Insight into immunocytes infiltrations in polymorphous light eruption.

Polymorphous light eruption (PLE) which is one of the most common photodermatoses has been demonstrated to be immune-mediated disorder. Resistance to UV-induced immunosuppression resulting from differential immune cells infiltration and cytokines secretion has been highlighted in the pathogenesis of PLE. In this study, we reviewed differential patterns of immune cells infiltrations and cytokines secretion that may contribute to PLE occurrence and development.

The clinical severity score of chronic actinic dermatitis correlates with in vivo photoallergic reactions and the immunologic parameters related to a shift towards Th2 immunity from the Th2/Th1 balanced status in patients with chronic actinic dermatitis.

BACKGROUND: Chronic actinic dermatitis (CAD) has a more complicated pathogenetic basis than others. The clinical grading system and its correlations with the clinical and immunological parameters still remained to be investigated to define the nature of CAD in a more detailed manner. OBJECTIVES: We investigated correlations of the clinical severity score of CAD (CSS-CAD) with the clinical and immunological parameters. METHODS: We evaluated 72 patients with CAD and classified them into three groups according to the CSS-CAD. We analysed total IgE level, peripheral blood (PB) eosinophil count, the ratio of Th2cell (CCR4 + CD4 +) percentage over Th1 cell (CXCR3 + CD4 +) percentage (Th2/Th1) and/or the sum of suppressor/cytotoxic T cells. RESULTS: The total IgE levels and the percentage of PB eosinophils were higher in the severer group than other groups. A shift towards Th2 from Th2/Th1 balanced status may be affected by total counts of suppressor T cells, and the patient with higher Th2/Th1 ratio than balanced status had the more proportion in the severer CSS-CAD group than other groups. CONCLUSION: The CSS-CAD correlates with total IgE level, PB eosinophil count and a shift towards Th2 immunity from Th2/Th1. So we suggest the Th1/Th2 dysbalance may be affected by the CSS-CAD.

NCTC 2544 and IL-18 production: a tool for the in vitro identification of photoallergens.

PURPOSE: Differentiation between photoallergenic and phototoxic reactions induced by low molecular weight compounds represents a current problem. The use of keratinocytes as a potential tool for the detection of photoallergens as opposed to photoirritants is considered an interesting strategy for developing in vitro methods. We have previously shown that IL-18 production in the human keratinocyte cell line NCTC 2455 is a good model for the in vitro identification of contact sensitizers. The purpose of this manuscript is to summarize data obtained in the NCTC 2544 assay as an in vitro model to identify photoallergens and discriminate them from phototoxic chemicals. METHODS: The effect of UVA radiation (3.5J/cm(2)) over NCTC 2544 cells irradiated and non irradiated, and treated with increasing concentrations of various compounds including negative compounds (irritants and allergens), ibuprofen and acridine (photoirritants); ketoprofen, promethazine and chlorpromazine (photoirritants/photoallergens); benzophenone, 4-tert-butyl-4-methoxy-dibenzoylmethane, 2-ethylexyl-p-methoxycinnamate and 6-methylcumarin (photoallergens) was investigated. Twenty-four hours after exposure, cytotoxicity was evaluated by the MTT assay, while a commercially available ELISA kit was used to assess the intracellular content of IL-18. RESULT: At no cytotoxic concentrations, allergens and photoallergens induce a dose-related increase in the production of IL-18, whereas irritants and photoirritants failed, indicating the possibility to use the NCTC 2544 assay to identify in vitro photoallergens.

[Photoallergic drug reactions]. / Fotoalergijske reakcije na lijekove.

Drug-induced hypersensitivity reactions include phototoxic and photoallergic reactions. Photoallergic reactions, which develop as cell-mediated immune responses to a light-activated compound, are described in this review article. The main topics include photobiology, list of common drugs inducing photoallergic reactions, immune response, clinical features, diagnostic and therapeutic approach. Photoallergic drug reactions can be avoided in most cases if the potential photoallergens are known and appropriate photoprotection is used.

UV-induced tolerance to a contact allergen is impaired in polymorphic light eruption.

