What is the treatment for histamine intolerance?

Treatment for Histamine Intolerance

The most effective treatment for histamine intolerance is a combination of H1 and H2 antihistamines along with a low-histamine diet to reduce symptoms and improve quality of life. 1

Pharmacological Management

First-line Treatment

• Nonsedating H1 antihistamines (such as fexofenadine and cetirizine) are preferred and can be increased to 2-4 times the standard dose for better symptom control of dermatologic manifestations like flushing and pruritus, as well as tachycardia and abdominal discomfort 1
• H2 blockers (ranitidine, famotidine, cimetidine) should be used alongside H1 antihistamines, particularly for gastrointestinal symptoms 1, 2
• Combined H1 and H2 antihistamine therapy shows greater efficacy for controlling symptoms than either agent alone 2

Additional Medications

• Cromolyn sodium (oral formulation) at 200 mg 4 times daily (before meals and at bedtime) helps reduce abdominal bloating, diarrhea, and cramps 1, 2
• Cyproheptadine, a sedating H1 antihistamine with antiserotonergic activities, is particularly effective for gastrointestinal symptoms 1, 2
• Leukotriene inhibitors (montelukast or zileuton) may reduce bronchospasm or gastrointestinal symptoms, especially when used with H1 antihistamines 1

For Severe Symptoms

• Corticosteroids may be used for refractory symptoms at an initial oral dosage of 0.5 mg/kg/day with a slow taper over 1-3 months, but are not recommended for long-term use due to side effects 1
• For patients with a history of systemic anaphylaxis or airway angioedema, an epinephrine autoinjector is essential, as epinephrine is the cornerstone of management for severe reactions 1

Dietary Management

• A low-histamine diet is currently the most advised strategy to prevent symptoms of histamine intolerance 3
• Fermented foods should be universally excluded as they consistently contain high levels of histamine 3
• Foods high in putrescine (such as citrus fruits and bananas) should be avoided as putrescine may interfere with histamine degradation by the DAO enzyme 3
• The histamine content of a food alone is not enough to predict its tolerance, requiring an individualized approach to dietary restrictions 4

Treatment Duration and Monitoring

• An initial treatment course of 4-6 weeks is typical, with reassessment of symptoms 2
• Long-term maintenance therapy may be required for chronic or recurrent symptoms 2
• Symptoms should be monitored for improvement within 1-2 weeks of initiating therapy 2

Special Considerations

• First-generation H1 antihistamines should be used with caution in elderly patients due to the risk of cognitive decline and sedation 2
• Antihistamines should never be used as monotherapy for severe reactions with cardiovascular or respiratory symptoms, as they have a slower onset of action compared to epinephrine 1
• For patients with overlapping irritable bowel syndrome symptoms, an integrated approach addressing both conditions may be necessary 1
• DAO (diamine oxidase) supplementation may be considered as subsidiary treatment for individuals with intestinal DAO deficiency 5

Diagnostic Approach

• Diagnosis of histamine intolerance requires a complex multidisciplinary approach, including systematic elimination of disorders with similar symptoms 5
• A good response to a low-histamine diet is considered confirmation of histamine intolerance 5
• It's important to rule out allergic conditions, as symptoms of IgE-dependent allergy can overlap with those of histamine intolerance 6

Common Pitfalls and Caveats

• Many patients self-impose overly restrictive low-histamine diets without medical guidance, which can negatively impact quality of life without providing long-term benefit 4
• Histamine intolerance is often misdiagnosed as food allergy, intolerance to sulfites or other biogenic amines, mastocytosis, psychosomatic diseases, or adverse drug reactions 7
• The variety and inconsistency of symptoms in the same individual following similar stimuli makes diagnosis challenging 5
• Endogenous histamine release could also be responsible for symptoms, which explains why dietary restrictions alone may not provide complete relief 4