Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions.

Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.

Cervical spine surgery in ankylosing spondylitis: is the outcome good?

OBJECTIVE: To assess retrospectively, the outcome of cervical spine surgery in patients with ankylosing spondylitis (AS). METHODS: A cross-sectional study of 3464 patients with identified AS, 19 patients of whom had cervical spine surgery. A self-administered questionnaire (including the use of 10 cm visual analogue scales, 0 = none, 10 = worst) assessing the complications of the surgery, patients' neck symptoms and post-surgery functional ability was sent to the 19 patients. Available casenotes and radiographs were reviewed. RESULTS: The mean duration of follow-up was 10 years. One patient had two separate cervical spine operations. The types of surgery performed included cervical fusion (n=7), osteotomy (n=7) and laminectomy (n=6). Six patients had minor complications as a result of surgery. The majority of patients (93%) felt that their surgery had been successful. Most patients (81%) had a reduction in neck pain (mean pain score=3.1, SD 2.8) but increased neck stiffness (mean stiffness score=8.0, SD 2.9). Postoperative radiographs of 7 patients showed complete ankylosis of the cervical spine. Generally, few patients reported difficulty with reading/watching television (6%), sleep (19%) or driving (36%). A third of the patients were still in full time employment. CONCLUSIONS: About 1 in 200 patients with AS undergo cervical spine surgery. The surgery is often successful and complications are usually minor. Neck pain is often better after surgery and any remaining neck symptoms do not significantly affect the patient's sleep or functional activities. In this retrospective study, the long term outcome of cervical spine surgery in patients with AS appears to be good.

Ankylosing spondylitis in Singaporean Chinese--a clinical profile.

The clinical characteristics of 38 local Chinese ankylosing spondylitis patients were studied by interview, clinical examination and review of casenotes. The sex ratio was 3.2:1 in favour of males. The average duration from onset of symptoms till diagnosis of disease was 7.25 years. Peripheral joint involvement occurred in 71% of the patients. Extra-articular complications were uncommon; only three patients had a history of uveitis and one patient had biopsy proven IgA nephropathy. 26.3% of patients had significant disability due to the disease. Early diagnosis of the disease should be made as it may improve the prognosis of the patients.

Left ventricular myxoma, adrenal tumour and cutaneous vasculitis--a case report.

Cardiac myxoma has myriad presentations including cutaneous vasculitis. It has also been associated with endocrine neoplasm in Carney's Complex. We report a Chinese patient with cutaneous vasculitis and Raynaud's phenomenon suggesting a collagen vascular disease. In the course of investigation, echocardiogram showed a possible left ventricular myxoma and computed tomography of the abdomen demonstrated a left adrenal tumour. Cardiac myxoma should be considered in the differential diagnosis of vasculitis.

Polyneuropathy following intra-muscular sodium aurothiomalate for rheumatoid arthritis--a case report.

A patient with rheumatoid arthritis developed rapid onset of peripheral neuropathy whilst on treatment with intra-muscular (IM) gold (Sodium Aurothiomalate). At the time of admission, the arthritis was relatively quiescent. Electromyogram showed evidence of sensorimotor polyneuropathy. Investigations excluded other causes of polyneuropathy. Sural nerve biopsy did not reveal inflammation or vasculitis. The patient's condition improved after cessation of gold therapy. Gold induced neuropathy should be considered in a patient with rheumatoid arthritis who presents with polyneuropathy while on gold therapy.

Open lung biopsy in systemic lupus erythematosus patients with pulmonary disease.

Open lung biopsy is an important diagnostic tool in immunocompromised patients with lung disease. This study evaluates the efficacy and safety of this procedure as part of the diagnostic work up in patients with Systemic Lupus Erythematosus (SLE) and lung disease. The casenotes of twelve SLE patients who had open lung biopsy were reviewed and the patients' clinical characteristics, laboratory investigations and outcome of the open lung biopsy were noted. Ten patients had bilateral reticulo-nodular opacities in the chest radiographic film while one had a persistent nodule in the right lower lobe and one had a normal chest X-ray. All the lung biopsy specimens had a diagnostic yield, e.g. interstitial pneumonitis, pneumonia, interstitial fibrosis and miliary tuberculosis. Three patients developed complications post-operatively, namely superimposed infection and pneumothorax. All responded to treatment. There were no deaths attributable to the surgical procedure. The high diagnostic yield and low morbidity in open lung biopsy support its use in the evaluation of pulmonary disease in SLE.

