Effectiveness of Nonpharmacologic Treatments of Burning Mouth Syndrome: A Systematic Review.

AIMS: To assess the efficacy of nonpharmacologic treatments for burning mouth syndrome (BMS). METHODS: PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were systematically searched. Reference lists from the latest systematic reviews (2015 to 2020) on BMS treatment in the PubMed, Scopus, Web of Science, and Cochrane Library databases were also scrutinized. Randomized controlled trials (RCTs) or clinical controlled trials (CCTs) in English were considered eligible. Trials on photobiomodulation were excluded to avoid redundancy with recent publications. Risk of bias was established through the Cochrane Risk of Bias tool for RCTs and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool for CCTs. RESULTS: This review included 27 RCTs and 6 open clinical trials (OCTs) describing 14 different nonpharmacologic interventions. Eleven trials experimented with 600 to 800 mg/day of alpha-lipoic acid for 30 to 120 days, with 7 placebo-controlled studies showing significant pain relief. Four trials tested topical and systemic capsaicin for 7 to 30 days, with 2 placebo-controlled studies revealing significant efficacy. Four of the 5 trials testing acupuncture offered favorable evidence of pain relief. Two trials reported significant pain relief after a 2- to 3-month regimen with tongue protectors and showed no difference after aloe vera addition. Short-term pain relief was reported in anecdotal placebo-controlled trials deploying tocopherol, catuama, ultramicronized palmitoylethanolamide, group psychotherapy, cognitive therapy, and repetitive transcranial magnetic stimulation of the prefrontal cortex. Most therapies were safe. CONCLUSION: Evidence was collected from highly biased, short-term, heterogenous studies mainly focused on BMS-related pain, with scarce data on quality of life, psychologic status, dysgeusia, and xerostomia. Long-term effectiveness of nonpharmacologic treatments should be further investigated, with a more rigorous, bias-proof study design.

The Cutaneous Spectrum of Lupus Erythematosus.

Systemic lupus erythematosus is a complex autoimmune disease with a wide spectrum of clinical and immunopathological features. Cutaneous and articular manifestations are the most common signs in patients with systemic lupus erythematosus. We here review the pathogenesis and the new classification of cutaneous lupus erythemathosus with a discussion of the significance of the various cutaneous signs. The lesions are classified according to the level of the cellular infiltrate and tissue damage in the epidermis, dermis, and/or subcutis. Furthermore, cutaneous lesions pointing to the presence of a thrombotic vasculopathy and those due to a distinct inflammatory, neutrophilic-mediated reaction pattern are highlighted. Particular attention will be given in describing the histology of skin manifestation. Treatment options for cutaneous lupus erythemathosus have increased with the introduction of new biological therapies. However, the majority of the patients still benefit from antimalarials, which remain the cornerstone of treatment. The evaluation and management of cutaneous lupus erythemathosus patients depend on the clinical findings and associated symptoms.

Ubiquinol Effects on Antiphospholipid Syndrome Prothrombotic Profile: A Randomized, Placebo-Controlled Trial.

OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. APPROACH AND RESULTS: Thirty-six patients with APS were randomized to receive Qred (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q10. Qred improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Qred ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Qred. Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Qred on thrombosis and endothelial function-associated molecules. CONCLUSIONS: Our results highlight the potential of Qred to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Qred might act as safe adjunct to standard therapies in APS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476.

Novel diagnostic and therapeutic frontiers in thrombotic anti-phospholipid syndrome.

The anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity, associated with a persistent positivity for anti-phospholipid antibodies (aPL). The current classification criteria for APS include three laboratory tests: lupus anti-coagulant (LA), anti-cardiolipin (aCL), and anti-ß2 glycoprotein-I (ß2GPI). To date, the therapeutic approach for thrombotic APS mainly centers on long-term anti-coagulation with a vitamin K antagonist (VKA). APS management may represent a challenge for the treating physicians. Patients with different aPL profiles need a tailored risk-stratified approach. Moreover, in patients with recurrent thrombotic events despite therapy with VKA, or in those with microvascular involvement, new therapeutic options are highly needed. In this review, we aim to elucidate recent findings about new aPL specifities, available risk scoring models, and novel therapeutic approaches in APS management.

