A quantitative comparison of the effect of local analgesics on argon laser induced cutaneous pain and on histamine induced wheal, flare and itch

A quantitative comparison was made of the effect of infiltration of local analgesics and topical analgesic cream (EMLA) on laser-induced pain and histamine-induced wheal, flare and itch. Wheal and flare were quantified by planimetry and analgesia was quantified by the pricking pain threshold to argon laser stimulation. The intensity of histamine-induced itch was scored on a 4-point scale. Local analgesics had no effect on the wheal area. The flare reaction was abolished by infiltrating lignocaine, and gradually inhibited by increased application times of EMLA. Itch was abolished after local lignocaine infiltration, but not significantly reduced after EMLA cream applied for less than 120 min, although the skin was anaesthetized to laser-induced pain. The reduction of flare area correlated to the level of analgesia, which may therefore reflect the cutaneous responsiveness to neurogenic inflammation. It is suggested that itch and pricking pain are mediated by different populations of nerve fibres, as itch can be evoked even when the sensation of pricking pain is abolished. Surgery, skin prick tests and other traumatic procedures should therefore be performed under local anaesthesia to reduce neurogenic inflammation.     

Correlations between histamine-induced wheal,flare and itch

Correlations between the skin reactions wheal and flare and the subjectively reported degree of itch were investigated in response to 1% histamine, intradermally applied by standardized skin prick and by iontophoresis. Experiments were performed with 15 male volunteers using a threefold repeated measures design (skin prick, and iontophoresis with 0.13 mA for 10 s and with 2.0 mA for 10 s). Skin reactions (perpendicular diameters) were determined at the time of their maximum (10 min). Itch was rated on a computerized visual analogue scale which was anchored upon the individual scratch threshold. Most effective in producing itch was the skin prick which caused strong sensations markedly above the scratch threshold during the entire period of measurement (30 min), whereas iontophoresis induced only transient itch sensations. On the other hand, the largest wheals were generated by iontophoresis of both intensities (mean 10 or 14 mm vs 6 mm with skin prick). The higher current induced higher itch, wheal and flare responses, but after eliminating this effect of stimulus intensity, no correlations were found. In contrast, skin prick-induced flare reactions varied with the degree of itch above the scratch threshold ( r = 0.56; P < 0.01). Repeated measurements showed a higher stability for the itch reaction with skin prick compared with iontophoresis. It is hypothesized that in iontophoresis the brief (10-s) histamine bolus passed the most superficial pruritoceptive C fibres too quickly to induce long-lasting itch sensations, whereas the skin prick caused a deposit at the dermal-epidermal junction releasing histamine during the entire time of measurement. Consequently, both the C fibre-mediated itch and the axon reflex flare were more pronounced with the skin prick, and the wheal resulting from a permeability increase in the postcapillary venule walls was an independent phenomenon. Received: 21 June 1995     

Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin

Abstract Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE. Received: 24 July 1997     

Effects of acrivastine, loratadine and cetirizine on histamine-induced wheal and flare responses

It is accepted that studies evaluating histamine-induced wheal and flare reactions in the skin represent a simple and reliable method for demonstrating pharmacodynamic activity and pharmacokinetics of the H1-receptor antagonists. In this study, the effects of single oral doses of acrivastine (8 mg), loratadine (10 mg) and cetirizine (10 mg) on the histamine-induced wheal and flare reactions were compared in 60 healthy volunteers. The wheal and flare responses were produced by prick test using 1% histamine solution. Measurements were performed before the ingestion of antihistamines (baseline values) and afterwards at 15, 30, 90, 240, 360 min and 24 h. The values obtained for each antihistamine were compared with each other and with baseline values. Cetirizine was found to be superior to acrivastine and loratadine for the suppression of wheal and flare responses at 240, 360 min and 24 h (P < 0.05) and acrivastine was superior to the other two antihistamines for the suppression of flare response at 30 min (P < 0.05). Our results indicate that a single dose of cetirizine provides a more effective and long acting suppression on wheal and flare reactions in urticaria when compared to acrivastine and loratadine.     

