Scleroderma treatment differs between experts and general rheumatologists.
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Comorbidity↗
Biomedical subjects
Janet E Pope
Publications and source records attributed to Janet E Pope.
Other manifestations of mixed connective tissue disease.
This article describes other manifestations of mixed connective tissue disease (MCTD). We focus on inflammatory arthritis, the gastrointestinal tract (the esophagus in particular), the kidney, skin, and hematologic changes such as thrombocytopenia. Due to the complexity of potential organ involvements in MCTD, vigilance with appropriate diagnosis and treatment is warranted.
Autoimmune Diseases↗
Osteoporosis in scleroderma.
OBJECTIVE: To review the literature describing the association of osteoporosis (OP) with scleroderma (SSc). METHODS: A Medline (PubMed) search identified all studies from 1966 to 2004 that investigated the association between OP and SSc. Search terms included "scleroderma," "systemic sclerosis," "osteoporosis, " "bone mineral density," "bone densitometry," and "prevalence." RESULTS: Eight case control studies and 1 retrospective study (comparing OP status to a reference standard) were identified. There is no clear association between bone mineral density (BMD) scores and scleroderma. Two of 4 studies have reported lower BMD scores in SSc, but appear not to have considered possible confounding risk factors. Earlier age of menopause has been reported in 2 of 3 studies, and thus, may be a confounder in some samples of women with SSc. Studies of bone metabolism markers have not provided any consistent explanatory mechanism for increased OP in SSc, and such markers may be unreliable in SSc as these are affected by the altered collagen turnover and fibrosis characteristic of SSc. CONCLUSIONS: It is unknown whether OP is truly increased in SSc or whether this association has been observed in some studies as a result of other confounding risk factors for OP. Clinical heterogeneity of SSc study samples and small sample sizes have contributed to the difficulty in obtaining valid estimates of the risk for the development of OP. There is no strong evidence in the literature for consistently lower BMD scores in SSc, or for altered biomarkers of bone resorption. Earlier menopause, corticosteroid use in some patients, and other factors secondary to SSc (such as malabsorption and inflammation), may be causal factors or may be confounders in studies of OP in SSc.
Biomarkers↗
Prevalence of elevated pulmonary arterial pressures measured by echocardiography in a multicenter study of patients with systemic sclerosis.
OBJECTIVE: To estimate the prevalence of elevated pulmonary arterial pressures (PAP) as a correlate for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) in rheumatology centers in Canada. METHODS: During the one-year study period (June 2002-May 2003), charts of patients with SSc were reviewed to determine demographics, SSc characteristics, percentage of patients with a PAH diagnosis, and the site criteria for such diagnosis. Subjects with no PAH that had symptoms of dyspnea and/or fatigue were invited to undergo Doppler echocardiography to estimate their systolic PAP (sPAP). RESULTS: A total of 539 patients with SSc (age 56 yrs +/- 13 SD, 84% female, 41% with diffuse SSc, 58% limited SSc, SSc disease duration 9 yrs +/- 7 SD) at 8 rheumatology centers were reviewed. Twenty-three percent of patients were diagnosed with elevated sPAP based on the site diagnosis criteria (i.e., > 30 mm Hg or > 35 mm Hg). From the non-PAH, not recently screened patients that had symptoms of dyspnea or fatigue, a total of 89 patients underwent a Doppler echocardiograph; 40% had sPAP > 35 mm Hg. CONCLUSION: Elevated PAP are common in both limited and diffuse SSc disease, occurring in 21% of limited and 26% of diffuse SSc patients. During the screening most patients had mild PAP elevations that would require further assessments such as right heart catheterization to diagnose PAH where appropriate. A high index of suspicion is important and routine echocardiography in symptomatic patients may allow earlier diagnosis of PAH and intervention. The proportion of SSc patients with mild to moderate elevations of PAP who will develop significant PAH is unknown and longterm studies are needed to address the natural progression.
Adolescent↗
Refractory polyarteritis nodosa successfully treated with infliximab.
