Undifferentiated Spondyloarthropathies: A 2-Year Follow-up Study

The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA). A prospective study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for seronegative spondyloarthropathies (SpA) and were aged between 18 and 50 years. Inclusion criteria included inflammatory low back pain (ILBP) (without radiographic sacroiliitis), asymmetric oligoarthritis (predominantly affecting large joints in the lower limbs) and heel enthesopathies (Achilles tendinitis and/or plantar fasciitis). Imaging methods included pelvic radiography (at study entry and after 2 years) and calcaneal radiography (at study entry). There was a predominance of male gender (78%), caucasoid race (72%) and positive HLA-B27 (54%), with a mean age of 31 years and mean disease duration of 5 years. The first disease manifestations were ILBP (49%), asymmetric oligoarthritis (35%) and heel enthesopathies (16%). A positive family history of a definite SpA was mentioned by 9% of the patients. Seventeen patients (25%) scored 5 points in the Amor set of SpA criteria; logistic regression analysis showed that HLA-B27, heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria ≥6, whereas ILBP was associated with Amor criteria <6. Male sex was associated with heel enthesopathies (p = 0.041) and ankle involvement (p = 0.015). Caucasoid race was associated with ILBP (p = 0.015) and buttock pain (p = 0.047). Positive HLA-B27 was associated with wrist involvement (p = 0.019) and Amor criteria ≥6 (p = 0.001). After a 2-year follow-up the following outcomes were observed: uSpA 75%; disease remission 13%; ankylosing spondylitis 10%; psoriatic arthritis 2%. Logistic regression analysis showed that buttock pain and positive HLA-B27 (trend) were statistically associated with progression to a definite SpA. In conclusion, uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease. Received: 2 June 2000 / Accepted: 5 January 2001     

Lipoprotein(a) and Lipids in Relation to Inflammation in Rheumatoid Arthritis

The aim of this study is to evaluate whether lipoprotein(a) (Lp(a)) acts as the acute phase reactant and whether changes of lipids are related to inflammation in rheumatoid arthritis (RA). Lp(a) and lipids were measured after an overnight fast, before and after 14 days use of antiinflammatory agents and correlated with laboratory findings in 21 untreated RA patients and 19 healthy controls. Nine (42.3%) of 21 RA patients and 6 (31.6%) of 19 controls had high Lp(a) levels (> 30 mg/dl) and the Lp(a) level was higher in RA patients compared with controls (27.1 ± 5.3 vs 19.0 ± 4.2 mg/dl) without significant difference (p > 0.05). There was no significant correlation between ESR and Lp(a) and lipids in RA patients except for HDL cholesterol (r=–0.563, p = 0.008). After antiinflammatory agent use for 14 days, change in ESR (ESRsample1–ESRsample2) was significantly and negatively correlated to changes in total and HDL cholesterols in RA patients. In conclusion, although Lp(a) tended to be higher in RA, we could not find a distinct acute phase pattern of Lp(a). But changes in total and HDL cholesterols were negatively correlated with inflammation in RA. Our data support the phenomenon that dyslipoproteinemia observed in RA is associated with inflammation. Received: 6 August 1999 / Accepted: 25 January 2000     