Ankylosing spondylitis in Singapore: a study of 150 patients and a local update.

This paper presents the results of a clinical study of 150 patients in Singapore with ankylosing spondylitis (AS) and reviews recent developments locally with regards to the disease. The patients were predominantly males (ratio 7:1) and Chinese (n = 147). The onset of disease is usually in the early twenties and there was a mean delay of 6.3 years before diagnosis was made. Peripheral joint involvement is common but apart from uveitis (17%), extra-articular manifestations are rare. AS patients have abnormal lipid profiles and lower bone mineral density compared to healthy controls. HLA*B2704 is the predominant subtype in our Chinese patients whilst HLA*B2706 was found only in healthy controls. Intensive group physiotherapy is beneficial for patients with spondyloarthropathy.

Clinical presentation and disease associations of gout: a hospital-based study of 100 patients in Singapore.

The aim of this retrospective study was to characterise the clinical presentation and disease associations of Oriental patients with gout seen in our hospital over a six-month period. One hundred patients comprising of 77 males and 23 females [89% Chinese, 7% Malays, 2% Indians and 2% others; mean age was 50.9 years (range 18 to 82 years), mean age at onset of disease was 43.7 years (range 16 to 78 years)] were studied. The disease was familial in 18% and 44% of patients had a history of alcohol ingestion. Co-morbid conditions included hypertension (36%), hyperlipidaemia (25%), renal failure (17%), ischaemic heart disease (13%), diabetes mellitus (4%), systemic lupus erythematosus (3%), psoriasis (2%) and ankylosing spondylitis (1%). The majority of patients (68%) had at least one associated disease. At the onset of disease, the joints commonly involved were the ankles (39%) and knees (27%) whilst the first metatarsophalangeal (MTP) joint was affected in only 26% of cases. Polyarticular onset was uncommon (n = 6). The precipitating factors reported by the patients included food (n = 23), alcohol (n = 12), drugs (n = 4), trauma (n = 3) and surgery (n = 2). Eleven patients had a history of renal calculi and 15% had tophaceous gout. Majority of patients (71%) had been treated with urate-lowering drugs (allopurinol). We concluded that gout in Singapore predominantly affects middle-aged men who often have an accompanying illness.

The safety of weekly low dose oral methotrexate in an Oriental population with rheumatoid arthritis.

A retrospective review of 50 oriental patients with rheumatoid arthritis treated with weekly oral methotrexate showed adverse events in 15 (30%) patients with 19 occurrences (38%) of leucopaenia (4%), pancytopaenia (2%), gastrointestinal symptoms (18%), hepatic transaminase elevation (6%), rash (2%) and infections (6%). The median duration of treatment with methotrexate was 11 months (range 1 to 105 months). Pancytopaenia occurred in 1 patient with renal failure. All adverse events resolved with cessation of therapy and on several occasions, despite continued therapy. Methotrexate was discontinued permanently in 2 and temporarily in 7 patients as a result of adverse events. No recurrence of adverse events was noted on restarting methotrexate therapy in patients with non life-threatening adverse events. No increase in adverse events was noted in 14 patients treated with a combination of methotrexate and anti-malarial therapy. We conclude that methotrexate was well tolerated by the Oriental patients with rheumatoid arthritis in our study and could be safely restarted in those patients with non life-threatening adverse events.

Clinical usefulness of needle muscle biopsy in twenty-four patients with proximal weakness.

Muscle biopsy is an important tool in the evaluation of muscle disease. This was performed on twenty-four patients using the percutaneous needle method. Useful findings were obtained in all twenty-four patients. The method is safe, convenient and reliable and should be considered as a practical alternative to open muscle biopsy.