We describe a woman with severe polyarteritis nodosa (PAN) with visceral involvement unresponsive to multiple immunosuppressive drugs. Infliximab treatment was very effective in this case. Infliximab may potentially be used as an alternative agent for the treatment of patients with PAN refractory to conventional therapy.
Adult↗
Access to care for rheumatology patients may be compromised: results of a survey to members of the Canadian Rheumatology Association.
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Attitude of Health Personnel↗
ANA+ (anti-nuclear antibody) is correlated with RF+ (rheumatoid factor) in rheumatoid arthritis.
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Adult↗
The efficacy and cost effectiveness of N of 1 studies with diclofenac compared to standard treatment with nonsteroidal antiinflammatory drugs in osteoarthritis.
OBJECTIVE: To determine whether or not N of 1 trials with diclofenac/misoprostol (Arthrotec) are superior and cost-effective compared with standard treatment in osteoarthritis (OA). METHODS: We randomized subjects with OA who were "uncertain that nonsteroidal antiinflammatory drugs (NSAID) were helpful" to 2 different groups. One group received conventional treatment whereby they were told to stop their NSAID and to wait and see what happened. If necessary, treatment with other NSAID and all other usual OA treatment strategies were used. The other group received a series of crossover trials with diclofenac 50 mg and misoprostol 200 micro g twice a day or an identical placebo for 2 weeks each in a random double-blinded manner. Every 4 weeks they chose which treatment they preferred. By 3 months, if there was no clear preference, the N of 1 trials were discontinued. All trial participants were seen monthly for 3 months and at 6 months. All costs (direct and indirect) were collected for both groups. Costs of research-generated visits were not counted in the "conventional treatment" group. RESULTS: Fifty-one subjects were randomized (stratified by most symptomatic OA area): 25 with knee, 7 with hip, and 19 with hand OA. Twenty-four were randomized into the N of 1 group. There were no differences in the baseline and followup variables including age, income, education, past and current NSAID use, global assessment, Health Assessment Questionnaire (HAQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Medical Outcome Study Short Form-36 (SF-36) scores. In the N of 1 group, 11 patients preferred diclofenac in total (of whom 7 did only one round, 2 did 2 rounds, and 2 did 3 rounds). None of the N of 1 patients preferred placebo and 11 had no preference (2 dropped out at baseline). At 6 months, 15 of 19 in "conventional therapy" and 17 of 21 in N of 1 were taking NSAID. That is, NSAID appeared to be effective in 81% of N of 1 subjects and 79% of conventionally treated patients, even though subjects were initially uncertain that their NSAID were helpful. The total OA-related costs in Canadian dollars per patient (in 1996) for N of 1 treated patients at 6 months were: 551.66 dollars +/- 154.02 dollars (SD) versus 395.62 dollars +/- 226.87 dollars for controls, excluding 2 research visits for controls (p < 0.009). The HAQ pain and disability, WOMAC scales, and physician global assessments improved more in the N of 1 group (at greater cost), but no between-group differences in efficacy were seen, possibly due to small numbers. CONCLUSION: N of 1 trials were time-consuming in these patients and are more expensive, but with slightly better outcomes. In addition, NSAID seem to be effective in a majority of subjects with OA who have been uncertain of their benefit.
Anti-Inflammatory Agents, Non-Steroidal↗
Close association of herpes zoster reactivation and systemic lupus erythematosus (SLE) diagnosis: case-control study of patients with SLE or noninflammatory musculoskeletal disorders.
