Andrew Gough

Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome.

Monocycline is the most widely prescribed systemic antibiotic for acne largely because it needs to be given only once or twice a day and seems not to induce resistance. Up to April 1994 11 cases of minocycline induced systemic lupus erythematosus and 16 cases of hepatitis had been reported to the Committee on Safety of Medicines. An analysis of these cases together with seven other cases shows the severity of some of these reactions. Two patients died while taking the drug for acne and a further patient needed a liver transplant. Acne itself can induce arthritis and is often seen in association with autoimmine liver disease, but the clinical and biochemical resolution seen after withdrawal of the drug, despite deterioration of the acne, suggests a drug reaction. In five cases re-exposure led to recurrence. Because reactions may be severe early recognition is important to aid recovery and also to avoid invasive investigations and treatments such as corticosteroids and immunosuppresants. Safer alternatives should be considered for treating acne.

Effect of the early use of the anti–tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis

OBJECTIVE To compare work disability and job loss in early rheumatoid arthritis (RA) patients receiving adalimumab plus methotrexate (adalimumab + MTX) versus MTX alone. METHODS In this multicenter, randomized, controlled trial, patients with RA for <2 years who had never taken MTX and who self-reported work impairment were randomized to adalimumab + MTX or placebo + MTX for 56 weeks. Primary outcome was job loss of any cause and/or imminent job loss at or after week 16. Secondary outcomes included disease activity, function (Health Assessment Questionnaire [HAQ] score), and RA quality of life (RAQoL) questionnaire score. Work was evaluated with work diaries and the RA Work Instability Scale. RESULTS Although job loss during the 56-week study was significantly lower with adalimumab + MTX (14 of 75 patients) compared with MTX alone (29 of 73 patients; P=0.005), the primary end point was not met (12 of 75 versus 20 of 73 patients; P=0.092), likely owing to early drop out in the MTX group. There were significant improvements in American College of Rheumatology 20% response criteria, 28-joint Disease Activity Score, DeltaHAQ, DeltaRAQoL, and working time lost in the adalimumab + MTX group. Twenty-four serious adverse events were reported in 17 participants, with no differences between groups. CONCLUSION Adalimumab + MTX reduced job loss and improved productivity in early RA when compared with MTX alone, which supports the early use of anti-tumor necrosis factor therapy and suggests its cost efficacy.

Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.

OBJECTIVE--To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS--Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS--The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p < 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p < 0.01). CONCLUSION--The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA.

Evaluation of finger ultrasound in the assessment of bone status with application of rheumatoid arthritis

Abstract: Osteoporosis associated with active rheumatoid arthritis (RA) has been demonstrated in both the axial and peripheral skeleton, especially the periarticular regions more directly affected by the disease. Quantitative ultrasound (QUS) is a recently accepted tool for the assessment of bone status, and therefore could be used to monitor bone changes in RA patients. In a cross-sectional study we measured ultrasound velocity (Ad-SOS) through the proximal phalanges in three groups of female subjects. These included: 51 patients with rheumatoid arthritis (group 1), 44 general practitioner (GP)-referred patients for osteopenia (group 2) and 52 young healthy volunteers (group 3). For groups 1 and 2 bone mineral density (BMD) of the lumbar spine and proximal femur were also measured. For the RA patients BMD of the hand, measurement of hand function (HAQ and grip strength) and disease activity (ESR and CRP) were also assessed. The precision of long-term Ad-SOS measurements on volunteers gave a root mean square coefficient of variation (CV) of 0.7% and standardized CV of 3.6%. No statistically significant effect of dominance was observed in the measured Ad-SOS between the dominant and non-dominant hand (r= 0.96, p<0.001). Ad-SOS was found to be significantly different in the three groups (p<0.0001). Ad-SOS was highly dependent on age (r=−0.67), with a gradual reduction (−5.2 m/s per year) after the age of 30 years for female patients in both group 1 and group 2. Ad-SOS was significantly correlated with lumbar spine, femoral neck and hand BMD, with correlation coefficients of 0.49, 0.51 and 0.72 respectively for RA patients. Finger ultrasound was moderately correlated with measures of hand function, with coefficients of 0.37 and 0.39 for HAQ and grip strength respectively. Hand BMD also correlated to the same power with these parameters. Neither finger ultrasound nor BMD was significantly correlated with ESR and CRP (measures of disease activity). We have demonstrated that bone status can be assessed quickly and cheaply using a portable QUS device. Ad-SOS relates to the measure of hand function in RA patients. Longitudinal studies are required to determine the usefulness of finger ultrasound for monitoring disease progression or the effect of treatment in RA.

Increased prevalence of poor sulphoxidation in patients with rheumatoid arthritis: effect of changes in the acute phase response and second line drug treatment.

A minority of normal subjects have an impaired ability to oxidise sulphur, which is associated with an increased risk of side effects when they receive sulphur containing drugs. In 114 patients with rheumatoid arthritis a greatly increased prevalence of poor sulphoxidation was found in 82 (72%) patients compared with 70/200 (35%) healthy controls, 45/121 (37%) controls matched for age, and 4/35 (11%) of the normal aged general population. In a longitudinal study of 37 patients there was no significant alteration in sulphoxidation status after the introduction of a second line drug or with marked changes in the acute phase response. It seems, therefore, that the poor sulphoxidation status in patients with RA is not an epiphenomenon and may be an important factor in determining the clinical features of rheumatoid disease.

