Solar urticaria. Further studies on the role of inhibition spectra

A 27-year-old woman exhibited an urticaria only to monochromatic light in the range from 400 to 525 nm, but not to polychromatic light longer than 360-nm ultraviolet (UV) and visible light. An urticarial response induced by 475-nm monochromatic light was completely inhibited by preirradiation, simultaneous irradiation, and postirradiation with light having wave bands longer than 650 nm. Two other patients with sunlight-induced solar urticaria, who had an erythema-and-wheal reaction during and after exposure to sunlight, had no suppressive wave bands in either the UV or visible-light range. These observations strongly indicate an important role for inhibition wave bands in the development of light-induced immediate erythema and urticaria. In some cases of solar urticaria, preirradiation and postirradiation with longer visible light wavelengths could be useful in preventing the development of urticaria.     

Solar urticaria. The relationship of photoallergen and action spectrum

We studied six cases of solar urticaria immunologically and photobiologically. Serum in five patients and plasma in one patient yielded an immediate reaction when injected into the patients' own skin after light irradiation. These photoallergens were gel filtrated, and the molecular weights were determined. The result was compared with the action spectrum obtained by a monochrometer. In three patients, with the action spectrum in short visible light ranges (400 to 500 nm), the molecular weight of the photoallergen was 25,000 to 45,000 daltons. In a patient with an action spectrum from ultraviolet-A to short visible light ranges (330 to 520 nm), there was another photoallergen molecular weight that was 300,000 to 1,000,000 daltons. In a patient with a wide action spectrum from ultraviolet-B to long visible light ranges (290 to 630 nm), photoallergens, which were believed to be multiple, were generated only from plasma.     

Production and inhibition of solar urticaria by visible light exposure

The mechanisms of production and inhibition of solar urticaria were investigated in two patients whose eruptions were induced by wavelengths ranging from approximately 400 to 500 nm. They developed urticarial reactions to their own sera, which had been exposed previously to light in vitro. The exposure of skin to light from which activating wavelengths were eliminated with a glass filter (O-55), immediately after the exposure to urticaria-eliciting light, significantly inhibited the development of urticaria. The irradiation with the filtered light prior to the exposure of urticaria-eliciting light revealed no inhibitory effect. The simultaneous exposure of action and inhibition spectra seemed to suppress urticaria formation. The exposure of the inhibition spectrum did not affect wheal formation produced by histamine and a histamine-releasing agent. The photosensitizer produced by the action spectrum may be inactivated by the inhibition spectrum, or the interaction between photosensitizer and antibody may be blocked by the irradiation with the inhibition spectrum.     

Immediate pigment darkening thresholds of human skin to monochromatic (362 nm) ultraviolet A radiation are fluence rate dependent

When human skin is irradiated with ultraviolet radiation (340-400 nm) there is an immediate pigment response, termed Immediate Pigment Darkening (IPD). This reaction is thought to be due to photooxidation of preexisting melanin, precursors and/or melanin metabolites because it appears during exposure. It has been demonstrated that UVA-induced skin reactions, including erythema and pigmentation, are oxygen dependent. Therefore, these reactions should also be irradiance (fluence rate) dependent. The purpose of this investigation was to determine the dependence of the IPD threshold on fluence rate. We exposed the forearm of 12 volunteers (skin type II-V) to monochromatic UVA radiation (362 nm) at a range of fluence rates of 6-115 mW/cm2 and determined the fluence at which pigment was perceptible. The threshold fluence for the IPD reaction increased by a factor of 2.7 as the fluence rate increased by a factor of 18. Therefore, we conclude that the IPD reaction following exposure to 362 nm radiation is dependent on fluence rate, and independent of skin type.     

Solar urticaria without inhibitory spectrum: demonstration of both circulating photoallergen and reaginic antibodies

An 18-year-old man with solar urticaria is described. The action spectrum ranged from 400 to 500 nm. No inhibition spectrum was found, i.e., the wheal that is induced by visible light was not inhibited by immediate pre- or postirradiation of test sites with light waves longer than 620 nm. The patient developed a wheal at the site of injection of his own serum that had previously been exposed to light in vitro. Though the ordinary passive transfer reaction yielded a positive result, a passive transfer study with the patient's serum preheated at 56 degrees C for 2 h showed a negative result. These data suggest that he had both circulating photoallergen and reaginic antibodies.     