OBJECTIVE: To investigate the prevalence of infections, particularly the frequency of shingles and the timing of varicella zoster virus (VZV) reactivation, and antibiotic use, vaccinations, and joint trauma prior to and at diagnosis of systemic lupus erythematosus (SLE). METHODS: We sent questionnaires to patients with SLE (n = 93) and controls with noninflammatory musculoskeletal disorders (MSK; n = 353) including osteoarthritis, fibromyalgia, and tendonitis. We matched SLE patients to controls for sex (up to 1:3). RESULTS: The response rate in SLE was 66% and in controls 69% (p < 0.53). Four of 61 SLE patients and 12 of 173 controls were men. The mean disease duration in the SLE group was 8 +/- 1 years compared to 10 +/- 1 years in controls (p < 0.23). SLE patients were significantly younger than controls (mean age of SLE patients 49 +/- 2 vs 57 +/- 1 years for controls; p < 0.0004), and results were adjusted for age. A significantly higher proportion of SLE participants had a history of VZV (shingles) (19% vs 7%, respectively; OR 2.98, p < 0.003), whereas rubella was reported less in SLE (23% vs 42%; OR 0.43, p < 0.03). VZV infections were clustered just prior to or after diagnosis in SLE but were more widely spaced temporally in the controls (1 +/- 4.5 years after the diagnosis of SLE vs -14.7 +/- 4 years before the diagnosis of noninflammatory MSK disorder; p < 0.003). Diagnosis of shingles was observed in 6 of 11 SLE patients within +/- 2 years of SLE diagnosis, whereas only 2 of 15 controls had shingles within +/- 2 years of diagnosis (OR 7.2, p < 0.03). Only 2 patients with SLE were taking immunosuppressive drugs or steroids at time of shingles, so immunosuppressive therapy was not usually concomitant at time of VZV reactivation. Common infections (respiratory, urinary tract, ear, and eye) in the SLE group exceeded controls, but not significantly (23% vs 9%; OR 2.98, p < 0.06) and SLE patients were more likely to have been vaccinated since 18 years of age with any type of vaccine (69% vs 51%; OR 2.21, p < 0.04). SLE patients were less likely than controls to report joint trauma within one year prior to their diagnosis (25% vs 40%; OR 0.49, p < 0.04). There were no differences with respect to streptococcal throat infection (p < 0.96), diarrhea/vomiting (p < 0.84), rash with fever (p < 0.07), parvovirus infection (p < 0.16), infection after surgery (p < 0.58), respiratory tract infection (p < 0.71), or ear (p < 0.09) and eye infection (p < 0.68) one year prior to diagnosis. A higher proportion of SLE patients had a history of urinary tract infections (46% vs 25%), but this was not significant (p < 0.17), nor was it significant one year prior to diagnosis (p < 0.63). Overall, the likelihood of having any infection one year prior to diagnosis was not significantly higher in the SLE group (p < 0.56). There were no differences one year prior to diagnosis in travel history (p < 0.69), hospitalizations (p < 0.47), use of antibiotics (p < 0.54), history of rheumatic fever, positive TB skin test, or hepatitis A, B or C infection. CONCLUSION: Varicella reactivation as shingles is increased in patients with SLE and clusters around diagnosis. Vaccinations are increased in those with SLE compared to controls. Common infections are not significantly increased in SLE patients prior to onset of symptoms. We cannot determine if VZV infections are causally associated with SLE in some people, are from an abnormal immune system response due to the lupus itself or from the use of steroids or other immunosuppressive drugs to control the disease, or are spurious.
Case-Control Studies↗
Erectile dysfunction associated with scleroderma: a case-control study of men with scleroderma and rheumatoid arthritis.