Conclusion

We investigated serum levels of interleukin (IL)-1β, IL-6, IL-8, IL-12 and tumour necrosis factor (TNF)-α in JRA patients during both active and inactive phases of the disease. The systemic JRA patients had the highest IL-1β and IL-6 levels during both active and inactive periods. In the systemic group IL-1β, IL-6 and IL-12 levels during the active period were elevated compared to the inactive period (p = 0.0173, p = 0.0359 and p = 0.0117, respectively). Levels of these cytokines during the inactive stage were still greater than those of controls. IL-8 and TNF-α levels during both active and inactive periods were comparable to controls. IL-1β correlated strongly with CRP and ESR (p = 0.008 and p = 0.031, respectively). IL-6 correlated significantly with CRP (p = 0.002). IL-12 levels were found to be correlated with ESR and CRP (p = 0.03 and p = 0.04, respectively). In active polyarticular JRA patients, IL-6 levels were elevated compared to the inactive phase, and the control (p = 0.001) IL-12 levels decreased significantly with clinical remission (p = 0.018). There was a strong correlation between Il-12 levels and number of joint with limited motion (p = 0). In oligoarticular JRA patients, IL-12 levels during active period were greater than in the controls and there was a marked decrease in IL-12 levels when the patients entered the inactive phase (p = 0.001) In conclusion, IL-1β, IL-6 and IL-12 may play an important role in JRA and may be used as a marker of disease activity. Received: 8 November 1999 / Accepted: 7 July 2000     

Rare copresent rheumatoid arthritis and gout: comparison with pure rheumatoid arthritis and a literature review

Copresent rheumatoid arthritis (RA) and gout is seldom reported. This study summarizes the findings of eight cases of copresent RA and gout and compares them with 31 pure RA cases. Additional reported cases were retrieved from the current literature by Medline search. Patients with copresent RA and gout were older (p = 0.014) and predominantly male (p < 0.01). Synovial fluid, positive for urate crystals, was aspirated most frequently from the knee (five out of eight), followed by the first metatarsophalangeal joint (three out of eight). Serum creatinine and urate levels in the copresent group were significantly higher (p < 0.01, both), and serum hemoglobin was lower (p = 0.04) than those with pure RA. Copresent subjects had much lower percentage of positive rheumatoid factor (RF) tests than patients with pure RA (37.5 vs 80.6%). Only one copresent subject had both RF and anti-cyclic citrullinated peptide antibody. Of copresent subjects, 75% had gouty arthritis before diagnosis of RA, which is consistent with earlier reports. Seven copresent subjects had gout attacks under disease-modifying antirheumatic drug use. This study revealed that polyarthritis negative for RF in a previously gouty patient may be RA and vice versa. This combination occurs more frequently in males. Moreover, anti-CCP antibody examination is not helpful for this diagnosis. Therefore, physicians must obtain synovial fluid for analysis in joints with intense swelling, especially in old RA subjects with renal insufficiency or involvement of lower extremities. Conversely, RA must be considered in gouty patients with polyarticular involvement.     

Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis

We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis clinic. At the time of recruitment, all had clinical evidence of synovitis. Patients were assessed at baseline and at 1-year follow-up. Periarticular and axial bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay. A total 38 patients were included in the study. Twenty had rheumatoid arthritis (RA) and 18 had a seronegative spondylarthropathy (SpA). At baseline, periarticular hand BMD measurements were similar in RA and SpA. At 1 year, the mean periarticular hand BMD was significantly lower in RA (p < 0.05). Significant inverse correlations between both the Ritchie articular index and C-reactive protein levels and the change in periarticular hand BMD at 1 year were observed in RA (r = −0.792, p < 0.001 and r = −0.478, p = 0.045, respectively). Baseline TIMP-1 levels correlated with the change in periarticular hand BMD at 1 year in RA (r = 0.519, p = 0.02). At 1 year, radiographic measures of joint damage were highest in RA. Inverse correlations between the change in periarticular hand BMD and the changes in erosion score (r = −0.90, p = 0.04) were observed in patients demonstrating significant periarticular bone loss. Persistent disease activity was associated with increased periarticular bone loss in the hands in patients with RA, consistent with synovitis-mediated periarticular bone loss. The correlation between baseline TIMP-1 levels and periarticular bone loss over 1 year suggests that TIMP-1 may have utility as a biomarker of periarticular bone loss in early RA.     