Clinical predictors of nephritis in systemic lupus erythematosus.

We identified clinical predictors of lupus nephritis presenting more than 6 months after the diagnosis of lupus in a cohort of 335 lupus patients. Almost 24% (80/335) of patients developed nephritis more than 6 months after the diagnosis of lupus. Using a Cox proportional hazards model, we found hypertension, thrombocytopaenia and leukopaenia to be associated with lupus nephritis presenting more than 6 months after diagnosis, with adjusted relative risks of 2.5 (95% CI 1.3 to 4.7), 4.3 (95% CI 1.7 to 10.8) and 3.2 (95% CI 1.7 to 6.2) respectively. In this cohort, hypertension, thrombocytopaenia and leukopaenia were associated with lupus nephritis presenting more than 6 months after the diagnosis of lupus.

Systemic lupus erythematosus: initial manifestations and clinical features after 10 years of disease.

We studied the initial manifestations and late features in our lupus patients. The clinical data of patients fulfilling the American College of Rheumatology criteria for systemic lupus erythematosus (SLE) were entered prospectively for newly diagnosed patients and cumulatively for those with at least 10 years of disease duration. Ninety-seven Group A (newly diagnosed; 86 females and 11 males; mean age 31 years; 83 Chinese, 11 Malays, and 3 Indians) and 58 Group B (more than 10 years disease duration; 56 females and 2 males; mean age 41 years; 50 Chinese, 5 Malays, and 3 Indians) lupus patients were studied. The commonest clinical features in Group A were: haematological (73%), arthritis (57%), malar rash (43%), renal disorder (31%) and photosensitivity (30%). Group B patients had haematological (78%), malar rash (73%), arthritis (69%), renal disorder (59%) and photosensitivity (33%). Renal disorder was significantly increased over the years (P < 0.001). Hypertension was present in 18% (Group A) and 59% (Group B) (P < 0.00001), diabetes mellitus in 5% (Group A) and 10% (Group B) (P = ns), atherosclerosis in 2% (Group A) and 7% (Group B) (P = ns). Cataract formation was not present in Group A patients but was present in 10% of Group B patients. Renal disorders and morbidity factors like hypertension and cataracts increased significantly over the years. Optimum treatment of lupus patients should therefore include close attention to these factors.

Pulmonary haemorrhage in Oriental patients with systemic lupus erythematosus.

We reviewed the case records of 10 Oriental patients with systemic lupus erythematosus (SLE) who developed pulmonary haemorrhage (PH) between 1987 and 1996 to determine their clinical presentation and outcome. All the patients had clinical evidence of PH including a sudden onset of dyspnoea, tachycardia, fall in haemoglobin (at least 1.5 gm%) and bilateral diffuse alveolar infiltrates on chest radiographs. At the time of PH, nine patients had a disease duration of 2 years or less and all the patients had clinical and/or laboratory evidence of active lupus disease. Fever and lung crepitations were present in 90% of patients while haemoptysis and chest pain occurred in only three and two patients, respectively. All the patients were treated with high dose intravenous corticosteroids and in addition seven had a combination of pulse methylprednisolone and cyclophosphamide, and four had received plasmapheresis. Four patients died as a result of PH. One patient died of pneumonia three years after recovering from PH while the remaining five had no recurrence of PH after a median follow-up of 22 months. Our study suggests that PH in Oriental lupus patients often occurs early in the disease, rarely presents with haemoptysis and has a high mortality despite aggressive immunosuppressive therapy.

Non-thyphoidal salmonellosis in patients with systemic lupus erythematosus. A study of fifty patients and a review of the literature.