OBJECTIVE: To determine if men with systemic sclerosis (SSc) are at increased risk of developing erectile dysfunction (ED) compared to men with rheumatoid arthritis (RA), and to investigate the temporal relationship of ED related to rheumatologic disease. METHODS: Men with SSc identified from the practices of 2 rheumatologists were age matched to men with RA and were sent a standardized, validated questionnaire (SHIM IIEF-5) to assess ED and related factors. The questionnaire also addressed information on the subject's overall health and rheumatic disease status. RESULTS: The response rate was 50% (48% in SSc and 55% in RA), thus 43 with SSc and 23 with RA were included. The mean age of respondents was 53 yrs +/- 1.34 (SEM), (range 34 to 83). No statistical differences were found for marital status, alcohol or drug use, or past/present smoking. Men with scleroderma weighed less than men with RA (p < 0.004) and were more likely to have Raynaud's phenomenon (p < 0.0001), and to have fewer biological children (2.0 +/- 0.2 vs 2.7 +/- 0.2, p < 0.01). The prevalence of erectile dysfunction was 81% (SSc) and 48% (RA), (relative risk for SSc vs RA: 4.77; 95% CI: 1.55, 14.66; p < 0.005). In subjects who had ED, 78% (both SSc and RA) reported it occurring after disease onset. Men with SSc noted their ED began 2.7 +/- 1.2 (mean +/- SEM) years after their disease was diagnosed, and similarly, men with RA noted their ED began 3.3 +/- 2.2 years after disease diagnosis, p = 0.82. Eighty-six percent of patients with SSc had Raynaud's phenomenon (RP) compared to 19% RA, p < 0.0001. Eighty percent of subjects with RP (SSc + RA) had ED versus 50% of men without RP, p < 0.01. In RA subjects with RP (n = 4), 75% had experienced ED, versus 39% of RA without RP, p = 0.18. Possible confounding factors for ED were examined including smoking, hypertension, diabetes, and steroid use; all except self-reported history of nerve damage (p < 0.0005) and diabetes (p < 0.02) were insignificant for predicting the likelihood of increased ED. Patients with SSc were not more likely than RA to have experienced nerve damage (p = 0.25), or diabetes (p = 0.19). CONCLUSION: ED occurs frequently in SSc, is more common than in RA, and occurs on average 3 years after disease onset. RP appears to be associated with ED in both SSc and RA, but is not necessarily an independent risk factor for ED in SSc alone.
Adult↗
Hypertension, NSAID, and lessons learned.
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Anti-Inflammatory Agents, Non-Steroidal↗
Clinical outcomes of patients with rheumatoid arthritis after switching from infliximab to etanercept.
OBJECTIVE: To assess the efficacy and monitor serious adverse events in patients with rheumatoid arthritis (RA) switching treatment from infliximab to etanercept. METHODS: Adult patients with active RA who were discontinuing treatment with infliximab were eligible to enroll in this prospective, 12-week, open label, single-arm, observational study. Four to 10 weeks after their last infusion of infliximab, patients began treatment with etanercept (twice weekly subcutaneous injections of 25 mg). Clinical assessments using the American College of Rheumatology (ACR) criteria for improvement were performed at baseline and at Weeks 6 and 12, and serious adverse events were monitored throughout the study. RESULTS: Twenty-five patients were enrolled, 18 of whom had discontinued infliximab because of lack of efficacy, and 22 completed 12 weeks of etanercept treatment. After 12 weeks, 14 of 22 patients (64%) achieved at least a 20% improvement in ACR criteria (ACR20), 13 (59%) experienced improvements in physical function that were considered clinically important (> or = 0.22 point decrease in overall Health Assessment Questionnaire score), and mean values of all individual components of the ACR criteria had improved. No serious adverse events were reported during the study and no patient discontinued because of lack of efficacy. CONCLUSION: Etanercept, a soluble tumor necrosis factor (TNF) receptor, provided a well tolerated and effective treatment option for some patients even when infliximab, a monoclonal antibody to TNF, had been ineffective.
Adult↗
Musculoskeletal involvement in scleroderma.
Scleroderma can be accompanied by arthralgias, inflammatory arthritis, flexion contractures, nerve entrapment, myositis, or myopathy. Antibodies in scleroderma can occur in other connective tissue diseases; overlap syndromes between scleroderma and Sjogren's syndrome, lupus, and rheumatoid arthritis are reported. Many of the musculoskeletal symptoms in scleroderma are treated symptomatically; most treatments are not proven in randomized controlled trials in these patients. Musculoskeletal manifestations are a major cause of morbidity and disability in scleroderma.
Humans↗
Are subjects satisfied with the informed consent process? A survey of research participants.