Serum IL-6, TNFα, p55 srTNFα, p75 srTNFα, srIL-2α Levels and Disease Acitivity in Systemic Lupus Erythematosus

The aim of this study was to determine whether the levels of serum cytokines IL-6 and TNFα and of the soluble receptors p55 srTNFα, p75 srTNFα and srIL-2α are valuable markers of disease activity in patients with systemic lupus erythematosus (SLE) compared with the established parameters of anti-dsDNA, C3, C4 and CH₅₀. Forty patients with SLE, 19 ambulatory and 21 hospitalised, were included in this study. On the day of blood sampling a clinical examination was performed and SLEDAI and ECLAM disease activity scores were used to assess disease activity. Nineteen patients had inactive disease and 21 patients had active disease. Thirteen patients from the second group developed nephritis. In these patients the blood sampling and disease activity assessment were performed twice (at presentation and 6 months after treatment). Serum levels of cytokines and soluble receptors were measured by ELISA. Serum levels of cytokines and soluble receptors of patients with active disease were significantly higher than in patients with inactive disease (IL-6 p = 0.0004, TNFαp = 0.0015, srIL-2αp<0.0001, p55 srTNFαp<0.0001, p75 srTNFαp<0.0001). Serum soluble receptor levels of patients with inactive disease were higher than those of healthy controls (p55 srTNFαp<0.0001, p75 srTNFαp = 0.0002, srIL-2αp = 0.0012). No significant difference was found for TNFα and IL-6 (TNFαp = 0.015, IL-6 p = 0.019). Serum TNFα levels and especially srIL-2α, p55 srTNFα and p75 srTNFα levels correlated strongly with SLEDAI and ECLAM disease activity scores, anti-dsDNA, C3, C4 and CH₅₀ (p<0.0001). Serum soluble receptor (srIL-2α, p55 srTNFα, p75 srTNFα) levels were higher in patients with nephritis before treatment and decreased significantly 6 months after treatment (p = 0.005). The same trend was noticed with SLEDAI and ECLAM disease activity scores (p = 0.005) and anti-dsDNA (p = 0.008). In contrast, no significant differences were observed for C3 and C4 levels before and after treatment, which suggests that soluble receptors of cytokines are more sensitive markers of disease activity than C3 or C4 in predicting improvement. Serum levels of srIL-2α, p55 srTNFα and p75 srTNFα could provide useful information about disease activity in SLE patients, especially in cases where the other markers do not. Received: 3 March 1998 / Accepted: 13 July 1998     

Associations of Isokinetic Knee Extensor and Flexor Strength with Steroid Use and Walking Ability in Women with Rheumatoid Arthritis

Seventy-five women with rheumatoid arthritis according to the 1987 criteria of the American Rheumatism Association were examined. Mean age was 61.9 ± 12.5 years, mean disease duration 14 years. Sixty-three were or had been on steroids (median cumulative prednisolone dose 2.5 g). Maximal voluntary knee extensor and flexor strength (Nm) was assessed at 30°/s by an isokinetic dynamometer. Walking ability was expressed as walking and stair-climbing time (s). Markers of disease activity included number of swollen and tender joints, pain as recorded by the patients on a visual analogue scale (VAS), and disability as scored by the Stanford Health Assessment Questionnaire (HAQ). Muscle strength, walking time (50 m) and stair-climbing time were reduced on average by 30%, and increased by 28% and 54% (p<0.0001), respectively, compared to 67 age-, weight- and height-matched healthy women. Associations between muscle strength and cumulative or current steroid dose were not found after correction for age and disease duration. Significant linear correlations were found between knee extensor strength and walking time (r=−0.78, p<0.0001) and stair-climbing time (r=−0.76, p<0.0001). Similar correlations were found for flexor strength. The correlations remained significant (R_partial ranging from −0.64 to −0.69, p<0.0001) in multiple regression analyses adjusting for age, height, weight, disease duration, number of swollen and tender joints, and VAS and HAQ scores. In conclusion, negative effects of steroids on muscle strength were not demonstrated. Leg muscle strength is an important and independent determinator of walking ability in RA. Received: 18 September 2000 / Accepted: 22 December 2000     

Why do Patients with Rheumatoid Arthritis use Alternative Treatments?

