Lessons from an international survey of paper cases of 10 real patients from an early arthritis clinic. CRI (Club Rhumatismes et Inflammation) Group.

OBJECTIVE: To determine how experts would classify 10 early-arthritis cases (7 atypical) and to study discrepancies in diagnoses relative to ACR criteria for rheumatoid arthritis (RA) or ESSG criteria for spondyloarthropathy (SpA). METHODS: Ten real cases (5 met ACR criteria for RA, 6 ESSG criteria for SpA, 3 both and 2 neither) followed for 28.5 +/- 4.8 months were sent as paper cases to 20 international and 12 French experts. Each expert selected a diagnosis among 8 possible choices and rated it on a 0-10 confidence scale. For each case, 3 analog scales (0-100 mm) were used to indicate the probability of RA, SpA or undifferentiated arthritis (UA). RESULTS: Experts often disagreed about diagnoses (up to 5 different diagnoses for a given case, with a mean of 3.9 per case). Similarly, expert opinions on probabilities for RA and SpA differed widely, with great overlap between confidence for RA, SpA and UA. Fulfilment of ACR or ESSG criteria was poorly related to the experts' diagnosis and evaluation of probabilities for RA and SpA. However, UA was a relatively infrequent choice (19%). CONCLUSIONS: There was no general consensus about the nosology of early RA and SpA. Classification of atypical early arthritis was not resolved by currently available criteria for RA and SpA. This may have implications for therapy in early disease.

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.

A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992.

OBJECTIVE: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors. RESULTS: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Cross cultural adaptation and validation of the Chinese Health Assessment Questionnaire for use in rheumatoid arthritis.

OBJECTIVE: The Health Assessment Questionnaire - Disability Index (HAQ), used as a disability and outcome measurement in rheumatoid arthritis (RA), has been validated in several languages, but not in Chinese. Our aim was to validate the Chinese version of HAQ (Chinese-HAQ) to suit the needs of Chinese speaking patients with RA in an Asian setting. METHODS: The original HAQ was modified in the context of Chinese culture and translated into Chinese by 2 translators aware of the objective of the questionnaire. The Chinese HAQ was self-administered by 42 patients with RA during their routine followup visit and one week later. RESULTS: The test-retest reliability assessed using Spearman's correlation coefficient was 0.84. Between dimensions measured in the HAQ, the highest test-retest reliability was observed for walking (Spearman correlation coefficient rs=0.80) and the lowest was for eating (rs=0.54). The internal consistency of the scale using Cronbach's alpha was high at 0.86. In terms of criterion validity, the Chinese-HAQ score was found to correlate well with American College of Rheumatology functional status (rs=0.501, p=0.01). The Chinese-HAQ scores also correlated well with markers of disease activity such as patient's perception of pain measured on a visual analog scale (rs=0.55, p < 0.001), grip strength in mm Hg (rs=-0.55. p < 0.001 ), and physician's assessment of disease activity (rs=0.59, p < 0.001). CONCLUSION: The Chinese HAQ is a reliable and valid instrument for studies measuring disability of patients with RA in Singapore.

The effects of ethnicity on disease patterns in 472 Orientals with systemic lupus erythematosus.

OBJECTIVE: To determine the effects of ethnicity on disease manifestations in Oriental patients with systemic lupus erythematosus (SLE) and to describe the risk of developing renal or central nervous system (CNS) involvement with time. METHODS: A retrospective study of 472 patients with SLE seen at the only Rheumatology Unit in Singapore. The effect of ethnicity on selected disease manifestations at diagnosis was assessed after adjusting for demographic variables using multiple logistic regression. The probability of developing selected disease manifestations with time was determined using the Kaplan-Meier product limit method. RESULTS: At diagnosis, Malays had a higher risk of renal or CNS involvement than Chinese (OR 2.26, 95% CI 1.21 to 4.21, and OR 3.07, 95% CI 1.01 to 9.34, respectively), and Indians a lower risk of malar rash and a higher risk of oral ulcers than Chinese (OR 0.30, 95% CI 0.13 to 0.68, and OR 2.90, 95% CI 1.45 to 7.34, respectively). The prevalence of renal or CNS involvement in the entire cohort increased with time, reaching 75.6% (95% CI 66.1% to 85.0%) and 16.7% (95% CI 11.7% to 21.6%), respectively, after 18 years of disease. CONCLUSION: Ethnicity influenced disease manifestations at diagnosis in this cohort of Oriental patients with SLE. Renal or CNS involvement developed in previously unaffected patients up to 18 years after diagnosis, highlighting the need for continued vigilance in patients with lupus.

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.

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 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.

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.

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.

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.

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.

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.

Mycotic aneurysm of a coronary artery in SLE--a rare complication of salmonella infection.

We describe a 27y old female systemic lupus erythematosus (SLE) patient with salmonella bacteraemia who presented with fever, back pain and an enlarging heart size. A two dimensional echocardiogram (2D Echo) showed a mass in the right atrium. Subsequent computer tomographic (CT) and magnetic resonance imaging (MRI) studies showed that this had become a ring shaped lesion at the posterior end of the interventricular septum with an area communicating with the right atrial cavity. At operation a ruptured mycotic aneurysm of the right coronary artery was found. This is the first report of an SLE patient with a coronary artery mycotic aneurysm due to salmonella and the first reported case of survival following rupture of such aneurysm.

Possible protective role of HLA-B*2706 for ankylosing spondylitis.

HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of the HLA molecule itself is still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found that the B*2706 allele has a significant negative association with disease (p = 0.047). Together with recent data indicating the existence of AS "protective" B27 alleles, our data shows that the HLA molecule itself plays a crucial role in disease development.

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.

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.

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.

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.