Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

Background: Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. the aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma.Methods: A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ).Results: There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them.Conclusions: Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Rheumatol, São Paulo, BrazilUniv Santo Amaro, Discipline Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Rheumatol, São Paulo, BrazilFAPESP: 01-13895-9Web of Scienc

The Repercussions of Spinal Cord Injury on the Action of the Diaphragmatic Crura for Gastroesophageal Reflux Containment

Study Design. Cross-sectional and nonexperimental.Objective. To detect and compare functional abnormalities in the esophagus and esophagogastric junction in 2 groups with chronic spinal injuries, 1 with injuries at the phrenic innervation level and the other at upper thoracic levels, and to relate these to gastroesophageal reflux containment.Summary of Background Data. There are no studies on esophageal manometry with pH metering among spinal cord injury patients. Worldwide statistics reveal that the prevalence of gastroesophageal reflux disease among spinal cord injury patients is greater than among the general population, at around 22% to 27%. the diaphragmatic crura has been recognized as an important antire-flux barrier and should functionally be considered to be a muscle separated from the costal diaphragm. However, doubts remain regarding whether this difference relates to its innervation.Methods. This was a cross-sectional study on 29 patients with complete spinal cord injuries: 14 quadriplegics (level C(4)) and 15 paraplegics (levels T(1)-T(7)). Functional abnormalities of the esophagogastric junction, esophagus, and diaphragm were investigated using esophageal manometry and diaphragmatic video fluoroscopy. Presence of gastroesophageal reflux was investigated subjectively (pyrosis and regurgitation) and objectively (pH metering and endoscopy).Results. the incidence of gastroesophageal reflux disease was 27.6%, without difference between the groups. This became statistically significant when the mean diaphragmatic crural pressures were compared (quadriplegics: 37.5 +/- 17.8; paraplegics: 26.6 +/- 7.2; P = 0.048). It was also significant in relation to the prevalence of at least one of the objective and/or subjective reflux findings and/or esophageal peristaltism (quadriplegics: 85.7%; paraplegics: 40.0%; P = 0.011).Conclusion. Spinal injury at the level of the phrenic innervation did not predispose the quadriplegics toward greater risk of developing gastroesophageal reflux disease. Paradoxically, manometry showed significantly greater crural contractility among the quadriplegics.Universidade Federal de São Paulo, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Digest Physiol Sector SEFIDI, Discipline Surg Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Digest Endoscopy Sector, São Paulo, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, Radiol & Ultrasonog Sector, São Paulo, BrazilUniversidade Federal de São Paulo, Rehabil Ctr, Lar Escola Sao Francisco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, São Paulo, BrazilUniversidade Federal de São Paulo, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Digest Physiol Sector SEFIDI, Discipline Surg Gastroenterol, São Paulo, BrazilUniversidade Federal de São Paulo, Digest Endoscopy Sector, São Paulo, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, Radiol & Ultrasonog Sector, São Paulo, BrazilUniversidade Federal de São Paulo, Rehabil Ctr, Lar Escola Sao Francisco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, São Paulo, BrazilWeb of Scienc