How to lower high plasma histamine levels?

Managing High Plasma Histamine Levels

Second-generation H1 antihistamines combined with H2 antihistamines are the first-line therapy for managing high plasma histamine levels, with dosing up to 2-4 times the FDA-approved amounts when necessary for symptom control. 1

Medication Approach

First-Line Medications

• H1 antihistamines:

  • Prefer second-generation options (cetirizine, fexofenadine, loratadine) over first-generation due to less sedation and fewer anticholinergic effects 2, 1
  • Can be used at higher doses (2-4× standard) for better control of symptoms 1
  • First-generation antihistamines (diphenhydramine, hydroxyzine) should be avoided, especially in elderly patients, due to sedation, performance impairment, and anticholinergic effects 2

• H2 antihistamines:

  • Add famotidine or cimetidine for better control, particularly helpful for abdominal and vascular symptoms 1
  • Combination of H1 and H2 blockers provides more comprehensive histamine receptor blockade

Additional Medications Based on Symptoms

• For bronchospasm: Albuterol inhaler or nebulizer 1
• For prostaglandin-mediated symptoms: Consider aspirin if urinary prostaglandin levels are elevated (use with caution) 1
• For leukotriene-mediated symptoms: Montelukast or zileuton if urinary LTE4 levels are elevated 1
• For severe episodes: Short-course corticosteroids (prednisone) 1
• For recurrent anaphylactic episodes: Omalizumab may be considered 1

Dietary Management

• Low-histamine diet is a critical intervention for reducing histamine intake 3, 4, 5
  • Avoid fermented foods (unanimously recommended across all low-histamine diets) 3
  • Eliminate high-histamine foods: aged cheese, fermented meats, fish (especially if not fresh), pickled vegetables, alcoholic beverages 3, 4
  • Consider eliminating foods high in putrescine (citrus fruits, bananas) which may interfere with histamine degradation 3
  • Maintain the diet for at least 4 weeks to evaluate effectiveness 4

Management of Acute Histamine-Related Episodes

• For anaphylactic reactions:

  • Intramuscular epinephrine is first-line therapy 2
  • Assume supine position for hypotensive episodes 2
  • Patients at risk should carry two epinephrine autoinjectors 1
  • Antihistamines should never be used in place of epinephrine but can be used as adjunctive therapy 2

• For non-anaphylactic histamine reactions:

  • H1 antihistamines for cutaneous symptoms (urticaria, pruritus, flushing) 2
  • H2 antihistamines for gastrointestinal symptoms 1

Diagnostic Considerations

• Measure urinary histamine metabolites (24-hour collection) which remain elevated longer (up to 24 hours) than plasma histamine 2, 1
• Consider measuring other mediators:
  • Serum tryptase (optimal timing: 15 min to 3 hours after symptom onset) 2
  • Urinary prostaglandin D2 and leukotrienes 1
• Compare acute with baseline levels for more accurate assessment 2

Important Cautions

• Avoid first-generation antihistamines in elderly patients due to increased risk of falls, cognitive impairment, and anticholinergic effects 2
• Glucocorticoids have no proven role in acute histamine reactions and should not be used in place of antihistamines or epinephrine 2
• Avoid medications that may increase histamine levels:
  • β-adrenergic antagonists (may decrease response to epinephrine) 2
  • ACE inhibitors and angiotensin II receptor blockers 2
  • α-adrenergic blockers 2

Special Considerations

• Identify and avoid triggers of histamine release (temperature extremes, mechanical irritation, alcohol, certain medications) 2
• For suspected histamine intolerance, consider diamine oxidase (DAO) supplementation before meals 6
• Normal levels of tryptase or histamine do not rule out clinical histamine-mediated conditions 2