Topical diclofenac and its role in pain and inflammation: an evidence-based review.

OBJECTIVE: Topical diclofenac is widely used in the treatment of pain and inflammation. This comprehensive review assesses the safety and efficacy of topical diclofenac in a range of painful and inflammatory disorders. METHODS: Double-blind, randomized, placebo- or active-controlled trials (RCT) evaluating topical diclofenac in soft-tissue injuries, soft-tissue rheumatic disorders and osteoarthritis were identified through detailed literature searches. In addition, non-RCT evidence from publications evaluating the pharmacologic characteristics of topical diclofenac were also included in this review to obtain a more complete picture of the drug's profile, its efficacy and safety. RESULTS: Studies demonstrate that the drug preferentially distributes to the target tissues in sufficient concentrations to produce a therapeutic effect. A total of 19 double-blind RCTs in more than 3000 patients, supported by single-blind or open trials, consistently show that topical diclofenac significantly reduces pain and inflammation in acute and chronic conditions compared with placebo and is comparable to other topical non-steroidal anti-inflammatory drugs (NSAIDs) and some oral NSAIDs (diclofenac, ibuprofen, naproxen). Improvements have also been observed in patients' functional capacity and mobility. Topical diclofenac is well tolerated, resulting mostly in mild, easily resolved local skin irritation, and is associated with fewer side-effects than other topical NSAIDs and a lower rate of gastrointestinal complications than oral NSAIDs (diclofenac, ibuprofen, naproxen). CONCLUSION: This evidence-based review shows topical diclofenac to be an effective and well tolerated treatment in painful and inflammatory conditions, at least in the short-term. However, only published RCT studies have been included in this analysis, which may exclude some interesting data from non-RCT studies. Future trials of topical diclofenac need to be of longer duration, be better reported and consider a broader spectrum of acute and chronic pain indications.

Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis--a randomized controlled, cross-over trial.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. AIM: To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole. METHODS: Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed. RESULTS: Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life. CONCLUSION: Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population.

[History and clinical examination in rheumatology--key to diagnosis and prognosis]. / Die Schlüssel zur Diagnostik in der Rheuma- tologie--Anamnese und klinische Untersuchung.

History and clinical examination are key to diagnosis and prognosis in rheumatology. In the area of soft tissue rheumatism, there is no other diagnostic possibility which could replace clinical examination. Clinical examination also plays a very important role in the diagnosis of the other rheumatic disorders. With a competent clinical examination one can often eliminate the need for additional costly and/or time consuming investigations. In addition, diagnosing by purely careful and competent clinical examination is a highly gratifying activity for the medical doctor. The competent examiner should also be able to derive prognostic conclusions directly from the clinical examination. This is especially important for the more frequent disorders such as soft tissue rheumatism or back problems, where diagnostic imaging is only helpful if interpreted in the context of the pertinent clinical question.

Overall tolerability and analgesic activity of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis.

OBJECTIVE: Viscosupplementation with intra-articular hyaluronic acid (HA) is an alternative to the treatment of symptomatic knee osteoarthritis (OA) with pain relieving drugs. Sinovial, is a sterile, non-pyrogenic 0.8% solution of highly purified sodium hyaluronate for intra-articular application. The aim of the present study was to investigate the safety and tolerability profile of this preparation in patients with symptomatic knee OA over 24 weeks. RESEARCH DESIGN AND METHODS: This was a single group, open-label study, including outpatients of both sexes, aged between 18 and 85 years, with symptomatic knee OA. All patients underwent weekly intra-articular injections of HA for 5 consecutive weeks and were followed-up for 19 additional weeks. The safety and tolerability profile (primary endpoint) was assessed by adverse event (AE) reporting. The secondary endpoint was efficacy evaluated by changes in the Western Ontario and McMaster Universities (WOMAC) score vs. baseline. Patient and physician satisfaction were also recorded. RESULTS: Intra-articular HA was generally well tolerated. The most frequent AE was pain at the injection site (5.8% of the injections); no serious treatment-related AE was reported. The WOMAC score was significantly reduced within the first 2 weeks of treatment (from 4.02 +/- 1.90 to 3.55 +/- 2.04, p = 0.0011), further decreased by the end of the injection series (week 6: 2.59 +/- 1.90; p < 0.0001) and maintained during the follow-up (week 24: 2.44 +/- 1.88; p < 0.0001). The WOMAC subscores were also significantly reduced from week 4 for 'pain' and from week 6 for 'stiffness' and 'physical function'. CONCLUSIONS: In the present study, intra-articular HA was well tolerated and safe in patients with symptomatic knee OA. Based on the sustained improvements in WOMAC score and subscores, a carry-over effect lasting for at least 19 weeks after the last injection may be proposed. These results further confirm the evidence of efficacy and safety of intra-articular HA in the management of knee OA.

