RESUMO
Brief resolved unexplained events (BRUEs) have numerous and varied causes posing a challenge to investigation and management. A subset of infants with the neuromuscular disorder sodium channel myotonia, due to mutations in the SCN4A gene, experience apnoeic events due to laryngospasm (myotonia) of the upper airway muscles that may present as a BRUE. We sought to ascertain the frequency, severity and outcome of infants carrying the G1306E SCN4A mutation commonly associated with this presentation. We report 12 new cases of individuals with the G1306E mutation from three unrelated families and perform a literature review of all published cases. Infants with the G1306E mutation almost universally experience laryngospasm and apnoeic events. The severity varies significantly, spans both low and high-risk BRUE categories or can be more severe than criteria for a BRUE would allow. At least a third of cases require intensive care unit (ICU) care. Seizure disorder is a common erroneous diagnosis. Apnoeas are effectively reduced or abolished by appropriate treatment with anti-myotonic agents. Probands with the G1306E mutation who are family planning need to be counselled for the likelihood of post-natal complications. There is readily available and extremely effective treatment for the episodic laryngospasm and apnoea caused by this mutation. Proactively seeking clinical evidence of myotonia or muscle hypertrophy with consideration of CK and EMG in high risk BRUEs or more complex apnoeic events may reduce avoidable and prolonged ICU admissions, patient morbidity and potentially mortality.
RESUMO
The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.