Medicine's inconvenient truth: the placebo and nocebo effect.

Placebo and nocebo effects are often regarded by clinicians as either a quaint reminiscence from the pre-therapeutic era, or simply as a technique for establishing the efficacy of therapeutic interventions within the locus of evidence-based practice. However, neither of these explanations sufficiently account for their complexity or their persistence and impact in clinical medicine. Placebo and nocebo effects are embedded in the very fabric of therapeutic relationships and are both a manifestation and outcome of the rituals that characterise clinical practice. They are also a stark reminder of the many personal and environmental factors, including the attitudes, beliefs and expectations of both doctor and patient, that shape the outcomes of health professional-patient interactions. We describe how recent biological and neuropsychiatric data have clarified the operation of placebo and nocebo effects in clinical practice - demonstrating the ability of the therapeutic context to modulate endogenous biological processes in a targeted manner. This, in turn, illustrates the potent philosophical and sociocultural aspects of medical praxis.

Infectious arthritis of the knee caused by Mycobacterium terrae: a case report.

Mycobacterium terrae is ubiquitous in our environment. M terrae infections most commonly involve tendon sheaths, bones, bursae, and joints. We report a case of infectious arthritis of the knee caused by M terrae in a 21-year-old man who had non-specific chronic synovitis. No organism was seen on microscopy or isolated from cultures until months later. Initially the M terrae culture was considered a contaminant and specific anti-mycobacterial treatment was not advised. The patient was commenced on suppressive therapy for persistent effusion and discomfort. Eventually, the M terrae infection was confirmed and he was commenced on clarithromycin, ciprofloxacin, and ethambutol. The triple antibiotic regimen was continued for 2 years. The knee improved but never completely settled. The patient chose to cease all antibiotic medication. The knee remained swollen and irritable, with little chance of eradicating the organism.

Tenoxicam compared with diclofenac in patients with ankylosing spondylitis.

A randomized study was performed on 24 patients with ankylosing spondylitis to compare the efficacy and tolerability of 20 mg tenoxicam daily with 50 mg diclofenac twice daily. There were 6 withdrawals from the group taking tenoxicam and 4 from the diclofenac group. Depression in 1 patient taking tenoxicam was the only significant adverse event. Both drugs were otherwise well tolerated. Tenoxicam and diclofenac were rated as good or excellent by 27% and 55% of patients, respectively. Global assessment, pain and duration of morning stiffness were improved with both drugs but this improvement was not statistically significant and there was no statistically significant difference between the two groups. This study confirms that tenoxicam is effective and well tolerated but larger numbers would be required to detect a small difference between groups.

The sensitivity and specificity of reduced CD8 lymphocyte levels in the diagnosis of polymyalgia rheumatica/giant cell arteritis.

The aim of this study was to determine whether the sensitivity and specificity of measuring CD8+ T lymphocyte percentages and numbers could be diagnostically useful in the assessment of polymyalgia rheumatica/giant cell arteritis (PMR/GCA). Double immunofluorescence and FACScan analysis were used to identify and quantify the CD3+CD8+ lymphocyte population. The absolute cell numbers were determined by a Coulter Counter. Random disease controls were used for comparison with 30 patients diagnosed as PMR/GCA. Both the percentage of CD3+CD8+ cells (17.4% PMR/GCA group vs 30.5% control) and the absolute numbers of CD8+ lymphocytes (310 cell/ml PMR/GCA vs 723 cells/ml control) were significantly reduced (p < 0.001) in the PMR group. The sensitivity of reduced CD8+ percentages for diagnosis was 73% and the specificity was 85%. Analysis of likelihood ratios showed that CD8+ lymphocyte percentages < 22.15% were five times more likely in patients with PMR/GCA than in controls. Data suggested that reduced CD8+ lymphocyte levels may be useful in the initial clinical assessment of patients with PMR/GCA. Only a larger study can establish whether these parameters should be used as diagnostic criteria.

Splenic and renal infarction in systemic lupus erythematosus: association with anti-cardiolipin antibodies.

A 37-year-old female, known to have systemic lupus erythematosus (SLE) and markedly raised anti-cardiolipin antibody levels in association with the lupus anticoagulant, presented with a symptomatic segmental splenic infarction. There was a past history of cerebral infarction. Abdominal computed tomography (CT) demonstrated the area of splenic infarction, and an asymptomatic right renal infarct. This patient illustrates the unusual occurrence of multiple visceral infarcts, in association with anti-cardiolipin antibodies, complicating SLE.

A destructive discovertebral lesion: septic discitis, ankylosing spondylitis, or rheumatoid arthritis?

