What is the diagnostic and treatment approach for a patient presenting with symptoms of esophageal spasm, to rule out other serious conditions and manage symptoms effectively?

Esophageal Spasm: Can't-Miss Diagnoses

Critical First Step: Rule Out Cardiac Ischemia

Before accepting an esophageal spasm diagnosis, cardiac evaluation must be completed first, as ischemic heart disease carries substantially greater morbidity and mortality than esophageal disorders. 1

• Esophageal spasm presents with squeezing retrosternal chest pain that mimics cardiac ischemia, making cardiac workup mandatory before pursuing esophageal evaluation. 1
• Only after excluding cardiac disease should you proceed with esophageal diagnostic workup. 1

Can't-Miss Diagnoses to Exclude

Achalasia (Including Secondary Causes)

• Query for recent COVID infections, Chagas disease risk, and symptoms/signs of eosinophilic disease during initial evaluation, as these can cause secondary achalasia that mimics spasm. 2, 1
• High-resolution manometry (HRM) is essential to differentiate achalasia from distal esophageal spasm—achalasia shows impaired lower esophageal sphincter (LES) relaxation with integrated relaxation pressure (IRP) >15 mmHg, while spasm has normal LES relaxation. 2, 1
• Type III achalasia (vigorous achalasia) can present with spasm-like symptoms but has fundamentally different treatment and prognosis. 2

Structural and Mucosal Disorders

• Perform endoscopy with biopsies at two esophageal levels before manometry to exclude structural causes including tumors, strictures, rings, and eosinophilic esophagitis. 2, 1
• Obtain at least 5-6 biopsies even if mucosa appears normal endoscopically—eosinophilic esophagitis can be latent and presents in up to 9% of patients with dysphagia. 1
• Consider barium esophagram (biphasic technique) as it has 80-89% sensitivity for motility disorders and may reveal dysmotility not detected on manometry. 1

Infectious Esophagitis

• In immunocompromised patients or those with odynophagia, consider infectious esophagitis (Candida, HSV, CMV) which can present with dysphagia and chest pain. 2, 1
• If esophageal infection is identified, assess for signs/symptoms suggesting systemic immunocompromise and consult infectious disease. 2

Systemic Rheumatologic Diseases

• Screen for systemic sclerosis, mixed connective tissue disease, SLE, or Sjögren's disease—these cause esophageal dysmotility from muscle layer involvement, with particularly severe dysfunction in systemic sclerosis and mixed connective tissue disease. 2, 1

Inflammatory Esophageal Disorders

• Consider lymphocytic esophagitis in patients with histologic inflammation—treat with PPI therapy or swallowed topical corticosteroids. 2
• In patients with hypereosinophilia (absolute eosinophil count >1500 cells/μL), work up non-EoE eosinophilic GI disease, hypereosinophilic syndrome, and eosinophilic granulomatosis with polyangiitis. 2
• Consider Crohn's disease in patients with active intestinal disease, as esophageal involvement can occur with inflammatory, stricturing, or fistulizing changes. 2

Medication-Induced Spasm

• Systematically search for medications that promote esophageal dysmotility, particularly opiates, which are a recognized secondary cause of distal esophageal spasm. 3

Diagnostic Algorithm After Excluding Can't-Miss Diagnoses

Step 1: Endoscopy with Biopsies

• Perform upper endoscopy with at least 5-6 biopsies from two esophageal levels to exclude structural/mucosal disease. 2, 1

Step 2: High-Resolution Manometry

• HRM is superior to standard manometry for diagnosing esophageal spasm, requiring at least two premature contractions (distal latency <4.5 seconds) with normal LES relaxation. 2, 1
• Use adjunctive testing (larger water volumes, solid/viscous swallows, or test meal) to unmask pathology not seen with standard water swallows—these are more representative of normal swallowing and more likely to induce symptoms. 2

Step 3: Barium Esophagram

• Obtain biphasic barium study as it provides complementary information to manometry and may reveal dysmotility missed by other tests. 1

Step 4: pH/Impedance Monitoring (If Needed)

• Use ambulatory impedance-pH monitoring to definitively rule out GERD if diagnosis remains unclear, as GERD can coexist with and potentially cause esophageal spasm. 1, 4

Treatment Approach Once True Esophageal Spasm Confirmed

First-Line Pharmacotherapy

• Start with proton pump inhibitors (PPIs), especially when symptoms overlap with GERD—use standard dosing (e.g., omeprazole 20 mg or lansoprazole 30 mg) 30-60 minutes before breakfast. 1
• Add smooth muscle relaxants (calcium channel blockers or nitrates) for spasm-specific symptoms. 1, 5
• Consider neuromodulators (tricyclic antidepressants or SSRIs) for esophageal hypersensitivity and visceral analgesia. 1
• Do NOT use metoclopramide—it is ineffective and potential harms outweigh benefits. 1

Second-Line: Botulinum Toxin Injection

• Endoscopic botulinum toxin injection (100 IU diluted in 10 mL saline) at multiple sites along the esophageal wall is the best-studied treatment option, with 78-89% immediate response rates and sustained benefit at 6 months. 5, 6, 3
• Botulinum toxin has been shown superior to placebo for symptom relief in controlled studies. 3
• Symptom relapse can be effectively retreated with repeated injections. 6

Third-Line: Surgical Intervention

• Per-oral endoscopic myotomy (POEM) is the preferred surgical approach for refractory distal esophageal spasm, with success rates >90% and advantage of unlimited proximal extension. 1
• Reserve surgical myotomy for patients with very severe symptoms refractory to pharmacologic and endoscopic treatment. 5

Adjunctive Therapies

• Cognitive behavioral therapy, esophageal-directed hypnotherapy, and diaphragmatic breathing are effective for patients with associated hypervigilance or hypersensitivity. 1

Common Pitfalls to Avoid

• Do not rely on a single diagnostic test—barium studies and manometry are complementary, and one may reveal abnormalities missed by the other. 1
• Do not skip biopsies even with normal-appearing mucosa—eosinophilic esophagitis can be endoscopically occult. 1
• Do not assume esophageal spasm based solely on symptoms—the intermittent nature of the disorder makes it almost impossible to definitively rule out, requiring comprehensive evaluation. 7
• Always reassess for eosinophilic esophagitis if symptoms persist despite treatment—some EoE patients develop motility disorders despite histologic remission. 2