Polymorphic light eruption (PLE) is a common skin disorder provoked by exposure to UVR. Its clinical symptoms resemble those of a contact allergic reaction. PLE is generally considered a T-cell-mediated autoimmune reaction toward a yet unidentified antigen formed in UVR-exposed skin. Predisposition to such an immune reaction may result from aberrant epitope formation, increased immune reactivity to a universal epitope, or diminished propensity to UVR-induced immunosuppression or to the induction of tolerance. In a study comprising a total of 24 PLE patients and 24 healthy sex- and age-matched controls, we found that both groups demonstrated similar immunosuppression of contact sensitization to diphenylcyclopropenone by earlier exposure to solar-simulating UVR. However, only 1 out of 13 PLE patients (8%) versus 6 out of 11 controls (55%) that had been immunosuppressed by UVR exhibited a state of immunotolerance toward the same allergen after 10-24 months (P=0.023). We conclude that the impaired propensity to UVR-induced allergen-specific immunotolerance may promote recurrent PLE.

Generation of reactive intermediates in photoallergic dermatitis.

PURPOSE OF REVIEW: Photosensitivity disorders are cutaneous reactions caused or amplified in their severity by sunlight, normally ultraviolet radiation (UVA or UVB). These reactions appear when xenobiotics are topically or systemically administered, and the individuals are exposed to solar or artificial light. RECENT FINDINGS: Photoallergic reactions seem to be initiated by covalent binding of the photosensitizer to a skin protein, forming adducts capable of interacting with the immune system. The most frequent reactions of this type (photoallergic dermatitis) are induced by drugs and mediated by T cells. Diagnosis of photoallergy requires identification of the responsible agent, which is not always clear-cut. Photopatch testing is the method of choice for definitive diagnosis. SUMMARY: In the current review, some specific examples of photoallergic xenobiotics are given. They include nonsteroidal anti-inflammatory drugs, antibiotics, platelet aggregation inhibitors, and sunscreens. In general, they are taken from the scientific literature published during the last decade, with particular emphasis on the most recent articles. The focus is on the mechanistic aspects, specifically on the generation of reactive intermediates capable of reacting with proteins.

Contact and photocontact sensitization in chronic actinic dermatitis: a changing picture.

BACKGROUND: Patients with chronic actinic dermatitis (CAD) frequently have positive patch or photopatch tests. In our previous study (period 1987-1992), the most prominent contact allergen was the sesquiterpene lactone mix (36% of patients with CAD). OBJECTIVE: To assess whether contact allergy profiles in CAD patients between 2000 and 2005 have changed in respect to our previous data (1987-1992). PATIENTS AND METHODS: Fifty CAD patient records from 2000 to 2005 for patch and photopatch testing were retrospectively analysed and data were compared with that from 86 patients seen between 1987 and 1992. RESULTS: Thirty-two (64%) and 64 (74%) patients had positive patch or photopatch tests in 2000-2005 and 1987-1992, respectively. The allergen profile has altered. A decline in sesquiterpene lactone mix positive reactions was noted: 29 (36%) patients were positive in 1987-1992 and 10 (20%) patients in 2000-2005, but this was not significant (P = 0.08). Reactions to non-fragrance consumer allergens (i.e. p-phenylenediamine and preservatives) had risen from 7 reactions (1987-1992) to 21 reactions in 13 individuals (2000-2005) (P < 0.001). Of these allergens, p-phenylenediamine was the most common (12%; P = 0.004). CONCLUSIONS: A significant rise in positive patch tests to non-fragrance consumer allergens, particularly p-phenylenediamine, was seen in CAD patients in 2000-2005. We speculate this alteration of allergen profile may be partly due to changes in exposure patterns.

A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis.

BACKGROUND: Retrospective chart reviews are periodically needed to update allergen series to detect changes in photoallergic contact dermatitis (PACD) over time. OBJECTIVE: We sought to evaluate photopatch test results during a 13-year period and extend the observations to 20 years. METHODS: A retrospective chart review was conducted in patients who were photopatch tested. RESULTS: In all, 76 patients were evaluated. A total of 69 positive photopatch and 45 positive patch test reactions were detected in 30 and 23 patients, respectively. The frequencies of the positive photopatch test reactions were sunscreens 23.2%, antimicrobial agents 23.2%, medications 20.3%, fragrances 13%, plants and plant derivatives 11.6%, and pesticides 8.7%. Of the positive photopatch reactions to antimicrobial agents, 60% were caused by Fentichlor. LIMITATIONS: This study was a retrospective chart analysis, and the number of patients was small. CONCLUSIONS: Sunscreens and antimicrobial agents were the most frequent allergens eliciting PACD, and there was a decrease in PACD caused by fragrances. The number of reactions to medications increased. This study also demonstrated that pesticides can be a cause of PACD. The detection of reactions to Fentichlor was unexpected and, although they have been attributed in some studies to cross-reactions to sulfanilamides and bithionol, such a robust association was not observed in this study. This study extends our experience of the changes in the allergens that elicit PACD to 20 years.