[The role of PCR for the diagnosis of Lyme arthritis]. / Der Stellenwert der PCR-Diagnostik bei der Lyme-Arthritis anhand von vier Fallbeispielen.

OBJECTIVE, PATIENTS AND METHODS: We studied retrospectively four patients with Lyme arthritis of the knee, the role of PCR for the detection of B. burgdorferi DNA and its influence on further therapeutic decisions. RESULTS: All four patients with Lyme arthritis suffered from knee pain and effusions. None of them remembered having had a tick bite or an erythema migrans. The diagnosis was confirmed by positive serology and in three cases by detection of B. burgdorferi DNA by PCR analysis of the joint fluid. In one patient, PCR was also positive in the synovial tissue. Because of persistent symptoms after adequate antibiotic therapy, PCR was repeated in the joint fluid of two patients. In one patient a positive PCR suggested an ongoing infection. Thus, the antibiotic treatment was changed. A further PCR was negative. Symptoms resolved slowly in all patients over a time of two to seven months after the end of the antibiotic treatment. CONCLUSION: PCR to detect B. burgdorferi DNA in synovial fluid or tissue respectively is a helpful tool for the diagnosis of Lyme arthritis. Moreover, in patients with refractory Lyme arthritis PCR may be helpful in monitoring the course of the disease.

Assessment of heart involvement.

Cardiac involvement frequently occurs in systemic sclerosis (SSc), contributing to the occurrence of symptoms, namely dyspnoea, fatigue, palpitations, and in some instances to the clinical evolution and prognosis of the disease. A thorough baseline screening of heart functioning and appropriate follow-up monitoring is therefore mandatory in all SSc patients. This consists of various simple, non-invasive ambulatory diagnostic procedures (visit, electrocardiogram, chest X-ray, Doppler-bidimensional echocardiogram), which provide information on the presence of rhythm and conduction disturbances, cardiac morphology and function, as well as on the possible presence of pulmonary hypertension (PH). When needed, added tests may be carried out, including long-term ambulatory electrocardiographic recording, assessment of cardiopulmonary performance by the six-minute walking test or cardiopulmonary stress test, cardiac catheterization (mandatory to confirm and better estimate PH), cardiac magnetic resonance imaging, and nuclear studies of myocardial function and perfusion.

Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial.

OBJECTIVE: To assess the efficacy and safety of a diclofenac hydroxyethylpyrrolidine (DHEP) patch in the treatment of symptomatic osteoarthritis (OA) of the knee joint. METHODS: A double-blind, randomised, placebo-controlled trial was carried out on 103 outpatients for 2 weeks. The main efficacy parameters were spontaneous pain and Lequesne's Index. Secondary endpoints were walking time over a standard distance, global assessment of efficacy and tolerability, and paracetamol consumption. RESULTS: The active treatment group showed a significant improvement in pain, Lequesne's Index, and the physician's and patient's global assessment of efficacy. For these parameters the difference between groups was statistically significant in favour of the DHEP patch. Adverse reactions were seen in a small number of probands and were similar in both groups. CONCLUSIONS: The results of this trial suggest that the DHEP patch appears to be an effective and safe treatment for patients suffering from symptomatic knee OA.

Prevalence of TTV DNA and GBV-C RNA in patients with systemic sclerosis, rheumatoid arthritis, and osteoarthritis does not differ from that in healthy blood donors.