The objective of this study was to characterize the clinical profile of lupus patients with non-typhoidal salmonellosis. A retrospective review of the clinical charts of lupus patients diagnosed with bacteriologically proven non-typhoidal salmonellosis over the last 20 y was undertaken, paying special attention to risk factors, clinical presentation and treatment outcome. Most episodes were bacteraemic without a localizing focus; and some patients were afebrile. They usually occurred in patients prone to opportunistic infections, and at times of increased immunosuppression given for lupus flares (especially nephritis). However, salmonellosis also occurred in some patients presenting with lupus. The C-reactive protein level was found to be significantly higher during the infective episodes compared to episodes of non-infective febrile lupus flare. All isolates were sensitive to the usual first-line antibiotics and eminently treatable with 3 weeks of appropriate antibiotics without recurrence/persistence or significant morbidity/mortality, the exceptions being spinal osteomyelitis and septic arthritis involving deformed joints requiring surgical debridement and prolonged antibiotic therapy for eradication. Mortality occurred in the setting of septic shock from mixed-microbial sepsis and major organ failure from active lupus. There is a high association of non-epidemic, non-typhoidal salmonellosis with SLE, especially in patients with active disease on intensified immunosuppression. The C-reactive protein value may be helpful in distinguishing between fever from a pure lupus flare and one complicated by infection.

Fatigue in ankylosing spondylitis: its prevalence and relationship to disease activity, sleep, and other factors.

OBJECTIVE: To assess the symptom of fatigue in patients with ankylosing spondylitis (AS) with regard to its prevalence and its relationship to disease activity and other factors. METHODS: A self-administered questionnaire, including visual analog scales to assess fatigue, other components of disease activity, and functional ability (the Bath AS Functional Index, BASFI) was sent to 350 patients with AS. Questionnaires were completed and returned by 295 patients (84% response rate). Statistical analyses were descriptive and predictive and included t tests, chi-squared tests, and multiple regression. RESULTS: Sixty-five percent of the patients (n = 192) described fatigue as a major symptom (F+ group) while 31% (n = 91; F- group) did not consider it to be important (4% noncommittal). Excluding fatigue, the mean of a disease activity composite score was significantly higher in the F+ group (5.26, standard deviation (SD) + or - 2.33) than in the F- cohort (3.67, SD + or - 2.09, p <0.001). The former group also had significantly worse scores on the functional index (BASFI mean 5.87, SD + or - 2.42 vs 4.29. SD + or - 2.46, p <0.001). Of the total, 55% had, on occasion, suffered fatigue without accompanying pain or stiffness. After controlling for other factors, pain (p <0.001), functional disability (BASFI, p <0.001) and stiffness (p <0.05) were significantly associated with level of fatigue. The F+ group reported more sleep disturbance, with 41 % (compared to 26% of the F- group) waking more than 3 times a night (p = 0.04). In addition, usual fatigue on waking was more common in the F+ group (71 vs 36%, p <0.001). CONCLUSION: (1) Fatigue is a major symptom in the majority of patients with AS, in particular those with more severe disease; (2) fatigue is more likely to occur with active disease but may also occur as a lone symptom. (3) those with severe fatigue function less well; and (4) the management of fatigue remains an enigma - exercise, for example, having only an equivocal effect.

Association of HLA-DRB1*0405 with extraarticular manifestations and erosions in Singaporean Chinese with rheumatoid arthritis.

OBJECTIVE: To determine the association of disease related HLA-DRB1 locus with disease severity and extraarticular features in Singaporean Chinese patients with rheumatoid arthritis (RA). METHODS: 70 patients with RA and 80 controls were typed for HLA class II alleles by the polymerase chain reaction-sequence specific oligonucleotide probe method. RESULTS: 56 patients (80%) had erosive disease; 51 were seropositive (73%), and 16 had extraarticular features (23%). Patients with HLA-DRB1*0405 had significantly higher prevalence of extraarticular features (43 vs 10%; p = 0.001) and erosions (93 vs 71%; p = 0.022) compared to those without the allele. There was also a greater frequency of seropositivity and joint surgery, and a higher number of second line agents used by patients with HLA-DRB1*0405 in comparison to those without, although the difference was not statistically significant. CONCLUSION: HLA-DRB1*0405 is associated with the presence of extraarticular features and erosions in Singaporean Chinese patients with RA.

Systemic lupus erythematosus in 61 Oriental males. A study of clinical and laboratory manifestations.

