Lab Update 10 – Urine Methylhistamine

July 2019
Ampath | ampath.co.za

Background

Histamine turnover increases due to either:

• Increased activity of mast cells (e.g. during allergic reactions)
• Proliferation of mast cells (e.g. mastocytosis) or basophils

Because histamine is released intermittently and has a short half-life, measuring its metabolite—urine 1-methylhistamine (1-MHIS)—offers better sensitivity and specificity for diagnosis.

• 1-MHIS (also known as N-Tele-methylhistamine) is measured at Ampath Esoteric Sciences using GC-MS/MS methodology.

Indications for Testing

• Screening for and monitoring of mast cell disorders, including:
  • Mastocytosis
  • Mast cell activation syndrome
  • Systemic allergic reactions
• Monitoring therapeutic progress in conditions involving low-grade, persistent mast cell proliferation or activation

Limitations of Testing

• Not all mast cell disorder patients will have elevated urinary 1-MHIS.
• Elevated 1-MHIS may also be caused by:
  • Non-compliance with a histamine-free diet
  • Certain medications
  • Myeloproliferative disorders
  • Carcinoid syndrome
  • Insulinoma
  • Medullary thyroid carcinoma
  • Pheochromocytoma
  • VIPoma
  • Glucagonoma
  • Scombroidosis
  • Bacterial conversion of histidine to histamine in urine

Symptoms of Mast Cell Disorders

Symptoms due to mast cell activation may include:

• Flushing
• Pruritus
• Urticaria
• Angioedema
• Nasal congestion
• Rhinorrhoea
• Wheezing
• Bronchospastic cough
• Headache
• Diarrhoea
• Gastric hyperacidity
• Abdominal cramping
• Nausea and vomiting
• Hypotension
• Tachycardia

Types of Mast Cell Disorders (WHO 2016 Classification)

1. Cutaneous Mastocytosis

• Most common form: Urticaria Pigmentosa (UP)
• Caused by mast cell infiltration in the skin
• Lesions are persistent, flat or slightly raised, red-brown in colour

2. Systemic Mastocytosis (SM)

• Mast cells infiltrate organs such as:
  • Bone marrow
  • Liver
  • Spleen
  • Small intestine
  • Lymph nodes
• Pediatric cases may resolve, while adult cases tend to be progressive
• Urticaria Pigmentosa may or may not be present
• Diagnosis requires:
  • One major and one minor criterion, or
  • Three minor criteria

Major criterion:

• Multifocal clusters of ≥15 abnormal mast cells in bone marrow or extracutaneous organs

Minor criteria:

• ≥25% atypical mast cells or spindle-shaped cells in bone marrow or other organs
• Presence of KIT D816V mutation
• Abnormal expression of CD25 and/or CD2 by mast cells
• Elevated serum tryptase level

3. Mast Cell Sarcoma

• A rare and aggressive local tumour with poor prognosis

Mast Cell Activation Syndrome (MCAS)

MCAS is a clinical presentation, not a specific diagnosis. Diagnostic criteria include:

1. Episodic symptoms affecting more than two organ systems
2. Lab evidence of mast cell mediator release during symptomatic episodes
   • Examples: Elevated serum tryptase, urine 1-MHIS
3. Response to treatment that targets mast cell mediators

Urine Methylhistamine Testing

Patient Preparation

Dietary Restrictions:

• Follow a histamine-free diet for 24 hours before and during collection

Foods to Avoid:

• Fruits: Bananas, pineapples, plums, grapes, kiwifruit, cherries, berries (blue, rasp, blackcurrants, strawberries), citrus, guava, mango, passionfruit, dried fruit
• Jams: All except apricot
• Vegetables: Tomatoes, mushrooms, avocado, spinach, broccoli, Brussels sprouts, cauliflower, eggplant, broad beans, pickled vegetables (e.g. sauerkraut)
• Nuts and seeds: Including peanut butter, tahini, muesli containing nuts/seeds or restricted fruits
• Dairy: All cheese and cheese spreads, yoghurt (chocolate/nut), flavoured milk, fruit smoothies
• Fish and seafood: All types including canned, salted, or dried
• Other items: Chocolate, cocoa, Milo, processed meats (salami, sausages, ham), chutney, malt vinegar, mayonnaise, tartare sauce, fermented foods (yeast extracts, soy sauce, meat gravy), alcohol (wine, beer, fermented beverages)

Foods Allowed:

• Plain bread, cereals (without seeds/nuts/fruit)
• Fruits: Apples, pears, apricots, peaches, rockmelon, watermelon
• Vegetables not listed above
• Coconut and coconut milk
• Dairy: Fresh milk, cream, vanilla yoghurt, plain ice cream, custard
• Freshly prepared meat and chicken
• Brown/white sugar
• Apricot jam, honey
• Clear vinegar, vanilla, nutmeg
• Drinks: Milk, plain or flavoured milkshakes (vanilla, caramel, coffee), tea, coffee, lemonade

Medication Considerations

Write all current medications on the request form. Do not stop any medication unless advised by a clinician.

May cause false increases in 1-MHIS:

• MAOI antidepressants → Test not recommended

May cause false decreases (Diamine oxidase inhibitors):

• Chlorquine
• Clavulanic acid
• Cimetidine
• Verapamil
• Acetylcysteine
• Aminophylline
• Amitriptyline
• Colistin
• Cyclophosphamide
• Diazepam
• Dihydralazine
• Framycetin
• Furosemide
• Haloperidol
• Isoniazid
• Metoclopramide
• Neomycin
• Orciprenaline
• Pancuronium
• Pentamidine
• Prilocaine
• Propafenone
• Promethazine
• Quinidine
• Thiamine (Vitamin B1)
• Thiopental

Specimen Requirements

• Preferred sample: 24-hour urine collection (Mnemonic: MHISU24)
  • Keep refrigerated during collection
  • No preservative needed (boric acid or HCl acceptable)
  • Preferred due to reduced variation and less dietary influence
• Alternative sample: Random urine (Mnemonic: MHISUR)

Sample Stability

• Room temperature: 24 hours
• Refrigerated: 8 days
• Frozen: 2 weeks

Turnaround Time

• 7 days

📌 For further information or assistance, contact your local Ampath pathologist.

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