OBJECTIVE: Letters of information (LOI) for clinical trials are becoming longer and more complicated. We investigated patients' perspectives of their ability to understand the information presented during a clinical trial. Satisfaction with and motivation for participation in clinical trials were also ascertained. Perceptions from various treatment disciplines were compared. METHODS: Participants were chosen from 14 clinical trials (departments of rheumatology, ophthalmology, and cardiology) conducted at the same university. Subjects were asked to complete a written questionnaire that assessed demographic information, recall and understanding of information, subjects' decisions to participate, and perceptions/opinions of the study. The response rate was 75% (rheumatology, n = 74; ophthalmology, n = 32; cardiology, n = 84). RESULTS: The majority of respondents (98%) indicated that they were satisfied with the informed consent process and with their involvement in a trial (97%). Subjects who reported having understood the LOI had better recall of placebo/active drug comparator (p < 0.03), and better understanding of why placebo was used (p < 0.04). No differences were found between those who reported understanding and those who did not on understanding the concept of concealed allocation (blinding). Subjects who felt they had received "the right amount of information" were more likely not to understand concealed allocation. The most frequent reason for trial participation was to help medical science (80%). Subjects with higher education were more likely to understand the reason for placebo use (p < 0.0003), but were not more likely to understand concealed allocation (p < 0.08). CONCLUSION: Subjects reported that they were satisfied with the informed consent process and their experience in a clinical trial, and that they understood trial concepts. Subjects may be able to self-assess their own level of understanding for trial concepts that intrinsically make sense within the context of their beliefs about medical care, but other trial concepts may be misunderstood/misinterpreted regardless of self-assessment of understanding or education level (i.e., concealed allocation). Subjects may prefer to believe that investigators know which treatment they are receiving, and have made a good treatment decision specific to their case, despite having being told about concealed allocation and placebo use.
Adult↗
Scleroderma overlap syndromes.
Scleroderma is a connective tissue disease that causes fibrosis and vascular abnormalities, but that also has an autoimmune component. Many patients with scleroderma have a positive antinuclear antibody, and there can be family histories of other connective tissue diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Some patients have features of scleroderma and other autoimmune conditions. This article will review recent literature to help in the understanding of scleroderma with overlap features. Recent reports of scleroderma overlap with rheumatoid arthritis suggest distinct features of diffuse scleroderma with positive Scl-70, pulmonary fibrosis, and later seropositive erosive rheumatoid arthritis. SLE rarely occurs with scleroderma. Sjögren syndrome symptoms are common in scleroderma. In primary Sjögren syndrome, anticentromere antibody positive patients have more Raynaud phenomenon. Antibodies that occur in scleroderma that are thought to be specific are present in other connective tissue diseases. For instance, Scl-70 antibody is reported in as many as 35% of patients with scleroderma but can be present in 25% of patients with SLE. Myositis or myopathy can be features of scleroderma. Scleroderma overlap with polymyositis is frequently anti-PM Scl antibody positive, whereas anti-Jo-1 does not normally occur in the overlap of scleroderma and polymyositis but is usually exclusively positive in polymyositis with arthritis and alveolitis. A better prognosis is found with PM Scl antibody in myositis. Vasculitis is not a typical feature of scleroderma, but has been reported. Eosinophilic fasciitis is rare, and the onset could be associated with simvastatin.
Arthritis, Rheumatoid↗
Alkaptonuria with atypical joint involvement.
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Aged↗
Prescribing trends in disease modifying antirheumatic drugs for rheumatoid arthritis: a survey of practicing Canadian rheumatologists.
