Nasal and skin histamine responses in allergic rhinitis
Authors: Y. I. Koh, I. S. Choi, I.‐J. Oh, S.‐N. Hong, M.‐K. Sim
Journal: Allergy (2002)

The realization that there are systemic cellular and molecular events that shape various allergic diseases has intensified interest in understanding the relationship between local target organ inflammatory events and associated systemic responses (1). Nasal histamine reactivity has been reported to be associated with development of allergen skin response in allergic rhinitis (2). The allergen skin response is associated with histamine skin response (3). Thus, our aim was to study whether a relationship exists between nasal and skin responses to histamine in allergic rhinitis. We studied 22 patients with persistent allergic rhinitis (4) who had mild to moderate symptoms (14 female, aged 26–67 years), 18 normals with positive skin prick test (4) to one or more aeroallergens (11 female, 26–65 years), and 22 normals without any allergen skin response (14 female, 26–63 years). The study was approved by the Hospital Medical Ethics Committee, and informed consent was given by all subjects. Nasal histamine challenge tests were performed according to the methods of Simola and Malmberg (2), with some modifications. The challenge was performed stepwise with control solution and doubling concentrations of histamine diphosphate solutions (0.25–16 mg/ml; Sigma Chemical Co., St. Louis, USA). Total nasal symptom scores were assessed after each step. The symptoms included nasal stuffiness (scored none = 0, unilateral = 1, bilateral = 2), rhinorrhea (none = 0, mild = 1, runny = 2), sneezing (none = 0, 1–3 sneezes = 1, > 3 sneezes or consecutive = 2), and nasal itchiness (none = 0, only nose = 1, nose and throat or eye = 2). The test was stopped if total nasal symptom scores increased 4 points or more from control or if the highest concentration of histamine was administered. Immediately, skin prick tests with different concentrations of histamine (5, 10, 50, and 100 mg/ml) were performed on the volar surface of the forearm. Each wheal area was analysed after 10 min and expressed as square mm. We found in random duplicate tests in 15 normal individuals that there was 9% variation in wheal areas. Absolute changes in nasal symptoms score from control were plotted against log-concentrations of histamine, and nasal symptoms score/histamine slope, representing nasal histamine sensitivity, was calculated by linear regression analysis. Similarly, wheal areas were plotted against log-concentrations of histamine, and wheal areas/histamine slope, representing skin histamine sensitivity, was calculated. The slope values were log transformed and results were expressed as mean ± SEM. Statistical analysis was done using a post hoc Scheffe's test and Pearson's correlation (P < 0.05 significant). Nasal log-slope was significantly higher in patients with allergic rhinitis (0.32 ± 0.06) than in allergen skin test negative normals (0.09 ± 0.05, P < 0.05), with allergen skin test positive normals (0.17 ± 0.07) presenting an intermediate value. Skin wheal areas at 5 and 10 mg/ml in patients with allergic rhinitis were significantly greater than in allergen skin test negative normals (P < 0.05, respectively), with allergen skin test positive normals presenting intermediate values. Wheal areas at 50 and 100 mg/ml did not differ significantly among the three groups (P > 0.05, respectively). There was no difference in skin log-slope among patients with allergic rhinitis (1.56 ± 0.06), allergen skin test positive normals (1.57 ± 0.07), and allergen skin test negative normals (1.56 ± 0.05). In patients with allergic rhinitis, nasal log-slope significantly correlated with skin log-slope (r = 0.47, P < 0.05), whereas no relation was found in allergen skin test positive normals (r = 0.01, P > 0.05) or allergen skin test negative normals (r = 0.18, P > 0.05). Our study demonstrated that nasal histamine sensitivity was related to skin histamine sensitivity in patients with allergic rhinitis, suggesting that allergic inflammation generated at the level of the nasal mucosa may affect the skin responsiveness to histamine. Histamine produces a triple response of nerves in the skin and causes an analogous pattern in the nose. During a nasal allergic reaction, histamine stimulates sensory nerves to release substance P (5) and produces neurogenic inflammation. A similar phenomenon is likely to occur in the skin of patients with allergic rhinitis, which may be supported by a study (6) showing that skin sensitivity to substance P is increased in allergic asthma. Many other factors might also contribute to the relationship: H1-receptor sensitivity, H1-induced production of vasodilators or other mediators, and action of histamine-releasing factors. Our finding may support the evidence that associates allergic rhinitis with systemic inflammatory processes. Accepted for publication 28 May 2002 Allergy 2002: 57:1082–1083 Copyright © Blackwell Munksgaard 2002 ISSN 0105-4538