Background: Chronic low back pain (LBP), the leading symptom of ankylosing spondylitis (AS) and undifferentiated axial spondyloarthritis (SpA), precedes the development of radiographic sacroiliitis, sometimes by many years. Objective: To assign disease probabilities and to develop an algorithm to help in the early diagnosis of axial SpA. Methods: Axial SpA comprises AS and undifferentiated SpA with predominant axial involvement. Clinical features include inflammatory back pain (IBP), alternating buttock pain, enthesitis, arthritis, dactylitis, acute anterior uveitis, a positive family history, psoriasis, inflammatory bowel disease, and good response to NSAIDs. Associated laboratory findings include raised acute phase reactions, HLA-B27 association, and abnormalities on skeletal imaging. Sensitivities, specificities, and likelihood ratios (LRs) of these parameters were determined from published studies. A 5% prevalence of axial SpA among patients with chronic LBP was used. The probability of the presence of axial SpA, depending on the presence or absence of the above clinical features of SpA, was determined. A probability of ⩾90% was used to make a diagnosis of axial SpA. Results: The presence of inflammatory back pain features increased the probability of axial SpA from the background 5% prevalence to 14%. The presence of 2–3 SpA features was necessary to increase the probability of axial SpA to 90%. The highest LRs were obtained for HLA-B27 and MRI. Diagnostic algorithms to be used in daily practice were suggested. Conclusions: This approach can help clinicians to diagnose with a high degree of confidence axial SpA at an early stage in patients with IBP who lack radiographic sacroiliitis.

https://ard.bmj.com/content/annrheumdis/63/5/535.full.pdf

How to diagnose axial spondyloarthritis early

Ankylosing spondylitis (AS) is a common chronic inflammatory disease with an estimated prevalence of 0.2–1.2% (1–4). The disease typically starts during the third decade of life and has a substantial socioeconomic impact on the patient and society (5–7). Until recently, the treatment options for AS were limited. The mainstays of treatment were regular physical therapy and nonsteroidal antiinflammatory drugs (NSAIDs) (8). In contrast, disease-modifying antirheumatic drugs (DMARDs) as well as corticosteroids, which are quite effective in some of the other chronic inflammatory diseases such as rheumatoid arthritis (RA), show only very limited or no efficacy in AS (9–11). Thus, in the past, a delayed diagnosis did not have much of an adverse consequence because of the lack of highly effective therapeutic choices. Most recently, it has been convincingly demonstrated that the tumor necrosis factor (TNF )– blocking agents infliximab and etanercept have a strong and prompt effect on almost all features of AS, such as clinical disease activity, physical function, spinal mobility, peripheral arthritis, enthesitis, and levels of acutephase reactants (12–19). In several studies of AS patients whose disease was refractory to NSAIDs and physical therapy, 50% of the patients have demonstrated at least a 50% improvement when treated with either of the two TNF -blocking compounds. It has also been shown that active juxtaarticular bony inflammation (“bone edema”), as detected by magnetic resonance imaging (MRI), can be suppressed (20,21), and it is hoped that this kind of treatment will also favorably influence long-term outcome, including reduction or prevention of radiologic progression. Recent data also show that AS patients with a short disease duration and good functional status are more likely to respond to TNF -blocking agents than patients with longstanding disease and impaired function (22). Thus, an early and reliable diagnosis of AS has now become an important and very relevant issue.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.20990

The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria?

We performed 2 metaanalyses of placebo-controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second-line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P < 0.0001), DP (P < 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second-line drugs. None of the reported interdrug comparative trials we reviewed were this large.