Photosensitivity due to the ''sunburn'' ultraviolet content of white fluorescent lamps

Six photosensitive patients are described, who also showed skin sensitivity to white fluorescent lamps. The results of tests with monochromatic irradiation showed that all patients were very sensitive to the ‘sunburn’ part of the spectrum (300–320 nm) with a lowered minimal erythema dose and a delayed papular-type reaction. Tests with a number of cut-off glass filters demonstrated that the fluorescent lamp sensitivity in these patients was due to the small amount of ‘sunburn’ UVR emitted. Spectral power analysis of the lamps showed that, with the exposures used in our tests, sufficient 300–320 nm UVR is emitted to produce skin reactions in very sensitive persons.     

The inhibition spectrum of solar urticaria suppresses the wheal-flare response following intradermal injection with photo-activated autologous serum but not with compound 48/80

BACKGROUND: The inhibition spectrum (IS) in solar urticaria was identified mainly in Japanese patients with solar urticaria, although the mechanism of action of the IS has not been elucidated. METHODS: Because an intradermal injection of action spectrum (AS)-irradiated serum in a case of solar urticaria induced a wheal response, we studied the responsiveness of the intradermal injection after an IS irradiation. RESULTS: An AS in this patient was composed of visible light shorter than 500 nm, while an IS was composed of visible light longer than 530 nm. When the IS was exposed immediately after the AS irradiation, the wheal response was inhibited. However, when the IS was exposed before the AS irradiation, the wheal response was not inhibited. An intradermal injection of her serum produced no reaction, whereas an intradermal injection of her serum pre-irradiated with visible light induced a wheal flare response. Further examination revealed that the in vivo wheal-inducing activity of her serum irradiated with visible light could be attenuated by post-IS irradiation at the injection site, while the wheal-inducing activity of her visible light-irradiated serum was not inhibited by irradiation of the activated serum with the IS. The wheal-flare response induced by compound 48/80 and histamine was not altered by IS irradiation at the site of skin tests. CONCLUSION: These findings indicate that photoallergens in the patient's serum that are activated by visible light irradiation are responsible for the development of her symptoms and that the IS may suppress the wheal response by inhibiting the binding of the photoallergens to mast cells, not by inactivating the photoallergens and stabilizing mast cells.     

Lichenoid tissue reaction in porphyria cutanea tarda

We report a patient presenting with lichenoid plaques on exposed skin who had the metabolic features of porphyria cutanea tarda (PCT). Histology of lesional skin demonstrated a lichenoid inflammatory cell infiltrate in the upper dermis, while direct immunofluorescence revealed immunoreactive colloid bodies. Monochromator irradiation testing demonstrated photosensitivity in the visible spectrum consistent with porphyria. Solar-simulated irradiation induced a papular reaction with lichenoid histological changes. We propose that this atypical presentation of PCT may reflect a lichenoid tissue response to a porphyrin-mediated photochemical reaction.     

Solar urticaria: A consideration of the mechanism of inhibition spectra.

BACKGROUND: Solar urticaria is a rare disorder characterized by pruritus, erythema and wheal upon sunlight exposure. Inhibition spectra (IS), which prevent wheal formation, have been found mainly in Japanese patients and lie mostly in longer wavelengths than the action spectrum (AS). The exact mechanism of AS and IS has not been clarified. PATIENTS AND METHODS: To elucidate the mechanism of AS and IS, we conducted photobiological studies including in vitro irradiated serum injection tests and measurements of plasma histamine levels in 3 patients with IS. RESULTS: All patients had AS ranging between 400 and 490 nm and IS ranging between 520 and 610 nm. A wheal reaction appeared soon after the termination of IS irradiation. The patients developed no wheal or erythema upon intradermal injection of preirradiated serum. Plasma histamine levels were not elevated during irradiation with slide projector light, but marked elevation of histamine was observed when wheals developed after the termination of inhibitory irradiation. CONCLUSION: These results suggest that the IS in our cases might inactivate photoallergens produced by AS and, additionally, stabilize mast cell degranulation.     

Effect of antioxidants and free radical scavengers on protection of human skin against UVB, UVA and IR irradiation

Background/aims: This study was designed to observe the effect of a mix of commercial antioxidants and free radical scavengers (AO) on protection of human skin against different wavelengths of the solar spectrum: 280-320 nm (UVB), 320-400 nm (UVA) and 400-900 nm (IR).
Methods: Healthy volunteers were chosen from the local population and exposed to the three aspects of the solar spectrum. Erythema at 24 h, immediate pigment darkening (IPD) and immediate erythema were employed as markers for UVB, UVA and IR exposure, respectively.
Results: Based on 24 h erythema measurements, the AO mix afforded about 2.6-fold (163%) protection against UVB-induced erythema (Table 1). IPD measurements after UVA exposure exhibited 76% protection afforded by the AO mix. The AO mix reduced IR-induced increases in erythema and blood flow by 43% and 52%, respectively (Table 1).
Conclusions: Data from these studies suggest that treatment with antioxidants prior to exposure to solar irradiation allows protection of human skin against IR as well as UVB and UVA. Antioxidants and free radical scavengers may be valuable adjuncts to traditional sunscreens, for protection of skin against the effects of actinic exposure that, over a long term, can result in formidable consequences such as skin cancer and photo-aging.     

Fatty acids and vitamins generate singlet oxygen under UVB irradiation

UVB radiation is already known as initiator and promoter of carcinogenesis in skin. UVB is well absorbed in proteins and DNA leading to products such as cyclobutane pyrimidine dimers. In contrast, UVA radiation generates reactive oxygen species such as singlet oxygen, which can initiate a variety of cellular damages and cellular signalling. It was the goal to investigate whether and to which extent UVB radiation is additionally able to cause oxidative damages via singlet oxygen. Potential endogenous photosensitizers such as vitamin B molecules or unsaturated fatty acids were irradiated in solution using monochromatic UVB radiation at 308 nm. Singlet oxygen was directly detected and quantified by its luminescence at 1270 nm. All investigated endogenous photosensitizers showed clear singlet oxygen signals with a quantum yield ranging from 5 to 40%. UVB radiation altered the photosensitizer molecules during irradiation yielding a change of absorption in the entire ultraviolet spectrum (280-400 nm). UVB irradiation of endogenous photosensitizers produced singlet oxygen that in turn changes the absorption of those molecules. Being an important prerequisite, the changed absorption may either reduce or increase singlet oxygen production. An increase in singlet oxygen generation may initiate a vicious cycle that has the potential to amplify UVB- or UVA-mediated effects in skin cells.     

Phototoxic reaction to xanthene dyes induced by visible light

Many dyes, for instance methylene blue, rose bengal, and eosin, are known as photosensitizers, and in the presence of molecular oxygen they induce cell lethality and skin photosensitivity (1-4). Several dyes are used in cosmetic products, particularly in lipsticks. Human lip skin is therefore exposed to potential danger from dye-sensitized phototoxic reactions. Using an in vivo system of mammalian skin, such as the abdominal skin of rabbits, we established screening tests for the phototoxic potential of synthetic dyes in two ways: (a) intracutaneous injection; (b) topical application with and without damaging the barrier property of the stratum corneum. In the intracutaneous injection assay, distinct phototoxic reactions were induced by rose bengal, eosin Y.S., and dibromofluorescein. When these dyes were applied topically to intact skin, no phototoxic reactions were observed. Phototoxic reactions were, however, elicited when the dye solutions were applied to abraded or scratched skin. The intensity of phototoxic reaction was found to be influenced by the vehicle in which the dyes were suspended. Phototoxic reaction to the dyes was induced by artificial light as well as by sunlight. By using commercially available fluorescent lamps with different spectral emissions, the action spectra for the phototoxic reaction to these dyes were investigated and it was found that the maximum phototoxicities of the dyes were manifested by light within a spectral range of 400-600 nm. Further studies on action spectra, using a monochromatic irradiation system, revealed a high correlation between the action spectra of the dyes and their absorption spectra. Maximum effective wavelength for the phototoxic reaction of eosin Y.S. was 525 nm. This topical as well as intradermal assay for assesing phototoxic reaction to synthetic dyes in living skin will be a practical and useful measure for studying the phototoxicity of the dyes.     

Action Spectrum for Bergamot-Oil Phototoxicity Measured by Sunburn Cell Counting

The present study investigated the phototoxic effect of bergamot oil and its photosensitive component, bergapten, on sunburn cell (SBC) production in guinea pig skin. The back skin was pretreated with bergamot oil or bergapten and exposed to monochromatic light under various conditions. After irradiation, skin specimens were excised, and histological sections were prepared. The number of sunburn cells in the interfollicular epidermis was counted. The SBC formation by bergamot oil or bergapten plus UVB radiation was the same as that without pretreatment with any photosensitizer. In contrast, a significant number of SBCs were induced by bergamot oil or bergapten plus UVA radiation, but no SBCs were found after the treatment with UVA alone. The result indicates that bergamot oil or bergapten was photosensitized by UVA irradiation. The SBCs were linearly increased in a UV-dose dependent manner. On the basis of the regression lines, an action spectrum and spectral peak for the photosensitizers plus UVA were obtained. The action spectrum for bergamot oil- and bergapten-induced SBC formation was in the ranges of 325–365 nm and 325–350 nm, and their spectral peaks were at 335–345 nm and 335–350 nm, respectively. The data are in good accordance with those estimated from skin erythema reactions. Therefore, counting SBCs is a very useful parameter for quantitative evaluation of phototoxicity.     

The spectrum of inflammatory cell response to dimethyl sulfoxide

Dimethyl sulfoxide (DMSO), depending upon the concentration and mode of application to the skin, can induce either a non-immunological immediate contact urticaria or an irritant reaction. The dermal cellular infiltrate after open application of varying concentrations of DMSO has been studied in an experimental guinea pig model. The composition of the dermal cellular infiltrate showed a spectrum dependent on the concentration and number of applications of DMSO. The immediate reaction infiltrate 3 h after application of 100% DMSO consisted of 50% granulocytes, basophils being predominant. On the other hand, 12% DMSO applied 3 x daily for 3 days (cumulative insult) caused histologically a cellular reaction in which 80% of the infiltrate consisted of mononuclear cells. The present findings are compared to the microscopic findings in 3 other cutaneous reactions previously studied in this animal model, namely, the Type I immediate hypersensitivity reaction, the Type IV delayed hypersensitivity reaction, and the irritant reaction. Differing cellular infiltrate patterns are discernible at the same time points. The study illustrates the spectrum of inflammatory reactions seen in the skin and provides background information for future clinical studies, for instance, on the role of the basophil granulocyte in immediate contact reactions.     

The contact urticaria syndrome

Contact urticaria may occur following contact of the skin or mucous membranes with a large number of diverse substances. When localized angioedematous reactions of the eyes or oropharynx are caused by proteinaceous substances, the distinction between contact urticaria and common inhalant or food allergies is subtle. The time course of the reaction, negative controls, or occurrence of generalized symptoms do not constitute unequivocal evidence of immunologic contact urticaria, and confirmation by RAST or passive transfer testing is required. Clinical symptoms range from mild, localized erythema to generalized anaphylaxis. When contact urticaria becomes superimposed on eczematous skin, immediate reactions that resemble eczema more than urticaria may occur. Dermatologists must increase their awareness of these clinical reactions and evaluate the external environment when searching for causes of localized urticarial reactions.     

Recent advances in phototherapy

This synopsis reviews recent developments in dermatological phototherapy. UVA1 phototherapy (340-400 nm) is effective in the treatment of inflammatory skin diseases such as acutely exacerbated atopic dermatitis, localized scleroderma, urticaria pigmentosa and disseminated granuloma annulare. Narrowband UVB radiation (311-313 nm) is used successfully as monotherapy or combined with dithranol, oral retinoids or 8-MOP in psoriasis, atopic dermatitis (AD) or photosensitivity disorders such as polymorphic light eruption. Bath water delivery of 8-methoxypsoralen and subsequent UVA-irradiation (PUVA bath therapy) for the treatment of psoriasis as well as for mycosis fungoides, localized scleroderma, urticaria pigmentosa or lichen planus is an effective alternative to its systemic application. The combination of salt water brine baths in different concentrations and subsequent UVA/B irradiation is used increasingly for the treatment of psoriasis or AD. Extracorporeal photopheresis (ECP) has proven to be a very effective treatment modality for cutaneous T cell lymphoma, chronic graft-versus-host disease and certain autoimmune diseases such as systemic scleroderma or pemphigus. However, despite the documented benefits of these new treatment modalities, little data exist as of yet on potential long-term side effects, thus the indications for these therapies should be considered carefully and patients should be followed up at regular intervals.     

