Achalasia and Associated Neuromuscular Diseases
Yes, achalasia is significantly associated with several autoimmune and neuromuscular conditions, most notably systemic sclerosis and Addison's disease, with an overall odds ratio of 1.49 for autoimmune conditions. 1
Strongest Autoimmune Associations
Systemic sclerosis (SSc) and Addison's disease demonstrate the strongest associations with achalasia in a large retrospective case-control study of 1,141 achalasia cases versus 3,423 matched controls (OR 1.49; 95% CI, 1.23-1.80). 1 These autoimmune conditions appear to share pathophysiologic mechanisms involving immune-mediated destruction of the myenteric plexus. 1
Eosinophilic and Allergic Disease Associations
The relative risk of eosinophilic esophagitis (EoE) in achalasia patients is dramatically elevated at 32.9 (95% CI, 24.8-42.8), particularly in patients 40 years or younger. 1
Esophagectomy specimens demonstrate dense eosinophil accumulation in the muscularis propria, where eosinophils and mast cells produce neuroactive and myoactive substances causing neuronal destruction characteristic of achalasia. 1
Atopic and allergic disorders show increased relative risk among achalasia patients. 1
A critical pitfall: esophageal eosinophilia may result from food stasis rather than primary eosinophilic disease, but when clinical suspicion is high for comorbid EoE, eradication of eosinophilic infiltration may improve esophageal function. 1
Infectious Causes Mimicking Primary Neuromuscular Disease
Chagas disease (Trypanosoma cruzi) causes esophageal dysfunction through immune cross-reactivity between the flagellar antigen and myenteric plexus, resulting in megaesophagus in 10-15% of chronically infected individuals. 1 This affects an estimated 300,000 individuals in the United States. 1 Serologic testing reliably diagnoses T. cruzi infection and excludes idiopathic achalasia. 1
COVID-19-associated achalasia has emerged as a new entity, with SARS-CoV-2 targeting neuronally expressed ACE2 receptors and triggering ganglionic cell destruction. 1 Tissue analysis shows 625-fold higher N protein in post-COVID achalasia patients compared to longstanding type 2 achalasia, with elevated inflammatory markers NLRP3 and TNF. 1
Paraneoplastic Associations
Achalasia occurs as a paraneoplastic phenomenon in lymphoma, lung cancer, and breast cancer (beyond esophageal adenocarcinoma). 1 This represents secondary achalasia from malignancy-related neuronal destruction. 1
Clinical Approach to Screening
Initial evaluation must include targeted history for concurrent autoimmune disease, allergic conditions, and immunosuppression risks. 1
- Screen specifically for systemic sclerosis symptoms (skin changes, Raynaud's phenomenon, dysphagia) 1
- Assess for Addison's disease features (hyperpigmentation, hypotension, electrolyte abnormalities) 1
- Evaluate atopic history and eosinophilic disease risk factors 1
- In endemic areas or at-risk populations, obtain Chagas serology 1
- Document recent COVID-19 infection, particularly with acute symptom onset 1
- Consider malignancy screening in appropriate clinical contexts 1
Important Caveats
The evidence does not support associations with infantile pyloric stenosis, Hirschsprung's disease, Hodgkin's disease, or motor neurone disease despite historical speculation. 2 Diabetes occurs at expected population frequencies in achalasia patients. 2
Guidelines for systematic evaluation of extra-esophageal or systemic etiologies remain lacking, but awareness of these associations empowers appropriate diagnostic testing and collaboration with rheumatology, allergy/immunology, and infectious disease specialists. 1