OBJECTIVE: To determine the prevalence of GB virus-C (GBV-C) RNA and TT virus (TTV) DNA in patients with systemic sclerosis (SSc), rheumatoid arthritis (RA), and osteoarthritis (OA) as well as to compare the autoantibody pattern in patients with SSc with and without evidence of viral infection. PATIENTS AND METHODS: The study included 168 patients (84 SSc, 41 RA, and 43 OA) diagnosed according to the American College of Rheumatology criteria and 122 volunteer blood donors. The presence of GBV-C RNA and TTV DNA in serum was assessed by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-nested PCR, respectively. Autoantibodies in patients with SSc were determined by enzyme linked immunosorbent assay (ELISA) and Hep-2 immunofluorescence. RESULTS: TTV-DNA was detected in 10/84 (12%) patients with SSc, 9/41 (22%) patients with RA, 3/43 (7%) patients with OA, and 16/122 (13%) blood donors. GBV-C RNA was present in 4/84 (5%) patients with SSc, 2/43 (5%) patients with OA, and 5/122 (4%) blood donors. No patient with RA was positive for GBV-C RNA. One patient with SSc and one patient with OA showed a double infection with GBV-C and TTV. 74/84 (88%) patients with SSc were positive for at least one autoantibody species tested: 18/84 (21%) showed anticentromeric autoantibodies, 55/84 (66%) a speckled (36/84 (43%) fine, 19/84 (23%) coarse), and 20/84 (24%) a homogeneous nuclear Hep-2 pattern, and 21/84 (25%) had antinucleolar autoantibodies. Anti-Scl-70 antibodies were found in 31/84 (37%) and anti-RNP antibodies in 5/84 (6%) patients with SSc. No differences in the autoantibody pattern in patients with SSc with or without viral infection could be detected. CONCLUSION: The prevalence of GBV-C RNA and TTV DNA in serum samples from patients with SSc, RA, and OA was low and comparable with that in blood donors. A continuing infection with TTV and or GBV-C was not associated with a significant change in the autoantibody pattern in patients with SSc. These data provide no evidence for an association between GBV-C and/or TTV infections and SSc and/or arthritis (RA and OA).

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes.

OBJECTIVE: To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS: Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS: A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients. CONCLUSIONS: Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

Osteoarthritis of the scaphoidtrapezium joint: an early sign of calcium pyrophosphate dihydrate disease.

The aim of this study was to determine the value of scaphoidtrapezium osteoarthritis (ST osteoarthritis) as an early sign of calcium pyrophosphate dihydrate disease (CPDD) in a cohort of patients undergoing surgery for osteoarthritis of the first carpometacarpal joint. We examined whether patients with cartilage calcification of the wrist at the time of operation had ST osteoarthritis, indicating CPDD at an earlier time (retrospective study), and whether patients with ST osteoarthritis but without cartilage calcification at the time of surgery develop radiological or clinical signs of CPDD at a later time (prospective study). From 1 January 1989 to 31 December 1995 a total of 169 patients (from an orthopaedic clinic) with a diagnosis of osteoarthritis of the first carpometacarpal joint were included in the study; 167 underwent surgery and two were treated without. Of the 16 patients showing calcification on surgery and therefore included in the retrospective study, 12 had prior radiographs, of which eight showed ST osteoarthritis. Among these, four had no concomitant cartilage calcification in the prior radiographs. Of the 32 patients in the prospective group having ST osteoarthritis but no calcifications at the time of surgery, 27 could be clinically examined. Of these, two showed cartilage calcifications on the follow-up radiographs of the hands. The presence of ST osteoarthritis is a helpful diagnostic finding for the diagnosis of CPDD, especially in cases without radiographic cartilage or fibrocartilage calcification of the wrist. ST osteoarthritis may then point to the correct diagnosis.

Altered diurnal rhythm of prolactin in systemic sclerosis.