Use of conservative and surgical foot care in an inception cohort of patients with rheumatoid arthritis

Objectives. To describe conservative and surgical foot care in patients with RA in England and explore factors that predict the type of foot care received. Methods. Use of podiatry and type of foot surgery were outcomes recorded in an inception cohort involving nine rheumatology centres that recruited patients with RA between 1986 and 1998 across England. Associations between patient-specific factors and service use were identified using univariate logistic regression analyses. The independence of these associations was then verified through multiple binary logistic regression modelling. Results. Data were collected on 1237 patients with RA [66.9% females, mean (s.d.) age at disease onset = 54.36 (14.18) years, median DAS = 4.09 (1st quartile = 3.04, 3rd quartile = 5.26), median HAQ = 1 (0.50, 1.63)]. Interventions involving the feet in the cohort were low with only 364 (30%) out of 1218 receiving podiatry and 47 (4%) out of 1237 patients having surgery. At baseline, female gender, increasing age at onset, being RF positive and higher DAS scores were each independently associated with increased odds of seeing a podiatrist. Gender, age of onset and baseline DAS were independently associated with the odds of having foot surgery. Conclusions. Despite the known high prevalence of foot pathologies in RA, only one-third of this cohort accessed podiatry. While older females were more likely to access podiatry care and younger patients surgery, the majority of the RA population did not access any foot care.

Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation

IntroductionGiant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis.MethodsGCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA incidence reported in different countries.ResultsIn our UK data (225 cases and 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, P = 1.5×10−11), but HLA-DRB1*01 was protective (adjusted OR = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2×10−6) and possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R2 = 0.51 on univariable analysis, adjusted R2 = 0.62 after also including latitude); latitude also made an independent contribution.ConclusionsWe confirm that HLA-DRB1*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of HLA-DRB1*04 and with latitude itself. We conclude that variation in population HLA-DRB1*04 frequency may partly explain variations in GCA incidence and that HLA-DRB1*04 may warrant investigation as a potential prognostic or predictive biomarker.

Dietary advice in systemic sclerosis: the dangers of a high fibre diet

Systemic sclerosis frequently affects the gastrointestinal tract.1 However, information on large bowel involvement and dietary advice for patients is scarce. Even the most recent and comprehensive rheumatological text discusses colonic involvement but gives no information on dietary advice or management.2 It is widely felt and advertised that a high fibre diet is “good for all”. We report on four cases, three of whom required emergency admission after receiving such advice. ### CASE 1 A 48 year old woman was admitted with a 10 day history of severe abdominal pain and distension. She had a four year history of diffuse systemic sclerosis and was taking penicillamine and indomethacin. Two weeks before admission she had recounted some difficulty with infrequent bowel motions to a friend, who had advised a high fibre diet. She obtained a high fibre breakfast cereal. Within three days she developed abdominal distension and colicky pain. This lead to colonic atony with no bowel action for 10 days before admission. She was treated with daily picolax and discharged three days later. A barium enema did not reveal any obstructive lesion. She has remained well on her normal low residue diet and has had no similar problems or investigations since. ### CASE 2 A 46 year old woman was admitted with a five day history of abdominal pain and vomiting. She had developed diffuse systemic sclerosis …

The outcome of knee synovitis in early arthritis provides guidelines for management.

Abstract: The aim of the study was to examine the clinical outcome of patients presenting to an early arthritis clinic with synovitis of the knee. The patients were assessed at presentation for evidence and pattern of joint inflammation. These patients were then reassessed at 3, 6 and 12 months and thereafter annually to determine clinical outcome. One thousand six hundred and thirty-three consecutive referrals were examined, 903 of whom had early synovitis. One hundred and thirty had knee synovitis at presentation, of whom 73 fulfilled ACR criteria for rheumatoid arthritis (RA) during the study. All 73 presented with a symmetrical polyarthritis that included the small joints and had persistent disease at 1 year. Of the remaining 57 patients, 61% of those presenting with an oligoarthritis and 33% with a polyarthritis (including knee synovitis) were in remission at 1 year. None of those presenting as a monoarthritis of the knee had inflammation at 1 year or fulfilled ACR criteria for RA at any time. It was concluded that patients presenting with knee synovitis in the absence of a small joint polyarthritis usually have a benign course following standard therapy. No patient who presented with monoarthritis developed RA. Knee synovitis as part of a polyarthritis (even when not fulfilling ACR criteria) probably justifies disease-modifying antirheumatic drug at presentation.

Current treatment of rheumatoid arthritis

Spence makes some challenging observations about rheumatoid arthritis.1 His assertion that it is becoming less common is difficult to answer as current criteria are different from those used in the 1950s, when most forms of inflammatory arthritis were thought to be rheumatoid. His view that the disease is now milder is also impossible to answer as treatment outcomes have improved dramatically. How can we …