The clinical and laboratory features of 61 oriental male lupus patients were compared to those of 86 oriental female patients to determine whether gender differences occur. Arthritis was significantly less common in the males. Neuropsychiatric disorders were less frequent but the difference did not reach statistical significance. Renal disease was the commonest clinical manifestation and diffuse proliferative glomerulonephritis the dominant histological finding on renal biopsy in the males. The prevalences of leucopenia and antibodies to extractable nuclear antigens in particular anti-Ro (SSA) and anti-La(SSB), were lower in men. Arthritis and serositis were less common in our oriental males in contrast to the caucasian patients. These findings provide further evidence of differences between the genders in SLE and suggest racial factors may affect clinical presentation.

Low dose amitriptyline in ankylosing spondylitis: a short term, double blind, placebo controlled study.

OBJECTIVE: To define the effect of low dose amitriptyline on fatigue, pain, and stiffness in patients with ankylosing spondylitis (AS). METHODS: One hundred consecutive patients with AS were randomized to receive low dose amitriptyline up to 30 mg nightly or placebo for 2 weeks. Patients were assessed by the Bath Ankylosing Spondylitis Disease Activity (BASDAI) and Functional (BASFI) Indices pre and post-treatment. RESULTS: Eighty-eight patients (44 amitriptyline, 44 placebo) completed the study. Eight (5 amitriptyline, 3 placebo) stopped treatment because of side effects (e.g., drowsiness, dryness of mouth) and 4 provided insufficient data. Compared to placebo, the patients taking amitriptyline showed significantly greater improvement in restful sleep (66 vs 20%; p < 0.001) and their disease activity scores [BASDAI amitriptyline 1.18 (23%) vs placebo 0.52 (10%); p = 0.024]. All other variables showed a trend to greater improvement by amitriptyline, although the differences were not statistically significant. CONCLUSION: (1) In a 2 week study, low dose amitriptyline significantly improved sleep in AS and was well tolerated; (2) as defined by BASDAI, there was a significant reduction in disease activity with amitriptyline; (3) compared to placebo, there was a nonsignificant trend toward improvement in function; and (4) in spite of improvement in pain, fatigue, and sleep with amitriptyline, stiffness was not increased.

Characterisation of anticytoplasmic antibodies and their clinical associations.

OBJECTIVES: To characterise the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) of human epithelial (HEp-2) cells and the antigens recognised using additional serological techniques. To define the disease associations of anticytoplasmic antibodies. METHODS: Sera from 1173 patients were screened for cytoplasmic IF staining on HEp-2 cells and the patterns characterised. The presence of antimitochondrial antibodies (AMA) was evaluated by a sensitive anti-pyruvate dehydrogenase complex enzyme linked immunosorbent assay (ELISA) (IgG) and by immunoblotting. Detection of antibodies to extractable nuclear antigens (ENA) was performed by double immunodiffusion and the presence of anti-ribosomal P antibodies was determined by immunoblotting. RESULTS: Cytoplasmic IF staining was demonstrated in 75 sera (6.4%). Six different patterns were recognised: coarse granular filamentous speckles (AMA, n = 9); condensed large speckles (anti-golgi apparatus antibodies, n = 3); cytoskeletal (n = 9); centriolar (n = 4); diffuse coarse speckles (n = 33); and fine speckles (n = 17). Of the nine sera with an AMA pattern, the presence of these antibodies was confirmed in seven by the ELISA (n = 6) and on immunoblotting (n = 7). One of the seven patients had primary biliary cirrhosis, and two had scleroderma. Two patients with anti-golgi antibodies had rheumatoid arthritis and two with anticentriolar antibodies had scleroderma. Of 33 sera that had cytoplasmic staining and were ANA negative, three were positive for anti-Ro and two were positive for anti-Jo-1 antibodies. CONCLUSIONS: In general, defined cytoplasmic IF patterns have no specific disease associations. However, the finding of cytoplasmic fluorescence should not be ignored, as it may indicate the presence of antibodies to ENA in the absence of nuclear staining.