of the disease, specific airway complications from RP have not been well described. This study examines the types of airway pathologies in patient with RP.

Objective. Oral administration of cartilagederived type I1 collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA. Methods. Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20,100,500, or 2,500 &day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed

The intent of this study was to compare, in a monotherapy framework, an optimal dose of the synthetic hexose sugar, amiprilose hydrochloride (HCl), to a placebo in the treatment of rheumatoid arthritis. In this double-blind, randomized, multi-center study, patients first underwent a washout period from disease-modifying antirheumatic drugs. Those who subsequently met flare criteria within 14 days of discontinuing previously stable doses of nonsteroidal anti-inflammatory drugs were randomized to amiprilose HCl (103 patients) or a placebo (115 patients) for the subsequent 20 weeks. Glucocorticoid or nonsteroidal anti-inflammatory drugs use was not permitted. At the baseline, demographic and disease characteristics were similar in both groups. Of patients completing the course of therapy, 73% were in the amiprilose HCl group and 66% were in the placebo group. Using an intent-to-treat analysis, numeric trends favoring amiprilose HCl treatment were found for clinical and laboratory parameters of disease activity. Compared with the placebo group, statistically significant degrees of improvement were achieved for the number of swollen joints (p = 0.04), number of patients who experienced a >/= \50% reduction in swollen joints (p = 0.04), number who improved by the Paulus composite score criteria (p = 0.02), improvement in the frequency distribution in Functional Class (p = 0.01), and improvement in the mean erythrocyte sedimentation rate (p = 0.03). Significant worsening in the duration of morning stiffness (p = 0.05) and in 4 of the 5 items in the clinical health assessment questionnaire (p = 0.004) occurred in the placebo but not in the amiprilose HCl group. No side effects clearly attributable to the drug were noted. This study provides an independent confirmation that the novel and nontoxic carbohydrate, amiprilose HCl, provides an effective approach to the treatment of rheumatoid arthritis. The Food and Drug Administration will now consider whether it should be approved for this indication.

OBJECTIVE:Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA.METHODS:Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite criteria: the Paulus criteria, the American College of Rheumatology criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts.RESULTS:Eighty-three percent of patients completed 24 weeks of treatment. Numeric trends in favor of the 20 microg/day treatment group were seen with all 3 cumulative composite measures. However, a statistically significant increase (P = 0.035) in response rate for the 20 microg/day group versus placebo was detected using only the Paulus criteria. The presence of serum antibodies to CII at baseline was significantly associated with an increased likelihood of responding to treatment. No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells.CONCLUSION:Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.

The basic science immunology community is quite accepting of the phenomenon of oral tolerance induction in animals; however, in contradistinction, the clinical community is somewhat agnostic regarding oral tolerance. Progress in multiple sclerosis has not been definitive and outcomes in RA have been modest at best. Recent reports in animal models have suggested that oral ingestion of autoantigen can have deleterious effects on the host. Although those experiments have had a highly artificial framework, they are consistent with the possibility that oral antigen therapy in human disease may be: (1) beneficial; (2) of no consequence; or (3) detrimental. An extremely open mind will hopefully be applied to future research efforts.

Based on its efficacy in rheumatoid arthritis 1 Minocycline in rheumatoid arthritis: a 48-week, double-blind, placebo-controlled trial. Ann Intern Med. 1995; 122: 81-89 Crossref PubMed Scopus (319) Google Scholar and anecdotal evidence, we did an open trial of minocycline in early diffuse scleroderma. Patients satisfied criteria for the diagnosis of scleroderma 2 Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria CommitteePreliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980; 30: 581-590 Google Scholar and did not have additional rheumatic disease. Inclusion criteria were clinical systemic sclerosis on the extremities proximal to the elbow and knee and on the trunk below the clavicles, and disease duration of 3 years or less from the onset of the first symptoms, including Raynaud's phenomenon, as determined by the patient's rheumatologist. Exclusion criteria included internal-organ damage.

Relapsing polychondritis, an uncommon, chronic, multisystem disorder characterized by recurrent episodes of inflammation of cartilaginous tissues, can be life-threatening, debilitating, and difficult to diagnose. This review is based on the authors' experience with 36 patients with relapsing polychondritis who were followed from 1980 to 1997, 30 patients located elsewhere who completed a detailed questionnaire and interview, and a perusal of English-language textbooks and papers located by a systematic search of the MEDLINE database. Relapsing polychondritis can present in a highly ambiguous fashion; therefore, in the authors' series, the mean delay from the time medical attention was sought because of symptom onset until diagnosis was 2.9 years. Although prednisone was the main form of treatment, methotrexate seemed to be of additional value. Survival was much more favorable than previously thought. Greater awareness of relapsing polychondritis would probably lead to earlier diagnosis and better outcomes.

OBJECTIVE:To (1) validate the Short-Form Health Survey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis (RA); and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS:We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter, placebo controlled, double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures. RESULTS:In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were most highly correlated (r = 0.58 and 0.66; p < 0.01, respectively) with the SF-36 bodily pain item. CONCLUSION:The SF-36 is a valid instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies.

Objective. To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial.Methods. A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and finer visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease.Results. Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 place bo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference.Conclusion. Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted ''newly involved'' joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.

OBJECTIVE:To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design.METHODS:Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores). These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment). The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available.RESULTS:Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004). Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate. Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group. Study design considerations indicated that application of the ACR criteria would reduce the required sample size.CONCLUSION:Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets. These findings support the use of the ACR criteria for defining improvement in RA clinical trials.

Annals of the New York Academy of SciencesVolume 778, Issue 1 p. 306-314 Evidence That Type II Collagen Feeding Can Induce a Durable Therapeutic Response in Some Patients with Rheumatoid Arthritis DAVID E. TRENTHAM, DAVID E. TRENTHAM Division of Rheumatology Beth Israel Hospital and Harvard Medical School 330 Brookline Avenue Boston, Massachusetts 02115Search for more papers by this author DAVID E. TRENTHAM, DAVID E. TRENTHAM Division of Rheumatology Beth Israel Hospital and Harvard Medical School 330 Brookline Avenue Boston, Massachusetts 02115Search for more papers by this author First published: February 1996 https://doi.org/10.1111/j.1749-6632.1996.tb21138.xCitations: 13AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume778, Issue1Oral Tolerance: Mechanisms and ApplicationsFebruary 1996Pages 306-314 RelatedInformation

OBJECTIVE:To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS:Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS:At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION:HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.