Rapid effects of olopatadine hydrochloride on the histamine-induced skin responses

Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines that are used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis. We examined the inhibitory effects of this drug on the flare and wheal responses induced by histamine iontophoresis at 30, 60, and 90 min after oral administration in a double-blind, cross-over, and placebo-controlled study. Olopatadine hydrochloride significantly inhibited the histamine-induced flare and wheal responses as early as 60 min after oral administration when compared with placebo. Significant inihibitory effects of olopatadine hydrochloride on the itch responses were seen at 90 min after administration. Thus, olopatadine hydrochloride exhibited a very rapid and potent antihistamine effect on the histamine-induced skin responses.     

Effects of cetirizine and epinastine on the skin response to histamine iontophoresis

Epinastine and cetirizine are second-generation, nonsedating and long-lasting antihistamines that are now frequently used for the allergic disorders. We have examined the inhibitory effects of these two drugs on the histamine-induced flare and wheal responses using iontophoresis at 1, 2, 4, 8 and 24 h after the oral administration by a double-blind, cross-over and placebo-controlled study. Both cetirizine and epinastine significantly inhibited the histamine-induced flare and wheal responses at 2 h after the oral administration when compared with placebo. The inhibitory effects of cetirizine and epinastine on the flare response lasted long until at 24 h, however, epinastine was less potent than cetirizine. The inhibitory effects on the wheal response was also clearly and significantly evident at 2-8 h by cetirizine and epinastine. At 24 h cetirizine only showed the significant inhibition on the histamine-induced wheal response. In contrast, epinastine seemed to exhibit the inhibitory capacity earlier than did cetirizine. The inhibitory action of the drugs on the histamine-induced wheal response peaked at 4 h after the oral administration. The histamine-induced itch sensation was also markedly or completely suppressed at 2-8 h by the drugs. Thus, both drugs exhibited the potent and long-lasting antihistamine activity on the skin responses induced by histamine iontophoresis.     

Neuronal sensitization for histamine-induced itch in lesional skin of patients with atopic dermatitis

OBJECTIVE: Lowered threshold of neurons (ie, neuronal sensitization) in atopic dermatitis was investigated by testing sensitivity to histamine. DESIGN: Comparative study. SETTING: A dermatological clinic and a research laboratory. PARTICIPANTS: Eighteen patients with atopic dermatitis (AD) and 6 patients with chronic plaque-type psoriasis as well as 14 healthy control subjects. INTERVENTIONS: Histamine prick was performed in lesional and nonlesional skin of patients and in control subjects. MAIN OUTCOME MEASURES: Axon reflex flare and wheal were measured planimetrically, and the itch intensity was rated on a numerical scale (0-10). RESULTS: In nonlesional skin of patients with AD, itch intensity and axon reflex flare were both significantly smaller compared with controls (mean +/- SEM maximum itch, 1.5 +/- 0.3 vs 3.1 +/- 0.2 [P<.05]; mean +/- SEM diameter, 12.3 +/- 2.0 vs 25.3 +/- 2.5 mm [P<.01]). In lesional skin of patients with AD, on the contrary, massive itch was provoked (maximum itch, 4.4 +/- 0.3), although flare was relatively small (diameter, 16.1 +/- 3.4 mm). Itch ratings in patients with psoriasis were low both in lesional and nonlesional skin (maximum itch, 1.3 +/- 0.6 and 1.0 +/- 0.4, respectively). CONCLUSION: As the area of axon reflex flare is an indirect measure of activity in primary afferent neurons, our results suggest a decreased activation of peripheral pruriceptors in patients with AD. The massively increased itch in lesional skin of patients with AD might therefore be based on sensitization for itch in the spinal cord rather than in primary afferent neurons. This sensitization does not appear to be simply based on skin inflammation because histamine-induced itch was not augmented in lesional skin of psoriasis.     

Reactions to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients.

Skin reactions and itch or burning pain sensations following intradermal injection of the neuropeptide substance P and topical application of the substance P releasing agent mustard oil were studied in 20 atopic dermatitis patients and 20 healthy controls. Changes in skin blood flow were measured with a Laser Doppler flowmeter. Areas of wheal and flare reactions were evaluated planimetrically. Simultaneous with Laser Doppler flowmeter measurements, subjective itch and burning pain ratings were verbally reported on a category partitioning scale at 10-second intervals. Substance P evoked dose-dependent wheal, flare, and itch reactions in both patients and controls. However, substance P doses of 10(-9) -10(-11) mol elicited smaller flares in patients than in the controls whereas the wheal sizes were similar in both groups. Substance P-induced itch ratings were lower in patients at a dose of 10(-10) mol, and the onset of itching was delayed at all substance P levels applied. Mustard oil elicited similar neurogenic inflammatory reactions in both groups, although pain sensations were significantly delayed in atopic dermatitis patients at two mustard oil concentrations, which is further indication of a desensitization of afferent nerve endings contributing to the neurogenic inflammatory reactions in the skin of these patients.     

Skin reactions and itch sensation induced by epicutaneous histamine application in atopic dermatitis and controls

Itch sensations and skin reactions induced by histamine iontophoresis at six different current intensities were studied in 27 atopic dermatitis (AD) patients and 20 healthy controls. Subjective itch ratings were assessed on a visual analogue scale (VAS) for 8-min periods after 10-sec histamine application, while changes of skin blood flow were simultaneously measured using two Laser Doppler flowmeters. Ten minutes after each histamine application, the areas of wheal and flare reactions were planimetrically evaluated. When no or weak current was applied, AD patients revealed stronger wheal and flare reactions than controls, possibly due to disturbed skin barrier function. Higher histamine doses, however, produced weaker subjective and vascular reactions in AD patients. In contrast to the controls, AD patients were unable to distinguish between weak and strong histamine stimulation, as shown by their VAS ratings. These results imply that AD patients have an altered histamine response. In particular, their afferent cutaneous nerve fibers show a decreased ability to signal itching to the central nervous system and to release vasoactive neuropeptides upon histamine stimulation.     

Processing of histamine-induced itch in the human cerebral cortex: a correlation analysis with dermal reactions

The subjective sensation of itch is a complex emotional experience depending on a variety of factors. In this study, the central nervous processing of pruritus was investigated in a human model. Activation of involved cerebral areas was correlated to scales of nociception and skin reactions. Six healthy male right-handed subjects participated in a standardized epidermal stimulus model with nine increasing doses of histamine dihydrochloride (0.03%-8%) on their right forearms. Controls consisted of three NaCl stimuli. Cerebral activation patterns were determined by H(2)(15)O positron emission tomography 120 s after stimulation. Dermal reactions to the stimulus (wheal, flare, temperature) were coregistered during the procedure. Itch sensation was determined by visual analog scale rating. Pain was not reported during the study; all volunteers had localized itch from 0.03% histamine on. Subtraction analysis versus control revealed significant activation of the left primary sensory cortex and motor-associated areas (mainly primary motor cortex, supplementary motor area, premotor cortex). Predominantly left-sided activations of frontal, orbitofrontal, and superior temporal cortex and anterior cingulate were also observed. Correlation analysis revealed coactivation of dermal reactions and cerebral response to itch in the following Brodmann areas with a Z score greater than 5: wheal, areas 5 (bilateral) and 19 (right); flare, areas 2-5 (left); temperature, area 10 (left) and left insula. Itch intensity ratings were mainly correlated with activation of the left sensory and motor areas. Functional covariates of the itch sensation in the central nervous system were identified. The intention to pruritofensive movements is probably mirrored by the activation of motor areas in the cortex. Other areas may be involved in emotional processing of sensations. Skin reactions wheal and flare also had significantly activated covariate areas in the central nervous system.J Invest Dermatol 115:1029-1033 2000     

Video-optical monitoring of wheal and flare reactions

Background/aims: In order to monitor the dynamics of experimentally-induced cutaneous inflammation in humans, we developed an objective, computerized video-optical method for wheal and flare area determination.
Methods: The method was used for evaluation of PAF-acether-induced experimental inflammations on the volar aspect of the forearms of human volunteers. The study design was double-blind, randomized, placebo-controlled. Repeated measurements can be performed, e.g., with intervals of 1 min to reveal the time-course of the inflammatory reaction. In the present study, the effect of topical application of creams containing 3 different concentrations of the putative anti-inflammatory drug sodium sucrose-sulphate (SoS) on cutaneous inflammation was investigated.
Results: 30 min after intracutaneous PAF-acether injection, a statistically significantly increased (p<0.05) wheal area was found in skin sites treated by either 1%, 3% and 9% SoS cream, whereas no influence of sucrose-sulphate could be demonstrated on the flare area. The reduction of the wheal area was significantly faster in the SoS-treated areas than in the placebo (p<0.05).
Conclusions: Computerized video-optical quantification of acute skin inflammatory reactions may be a suitable experimental tool for objective dynamic monitoring of both wheal and flare reactions and hence for quantification of the effect of anti-inflammatory drugs in humans. Topical application of SoS surprisingly increased PAF-acether-induced skin oedema (wheal), significantly whereas no effect was found on the flare reaction. No concentration-related effect of SoS could be shown.     

Study of reservoir effect of clobetasol propionate cream in an experimental animal model using histamine-induced wheal suppression test

Background:

Topical corticosteroids used in various dermatological diseases several times a day led to an increase risk of side effects. By demonstrating a significant reservoir of corticosteroids in the stratum corneum, one can maximize their efficacy and safety as therapeutic agents.

Aim:

The study was designed to demonstrate a reservoir of topically applied corticosteroid clobetasol propionate cream experimentally in rabbits using histamine-induced wheal suppression test.

Materials and Methods:

The work was carried out on albino rabbits, as rabbit skin is akin to human skin, using a topical steroid. The topical steroid clobetasol propionate 0.05% cream was applied on the back of rabbit, and after 1-h occlusion histamine-induced wheal suppression test was performed and wheal area measured at 10 min till day 7. Statistical analysis was done by ANOVA followed by “Post Hoc” test.

Results:

Maximum wheal suppression was seen on day 1 (P < 0.001). Interday comparison of mean wheal size showed no significant difference (P > 0.05) on day 2, 3, and 4 as compared to day 1. Day 5-7 show highly significant difference (P < 0.001) as compared to day 1, thereby suggesting that the reservoir effect of topical clobetasol propionate 0.05% cream persisted till day 4.

Conclusions:

This work demonstrated that histamine-induced wheal by the topical steroid clobetasol propionate 0.05% cream was suppressed till day 4, indicating that the reservoir of topical corticosteroid persisted till day 4.     

Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema

BACKGROUND: Atopic eczema (AE) is a chronic inflammatory skin disease with strong itching as the prominent symptom. The pathology of itch is still in discussion, but acetylcholine (ACH) seems to be a relevant pruritogenic mediator in AE. Since efficient benefit on pruritus and excoriations has been demonstrated with tricyclic agents, we investigated how the topical treatment with doxepin (5%, Boehringer Standard, Mannheim, Germany), a tricyclic compound with anticholinergic properties, may influence ACH induced itch and cutaneous sensations (erythema, wheal, axonreflex flare). METHODS: Eleven patients with AE were included in this double blind study. For 3 days we applied doxepin cream to a defined area on the volar forearm and basic ointment to the other side 4 times daily. On day 4, ACH and sodium chloride were i.c. injected into the pretreated arms. Vasoreactions and cutaneous sensations were measured similar to studies described in previous publications from our group. RESULTS: Doxepin treatment over 3 days reduced ACH provoked flare size more than 53% (P<0.005) and wheal size about 48% (P<0.005) whereas the maximal antipruritic effect was similiar to the basic therapy. The itch intensity, which is expressed as the mean AUC value, was rated at 6.12 arbitrary units after the neutral cream application and 5.9 arbitrary units after doxepin. CONCLUSIONS: The clinical and experimental effectiveness of doxepin as an antipruritic drug has been known for years. However, studies focusing on ACH as a pruritogenic mediator have not been performed. The duration of the doxepin application in our study seems to be appropriate since flare and wheal development were diminished. The reason why doxepin did not develop more antipruritic action compared to the vehicle cream may be due to the fact that the doxepin free cream already possessed an antipruritic action in this experimental study design. This is probably caused by rehydrating and moisturizing effects.     

Effects of histamine receptor antagonists on histamine-induced responses in human skin.

The effects of intradermally administered histamine H1- and H2-receptor antagonists on the cutaneous responses--redness, weal, flare and itch--induced by intradermal injection of histamine were studied in man. Weal and redness were studied after blockade of the axon reflex by local infiltration with lidocaine. All responses were significantly inhibited by the H1-receptor antagonist mepyramine. The H2-antagonists cimetidine and metiamide reduced flare and itch significantly but not to the same extenet as mepyramine and not in a clearly dose-related manner. The size of weal and redness was not significantly reduced by cimetidine. No further reduction of flare, itch or weal was obtained by adding metiamide or cimetidine to mepyramine. After blockade of the axon reflex with lidocaine the histamine-induced weals turned white at the centre. This blanching was more prominent when histamine was injected in combination with cimetidine. Substituting mepyramine for cimetidine resulted in small weals with an intense red colour. It is concluded that, apart from being engaged in the direct vasodilatory response to histamine, H2-receptors do not seem to be involved in the other cutaneous responses to histamine studied.     

Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: a randomized,double-blind,placebo-controlled study of histamine and other inducers of itch

BACKGROUND: Investigations of pruritogenic substances in humans have involved intradermal injections in normal skin; itching of inflamed skin has been little studied. OBJECTIVES: To develop an itch model with provocation of itch in experimentally inflamed skin as well as in normal skin, using subjects as self-controls. METHODS: In 32 non-atopic volunteers aged 21-30 years, the skin of five selected test sites on one volar forearm was pretreated for 24 h with large Finn chambers containing 1% sodium lauryl sulphate (SLS) used as a standard contact irritant to induce inflammation. Twenty microlitres of different pruritogenic substances [histamine, substance P, neurokinin A, neurokinin B, trypsin, platelet-activating factor (PAF) and serotonin] and saline as control were injected intradermally into the inflamed test sites and in corresponding non-treated sites on the opposite forearm. The test individuals scored itch intensity on a visual analogue scale for 20 min, and weal area was then measured. : RESULTS: Histamine and substance P induced itch in both normal and inflamed skin compared with a saline reference. Neurokinin A, trypsin, PAF and serotonin only elicited itch in normal skin, and neurokinin B neither elicited itch in normal skin nor in inflamed skin. Itch was induced in normal and SLS-inflamed skin to a similar magnitude. However, weal area after histamine was significantly (P < 0.001) larger in inflamed skin when compared with normal skin. CONCLUSIONS: Histamine and substance P elicited itch to the same degree in normal skin and inflamed skin pretreated with SLS despite a stronger weal response in inflamed skin. Mediators present in inflamed skin did not potentiate itch, a c-fibre-mediated neuronal response. The weal reaction is based on enhanced vascular permeability (protein extravasation). A greater skin perfusion in inflamed skin may therefore have increased the weal size. We propose an experimental model in humans for testing of itch involving both normal and inflamed skin. The model has the potential for use in evaluating new topical and systemic treatments of itch.     

Separate effects of topical indomethacin on the itch response and on the flare reaction induced by histamine in human skin

The effects of topical indomethacin on histamine responses and histamine release were studied in 15 healthy volunteers. Three hours before testing, the indomethacin solution was applied under occlusion on one arm and the corresponding vehicle on the other. Solutions of histamine and the histamine releasing compound 48/80 were injected intradermally in both arms. Indomethacin treatment inhibited the flare reactions induced by histamine and compound 48/80 to about 50%, whereas no influence was seen on the itch responses. Our results indicate that indomethacin has no effect on the release of histamine, but it selectively suppresses the histamine-induced flare reaction leaving the itch duration unaffected.     

