Cetirizine for Solar Urticaria in the Visible Spectrum

Solar urticaria (SU) is an uncommon but well-recognized disorder characterized by the rapid development of an urticarial reaction in sun-exposed skin areas [1]. Various wavelengths, such as ultraviolet B (UVB:290–320 nm), ultraviolet A (UVA:320–400 nm) and visible light (VIS:400–760 nm), can be responsible for the condition [2, 3, 4, 5]. Many therapies, such as phototherapy, photochemotherapy, H1 and H2 antihistamines, steroids, carotenoids or hydroxychloroquine, have been proposed, but their effectiveness is disappointing [6]. We report the data concerning the treatment of patients, suffering from SU elicited by VIS, with oral cetirizine and increasing whole-body sun exposure.Seven patients (table 1), 6 females and one male, skin types II and III (according to Fitzpatrick), aged from 17 to 36 years (mean 28 years) were enrolled in the study. Each patient had a history of marked urticarial reaction on sun-exposed skin, with the onset varying from 1 to 10 years previously. Wheals developed after a few minutes of both direct or window-pane-filtered sun irradiation, spontaneously disappearing after 1–5 h. There was no contributory personal or family history of allergy or systemic medication prior to the onset of this condition. Results of laboratory investigations were normal. They included ANA, fluorocytes in fresh peripheral blood smears and porphyrins in stools. Urine and blood results were also normal. In 2 patients (M.D. and A.R.), the serum IgE levels were high. Dermographism occurred in 4 of the subjects, whereas tests for other physical urticarias, such as pressure, cholinergic, cold and contact heat urticaria, were negative.Six circular areas located on the back of each patient (2 cm diameter) were irradiated respectively with 30, 60, 90, 120, 150 and 180 mJ/cm2 of UVB (6 Philips TL20W/12 tubes, with an irradiance of 2.4 mW/cm2 at 20 cm distance); 6 areas received 5, 10, 15, 20, 25 or 30 J/cm2 of UVA (6 Philips TL40W/09 tubes, with an irradiance of 7 mW/cm2 at 20 cm distance) and 6 areas were irradiated with 12, 24, 36, 48, 60 or 72 J/cm2 of VIS (slide projector, 150-watt tungsten lamp with an irradiance of 40 mW/cm2 at 20 cm distance).The test sites were examined immediately after irradiation and at intervals of up to 10 min in order to determine: (i) the possible wheal formation, (ii) the action spectrum of the disease and (iii) the minimal dose of irradiation required to produce this reaction (minimal urticarial dose, MUD).After phototesting each patient was treated for 4 weeks with a daily oral dose of 10 mg of cetirizine. During the third and fourth weeks, patients were advised to gradually expose themselves to sunlight; this they performed each afternoon, increasing the exposure time by 10 min each day. If, at the end of the cetirizine treatment, patients were able to tolerate at least 1 h of sunlight without cutaneous discomfort, they were recommended to continue with the sun exposures. In order to evaluate the therapeutic effectiveness of cetirizine, reflected by an increase in MUD values, the same phototesting procedure was repeated: (i) after 15 days of treatment with only oral cetirizine, (ii) after 15 days of treatment with oral cetirizine and daily sun exposure and (iii) 15 days after suspending cetirizine.All patients experienced an urticarial reaction after being exposed to the irradiation of a slide projector, indicating that the part of the solar spectrum able to elicit cutaneous response was VIS. In 1 patient (G.G.) wheals also developed after UVA irradiation (table 1).After 15 days of orally administered cetirizine a 2- to 6-fold increase in MUD was observed in all patients; after 15 days of combined treatment (oral cetirizine + sun exposure) a 3.5- to 10-fold increase in MUD values was noted;15 days after discontinuing treatment 4 patients who had continued the photo-exposure therapy displayed a MUD value that was even higher than before they started therapy. By contrast MUD values in the remaining subjects who had interrupted their sun exposure therapy were the same as those detected at the beginning of the study (table 2).The treatment of SU is very difficult: sunscreens, even when necessary, are of limited value as they are not very practical in daily life [7]. Indomethacin and oral β-carotene are also ineffective [6, 8]whereas hydroxychloroquine has been reported to determine a slight increase in solar radiation tolerance [9].The production of tolerance to SU by repeated sun exposure (hardening phenomenon) was observed several years ago and gave rise to certain therapeutical regimens [6, 10, 11, 12]. The most effective to date is that of PUVA photochemotherapy. This involves the oral administration of methoxsalen (0.6 mg/kg b.w.) 3 times a week for 4–8 weeks with a subsequent 2-hour total-body exposure to UVA radiation [6, 13]. The treatment is known to have produced effects lasting weeks or even months.Plasmapheresis, either on its own or followed by PUVA photochemotherapy, has also been reported to induce a clinical remission of some SU cases. This is presumably achieved by removing the circulating photoallergen [14].Medication with antihistamines has produced variable results; the first generation of H1 receptor antagonists (i.e. chlorpheniramine) was seen to suppress symptoms in some patients, but large doses are usually required. This sometimes leads to such adverse effects as sedation on the central nervous system making this an unacceptable therapy [15]. Terfenadine and astemizole have been reported to be effective in few cases of SU [16, 17]; however, their use, especially when combined with some drugs, was associated with such cardiovascular effects as the prolongation of the QT interval in ECG [16]. Indeed, due to their cardiotoxicity these drugs were withdrawn from the market. Cetirizine, a second-generation H1 metabolite antagonist of hydroxyzine [18], has recently been used in many allergic disorders. It prevents the in vivo release of not only histamine, but also other inflammation mediators, exerting an anti-inflammatory activity on human eosinophils, neutrophils, basophils and mast cells. Lastly, it has been suggested that it could modulate ICAM-1 expression on epithelial cells [15]. In 1991, Bilsland and Ferguson [19]compared the efficiency of cetirizine and terfenadine in combating SU. This double-blind study showed that both drugs were equally effective in raising sensitivity thresholds in 4 out of 6 treated patients and that cetirizine appeared to be no more effective than terfenadine. Nevertheless with cetirizine the undesired cardiac side-effects associated with terfenadine are absent.In our study the use of cetirizine (a daily dose of 10 mg for 15 days) resulted in an immediate symptomatic improvement. This was confirmed by a phototest that showed MUD variables to be 2–6 times higher than values recorded in the initial survey.The MUD increment induced by cetirizine was probably sufficient to allow our patients gradual sun exposure, thus permitting melanization and the thickening of the stratum corneum to naturally produce an increased urticarial threshold. Despite sun exposure, once cetirizine was suspended, tolerance was only moderate (MUD values 1.5–4 times the baseline). This could be explained by taking into account the possibility that patients did not expose their skin to sunlight regularly or long enough or that, during exposure, sun irradiance was inconstant.In conclusion we believe our study should be seen as a preliminary report. In order to confirm the role played by cetirizine (together with daily sun exposure) in the treatment of SU we feel there is need for more extensive studies involving longer follow-up periods.