Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.
BACKGROUND
The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU).


METHODS
Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine.


RESULTS
For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients.


CONCLUSIONS
Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.
Di Lorenzo
G
G
Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università degli Studi di Palermo, Italy.
Pacor
M L
ML
Vignola
A M
AM
Profita
M
M
Esposito-Pellitteri
M
M
Biasi
D
D
Corrocher
R
R
Caruso
C
C
D000284:Administration, Oral; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000652:urine; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects; D002908:Chronic Disease; D018849:Controlled Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000209:etiology / Q000652:urine; D005260:Female; D005503:Food Additives / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007558:Italy; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008761:Methylhistamines / Q000652:urine*; D008875:Middle Aged; D020160:Sodium Benzoate / Q000008:administration & dosage / Q000009:adverse effects; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000009:adverse effects; D013447:Sulfites / Q000008:administration & dosage / Q000009:adverse effects; D013645:Tartrazine / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D014581:Urticaria / Q000652:urine*
D015415:Biomarkers; D016085:Bronchoconstrictor Agents; D016861:Cyclooxygenase Inhibitors; D005503:Food Additives; D008761:Methylhistamines; D013447:Sulfites; C005200:sodium metabisulfite; D017999:Leukotriene E4; D013645:Tartrazine; D020160:Sodium Benzoate; D001241:Aspirin; D012970:Sodium Glutamate; C048140:N-methylhistamine