A 41-year-old male with a 20-year history of classical ankylosing spondylitis, psoriasis and seropositive, nodular erosive rheumatoid arthritis presented with a 12-month history of thoracolumbar junction pain following minor trauma. A pseudoarthrosis was noted at the T11/12 level on plain radiographs and tomograms. A gallium scan showed no increased isotope uptake, and a computed tomogram (CT) revealed no evidence of a paraspinal collection. Conservative management including cast immobilisation and local radiotherapy was ineffective, and spinal fusion was required. A typical Andersson lesion was found at operation. The diagnostic and therapeutic problems of such discovertebral lesions are discussed.

Infra-red surface thermography. Evaluation of a new radiometry instrument for measuring skin temperature over joints.

A study is reported of the evaluation of a new portable, light-weight, infrared thermometer, for the measurement of the skin temperature over joints. A high degree of reproducibility was observed, but no increase in heat was found over selected rheumatoid joints. The instrument will prove useful in detecting temperature changes in disease states where the changes are considerable, and where the ambient temperature can be strictly controlled.

Poststreptococcal reactive arthritis.

Five cases (three children and two young women) of sterile inflammatory arthritis are described, each preceded by a streptococcal infection. A throat swab from one patient grew group A, beta haemolytic streptococci, and in each case unequivocal evidence of seroreaction to streptococcal antigens was present. The long term outcome in all cases was excellent, though one patient (female, 24 years of age) required prophylactic penicillin for three months. The diagnosis of a definite recent streptococcal infection is sometimes difficult as throat swabs may be negative and the diagnostic serological reaction missed unless antibodies to multiple antigens (particularly antistreptolysin O and DNAase B) are tested. These cases may represent a reactive arthritis and should be distinguished from rheumatic fever, streptococcal septic arthritis, viral arthritides, acute rheumatic diseases such as juvenile chronic arthritis, and a monoarticular presentation of a seronegative spondyloarthropathy.

Sjögren's syndrome beyond the eye.

Sjögren's syndrome is a common systemic disease with major clinical manifestations in the eye, mouth and musculoskeletal system. The major clinical presentations of Sjögren's syndrome are reviewed with emphasis on diagnostic criteria, laboratory features, complications and treatment.

Tophaceous gout of the axial skeleton.

A 72-year-old female with a recent episode of podagra, without peripheral tophi, presented with nocturnal back pain and a destructive lesion of the right lamina of L4. A tophus was excised at laminectomy. Evidence of an axial skeletal tophus causing an irritative radiculopathy via mass effect is presented.

Variability in response to nonsteroidal anti-inflammatory analgesics: evidence from controlled clinical therapeutic trial of flurbiprofen in rheumatoid arthritis.

1. A clinical trial was conducted with flurbiprofen 100 mg three times a day by mouth in rheumatoid arthritis to determine variability in response. 2. Forty patients entered the study, but only 32 completed it. Patients were treated with flurbiprofen on two occasions at a month's interval, each being preceded by a 3 day wash out period. Pain relief and a Ritchie articular index of joint tenderness was assessed at the beginning and end of each treatment period. 3. Flurbiprofen produced significant improvement in both pain relief and articular tenderness. No significant differences were observed between the two trial periods in the mean of these outcome measures. 4. No evidence was found to support the concept of responders and non-responders.

Comparative analgesic and anti-inflammatory properties of sodium salicylate and acetylsalicylic acid (aspirin) in rheumatoid arthritis.

1. Enteric coated sodium salicylate 4.8 g daily was compared with the same dose of enteric coated aspirin in 18 patients with rheumatoid arthritis. 2. After an initial washout period lasting 3 days, patients were randomly allocated to treatment with sodium salicylate or aspirin. After 2 weeks the two treatments were crossed over. 3. Pain relief, reduction in articular index of joint tenderness, increase in grip strength, decrease in digital joint circumference and patients' assessment showed significant improvement with both treatments compared with the washout period. No significant differences were found between the two therapies. 4. No correlation was found in the degree of improvement in any of the clinical outcomes and the salicylate concentrations at steady state.

Comparative controlled trial of low-dose weekly methotrexate versus azathioprine in rheumatoid arthritis: 3-year prospective study.

Fifty-three patients with rheumatoid arthritis who required immunosuppressive therapy were commenced in a randomized trial comparing azathioprine to weekly oral pulse methotrexate. After an initial 24-week period, both groups had significantly improved from baseline measures of pain and functional capacity and there were no significant differences in clinical outcomes between the two groups. Laboratory variables of disease activity showed a significant improvement in haemoglobin and ESR in the methotrexate group. Subsequently, the patients were followed for up to 3 years. After one year, more than half of the patients in both groups had discontinued therapy due to inefficacy or adverse events. Adverse effects were more frequent in the patients treated with methotrexate, but withdrawal rates were similar in both groups. From these data, the probability of a patient continuing therapy with either agent for greater than 18 months is low.

The cycling of combination antirheumatic drug therapy in rheumatoid arthritis.

In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications. Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein. This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment. Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months. Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects.