Role of Urinary N-Methylhistamine in Chronic Urticaria

Rationale: Histamine is thought to play an important role in chronic urticaria (CU) as evidenced by its detection in urticarial lesions and symptomatic treatment of CU with anti-histamines.  However, there are limited studies evaluating the utility of urinary n-methylhistamine (uNMH) in chronic urticaria.  We analyzed associations between uNMH and clinical features of patients with CU.

Methods: This was a retrospective review of 33 CU patients seen at Mayo Clinic between 8/30/13 and 4/22/15 that had uNMH measured around the time of their first visit.  Clinical features were derived from a standard questionnaire and associated laboratory tests were reviewed.

Results: NMH values in all subjects were essentially within the normal range [55 to 208 mcg/g Cr, median 125 mcg/g Cr].  There was no significant age or gender difference in uNMH excretion. Subjects in the study had hives for a median of 40 weeks [interquartile range (IQR) 16 weeks to 160 weeks]. We noted a significant and moderate negative correlation (-0.56) between uNMH levels and duration of urticaria (P=0.0006).  We also found a difference in uNMH excretion in patients with angioedema [median 135 mcg/g Cr, IQR 58 – 119] compared to those without angioedema [median 75.5 mcg/g Cr, IQR 113 - 160] (P=0.02). 

Conclusions: Reduction of uNMH excretion with increasing duration of urticaria may be a reflection of histaminergic ‘burn out’ and increased NMH excretion in angioedema suggests a greater histamine burden in this subset of patients. Larger studies aimed at deriving algorithms based on biomarker excretion to predict response to therapy and disease evolution may be beneficial.