The aim of this study was to analyse the characteristics of patients with rheumatoid arthritis (RA) who make use of alternative or complementary medicine (CM). Two hundred and sixty-two randomly chosen patients with RA filled out self-assessment health status and pain questionnaires. Differences between the group of patients making use of both CM and conventional treatment (n = 52) and the group of patients who relied only on conventional treatment prescribed by their rheumatologists (n = 210) were explored with respect to demographic characteristics, duration of RA, levels of physical, psychological and social functioning, and pain-coping behaviour. We found that female patients used CM more often than did male patients, and those who used CM were younger than those who did not. There were no differences with respect to duration of RA, physical, psychological or social functioning or pain coping; however, the perceived impact of RA on several domains of life was higher in patients who used CM than in those who did not. Nevertheless, the patient groups did not differ in terms of medical consumption, except that those who used CM visited medical specialists for RA-related complaints less than those who relied only on conventional treatments. We concluded that the higher impact of RA, in the absence of worse disease, perceived by users of CM in several domains of life, especially psychosocial functioning, could be the reason they use CM. This suggests that CM cannot be substituted by additional conventional treatment prescribed by the rheumatologist, but rather by psychosocial intervention. Received: 10 June 2000 / Accepted: 25 October 2000     

Attained adult height in juvenile rheumatoid arthritis with or without corticosteroid treatment

Growth impairment has been described in patients with juvenile rheumatoid arthritis (JRA). Both the direct action of underlying disease and prolonged corticosteroid usage for disease management may contribute to growth impairment. The purpose of this retrospective study was to evaluate the effect of systemic corticosteroid treatment on attained adult height in patients with JRA. We reviewed patients who first visited our hospital from 1973 to 1995 with a diagnosis of JRA. Adult height (AH) and the reported parental heights of these patients were recorded. Target height (TH) is estimated according to midparental height. Patients who never had or had only transient (less than 1 week) systemic corticosteroid therapy were classified as group 1. Group 2 included patients who had corticosteroid therapy for more than 1 week but never continuously for more than 12 months, and group 3 included patients on long-term steroid treatment (continuously for more than 1 year). Height data were analysed using adult height and the difference between adult height and target height (AH minus TH). Thirty-three patients fulfilling the diagnostic criteria for JRA were reviewed. Fourteen belonged to group 1, 13 to group 2 and six to group 3. The difference between adult height and target height in group 1 was 2.96 ± 4.54 cm, in group 2 0.71 ± 6.08 cm (group 1 vs. group 2, P = 0.28), and in group 3 −11.65 ± 10.71 cm (group 1 vs. group 3, P<0.05). In 15 patients who never received corticosteroid therapy continuously for more than 1 year, AH–TH was statistically correlated neither with the cumulative corticosteroid exposure dose nor with cumulative corticosteroid exposure period by linear regression (P= 0.408, P= 0.278, respectively). We concluded that continuous systemic corticosteroid usage for less than 1 year does not affect attained adult height in JRA patients; however, prolonged corticosteroid treatment for more than 1 year can lead to irreversible growth impairment. Received: 23 May 2001 / Accepted: 11 February 2002     

Proteus IgG Antibodies and C-Reactive Protein in English, Norwegian and Spanish Patients with Rheumatoid Arthritis