Ketoprofen allergic reactions.

Topical ketoprofen (KP) is widely used because of its anti-inflammatory effect. Parallel with its popular usage, the number of reported cases of ketoprofen-induced photoallergic contact dermatitis has increased. A review of the literature was made to evaluate the spectrum of cross sensitization in patients with ketoprofen-induced photoallergic contact dermatitis using ketoprofen and other structurally similar chemicals and sunscreens, fragrance components, as well as the presence of prolonged photosensitivity related to it. Furthermore, the distinction between true cross-reactivity and concomitant sensitization may be difficult. Therefore, further investigations are needed to gain a more complete understanding of this important topic. This article also reviews some patents related to alternative treatment of musculoskeletal diseases and/or treatment of allergic reactions due to NSAIDs use.

Photoallergic contact dermatitis.

Photoallergic contact dermatitis (PCD) is a delayed-type hypersensitivity cutaneous reaction in response to a photoantigen applied to the skin in subjects previously sensitized to the same substance. For the development of PCD, irradiation with ultraviolet (UV) radiations, usually UVA, is required to create a complete antigen, and the culprit substance needs to be within the skin at the time of UVA exposure. The incidence of PCD in the general population is unknown and is considered uncommon. Epidemiological data have been obtained from studies performed using photo-patch tests in patients with suspected photodermatoses in tertiary care outpatient units. Prevalence of PCD over time has been also dependent on prescription and/or usage patterns of potential photosensitizers, and was particularly high in the past, causing mini-epidemics in some countries because of the widespread use of halogenated salicylanilides and other photosensitizing compounds. Many topical substances with photosensitizing properties are currently available, with the most important ones being sunscreen agents and nonsteroidal antiinflammatory drugs. The diagnosis of PCD, in patients with a history of photosensitivity and especially with an eczematous form of photodermatosis, should be confirmed by photo-patch testing.

Occurrence of plant sensitivity among patients of photodermatoses: a control-matched study of 156 cases from New Delhi.

BACKGROUND: Photodermatitis is an abnormal response to ultraviolet radiation (UVR). The photoallergic contact dermatitis caused by plant allergens is a serious cause of morbidity in India. Airborne contact dermatitis is the classical presentation of plant-induced dermatosis, which may become difficult to differentiate from chronic actinic dermatitis in chronic cases. The rapid growth of parthenium weed in India and its ill effects on the population make it important to detect all cases of parthenium sensitivity, which in some cases might simulate photodermatitis. AIMS: This study aims to detect the occurrence of plant sensitivity and photosensitivity in idiopathic-acquired photodermatoses, airborne contact dermatitis and general population taken as controls. METHODS: One hundred and fifty six consecutive patients suffering from polymorphic light eruption (PMLE), chronic actinic dermatitis (CAD) and airborne contact dermatitis (ABCD) were enrolled in the study over a period of three years (June 2004 to May 2007). An equal number of age and sex matched healthy subjects were enrolled in the study as controls. All the patients were subjected to detailed history taking, clinical examination and histopathological examination for diagnosis. Patch and photopatch testing were perfomed in all the patients and healthy controls for detection of allergic and photoallergic reactions to parthenium, xanthium and chrysanthemum plant antigens and control antigens. RESULTS: Out of 156 patients enrolled in the study, 78 (50%) had CAD, 67 (42.9%) had PMLE and 11 (7.05%) had ABCD. The occurrence of parthenium/xanthium allergy and photoallergy, either to parthenium or both was most commonly found in ABCD (72.7%), followed by CAD (32%). In PMLE 4.5% cases showed photoallergy. Only 1.9% in the control group showed sensitivity to parthenium and xanthium. CONCLUSION: This study indicates that parthenium (and possibly xanthium) may act as important environmental factors in the initiation and perpetuation of not only ABCD but of CAD as well. Photoexacerbation to UVA at positive parthenium/xanthium sensitivity sites in ABCD and CAD indicates that ABCD with photosensitivity to compositae can lead to CAD.

