Objective. Systemic sclerosis (SSc) has a female predominance, however, little is understood about the effect of sex on SSc manifestations and survival. The objectives of our study were to evaluate differences in disease manifestations, and survival rates between males and females with SSc.Methods. A retrospective cohort study of the Toronto Scleroderma Program was conducted to evaluate sex- based differences in disease manifestations and survival. A relative survival analysis compared SSc survival to the general population.Results. There were 959 patients (791 females, 168 males) identified, with a female: male ratio of 4.7: 1. Males more frequently had diffuse SSc [45% vs 30%, relative risk (RR) 1.44, 95% CI 1.18- 1.75] and interstitial lung disease (ILD; 41% vs 33%, RR 1.24, 95% CI 1.01- 1.52). There were 324 deaths (65 males, 259 females). Males had increased unadjusted mortality compared to females (HR 1.57, 95% CI 1.19- 2.06). In an adjusted model including immunosuppressive use, male sex (HR 1.40, 95% CI 1.06- 1.85), ILD (HR 1.58, 95% CI 1.26- 1.98), and older age at diagnosis (HR 1.05, 95% CI 1.04- 1.06) were independently associated with increased mortality, whereas the limited subtype (HR 0.70, 95% CI 0.49- 0.77) and anticentromere antibodies (HR 0.70, 95% CI 0.49- 0.98) were independently associated with decreased mortality. Male sex was associated with increased risk of mortality (HR 1.16, p = 0.003) in patients with SSc above that observed for males in the general population.Conclusion. The differential effect of disease between sexes is small, yet males have decreased survival compared to females with SSc.

OBJECTIVE:Warfarin is recommended in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and idiopathic PAH (IPAH) to improve survival. There is no evidence to support this in SSc-PAH and the evidence in IPAH is conflicting. We evaluated the ability of warfarin to improve survival using 2 large SSc-PAH and IPAH cohorts.METHODS:The effect of warfarin on all-cause mortality was evaluated. Bayesian propensity scores (PS) were used to adjust for baseline differences between patients exposed and not exposed to warfarin, and to assemble a matched cohort. Bayesian Cox proportional hazards models were constructed using informative priors based on international PAH expert elicitation.RESULTS:Review of 1138 charts identified 275 patients with SSc-PAH (n = 78; 28% treated with warfarin) and 155 patients with IPAH (n = 91; 59% treated with warfarin). Baseline differences in PAH severity and medications were resolved using PS matching. In the matched cohort of 98 patients with SSc-PAH (49 treated with warfarin), the posterior median hazard ratio (HR) was 1.06 [95% credible interval (CrI) 0.70, 1.63]. In the matched cohort of 66 patients with IPAH (33 treated with warfarin), the posterior median HR was 1.07 (95% CrI 0.57, 1.98). The probability that warfarin improves median survival by 6 months or more is 23.5% in SSc-PAH and 27.7% in IPAH. Conversely, there is a > 70% probability that warfarin provides no significant benefit or is harmful.CONCLUSION:There is a low probability that warfarin improves survival in SSc-PAH and IPAH. Given the availability of other PAH therapies with demonstrable benefits, there is little reason to use warfarin to improve survival for these patients.

Objective. To assess the effect of gastrointestinal (GI) manifestation on the quality of life in patients with systemic sclerosis (SSc). Methods. The University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2 questionnaire was completed by 87 consecutive patients with SSc attending the scleroderma clinic at a single center. Their clinical features and current therapies were recorded; 100 patients with rheumatologic disorders other than SSc were used as controls. Individual scores were compared between SSc and controls, and between SSc subgroups. Results. Of 87 patients, 76 (90%) were women. Median age was 55 years and disease duration 105 months. Thirty-three (38%) had diffuse and 54 (62%) had limited SSc. Patients with SSc had a higher score than controls in all domains (p < 0.05). Numbers of patients who responded positively to individual questionnaire components are as follows: any GI symptom 86 (99%), reflux 77 (89%), distension 73 (84%), soilage 19 (22%), diarrhea 44 (51%), constipation 51 (59%), well-being 43 (49%), and social 43 (49%). There was no difference between the scores of patients with diffuse and limited disease subtypes. The use of calcium channel blockers did not significantly increase the constipation score (p = 0.99). Patients who responded positively to the reflux, distension, diarrhea, and constipation domains had lower scores in the well-being and social domains. Conclusion. GI manifestations, especially fecal incontinence (affecting 22% of patients), have a negative influence on the quality of life of patients with SSc. There was no difference between SSc disease subtypes.