The distribution of Proteus antibody levels was compared in English, Norwegian and Spanish patients with rheumatoid arthritis (RA). Using an indirect immunofluorescence method, the IgG antibody titre against Proteus mirabilis was measured in the sera of 27 English, 53 Norwegian and 34 Spanish patients with RA and divided into active and inactive disease groups according to the serum C-reactive protein (CRP) level (≥10 mg/l). Serum samples were also collected from 25 English, 30 Norwegian and 14 Spanish healthy individuals who served as controls. The levels of Proteus IgG antibodies were significantly higher in the sera of active RA patients (p<0.001) when compared with the corresponding healthy controls, whether these groups belonged to the English, Norwegian or Spanish populations. Furthermore, active RA patients from each country showed significantly higher levels of Proteus antibodies when compared with inactive English (p<0.01), Norwegian (p<0.001) or Spanish (p<0.001) RA patients. Finally, a significant correlation was observed between Proteus IgG antibody levels and the CRP concentrations in RA patients whether each population was tested individually or all together (p<0.001). The increased levels of Proteus antibodies in RA patients from three different European countries support the concept of a possible aetiopathogenetic role for Proteus microorganisms in the development of RA. Received: 20 October 1997 / Accepted: 14 October 1998     

Prediction of Creatinine Clearance from Serum Creatinine in Patients with Rheumatoid Arthritis: Comparison of Six Formulae and One Nomogram

The estimation of glomerular filtration rate is important for the medical treatment of patients with rheumatoid arthritis (RA). However, the determination of endogenous creatinine clearance (Clcr) from a 24-h urine collection is an unreliable and time-consuming procedure. We therefore tested the accuracy of six equations and one nomogram for the prediction of Clcr from serum creatinine (Scr) in 38 patients with RA and 20 controls. A positive correlation was found for all methods in the controls (r= 0.83–0.94) and RA patients (r= 0.51–0.69). The methods did not overestimate Clcr in RA. In the RA group the simple formula published by Cockcroft [Clcr = ((140 − age) × body weight)/(72 × Scr), × 0.85 for females] showed the best correlation with the measured Clcr. In RA the Cockroft formula can reliably be used to predict Clcr from Scr. Received: 8 February 1999 / Accepted: 4 June 1999     

Subsets in Psoriatic Arthritis formed by Cluster Analysis

The aim of the study was to create subgroups among psoriatic arthritis patients on the basis of dermatological features, clinical pattern of arthritis, and laboratory, immunological and radiological findings. Data on 100 patients were expressed in a standardised form and entered into hierarchical cluster analysis according to Ward”s method. Seven subgroups were created. Fifty-six patients with mild psoriasis were sorted into a “polyarticular group”. Two “RA-like groups” were formed, differing from each other serologically and in axial involvement. In an “oligoarticular group” (18 patients) serious skin disease and female gender predominancy were found to be characteristic. Eight patients with polyarticular arthritis were assigned to an “erythrodermal group”, in which polyarticular arthritis, mutilating, severe arthritis and a history of erythroderma were characteristic. Close to this group on the dendrogram eight women were sorted into a “distal form”. Sausage fingers were frequent, and nail dystrophy was present in every case. In a “pustular group” (three patients) the different type of skin involvement was considered and nail dystrophy was common. In the newly created subgroups not only the arthritic status, but also the type of the skin disease, played a determining role. Received: 23 November 1999 / Accepted: 7 July 2000     

Spot Urine Concentrations of Type I Collagen Cross-Linked N-Telopeptides and Deoxypyridinoline in Psoriatic Arthritis

The main objectives of this study were to investigate whether the spot urine concentrations of type I collagen cross-linked N-telopeptides (NTx) and deoxypyridinoline (Dpd) can be used to distinguish between active and suppressed disease in psoriatic arthritis (PsA) and to study the relationship between these markers of bone resorption and disease activity indices. Using enzyme-linked immunosorbent assays, concentrations of NTx and Dpd were estimated in spot urine samples from 25 patients with active disease, 10 patients with suppressed disease and 35 age- and sex-matched healthy control subjects. In patients with active disease, urine concentrations of NTx and Dpd were significantly elevated (p<0.001) compared with healthy controls and there were no significant differences (p>0.05) when compared with those with suppressed disease. In active disease, there was no significant positive correlation between urinary NTx and erythrocyte sedimentation rate (ESR) (r= 0.025, p>0.05) nor between Dpd and ESR (r=−0.208, p>0.05). In conclusion, NTx and Dpd concentrations in spot urine have no association with disease activity in patients with PsA. Received: 10 November 1998 / Accepted: 11 May 1999     

Latitude gradient influences the age of onset in rheumatoid arthritis patients

The mean age of rheumatoid arthritis (RA) onset is around 50 years as reported in several clinical trials involving Caucasian patients. However, clinical observations suggest that Mexican RA patients’ disease is initiated at a younger age. The objective of the study was to assess whether the age of onset of RA is different in Mexican and in Canadian RA patients. Certified rheumatologists from Canada and Mexico directly interviewed consecutive RA patients attending their clinics regarding the date patients first noticed a swollen joint. None of the participant rheumatologists were aware of the primary aim of this exploratory study at the time of the interviews. Data was gathered from 161 Mexican (91% women) and 130 Canadian (77% women) RA patients collected by three rheumatologists in each country. Duration since disease onset was not different within countries (mean 95% confidence interval [CI] for differences −10 to 16 years, p = 0.12 for Canadians, and −6 to 10 years, p = 0.26, for Mexicans). However, there was a significant difference between the two countries. Mexicans patients on average developed RA almost 12 years younger than Canadians (95% CI for difference 9 to 15 years, p < 0.001). Frequency distribution showed that 35.5% of Canadians but only 4% of Mexicans had the onset of the disease after the age of 55 (all p < 0.001). It appears that RA begins at a much younger age in Mexican than Canadian patients. If this were confirmed after controlling for different confounders and biases, it would have important societal, economic, and therapeutic implications.     

Antinuclear Antibody (ANA) and ANA Profile Tests in Children with Autoimmune Disorders: A Retrospective Study

The study objective was to determine the clinical value of positive antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders. A retrospective chart review was carried out of all patients under 18 years of age with a positive ANA test (HEp-2 cell substrate, titre ≥1:40) and ANA profile (ELISA) referred to the paediatric rheumatology service at the authors” institution between 1992 and 1996. Of 245 children with a positive ANA test, 134 (55%) had an autoimmune disease, including juvenile rheumatoid arthritis (n = 49), systemic lupus erythematosus (SLE) (n = 40) and others (n = 45). The remaining 111 patients did not have identifiable autoimmune diseases. Patients with autoimmune disorders had significantly higher ANA titres of ≥1:160 (χ²= 16, P<0.0001). In addition, of the 245 patients with a positive ANA test, 86 had an ANA profile performed; this was positive in 32 and negative in 54. All 32 patients with a positive ANA profile (100%) had an autoimmune disorder, compared to 22 ( 41%) of 54 with a negative ANA profile who had autoimmune disorders. Of 22 SLE patients with a positive ANA profile, 16 (73%) had positive anti-dsDNA and 15 (68%) had positive anti-Sm and positive anti-RNP. A positive ANA profile correlated strongly with an ANA titre ≥1:640 (χ²= 5.7 , P<0.02). The study demonstrated that only 55% of children with a positive ANA test had a definitive diagnosis of autoimmune disorder. These children tend to have higher ANA titres of ≥1:160. However, a positive ANA profile was strongly correlated with an ANA titre ≥1:640 and highly indicative of an autoimmune disorder (100%). We suggest that in order to reduce cost, an ANA profile should not be performed on all patients with positive ANA, but reserved for those with an ANA titre of ≥1:640 and/or those with a high clinical index of suspicion for autoimmune disorder, especially SLE. Received: 14 September 1999 / Accepted: 23 December 1999     

Fucosylation of serum α<Subscript>1</Subscript>-acid glycoprotein in rheumatoid arthritis patients treated with infliximab

To analyze fucosylation of α₁-acid glycoprotein (AGP) and to identify relations between AGP fucosylation and clinical and biochemical indices of disease activity in patients with rheumatoid arthritis (RA) treated with monoclonal antitumor necrosis factor (TNF) antibody infliximab, we examined 22 patients with RA who underwent a 54-week treatment with infliximab according to ATTRACT protocol. Blood samples were collected at baseline and before every infusion of infliximab. AGP fucosylation was measured using lectin-binding enzyme-linked immunosorbent assay utilizing fucose-specific lectin Aleuria aurantia (AAL). Moreover, the clinical status/activity, erythrocyte sedimentation rate, serum C-reactive protein (CRP), antitrypsin, α₁-antichymotrypsin, AGP reactivity with concanavalin A, serum C3 and C4 complement components, and serum concentrations of TNF and soluble TNF type 1 and type 2 receptors were determined. In most patients, the fucosylation of AGP decreased rapidly after first infusion of infliximab and remained low during the 54-week therapy (p < 0.001). The decrease in AGP affinity to AAL closely followed changes in clinical and laboratory activity of RA and correlated with pretreatment concentrations of CRP (r = 0.4986, p < 0.05) and TNF (r = 0.5181, p < 0.05). The fucosylation of AGP can be a part of a negative feedback loop regulating migration of inflammatory cells and collagenase-3 activity in RA. The decrease in AGP fucosylation accompanied by improvement in clinical and biochemical parameters of RA could possibly reflect reduced migration of inflammatory cells to inflamed joints and AGP-mediated inhibition of collagenase-3 as a response to infliximab treatment.     

The predictors of foot ulceration in patients with rheumatoid arthritis: a preliminary investigation

We explored the predictors of foot ulceration in patients with rheumatoid arthritis (RA). The cases were 15 patients with RA reporting foot ulceration in response to a postal survey of patients sampled from a diagnostic register in secondary care (n = 1,130). The controls were 66 patients with RA randomly sampled from the survey respondents (n = 883) after matching for age, sex and disease duration. Patients with co-existent diabetes were excluded. Clinical examination included the assessment of known risk factors for foot ulceration in diabetes including: neuropathy (insensitivity to 10 g monofilament), peripheral vascular disease (ankle brachial pressure index [ABPI]), foot deformity (Platto indices) and raised plantar pressure (PressureStat™ readings). A 44 swollen-joint count, the presence of pre-ulcerative lesions and current steroid therapy were identified through univariate analysis as additional potential predictors in patients with RA. Forward step-wise logistic regression analysis showed that the following variables were significant predictors of ulceration: steroid therapy (OR = 9.70, 95%CI = 2.09–45.11, p = 0.004), abnormal ABPI (OR = 13.45, 95%CI = 1.19–151.43, p = 0.035), the presence of pre-ulcerative lesions (OR = 7.40, 95%CI = 1.51–36.30, p = 0.014) and swollen-joint count (OR = 1.25, 95%CI = 1.02–1.53, p = 0.034). Abnormal sensation, foot deformity and raised plantar pressures were not significant predictors of ulceration. The wide confidence intervals for ABPI were due to sparse data with very few abnormal values, and the results of exact logistic regression (more accurate where data is sparse and case matching employed) found that ABPI was no longer a significant predictor (p = 0.054). The significance of the other predictors did not differ substantially. In this preliminary study, abnormal sensation, foot deformity and raised plantar pressures were not significantly associated with foot ulceration but active disease and current steroid therapy were. The contribution of peripheral vascular disease to risk is unclear and further investigation is needed in a larger cohort.     