Photonucleophilic addition of the epsilon-amino group of lysine to a triflusal metabolite as a mechanistic key to photoallergy mediated by the parent drug.

A mechanism for triflusal-induced photoallergy involving complexation of 2-hydroxy-4-trifluoromethylbenzoic acid with site I of human serum albumin and subsequent formation of a covalent adduct by photoreaction between a metabolite and a neighboring lysine residue is proposed. This is supported by the observed photobinding to poly-L-lysine. Thereby, a photoantigen is generated, which is a likely trigger of the immune response.The goal of the work presented herein is to gain deeper insight into the molecular basis of photoallergy mediated by triflusal through its active metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). For this purpose, the interaction between HTB and human serum albumin (HSA) was investigated by fluorescence and laser flash photolysis to monitor inclusion into the protein binding sites through variation in the excited-state properties. A remarkable lengthening of HTB triplet lifetime in the presence of HSA was observed. The use of oleic acid as a displacement probe clearly suggests the preference for dark binding in site I. The mechanism of photobinding was studied by irradiation of HTB in the presence of amino acids, and, in the case of lysine, a photoadduct was detected that arises from nucleophilic attack by the epsilon-amino group to the trifluoromethyl substituent of HTB. Accordingly, photobinding of the metabolite to poly-L-lysine was also observed. Overall, these results are consistent with a mechanism for triflusal photoallergy involving complexation of HTB to site I of HSA and subsequent formation of a covalent photoadduct with one neighboring lysine residue.

Induction of eosinophil-infiltrating drug photoallergy in mice.

BACKGROUND: Drug photoallergy is one of the highly incident adverse effects. Several different histological patterns have been recognized. OBJECTIVE: To establish a murine model of the eosinophil-infiltrating type of drug photoallergy by using afloqualone (AQ), a representative photosensitive drug. METHODS: AKR/J mice were sensitized by intraperitoneal injection of afloqualone solution (2mg/kg/mouse) and irradiation of shaved abdomen with ultraviolet A light (UVA) (12J/cm(2)). This sensitization procedure was repeated 2-12 times, and 3 days after the last immunization, mice were challenged by a subcutaneous injection of AQ solution and irradiation of the same site with UVA. The draining lymph node cells (LNCs) were used for transfer and cytokine production studies, and the challenged skin was analyzed for chemokine expression. RESULTS: More than 10 times of sensitization induced a massive infiltrate of eosinophils and lymphocytes at the challenged site. AKR/J mice were a high responder strain. The sensitivity was transferred with 5-8 x 10(7) immune lymph node and spleen cells into naïve mice. CD4(+) T cells were mainly responsible for this sensitivity, since 1 x 10(7) CD4(+) cells alone induced a high level of sensitivity, but CD8(+) T cells evoked the sensitivity to a lesser degree. Culture supernatants from AQ-photoimmuned lymph node cells contained a higher level of IL-4 and lower interferon-gamma than those from mice immunized with dinitrofluorobenzene. Finally, the skin of AQ-photochallenged site exhibited high expression of CCL24/eotaxin-2, a chemokine for eosinophils. CONCLUSION: It is suggested that eosinophilic drug photoallergy is mediated by sensitized Th2 cells and locally produced eosinophil-attracting chemokines.

Allergic and photoallergic contact dermatitis from ketoprofen: evaluation of cross-reactivities by a combination of photopatch testing and computerized conformational analysis.

Allergic contact dermatitis (ACD) and photo-ACD are cell-mediated delayed hypersensitivity reactions of the skin caused by a wide range of substances. Topical ketoprofen (KP), a nonsteroidal anti-inflammatory drug (NSAID), can induce ACD and photo-ACD. Patients with ACD and/or photo-ACD to KP frequently show concomitant sensitization to other substances. The aim of this study was to identify the substances most frequently associated with sensitization to KP, and to evaluate, by means of computerized conformational analysis, whether this association could be due to cross-allergy. 15 subjects with ACD and photo-ACD to KP were tested with the SIDAPA (Società Italiana di Dermatologia Allergologica Professionale ed Ambientale) patch test standard series, including fragrance mix and its components (eugenol, isoeugenol, oak moss, geraniol, hydroxycitronellal, amylcinnamaldehyde, cinnamyl alcohol and cinnamaldehyde) and with the SIDAPA photopatch test series. Allergic reactions to cinnamyl alcohol were noted in all patients, whereas some patients also showed positive reactions to fenticlor, octocrylene and benzophenone-10. Computerized conformational analysis demonstrated that the structure of cinnamyl alcohol is similar to that of KP, whereas the structures of benzophenone-10, octocrylene and fenticlor are completely different. These results suggest that in patients with contact allergy to KP, concomitant positive reactions to cinnamyl alcohol are due to cross-sensitization, whereas simultaneous allergic reactions to fenticlor, octocrylene and benzophenone-10 should be regarded as co-sensitizations.