The aim of the study was to describe the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in systemic sclerosis (SSc) patients. SSc patients who developed biopsy-proven AAV were identified. Their clinical manifestations, autoantibodies, presentation with vasculitis, treatment and outcome were described and compared with previously reported patients with these two conditions. Of 985 patients, 3 were identified. All patients had interstitial lung disease, and all presented with acute renal failure, proteinuria and hematuria, and were P-ANCA- and anti-Scl-70-positive. One required hemodialysis. Two were hypertensive; additionally, one patient had sinusitis, and another had monoarthritis and a macular rash. All were treated with high-dose corticosteroids and responded to therapy and attained remission at 6 months. At 1 year, one patient died of pneumonia. ANCA-associated vasculitis is a rare but serious finding in SSc patients. Positive anti-Scl-70 antibody is found commonly in these patients. Different treatment modalities are effective. Serious infections can complicate therapy and lead to death.

To the Editor: Anti-tumor necrosis factor-α (anti-TNF) therapy is a frequent therapeutic modality in patients with autoimmune disease. There is increased recognition that these agents may cause various inflammatory demyelinating neuropathies. We describe a 36-year-old man with Crohn's disease who developed multifocal motor neuropathy with conduction block (MMNCB) after treatment with infliximab. He was diagnosed in 1997 with severe fistulizing Crohn's disease. He was started on infliximab in hospital in February 2000 as he had not responded to treatment with azathioprine, metronidazole, and ciprofloxacin. He had 2 further infusions of infliximab in April and May 2000. On May 30, 2000, he underwent ileocolic resection. Preoperatively he reported mild hand numbness; postoperatively he developed progressive bilateral weakness of his wrists, finger extensors, and interossei as well as marked weakness in the extensors of his toes and moderate weakness of his ankle dorsiflexors. Sensation was preserved. Nerve conduction studies revealed mildly delayed ulnar F-wave latency at 32.7 ms. The remainder of the study was normal. Conduction block was not found. Electromyography revealed reduced recruitment in muscles of the upper and lower extremity, with fibrillation potentials and positive sharp waves identified in tibialis anterior, medial gastrocnemius, extensor digitorum, and first dorsal interosseus. The electrophysiological diagnosis was a motor neuropathy … Address correspondence to Dr. Barber. E-mail: claire.barber{at}utoronto.ca

To the Editor: Scleredema, originally described by Buschke in 19021, is a rare sclerodermatosis of unknown etiology, characterized by nonpitting induration of the skin. In general, scleredema first affects the face and neck, and then may spread symmetrically to the shoulders, trunk, arms, and legs. Cardiac and other organ involvement is rare but restrictive lung disease can be a manifestation. Three clinical groups of scleredema have been described by Graff2. In the first group, the disease starts abruptly after an acute upper respiratory tract infection, often with streptococcal pyogenes and having a tendency to resolve after a period of months to years. The second group begins insidiously without a preceding respiratory tract infection, is of longer duration, and persisting over a period of several years. The third group, known as scleredema diabeticorum (SD), is a chronic form of scleredema associated with severe, often complicated, diabetes mellitus (DM). SD is characterized by an insidious onset of skin thickening, occurring diffusely over the posterior neck and upper back and occasionally extending to the deltoid and lumbar regions (Figure 1)3. It has been reported to occur in 2.5% to 14% of all patients with diabetes. Although numerous treatments have been tried, none have been reported to be effective. We describe 2 cases of SD that showed marked clinical regression following treatment with tamoxifen (tamoxifen citrate). Figure 1. Skin thickening and hyperpigmentation on the back and extending forward to involve the shoulders and chest in a patient with scleredema diabeticorum not treated with tamoxifen. A 61-year-old Chinese woman presented to our Scleroderma Clinic in April 2002 with a 2-year history of progressive skin thickening involving her back, chest, and shoulders but sparing her extremities. There was tightness of her chest with restricted movement of her shoulders, especially with reaching … Address correspondence to Dr. S. AlSaeedi, Mount Sinai Hospital, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, 60 Murray Street, Box 9, Rm 2-004, Toronto, Ontario M5T 3L9, Canada. E-mail: sa2005saa{at}hotmail.com