Different Articular Outcomes of Still’s Disease in Chinese Children and Adults

The clinical manifestations, treatment and course, and articular outcomes of 24 children with juvenile-onset Still’s disease (JOSD) and 21 adults with adult-onset Still’s disease (AOSD) were compared retrospectively. There was no significant difference in the initial clinical and laboratory manifestations except that more adults presented with a sore throat (81% vs 46%, p = 0.03). Although serum ferritin was almost always elevated in both diseases, adults had significantly higher serum ferritin concentrations compared with those of children. Steroid treatment was required in 71% of children and 52% of adults, while disease-modifying antirheumatic drugs were used in 42% of children and 24% of adults during the course. Chronic arthritis (>6 months) occurred in comparable proportions of patients with JOSD and AOSD (46% vs 38%, p = 0.82), irrespective of the disease pattern (monocyclic or polycyclic). However, severe deforming arthritis with marked functional limitation occurred only in JOSD, particularly with polyarthritis at disease onset (more than five affected joints). In contrast, AOSD patients with chronic arthritis had a favourable functional outcome at the end of the follow-up. Our study suggested different articular outcomes of Still’s disease in Chinese children and adults. Received: 19 April 1999 / Accepted: 6 August 1999     

Efficacy and Safety of a Combination Therapy of Methotrexate, Chloroquine and Cyclophosphamide in Patients with Refractory Rheumatoid Arthritis: Results of an Observational Study with Matched-Pair Analysis

The efficacy and safety of a combination of methotrexate (MTX), chloroquine (CQ) and cyclophosphamide (CYC) were studied in patients with refractory rheumatoid arthritis. A single-centre, matched-pair observational study with prospectively gathered data was performed. Fifty-six patients who had previously failed with MTX were treated with 15 mg MTX per week, 50 mg CYC three times a week and 250 mg CQ per day (group A). A 50% improvement of the swollen joint count was required to continue therapy. Data were compared with the results of the previous MTX therapy in the same group and with a matched-patient cohort receiving MTX monotherapy for the first time (group B). In group A, the combination therapy resulted in a significant decline of the swollen joint count after 1 year, in contrast to the previous MTX monotherapy in the same group. Complete remission of joint swelling was achieved in 13 patients (23%), compared with 26 patients in group B (47%). The median duration of effective combination treatment in group A was significantly longer than preceding therapies with MTX alone (19 vs 13 months, p <0.05). However, patients in group B could be treated for a median of 57.5 months (p <0.0001 compared with group A). Side-effects were comparable in both groups. The applied DMARD combination is safe and beneficial in a significant proportion of patients if MTX monotherapy is ineffective. Received: 6 March 1998 / Accepted: 5 October 1998     

Lower extremity ulcers in rheumatoid arthritis: features and response to immunosuppression

Lower extremity ulcers are a recognized complication of rheumatoid arthritis (RA). Their prevalence has not been assessed since the advent of more aggressive disease modifying antirheumatic therapies. The purpose of this study was to establish the period prevalence of lower extremity ulcers in a modern-day unselected cohort of patients with RA, and to report the features associated with ulcer development and response to therapy. Between June 2007 and June 2010, 366 RA patients were evaluated at the Georgetown Division of Rheumatology. Data were collected and analyzed retrospectively on demographics, antibody and prothrombotic profile, comorbidities, disease activity, and outcomes. The period prevalence of ulcers in this cohort of 366 patients with RA followed over 3 years was 4.37%. Patients with ulcers were predominantly female (81.25%) and more commonly African American (56.2%). The mean disease duration at ulcer development was 25.9 years. All patients with ulcers had erosive disease and 63% were seropositive. Only five patients (31.25%) healed over a mean follow-up of 22.8 months. However, in this small sample, treatment with anti-tumor necrosis factor-α (anti-TNFα) therapy was associated with significantly higher likelihood of healing (p = 0.039). In this modern-day cohort of patients with RA, we found a prevalence of lower extremity ulcers of 4.37% over 3 years. Only 31.25% of patients healed after a mean 22.8 months of follow-up. However, treatment with a biologic agent was associated with a significant increased likelihood of healing (RR 3.27, 95% CI 0.59-18.29, p = 0.039).