OBJECTIVE: Mild hyperprolactinemia has been reported in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We investigated whether the elevated serum level of prolactin (Prl) detected in SSc is due to a sustained increase over 24 h and/or a shift in the diurnal rhythm, and whether Prl autoantibodies--originally described in SLE--may interfere in the assay. METHODS: The serum level of Prl was measured by ELISA and compared between 73 patients with SSc and 73 age and sex matched controls (78% women, age 56 +/- 11 years). The diurnal rhythms of Prl and thyrotropin (thyroid stimulating hormone, TSH) were compared between 3 patients with SSc and 10 healthy controls. Blood was taken at 2-3, 6-7, 10-11 a.m., and 2-3, 6-7, 10-11 p.m. The serum level of Prl autoantibodies was measured by ELISA and compared between matched patients with SSc and SLE and controls (n = 42 each). Standard curves of the Prl ELISA were spiked with 10% sera containing high levels of Prl autoantibodies to test interference. RESULTS: Serum levels of Prl measured in the morning (8-10 a.m.) were significantly higher in patients with SSc (17.9 +/- 7.7 ng/ml), compared with controls (9.3 +/- 4.2 ng/ml; p < 0.05). In SSc, 40% of patients had Prl levels > 20 ng/ml, but no correlation was found with Scl-70 or Prl autoantibodies. Younger patients (< 50 years, n = 23/73) showed higher serum levels of Prl than older patients (21.3 +/- 10.3 vs 16.3 +/- 6.2 ng/ml; p < 0.05). The diurnal rhythm of Prl revealed that both a sustained increase over 24 h and some shift occurred in SSc. Peaks of secretion were detected between 6 and 11 a.m., instead of 2-6 a.m. The median levels of TSH over 24 h in patients with SSc ranged within the normal limits. Nevertheless, in SSc, a significant correlation (r = 0.59, p < 0.01) was found between diurnal rhythms of Prl and TSH. The prevalence of Prl autoantibodies in serum was 8% in SSc, 27% in SLE, and < 5% in controls. However, the presence of Prl autoantibodies did not interfere with our assay. CONCLUSION: Our data confirm that mild hyperprolactinemia occurs in a subgroup of patients with SSc, and showed that the elevated serum level of Prl is due to both a sustained increase over 24 h and a shift in the diurnal rhythm. The correlation between diurnal rhythms of Prl and TSH suggests common regulatory mechanisms.

Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. Oral administration of creatine has been shown to improve muscle strength in healthy subjects. The objective of this study was to examine the effect of oral creatine supplementation on muscle weakness, disease activity and activities of daily living in patients with RA. METHODS: During a period of 3 weeks, 12 patients with RA were treated with creatine monohydrate (20 g/day for 5 days followed by 2 g/day for 16 days). They were examined on entry and at the end of the study. The patients were investigated clinically, blood and urine samples were obtained, muscle biopsies were performed before and after treatment, muscle strength was determined, and self-administered patient questionnaires were completed. RESULTS: From all patients we were able to obtain full clinical and questionnaire data, while biopsies were taken from 12 patients at the start and from nine patients at the end of the study. Muscle strength, as determined by the muscle strength index, increased in eight of 12 patients. In contrast, physical functional ability and disease activity did not change significantly. The creatine concentration in serum and skeletal muscle increased significantly, while creatine phosphate and total creatine did not increase in skeletal muscle. The skeletal muscle creatine content was associated with muscle strength at baseline but not after administration of creatine. The changes in muscle strength were not associated with the changes in skeletal muscle creatine or creatine phosphate. CONCLUSION: Although the skeletal muscle creatine content and muscle strength increased with creatine administration in some patients with RA, a clear clinical benefit could not be demonstrated for this treatment when the patients were considered as one group.

Development and validation of a self-administered systemic sclerosis questionnaire (SySQ).

OBJECTIVE: To develop a self-administered systemic sclerosis questionnaire (SySQ) covering condition-specific functional limitation and symptoms. METHODS An initial item pool was generated by open patient interviews. A preliminary questionnaire was devised using 62 systemic sclerosis (SSc; scleroderma) patients. Factor analysis was used for further selection and grouping of items into distinct scales. The retrieved scales were tested for internal consistency and test-retest reliability. Spearman's rank correlation and Wilcoxon's rank sum test were used to examine hypothesized associations of the SySQ with various clinical and laboratory features. RESULTS: Altogether 32 SySQ items were selected and aggregated into 12 scales addressing 'pain', 'stiffness', 'coldness', 'complex functions', 'strength of hands', 'rising', 'walking', shortness of breath', 'upper airway symptoms', 'eating', 'swallowing' and 'heartburn/regurgitation'. Internal consistency ranged from 0.93 ('complex functions') to 0.73 ('heartburn/regurgitation'); Spearman's correlation coefficient for test retest reliability ranged from 0.93 to 0.73 (P < 0.001). While the scales were associated with corresponding functional impairments, there was generally less association with morphological impairments. CONCLUSION: The SySQ is a valid and reliable condition-specific measure in patients with SSc. Individually applicable scales cover a wide spectrum of general and organ-specific SSc symptoms and functional limitation. After further validation with respect to its ability to measure change, it may be used in clinical, health services and epidemiological research.