Frequency of immediate reactions to the European standard series

Immediate contact reactions (contact urticaria) can occur after skin contact with a wide range of substances. We studied the incidence of immediate contact reactions (wheal and flare) to the European standard series allergens in 664 patients. Patch tests were first examined at 30 min for immediate patch test (IPT) reactions, and again at D2 and D4 for delayed patch test (DPT) reactions. Almost all the allergens of the European standard series caused IPT reactions. IPT reactions were most commonly seen with Myroxylon Pereirae (balsam of Peru) (113 reactions), fragrance mix (112 reactions), paraben mix (30 reactions) and clioquinol (13 reactions); these reactions were followed by DPT reactions to the same substance in 13.4%, 8.8%, 10% and 7.7%, respectively. For certain substances, patients with (+) IPT reactions had a significantly higher incidence of DPT reactions to the same allergen, as compared to patients with (-) IPT reactions (fragrance compounds p<0.001, formaldehyde p<0.005, thiuram mix p<0.01, paraben mix p<0.05). Thus, perhaps the mechanisms involved in IPT reactions are not the same for all substances. At least for certain substances, an IPT reaction may be related to the development of a DPT reaction.     

Effect of topical corticosteroid application frequency on histamine-induced wheals

BACKGROUND: Very few studies have been conducted to assess the effect of corticosteroid application frequency to attain maximum benefit with minimum side-effects. OBJECTIVES: Compare the efficacy of twice-daily, once-daily and alternate-day applications of clobetasol propionate (0.05%) and compare whether an initial once-daily application followed by a subsequent alternate-day application is as effective as a once-daily application. METHODS: The ability of corticosteroids to suppress histamine-induced wheals on human skin was used as a human bioassay model. Of the 26 subjects included, 21 completed the 1st phase. In the 2nd phase, 11 subjects were included and all completed the study. Four sites were chosen on the left forearm. Clobetasol propionate (0.05%) was applied twice daily, once daily, and on alternate days, and on the control site a color, texture and odour-matched vehicle was applied. Prick test with histamine was carried out after 10 days. In the 2nd phase, clobetasol propionate (0.05%) was applied once daily for 14 days and compared with the initial once daily for 7 days and the subsequent alternate-day application for 7 days. Prick test was carried out after 14 days. RESULTS: The once-daily application of clobetasol propionate (0.05%) was as effective as the twice-daily application, but the alternate-day application was less effective than the once-daily application (P < 0.01). Also, the initial-daily and subsequent alternate-day applications were not as effective as the continuous once-daily application (P < 0.05). CONCLUSION: A once-daily application of clobetasol propionate (0.05%) is likely to provide the required therapeutic effect.     

Suppression of immediate-type hypersensitivity elicitation in the skin prick test by ultraviolet B irradiation

Reproducibility of skin prick testing (SPT) and its modulation by ultraviolet B (UVB) radiation is of clinical interest. Sensitized atopic volunteers (groups A and B, n=21) were prick tested with common commercial allergen solutions (undiluted, diluted 1:10 and diluted 1:100) before, 24 h after one and 24 h after three suberythematous UVB irradiations. Volunteers in group A (n=8) received local UVB irradiation of prick test areas, whereas volunteers in group B (n=13) received whole body UVB irradiation, with prick test areas covered. In group A, the wheal intensities, expressed as the ratio allergen wheal size to histamine wheal size, were decreased by 28% (1:10 dilution) (P=0.01) and 45% (1:100 dilution) (P=0.02) after one UVB irradiation. Flare intensities were decreased by 48% (1:10 dilution) (P=0.03) after three UVB irradiations. In group B, the wheal and flare responses tended to decrease. Possible mechanisms of this short-term suppressive effect of UVB irradiation on SPT reactions include a direct effect on mast cells. It is concluded that UV irradiation, even a single exposure, prior to skin testing may compromise the validity of SPT testing.     

Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)-antihistamines

Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H(1)-antihistamine. Intradermal injection of 100 μl of 100 μg/ml histamine and 10 mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1 × 10(-4) and 1 × 10(-5) M caused significant (P < 0.05) histamine release from isolated human cutaneous mast cells. In conclusion, icatibant induces histamine-mediated wheal and flare responses that may be reduced in severity by prophylactic administration of an H(1)-antihistamine.