Oral manifestations associated with inherited hyperhomocysteinemia: A first case description.

Hyperhomocysteinemia is a rare disease caused by nutritional deficiencies or genetic impairment of cysteine metabolism. To date, no oral manifestations of hyperhomocysteinemia have been described in humans. Therefore, to our knowledge, the present case report is the first description of a hyperhomocysteinemic patient showing oral tissue alterations leading to both early tooth loss and failed implant osseointegration. The patient presented with a methylenetetrahydrofolate reductase gene mutation (677T polymorphism) leading to mild hyperhomocysteinemia. The radiologic analysis showed hyperdense lesions scattered in the maxillae. The histologic observations indicated alterations in both collagen and elastic networks in the gingiva and dermis. Interestingly, the presence of ectopic mineralized inclusions was noted in both periodontal ligament and gingiva. Strong osteoclastic activity was associated with abnormal calcification of trabecular spaces. Uneven oral tissue remodeling due to high tissue levels of homocysteine could explain the pathologic manifestations observed in this case.

Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence.

Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP.

HLA-B27 prevalence in axial spondyloarthritis patients and in blood donors in a Lebanese population: Results from a nationwide study.

AIM: To calculate the prevalence of human leukocyte antigen (HLA)-B27 in axial spondyloarthritis patients (axSpA) compared to blood donors (BD) in Lebanon, to identify the clinical and radiological findings associated with HLA-B27 and to estimate the proportion of patients fulfilling the clinical arm of the Assessment of the Spondyloarthritis International Association (ASAS) criteria. METHOD: Consecutive Lebanese adult axSpA patients fulfilling the ASAS classification criteria were included from 12 rheumatology clinics across Lebanon. BD served as controls. A binary logistic regression was used to study the association between HLA-B27 and the disease features. RESULTS: A total of 247 individuals were included (141 axSpA patients and 106 BD). The prevalence of HLA-B27 was 3.8% in BD and 41.1% in axSpA. Overall, 39.7% of the axSpA patients fulfilled the clinical arm of the ASAS classification criteria. Sensitivity of HLA-B27 for axSpA was 41.1%, specificity was 96.2%, positive predictive value was 93.6%, and negative predictive value was 55.13%. Positive likelihood ratio (LR) was 10.9 and negative LR was 1.63. We found a positive association of HLA-B27 with family history of SpA and psoriasis. CONCLUSION: Our study confirmed a low prevalence of HLA-B27 in axSpA patients and BD in this Lebanese population, However, we found a high specificity and positive LR, as well as the same number of axSpA patients fulfilling the clinical arm of the ASAS criteria as in European studies. HLA-B27 is therefore valuable for identification of axSpA in Lebanese patients despite the overall low prevalence in this population. Our results may guide future evaluations the role of HLA-B27 in planning local referral strategies.

Effects of clopidogrel on soluble CD40 ligand and on high-sensitivity C-reactive protein in patients with stable coronary artery disease.

BACKGROUND: Antiplatelet therapy with clopidogrel decreases ischemic complication especially in patients with acute coronary syndromes or after percutaneous coronary interventions. Our study was designed to test the effects of clopidogrel on soluble CD40 ligand (sCD40l) and on high-sensitivity C-reactive protein (hs-CRP) in patients with stable coronary artery disease (CAD). METHODS: This is a randomized, double-blind, placebo-controlled study. A total of 73 patients with stable CAD for > 6 months were randomized to receive either clopidogrel (loading dose 300 mg followed by 75 mg/d) for 8 weeks or placebo. Soluble CD40 ligand and hs-CRP were measured at baseline and at completion of the study. RESULTS: All patients were on aspirin therapy, and 74% were on statins. Median and interquartile ranges (IQR) of sCD40l decreased from 64 pg/mL (43-99) at baseline to 53 pg/mL (35-77) at 8 weeks (P = .03) in the clopidogrel group and remained unchanged in the placebo group (59 pg/mL, IQR 35-77 vs 55 pg/mL, IQR 35-78) (P = non significant). Levels of hs-CRP were not affected by therapy and remained unchanged in both groups. CONCLUSIONS: In patients with stable CAD, clopidogrel inhibits the release of sCD40l by platelets, which may contribute to the clinical benefit provided by this drug. This, however, does not translate in a reduction of subclinical inflammation, as measured by hs-CRP.