Upcoming biological therapies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, intermingled with flares and periods of remission. Although the prognosis of the disease has improved in the past decades, current therapies are still associated with treatment-related complications. Recently, there has been major progress in the understanding of the pathogenesis of SLE, paving the way for the development of new biological agents, potentially revolutionizing the treatment of SLE. This review summarizes available data on novel biological therapies for SLE, focusing on recent results from clinical trials. As a result of treatment strategies based upon an individualized therapeutic approach, it is hoped that the clinical view of SLE will change from a severe autoimmune disease to a condition in which significant damage, mortality and treatment related complications can be prevented in the majority of SLE patients.

Rheumatoid arthritis: Biological therapy other than anti-TNF.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and is characterized by synovitis that causes joint damage. The introduction of biologic agents has made it possible to induce remission in many patients and inhibit joint damage. Activated T cells in RA patients proliferate and stimulate the production of pro-inflammatory cytokines including tumor necrosis factor (TNF) and interleukin 6 that play important roles in RA pathogenesis. The most widely used biologic agents indicated for RA inhibit the activity of TNF. However, newly developed biologic drugs targeting different pathways are now currently part of the therapeutic options to induce remission in patients with RA. The present review focuses on biologic agents directed at molecular targets different from TNF and addresses the possible advantages of these drugs.

Unexplained chronic cough and vitamin B-12 deficiency.

BACKGROUND: Chronic cough is characterized by sensory neuropathy. Vitamin B-12 (cobalamin) deficiency (Cbl-D) causes central and peripheral nervous system damage and has been implicated in sensory neuropathy and autonomic nervous system dysfunction. OBJECTIVE: We evaluated whether Cbl-D has a role in chronic, unexplained cough. DESIGN: Laryngeal threshold (histamine concentration that provokes a 25% decrease in the midinspiratory flow), bronchial threshold (histamine concentration that provokes a 20% decrease in the forced expiratory volume in 1 s), and cough threshold (histamine concentration that causes ≥5 coughs) in response to an inhaled histamine were assessed in 42 patients with chronic, unexplained cough [27 Cbl-D patients and 15 patients without Cbl-D (Cbl-N)] before and after intramuscular injections of cobalamin for 2 mo. Laryngeal, bronchial, and cough hyperresponsiveness was diagnosed when histamine concentration thresholds were ≤8 mg/mL. Seven Clb-D and 3 Cbl-N patients underwent an oropharyngeal biopsy before treatment. RESULTS: Cbl-D patients had a higher prevalence of laryngeal hyperresponsiveness than did Cbl-N patients (92.6% compared with 66.7%; P = 0.03), a thinner oropharyngeal epithelium [133.7 µm (95% CI: 95, 172 µm) compared with 230.8 µm (95% CI: 224, 237 µm); P = 0.002], a lower number of myelinated nerve fibers [2.25/mm(2) (95% CI: 1.8, 2.7/mm(2)) compared with 3.44/mm(2) (95% CI: 3, 3.8/mm(2)); P = 0.05], and a higher immunoreactive score for nerve growth factor (NGF) [6.7 (95% CI: 6, 7.3) compared with 2.8 (95% CI: 2.5, 3.1); P = 0.02]. After cobalamin supplementation, symptoms and laryngeal, bronchial, and cough thresholds were significantly improved in Cbl-D but not in Cbl-N patients. CONCLUSIONS: This study suggests that Cbl-D may contribute to chronic cough by favoring sensory neuropathy as indicated by laryngeal hyperresponsiveness and increased NGF expression in pharyngeal biopsies of Cbl-D patients. Cbl-D should be considered among factors that sustain chronic cough, particularly when cough triggers cannot be identified.