An action spectrum for photoinduction of prolonged cutaneous photosensitivity by topical 8-MOP

Suberythemogenic exposure of human skin treated with aqueous 8-MOP to radiation greater than 380 nm prolongs photosensitization to subsequent UVA from 6 to 24-72 h. One hypothesis for prolonged photosensitization is that greater than 380 nm irradiation forms 8-MOP-DNA monoadducts, which are removed more slowly than free 8-MOP and serve as a substrate for crosslinking by further UVA exposure. Sufficient DNA crosslinking results in erythema. We have examined this hypothesis by measuring the action spectrum for induction of prolonged photosensitization. Skin of normal volunteers was treated with aqueous 8-MOP (0.003%) and immediately received suberythemogenic monochromatic exposures between 334 and 430 nm. twenty-four hours later, the presence of prolonged sensitization was tested by small exposures of UVA. Erythema was evaluated 3 and 5 d later, and an action spectrum for prolonged sensitization was determined. The minimum phototoxic dose (MPD) was also determined at each wavelength. The action spectrum for prolonged photosensitization declined gradually between 334 and 425 nm. The action spectrum for delayed erythema induced by a single exposure of 8-MOP-treated skin declined rapidly from 334-390 nm. These findings are consistent with prolonged binding of 8-MOP in the skin by an initial exposure, possibly as 8-MOP-DNA monoadducts, allowing the second exposure to induce an erythemogenic event, possibly crosslinking of DNA.     

Immediate contact reactions to cow's milk and egg in atopic children.

Forty children (0-5 years old), presented with immediate contact urticaria, rash and often atopic dermatitis (n = 34). Redness or urticaria around the mouth appearing after consuming cow's milk or egg, were the major complaints in all. These symptoms suggested a food-induced immediate contact reaction, which can be immune-mediated or irritative. To reinduce this reaction, a skin provocation test, called SAFT, was performed. SAFT stands for Skin Application Food Test. This test is based on direct skin contact, during a maximum of 30 min with food in its 'ordinary consumptive state'. The SAFT can be regarded as a 'physiological' provocation patch test. If positive, contact urticaria develops most often within a few minutes. The results of SAFT and IgE RAST correlated significantly well. Total IgE values were not informative. The rapid onset of the SAFT reaction, induced by proteins, supported by RAST results, strongly indicates an immune-mediated mechanism. In 52% of the 34 patients with atopic dermatitis, dermatitis was exacerbated following food-to-skin contact. Immune-mediated contact reactions to foods play an important role in (dermal) food allergy.     

Lysosome destruction and lipoperoxide formation due to active oxygen generated from haematoporphyrin and UV irradiation

The lysosomal enzymes, acid-phosphatase and β-glucuronidase, were released from rat liver lysosome when exposed to 400 nm irradiation in the presence of haematoporphyrin, and the release was prevented by adding vitamin E., diazabicyclo-octane, bovine serum albumin, superoxide dismutase or d -mannitol to the reaction mixture. Monochromatic irradiation with wavelengths from 380 to 410 nm caused no significant differences in the release of lysosomal enzymes, but 420 nm irradiation caused three fifths of that of 400 nm irradiation. The malondialdehyde level in rat liver homogenate increased after 400 nm irradiation in the presence of haematoporphyrin. Reduction of nitroblue-tetrazolium was not observed when haematoporphyrin was excited by 400 nm; it was considered that superoxide anion radical (O^–₂) was not primarily generated. The following mechanism was assumed: that porphyrin which had been excited by 400 nm, converted ground-state molecular oxygen (³O₂) to excited singlet oxygen (¹O₂), which formed lipid peroxides in lysosomal membrane resulting in destruction of the membrane; skin changes would occur from these released lysosomal enzymes.     

FIBRINOLYTIC ACTIVITY IN LESIONS PRODUCED BY MONOCHROMATOR ULTRAVIOLET IRRADIATION IN VARIOUS PHOTODERMATOSES

SUMMARY.– Histological and fibrinolytic activity (FA) changes were studied in skin exposed to visible light and u.v. radiation from a monochromator. There was a marked difference in the early and late lesions produced by irradiation. Late lesions showed loss of fibrinolysis and early lesions showed little or no such change.
Absence of fibrinolysis was found in upper dermal vessels in the more delayed sunburn papule reaction and in the delayed reaction in polymorphic light eruption (PLE) and actinic reticuloid, with heavy mononuclear infiltrates appearing as early as I hr. after irradiation. The lesions of PLE and "actinic reticuloid" showed absence of FA. There was no loss of fibrinolysis in the urticarial lesions of solar urticaria (as long as 5 hr. after irradiation) and in the porphyric skin reaction, or in light exposed porphyric skin.
These results suggest that impairment of fibrinolysis may play an important part in the delayed reaction to sunburn in the normal, in PLE, actinic reticuloid and photosensitivity with tetrachlorsalicylanilide. By contrast, impairment of fibrinolysis is not a feature of idiopathic solar urticaria or of the more or less acute porphyric photosensitive skin reaction.