Lymphatic microangiopathy of the skin in systemic sclerosis.

METHODS: The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. RESULTS: At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. CONCLUSION: Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

Synovial fluid CD146 (MUC18), a marker for synovial membrane angiogenesis in rheumatoid arthritis.

OBJECTIVE: CD146 (MUC18/MCAM/S-Endo) is a marker of tumor progression and metastasis formation in human melanoma. This molecule has also been identified in smooth muscle, endothelial cells, and activated T lymphocytes. We measured the synovial fluid levels of soluble CD146 in various human joint diseases, including rheumatoid arthritis (RA). In addition, we studied the distribution of CD146 in normal and RA synovial tissues. METHODS: CD146 was isolated from MEL-OH melanoma cells and characterized by Coomassie blue staining and Western blotting. Soluble CD146 was measured by competitive enzyme-linked immunosorbent assay in synovial fluids of 3 healthy individuals and 7 cadavers (controls), as wells as in patients with traumatic joint injury (n = 10), osteoarthritis (OA; n = 10), psoriatic arthritis (PsA; n = 10), other non-RA polyarthritis (NRAP; n = 10), and RA (n = 31). Immunohistochemistry was performed on 3 normal and 3 RA synovial tissues. Flow cytometric, reverse transcription-polymerase chain reaction, and Western blot analyses were performed on enzymatically separated RA synovial tissue cells. RESULTS: Compared with controls (mean +/- SD 10 +/- 2 ng/ml), significantly elevated synovial fluid levels of soluble CD146 were detected in patients with OA, PsA, and RA (17 +/- 7, 21 +/- 11, and 39 +/- 16 ng/ml, respectively; P < 0.02-0.001), but not in patients with traumatic joint injury or NRAP. Patients with early RA (<1 year after diagnosis) revealed the highest levels (51 +/- 15 ng/ml, n = 10; P < 0.001 versus controls). In RA, soluble CD146 correlated significantly with morning stiffness (P < 0.001), the number of tender joints (P < 0.02), and the number of swollen joints (P < 0.005), but not with the erythrocyte sedimentation rate (P = 0.07) or the C-reactive protein level (P = 0.57). CONCLUSION: Since CD146 is expressed almost exclusively by vascular endothelium, high levels of soluble CD146 found in RA synovial fluid, particularly in patients with early disease, could reflect increased activity of endothelial cells and angiogenesis.

Carnitine homeostasis in patients with rheumatoid arthritis.

Myopathy is a frequent finding in patients with rheumatoid arthritis (RA). Since carnitine is important for skeletal muscle energy metabolism, carnitine metabolism was investigated in patients with RA and myopathy. Muscle strength was estimated by determination of a muscle strength index (MSI) which is derived from isometric measurements of muscle strength at knees and elbows. Carnitine was determined by a radioenzymatic method and 3-methylhistidine by high-performance liquid chromatography. In comparison to control subjects, patients had a reduced MSI. Both the 24-h creatinine and 3-methylhistidine excretions were reduced in patients. The plasma carnitine pool was not different between patients and control subjects, except for a higher long-chain acylcarnitine concentration in patients. Urinary excretion of carnitine was decreased in patients, also after normalization for body weight. Accordingly, renal carnitine clearance and excretion fraction were both decreased in patients. Skeletal muscle free- and total carnitine levels were increased in patients, whereas the long-chain acylcarnitine content was markedly decreased. The total skeletal muscle carnitine content showed a negative correlation with the MSI and no association with disease activity. Carnitine deficiency does not explain reduced skeletal muscle strength in patients with RA. Decreased renal carnitine excretion in patients is most likely due to reduced carnitine biosynthesis, leading to more efficient tubular carnitine reabsorption for maintaining the carnitine body stores.