OBJECTIVE: To determine the prescribing and monitoring practices of disease modifying antirheumatic drugs (DMARD) for Canadian rheumatologists in their treatment of rheumatoid arthritis (RA). METHODS: A survey questionnaire was mailed to 279 rheumatologists with a 70% response rate after 2 mailings. RESULTS: Antimalarials are prescribed commonly, with the preference being hydroxychloroquine (HCQ). For antimalarials, 78% do not routinely monitor laboratory results. There was wide variability in monitoring for ocular complications. Thirty-eight percent of rheumatologists never do a baseline eye examination and 39% always do. All rheumatologists frequently use methotrexate (MTX) in RA. The reported mean maximum dose for MTX was 25.1 mg/week (range 7.5-50), with 86% routinely using folate. Ninety-eight percent prescribe sulfasalazine (SSZ) for RA. Mean maximum dose prescribed for SSZ was 2.8 g/day. Most never used oral gold, while IM gold was used by 95%. Only 9% frequently use azathioprine in RA, to a mean maximum dose of 185 mg/day. Less commonly prescribed DMARD included cyclosporine (66% frequently; 25% never) and D-penicillamine (2% frequently; 53% never). There was a wide range of what exactly was monitored with respect to laboratory tests, and at what frequency, for many of the DMARD. Nearly all (99%) used combination DMARD, the most popular combination being MTX-HCQ. There were some significant differences in treatment trends when comparing year of fellowship completion, but no sex or type of practice differences were found. Those completing fellowships prior to 1984 were more likely to prescribe azathioprine (p < 0.03), chloroquine (p < 0.01) and chronic steroids (p < 0.1) in RA. There was, however, regional variability in the use of IM gold and newer DMARD--they were most prescribed in Western Canada and least in Quebec. Cyclosporine was prescribed most frequently in Quebec compared to Western Canada and least in Ontario and the Atlantic Provinces. CONCLUSION: Canadian rheumatologists are fairly similar in their use of common DMARD and combination therapies in RA. There is variability in the use of some older medications including azathioprine and chloroquine, depending on when rheumatology training was completed, and use of some drugs varies by region.
Antirheumatic Agents↗
Increased prevalence of scleroderma in southwestern Ontario: a cluster analysis.
OBJECTIVE: To estimate the prevalence of scleroderma (systemic sclerosis, SSc) in 3 cities, Windsor, Sarnia, and Woodstock, Ontario, within our referral area, which has a referral base population of 1 million. METHODS: To compare the addresses and exposures of referrals with SSc, we performed a case control study using our patients with scleroderma and 2 age and sex matched controls from the same rheumatologist's practice. RESULTS: Sixty-seven of 91 patients with SSc and 87 of 154 controls responded. The mean age of patients with SSc was 53.2 years versus 52.8 years in controls. There was no statistically significant increase in the number of SSc patients from Windsor (population 197,694): 14 patients (15.4%) with SSc versus 18 controls (11.6%) (p < 0.41); or Sarnia (population 72,738): 7 patients (7.7%) with SSc versus 7 controls (4.5%) (p < 0.31). However, there were 9 cases (9.9%) from Woodstock (population 32,086) versus one control (0.64%) (p < 0.0004). The point prevalence of scleroderma was at least 0.71/10,000 in Windsor, 0.96/10,000 in Sarnia, and 2.8/10,000 in Woodstock. There were no significant between-group differences in exposure to industrial toxins or chemicals including vinyl chloride, silica, and benzene, but exposure rates in both groups were low. Occupations and proportion of those who were work disabled were not different. Patients with SSc were not more likely to have smoked cigarettes (p < 0.43); however, they were more likely to drink at least 6 drinks of alcohol per week (p < 0.04) and had more dental fillings (p < 0.05). Patients with SSc knew on average 3.2 others with this disease, and controls knew only 0.25 others with scleroderma (p < 0.00001). Two patients with SSc knew someone with SSc in their workplace versus none of the controls. CONCLUSION: Our a priori expected higher prevalence of scleroderma in Windsor and Sarnia did not reach significance, but the cluster in Woodstock seems statistically validated, and the exact reason for this cluster remains unclear. It is unlikely that all patients with SSc in Woodstock were seen by us, so the prevalence of scleroderma is at least 2.8/10,000, which is a medium to high prevalence compared to other studies. Associations with alcohol and dental fillings require further study.
Adult↗