For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P < 0.05) and higher total dropout rates (P < 0.01) than any other drug; 30% of goldtreated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second-line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs. If a curative drug is not found, large multicenter trials or data synthesis from multiple drug trials may be necessary to identify new treatment regimens that have promise.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780331001

The comparative efficacy and toxicity of second‐line drugs in rheumatoid arthritis results of two metaanalyses

Hemodynamics and Survival in Patients With Pulmonary Arterial Hypertension Related to Systemic Sclerosis

Study Design. Systematic review. Objective. To systematically assess benefits and harms of nonsurgical interventional therapies for low back and radicular pain. Summary of Background Data. Although use of certain interventional therapies is common or increasing, there is also uncertainty or controversy about their efficacy. Methods. Electronic database searches on Ovid MEDLINE and the Cochrane databases were conducted through July 2008 to identify randomized controlled trials and systematic reviews of local injections, botulinum toxin injection, prolotherapy, epidural steroid injection, facet joint injection, therapeutic medial branch block, sacroiliac joint injection, intradiscal steroid injection, chemonucleolysis, radiofrequency denervation, intradiscal electrothermal therapy, percutaneous intradiscal radiofrequency thermocoagulation, Coblation nucleoplasty, and spinal cord stimulation. All relevant studies were methodologically assessed by 2 independent reviewers using criteria developed by the Cochrane Back Review Group (for trials) and by Oxman (for systematic reviews). A qualitative synthesis of results was performed using methods adapted from the US Preventive Services Task Force. Results. For sciatica or prolapsed lumbar disc with radiculopathy, we found good evidence that chemonucleolysis is moderately superior to placebo injection but inferior to surgery, and fair evidence that epidural steroid injection is moderately effective for short-term (but not long-term) symptom relief. We found fair evidence that spinal cord stimulation is moderately effective for failed back surgery syndrome with persistent radiculopathy, though device-related complications are common. We found good or fair evidence that prolotherapy, facet joint injection, intradiscal steroid injection, and percutaneous intradiscal radiofrequency thermocoagulation are not effective. Insufficient evidence exists to reliably evaluate other interventional therapies. Conclusion. Few nonsurgical interventional therapies for low back pain have been shown to be effective in randomized, placebo-controlled trials.

Nonsurgical interventional therapies for low back pain: a review of the evidence for an American Pain Society clinical practice guideline.

We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 +/- 32 ml/minute/100 gm, mean +/- SD) and in controls (100 +/- 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 +/- 45 ml/minute/100 gm) than in controls (399 +/- 58 ml/minute/100 gm) (P less than 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.

Decreased coronary reserve in primary scleroderma myocardial disease

Destructive arthropathy in chondrocalcinosis articularis.

Two sets of criteria have been proposed to discriminate spondylarthropathies (SA) from other rheumatic diseases. To evaluate their performance, we conducted a cross-sectional study in the patients observed during one week in 28 French Departments of Rheumatology by 91 staff-teaching physicians. The physicians had to apply these criteria to all their patients and had to classify them as definite SA, definite other rheumatic disease or possible SA. The analysis performed on the 2,088 patients with a definite diagnosis (124 SA and 1,964 controls) showed the following results: (table; see text) Of the 140 patients with possible SA, 37 fulfilled both sets of criteria, 22 the ESSG criteria alone and 12 the Amor criteria alone. These data suggest that a) the overall performance of these two sets of criteria is similar; b) this performance is better in the group of patients with a definite diagnosis; c) the patients without a definite diagnosis require a longer follow-up to assess the clinical relevance of these two sets of criteria.

[Evaluation of the Amor criteria for spondylarthropathies and European Spondylarthropathy Study Group (ESSG). A cross-sectional analysis of 2,228 patients].

The findings are reported of a controlled clinical trial comparing in 66 rheumatoid arthritis patients 0 g (placebo), and 0.50 g a day and 1 g a day of penicillamine. Each of these groups has been subdivided into two, one part receiving 5 mg a day of zinc metal supplement, the other a placebo. The trial was planned to be double-blind, and for each patient to take part for 4 months. The results prove the effectiveness of penicillamine in rheumatoid arthritis. 0.50 g a day has the same effect as 1 g a day but gives less side effects. Zinc supplement inhibits the clinical effects of penicillamine but does not prevent the side effects.

Menkes Cj

Papers

Decreased coronary reserve in primary scleroderma myocardial disease

Destructive arthropathy in chondrocalcinosis articularis.

[Evaluation of the Amor criteria for spondylarthropathies and European Spondylarthropathy Study Group (ESSG). A cross-sectional analysis of 2,228 patients].

Controlled Trial of D-Penicillamine in Rheumatoid Arthritis: Dose Effect and the Role of Zinc

Reduced coronary flow and resistance reserve in primary scleroderma myocardial disease.