Study ObjectivesTo report the clinical, imaging, and pathologic manifestations of case series of patients in whom the only systemic expression of relapsing polychondritis (RP) was their airway complications. DesignRetrospective review of the medical records of all patients with respiratory complications of RP between 1995 and 2007. SettingTertiary care, university-affiliated hospital. ResultsThree patients with RP had just lower airway manifestations as the only sign of their RP. All 3 were women, aged 44, 49, and 54 years. All had an abnormal chest computed tomography scan, although 2 had a completely normal chest x-ray. All had positive tracheal biopsy, which was consistent with the diagnosis of respiratory chondritis. Pulmonary function tests showed severe reduction in forced expiratory volume in 1 second in all patients. Bronchoscopy revealed tracheal narrowing with variable degrees of inflammation and collapsibility in all patients. Two of the 3 patients underwent tracheal and bronchial stent insertion. Pharmacotherapy included prednisone, methotrexate, cyclophosphamide, and leflunomide. The overall outcome was poor. Two patients died as a result of respiratory complications, 25 and 30 months from diagnoses, and 1 is still alive with follow-up of 85 months after presentation. ConclusionsLower airway manifestations of RP can be the only sign of the disease. RP has to be considered in the differential diagnosis of patients with recent onset of progressive dyspnea and severe airflow limitation even without other systemic signs of cartilage damage.

Objective. To investigate ethnic influence on disease manifestations and autoantibody profile in patients of Chinese descent with systemic sclerosis (SSc). Methods. In a retrospective study of a multiethnic SSc cohort followed over a 17-year period, disease manifestations and autoantibody profile of patients of European and Chinese descent were compared. Results. There were 300 patients of European descent and 36 of Chinese descent, with similar proportions of women (81% and 72%, respectively) and patients with diffuse SSc (50% and 56%). Patients of Chinese descent [mean age ± standard deviation (SD) 52 ± 16 yrs; p = 0.05] were diagnosed at an older age compared to patients of European descent (mean ± SD 46 ± 12 yrs). Patients of Chinese descent compared to those of European descent had less frequent joint (69% vs 86%; p = 0.01) and gastrointestinal involvement (78% vs 94%; p = 0.004), but increased prevalence of myositis (17% vs 5%; p = 0.01). Patients of Chinese descent had less frequent digital ulceration (36% vs 55%; p = 0.04), and an absence of renal crisis. The frequency of cardiac and pulmonary involvement was similar in both groups. More patients of Chinese than of European descent were positive for anti-topoisomerase-I (47% vs 27%; p = 0.02), anti-Ro (36% vs 10%; p = 0.001), and anti-U1RNP (17% vs 5%; p = 0.03) antibodies. The observed differences for anti-topoisomerase-I, anti-Ro, and joint and gastrointestinal manifestations persisted in the subgroup analysis of patients matched for sex, disease subtype, and age at diagnosis. Conclusion. Patients of Chinese descent have milder SSc disease with less frequent joint and gastrointestinal manifestations, less severe vasculopathy, but increased prevalence of myositis and certain autoantibodies. Research is needed to identify determinants (genetic, environmental, and cultural factors) of the relationship between ethnicity and disease.

We were most interested to read Prof. Pritzker's assessment of the state of research into the crystal induced arthropathies 1 .We wish to assure Prof. Pritzker and the wider rheumatology community that, rather than being a "dwindling endangered species whose interests are seen to be peripheral to those of most rheumatologists," those researchers involved in studying the crystal induced arthropathies are enthusiastic, energetic, and productive.In recent years, work in this field has led to critical advances in our understanding of the basic science and epidemiology of crystal induced arthropathies 2-6 .Further, the prospect of new agents to treat these diseases is cause for great enthusiasm.For management of acute crystal induced arthropathies, components of the inflammasome, and particularly interleukin 1, provide new therapeutic targets.The development of novel uratelowering therapies, such as febuxostat and PEG-uricase for treatment of chronic gout, should also have a major impact on longterm management of this prevalent disease, in preventing acute gout attacks and the consequences of chronic gout such as disfiguring tophi, joint damage, and disability 7,8 .As a reflection of the interest in gout within the rheumatology community, gout sessions have been included in the scientific programs of the 2 last EULAR annual meetings, the 2 last ACR annual meetings, and as Special Interest Groups (SIG) or Workshops in the last 3 OMERACT meetings.EULAR has recently supported a Task Force on Gout, resulting in the publication of Evidence Based Recommendations for Diagnosis and Management 9,10 , and the ACR and EULAR have funded an international project for validation of acute gout flares.The number of presentations at ACR and EULAR meetings is 10 times that of a decade ago, and the number of original papers on gout in high impact international journals now exceeds that of reviews, a situation inverse to that observed a decade ago.In addition, as the reader may observe, the group of investigators devoted to gout does not have the appearance of an endangered species (Figure 1).It is for these reasons that we do not share Prof. Pritzker's pessimistic view regarding the state of research into the crystal induced arthropathies.The number of investigators may be small, but recent progress has been significant and is likely to translate into important new treatments for patients with these diseases.