Photocontact dermatitis to ketoprofen presenting with erythema multiforme.

A 74-year-old Japanese man developed erythema multiforme on the inner aspect of his left elbow where ketoprofen-containing tape was applied and exposed to sunlight, and the eruption subsequently spread to the four limbs and trunk. The lesions were successfully treated with systemic corticosteroids without recurrence. Lymphocyte stimulation tests with ketoprofen-photomodified peripheral blood mononuclear cells revealed that the patient had circulating lymphocytes reactive with a photohaptenic moiety of ketoprofen. To our knowledge, this is the first case of erythema multiforme induced by photocontact dermatitis. The presence of circulating photoantigen-reactive T cells seemed to induce erythema multiforme as an unusual manifestation in this patient.

Visible light photopatch testing of common photocontactants in female filipino adults with and without melasma: a cross-sectional study.

BACKGROUND: Although consistently associated with sun exposure, melasma is common among sun-shy Filipino women who generally prefer to have lighter skin, use skin lighteners, regularly practice sun avoidance, and are more exposed to indoor lights. OBJECTIVE: To determine presence/absence of photocontact dermatitis in melasma/no-melasma patients using photopatch testing (PhPT) with standard photocontactants and an indoor visible light (VL) source. DESIGN: Cross-sectional study: random population of 40 female patients aged 30-55 years, 20 with and 20 without melasma. The PhPT included 67 photocontactant allergens: 59 from Chemotechnique Diagnostics (24 fragrance, 22 North American photopatch, 13 plants) and 8 cosmetic allergens from Skin Sciences Laboratory Inc. (Pasig, Philippines) in sets of paired test patches. One of the pairs was irradiated with a 500-watt tungsten halogen lamp as the VL source; the other was the nonirradiated control. The standard protocols of the North American Contact Dermatitis Group (NACDG) was used to examine the nonirradiated control patches after 48 and 72 hours, the DAPT (German/ Austrian/ Swiss Photopatch Study Group) was used to examine the VL-irradiated patches, and both protocols were used to interpret relevance of the readings as to the presence or absence of contact dermatitis (CD) or photocontact dermatitis (PhCD). RESULTS: Fifty-five percent of patients in the melasma group (N = 11/20) had 29 positive (+) PhPT reactions to VL-irradiated allergens (11 fragrances, 11 North American, 7 plants). In the no-melasma group, none had (+) PhPT. This association is highly significant (P = 0.00 using 2-tailed Fischer's exact test), such that compared to a (-) PhPT, a (+) PhPT has 12.67 times more likelihood to develop melasma (P = 0.05: 1.402-114). All 29 (+) PhPT were decrescendo type, replaced by pigmentation observed up to 7 days suggesting phototoxic reactions, and all had (+) clinical relevance establishing phototoxic low-energy VL-PhCD. CONCLUSION: Melasma worsens with sun exposure, but this study shows that the low energy of artificial indoor VL is enough to react with photocontactants followed by a pigmentation response that may account for its clinical appearance as a mostly noninflammatory slowly evolving facial pigmentation.

Drug-induced photoallergic and phototoxic reactions.

Drug-induced photosensitivity involves reactions to medication triggered by exposure of the skin to ultraviolet light. Medications that trigger reactions can be topical or oral. Following interaction of ultraviolet radiation with a chemical present in sufficient amounts in the skin, one of the several reactions may occur in susceptible patients, most commonly photoallergy or phototoxicity. These reactions can be diagnosed separately based on pathogenesis, clinical characteristics and histopathology. Phototoxic disorders have a higher incidence than photoallergic disorders. The action spectra for most photoallergens and phototoxins lie in the ultraviolet A range. Subtypes of drug-induced photosensitivity include dyschromia, pseudoporphyria, photo onycholysis, and lichenoid and telangiectatic reactions.