Background:The clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition disease (CPPD) still remains a hurdle in daily practice without imaging or arthrocentesis. Although a plethora of clinical data exists, reliable predictor biomarkers for all but gout are still missing.Objectives:To explore an association between common physical examination, ultrasound and laboratory findings and gout, OA, and CPPD, which can in turn provide reliable diagnostic predictions.Methods:277 patients were retrospectively analysed using ANOVA with Scheffe’s post hoc tests and conditional inference trees regarding biomarkers such as age, sex, body mass index, hypertension, renal status, cumulative affected joint size, number of afflicted joints, double contour sign, intracartiliginous double contour sign, degree of vascularization on ultrasound (DoV), uric acid, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and leucocyte count. Simple linear regressions were carried out to explore associations between increased inflammatory parameters and the above-mentioned biomarkers. Statistically significant associations were defined as p values < 0.05.Results:The male sex was associated with gout (p value < 0.05 vs CPPD and < 0.05 vs OA). OA affected younger patients than CPPD (mean 64.5 vs 73.1 years, p < 0.05). Hypertension was correlated with gout (p < 0.05) and CPPD (p < 0.05), impaired renal status with gout when compared to OA (p < 0.05) but not compared to CPPD (p 0.21). A higher number of involved joints was associated with gout (mean 2.2 joints) compared to OA (1.0, p < 0.05) and CPPD (1.6, p 0.01). The double contour sign was not able to differentiate gout and CPPD with a sensitivity/specificity of 71%/55% for gout and 59%/39% for CPPD. The intracartilaginous double contour sign was specific for CPPD (99%) but with a low sensitivity of 26%. DoV was significantly associated with gout (vs OA, p < 0.05) and CPPD (vs OA, p < 0.05). Unsurprisingly, uric acid was associated with gout while ESR and CRP were increased in gout and CPPD, but not in OA. Some associations were statistically significant but arguably clinically unimportant. Conditional inference trees were able to exclude OA (specificity 97.5%) and CPPD (specificity 94.0%) as possible differentials based on just uric acid, CRP, hypertension, and sex, and diagnose gout with a sensitivity of 95.1%, summarized in Figure 1. Linear regressions demonstrated an elevated CRP response in people suffering from type II diabetes, higher cumulative joint points score, number of affected joints, as well as elevated uric acid, ESR, and leucocyte count.Figure 1.Conditional inference tree using unbiased recursive partitioning to reliably differentiate between gout, osteoarthritis, and calcium pyrophosphate deposition disease.Conclusion:Gout can be reliably diagnosed, simultaneously excluding OA and CPPD as differential diagnoses by conditional inference trees using just four biomarkers. A correlation between inflammatory reaction severity based on CRP levels was found in patients suffering from type II diabetes, more or larger joint involvement and elevated uric acid levels. The double contour sign remains a questionable differentiator between gout and CPPD with a sensitivity/specificity of 71%/55% for gout and 59%/39% for CPPD, similar to findings reported by Löffler et al (1) with a sensitivity/specificity of only 64%/52% for gout.References:[1]Löffler C, Sattler H, Peters L, Löffler U, Uppenkamp M, Bergner R. Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides. J Rheumatol 2015; 42(3):513–20.Disclosure of Interests:Dmitrij Kravchenko Shareholder of: Pfizer, Raoul Bergner: None declared, Charlotte Behning: None declared, Valentin Schäfer Speakers bureau: AbbVie, Novartis, BMS, Chugai, Celgene, Medac, Sanofi, Lilly, Hexal, Pfizer, Janssen, Roche, Schire, Onkowissen, Royal College London, Consultant of: Novartis, Chugai, AbbVie, Celgene, Sanofi, Lilly, Hexal, Pfizer, Amgen, BMS, Roche, Gilead, Medac, Grant/research support from: Novartis, Hexal, Lilly, Roche, Celgene, Universität Bonn.
Inquiry Is Fatal to Certainty-Is the Ultrasonography Double Contour Sign Specific for Uric Acid-Induced Arthritis?