Achalasia and thyroid disease: possible autoimmune connection?

Abstract

SUMMARYMany cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B-and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. Arq Bras Endocrinol Metab. 2012;56(9):677-82 SUMáRioMuitos casos têm sido publicados mostrando uma coexistência entre as doenças autoimunes da tireoide (DAIT) e outras doenças autoimunes. Cerca de um quarto dos pacientes com acalasia têm doenças da tireoide concomitantemente, sendo a mais comum a associação com hipotireoidismo. Apesar de ser relativamente rara, a associação da acalasia e hipertireoidismo requer atenção. A fisiopatologia da doença de Graves (DG) envolve os linfócitos B e T-mediados, os quais têm afinidade pelos antígenos da tireoide: tireoglobulina, tireoperoxidase e receptor de tireotrofina. Atualmente, a real fisiopatogenia da acalasia continua desconhecida. No entanto, alguns importantes achados em análise são sugestivos de mecanismo autoimune: infiltração significativa do plexo mioentérico pelos monócitos, presença do antígeno-DQwl do Complexo Humano de Histocompatibilidade classe II e presença de anticorpos contra neurô-nios mioentéricos. Este presente caso aborda um paciente que, apesar de testes negativos para doença de Chagas, tem acalasia que progrediu para o desenvolvimento de significativa perda ponderal e piora da sua qualidade de vida, posteriormente, diagnosticado com hipertireoidismo. Após dilatação endoscópica esofágica e ablação da glândula tireoide com radioiodo, houve grande melhora na condição clínica do paciente. Arq Bras Endocrinol Metab. 2012;56(9):677-82

Expression and significance of interleukin-17 and interleukin-22 in the serum and the lower esophageal sphincter of patients with achalasia

“…A number of reports from China and abroad have described an association between AC and a variety of IMIDs. [ 15 16 17 ] As discussed earlier, AC has been observed to be closely related to other IMIDs, and a large number of immune complexes have been identified in patients with AC. Storch et al .…”

Autoimmune comorbidity in achalasia patients

“…Furthermore, there is evidence of autoantibodies against myenteric neurons in serum samples from patients with achalasia, especially in carriers of HLA DQA1*0103 and DQB1*0603 allele . Indeed, a cluster of diverse autoimmune diseases has been linked to achalasia: autoimmune thyroid disease, rheumatoid arthritis, Sjögren's syndrome, scleroderma, myasthenia gravis, Guillain–Barré syndrome, and vitiligo, among others …”

“…The proposed virus candidates include the Herpes simplex virus‐1 and the Varicella zoster virus, acting as causative and/or promoting factors in development of the chronic and recurrent inflammation that accompanies the disease state . Furthermore, isolated cases of patients with achalasia and a concomitant autoimmune diagnosis (i.e., uveitis, type I diabetes, rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, myasthenia gravis, hypothyroidism, polymyositis, vitiligo, and Guillain–Barré syndrome) have been reported …”

Megaesophagus in a Line of Transgenic Rats

“…59 The current leading hypothesis is that achalasia is due to inflammation of the myenteric plexus in the esophagus triggered by an initial insult such as a familial, infectious, or autoimmune cause. 14,34,61,64 The denervation and loss of ganglion cells in the myenteric plexus both in the esophageal body and the LES is a common feature directly linked to abnormal esophageal function 36,61 but is not a consistent finding in all achalasia cases. 61 Similarly, in dogs, it is debatable if the difference in the numbers of myenteric ganglion cells plays a significant role in this disease.…”