Objective. To evaluate the utility of magnetic resonance imaging (MRI) in systemic sclerosis (SSc)-associated arthropathy. Methods. MRI of the hand was performed in patients presenting with joint pain/swelling in order (1) to determine the frequency of inflammation oil MRI, and (2) to compare MRI with radiography. Results. Of 17 patients with SSc, 10 (59%) had inflammatory MRI findings with synovitis (n = 8), erosions (n = 7), joint effusion (n = 7), or tenosynovitis (n = 8). Bone edema was present in 9 patients. Of 7 patients with MRI erosions, only 2 had radiographic erosions. Conclusion. Our study illustrates the usefulness of MRI in the accurate diagnosis and characterization of SSc-associated arthropathy. (First Release April 1 2009; J Rheumatol 2009 36:961-4; doi: 10.3899/jrheum.080795)

Volume 35, no. 9 Polychondritis Critical Coronary Artery Stenosis and Aortitis in a Patient with Relapsing DAVID LORRETTA B. DANIEL, JAGDISH BUTANY, YVES L. PROVOST and TYRONE E. JONATHAN D. STEIN, PETER LEE, BINDEE KURIYA, JERRY TENENBAUM, http://www.jrheum.org/content/35/9/1898 J Rheumatol 2008;35;1898-1901 http://www.jrheum.org/alerts 1. Sign up for TOCs and other alerts http://jrheum.com/faq 2. Information on Subscriptions http://jrheum.com/reprints_permissions 3. Information on permissions/orders of reprints

To the Editors: Relapsing polychondritis (RP) is a multisystem autoimmune disease with cartilage inflammation. Cardiovascular manifestations are associated with significant morbidity and mortality1,2. Vasculitis involving the coronary arteries is rare. Our patient developed severe ostial lesions in 2 major coronary arteries and aortitis requiring surgical intervention despite intensive medical treatment. A 30-year-old male Caucasian dental surgeon developed a painful, swollen left ear in January 2001. He was otherwise asymptomatic. Initial laboratory investigations were normal. A clinical diagnosis of relapsing polychondritis was made. His ear inflammation resolved after prednisone 30 mg daily for 3 weeks. Over the next 5 years he…

OBJECTIVE:To assess clinical factors associated with disability and physical health in patients with systemic sclerosis (SSc) compared to psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and healthy controls. METHODS:Eighty-two patients with SSc, 82 with PsA, 74 with SLE, 42 with RA, and 60 controls were recruited from various rheumatology clinics and underwent physical examination, tender point count, Health Assessment Questionnaire Disability Index (HAQ-DI) and Short Form-36 Health Survey (SF-36) assessments. RESULTS:SSc patients were younger and had shorter disease duration than the comparator groups. SSc patients with joint involvement had significantly poorer HAQ-DI scores than patients with PsA (1.43 vs 0.84; p < 0.05), and had higher visual analog scale pain scores than RA patients (1.37 vs 1.01; p < 0.05). The SF-36 Physical Component Summary and HAQ-DI score in SSc patients were adversely affected by joint involvement (p < 0.01, p < 0.001, respectively), >or= 11 tender points (p < 0.01, p < 0.001), gastrointestinal (GI) involvement (p < 0.01, p < 0.01), and high skin score (p = 0.02, p < 0.001). CONCLUSION:Physical health relating to quality of life is adversely affected in patients with SSc. Disability is associated with the presence of >or= 11 tender points, a high skin score, and joint and GI involvement. Joint involvement in SSc is more disabling than joint involvement in PsA; and patients with SSc experience more severe pain than patients with RA.