Experimental studies on phototoxic and photoallergic reaction by the skin window technique.

The differentiation of photoallergic contact dermatitis by 3,3', 4', 5-tetra-chlorosalicylanilide from phototoxic contact dermatitis by 8-MOP in guinea pigs was studied by skin window technique. Based upon the results, it may be concluded that the photoallergic reaction can be differentiated from phototoxic reaction by the appearing pattern of basophilic leukocytes.     

The role of oxygen in the photodamaging effect on erythrocytes of some photoallergic and phototoxic compounds.

Red blood cells irradiated with longwave ultraviolet light in the presence of a number of photoallergic or phototoxic compounds showed a marked loss of K+ ions. This process was strongly restricted by anaerobic conditions. During irradiation, oxygen was consumed. Since pre-irradiated photosensitizers were not toxic to erythrocytes, it is concluded that during irradiation, oxidative processes take place in the erythrocyte. The concentrations of the investigated photoallergic compounds required to induce photohaemolysis, were several times higher than those required for the phototoxic compound protoporphyrin. These findings indicate that photoallergic compounds, like the photodynamic compounds, also have photo-oxidative capacities, but to a much lower degree.     

Giant cell (temporal) arteritis involving both external and internal carotid arteries.

A 76-year-old woman with giant cell (temporal) arteritis was described; she presented with a one year history of headache and tinnitus. Histopathological findings from a superficial temporal artery showed arteritis with granulomatous changes. Bilateral carotid arteriograms demonstrated the stenoses of both internal carotid arteries as well as the narrowing of the superficial temporal arteries. Although we dermatologists rarely encounter the disease in daily clinical practice, it is of clinical importance to perform cerebral angiography in patients suspected of temporal arteritis.     

Contact urticaria, allergic contact dermatitis, and photoallergic contact dermatitis from oxybenzone.

There is little literature regarding conventional patch tests and photopatch tests to oxybenzone resulting in both immediate- and delayed-type hypersensitivity reactions. A patient was patch-tested and photopatch-tested to various sunscreen chemicals. Both immediate- and delayed-type hypersensitivity reactions were observed with oxybenzone. The positive patch tests were also photoaccentuated. Oxybenzone, a common sunscreen allergen, can result in both contact urticaria and delayed-type hypersensitivity on both conventional patch testing and photopatch testing. Allergic contact dermatitis to sunscreen chemicals has traditionally included contact urticaria, allergic contact dermatitis, and photoallergic contact dermatitis. Due to the recognition of p-aminobenzoic acid (PABA) and its esters as sensitizers, the presence of benzophenones in "PABA-free" sunscreens has become more prevalent, especially in sunscreens with a sun protection factor (SPF) greater than 8. In our patient, immediate- and delayed-type hypersensitivity reactions were seen to oxybenzone (2-hydroxy-4-methoxybenzophenone, 2-benzoyl-5-methoxyphenol, benzophenone-3, Eusolex 4360, Escalol 567, EUSORB 228, Spectra-Sorb UV-9, Uvinul M-40) upon conventional patch testing and photopatch testing.     

Adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib

Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis of these first- and second-generation TKIs' cutaneous side effects, and approaches to their treatment. The wide range of adverse effects clarifies the difficulty in designing a truly antitumoral TKI.     

Interaction of methotrexate and betamethasone with experimental phototoxic inflammation to PUVA (Psoralen and UVA) in mice

Summary The influence of methotrexate and of betamethasone on a following phototoxic reaction to 8-methoxypsoralen and long-wave ultraviolet light (PUVA) was studied in the mouse. High PUVA doses were not influenced by the two drugs tested. Both methotrexate and betamethasone tended to diminish the PUVA response when psoralen was given in a medium dose.     

Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients

Background: Photoallergic contact dermatitis from topical ketoprofen (KP), a nonsteroidal anti‐inflammatory agent, is a well‐known side effect. Objectives: To investigate photo‐contact allergic reactions to KP and other nonsteroidal anti‐inflammatory drugs (NSAIDs), sunscreens, and fragrance components as well as the presence of prolonged photosensitivity related to it. Patients/Methods: From June 1993 to June 2007, 42 patients were patch tested and photopatch tested with the ingredients of a KP preparation and other relevant substances. A questionnaire was performed in order to determine the importance of prolonged photosensitivity; 40/42 did respond. Results: 38 patients showed photo‐contact reaction, 1 photoaggravated reaction, and 3 contact allergic (CA) reaction to KP. Simultaneous photo‐contact allergic reactions were frequently observed not only to structurally related but also to non‐structurally related NSAIDs and sunscreens. Simultaneous CA to fragrance components was common. 1/3 of the patients reported prolonged photosensitivity, i.e. from 1 up to 14 years after having stopped KP application. Conclusions: The history is often not a good guidance to determine KP‐related (photo) allergic contact dermatitis and the severe clinical symptoms sometimes require hospitalization, and/or systemic corticosteroids. As for the association between KP and sunscreen intolerance (being 1 of the possible causal factors for recurrent dermatitis), routine standard photopatch testing with KP might be indicated.     

Concomitant development of photoallergic contact dermatitis from ketoprofen and allergic contact dermatitis from menthol and rosin (colophony) in a compress

We describe a case of a 40-year-old non-atopic woman with recurrent leg ulcers because of the factor V Leiden mutation who developed a severe eczematous lesions of the skin surrounding an ulcer of the right leg after the use of a protease-modulating matrix (Promogran, Johnson and Johnson, Gargrave, Skipton, UK). The patient was patch tested with the SIDAPA (Italian Society of Allergological, Occupational and Environmental Dermatology) standard series, a piece of the device as is, of the bovine collagen (Zyderm, Collagen Corporation, Palo Alto, CA, USA) as is, a piece of the gauze containing only regenerated oxidized cellulose (Tabotamp, Johnson and Johnson, Gargrave, North Yorkshire, UK) and of a fold towels in pure cellulose (Foscart, Bassano del Grappa, Italy). Patch tests gave a positive reactions to nickel sulphate and Promogran as is. We showed that the sensitizing agent was regenerated oxidized cellulose, a substance the treatment of ulcers and as is in and in combination with collagen in surgery for intraoperative hemostasis. The case reported suggests that regenerated oxidized cellulose can cause allergic contact dermatitis.     

Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis

Patch testing may help to assess the culpability of a drug in an adverse reaction. Our aim was to study patch testing in severe cutaneous ad verse drug reactions [ADRs] (Stevens-Johnson syndromeitoxic epidermal necrolysis (SJS/TEN). acute genera exanthematous pustulosis (AGEP), and other cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had SJS/TEN. 14 AGEP, and 23 other cutaneous ADRs. Patients were patch tested with the suspect drug and with H standard series of drugs. 2 patients among the 22 SJSTEN cases had a relevant positive test. 7 patients among the 14 AGEP cases had a relevant positive test. 6 patients among the 23 other cutaneous ADRs had a relevant positive test. Our results suggest that patch testing has a weak sensitivity in SJS'TEN and is not appropriate in these diseases. Patch testing seems more adapted to other cutaneous ADRs, such as AC it: P. in which the proportion of positive patch tests was significantly higher (P<0.02). Nevertheless, the difference of sensitivity of patch testing in SJS TEN, AGEP or other cutaneous ADRs could be linked not only to the clinical type of eruption, but also lo the different spectrum of culprit drugs in each type of eruption.     

Photodiagnosis: the modified intradermal test in comparison with other procedures for the detection of phototoxic and photo-allergic drug reactions

In systemic photosensitivity to drugs, the modified irradiated intradermal assay is a valuable diagnostic tool. We discuss its advantages in comparison to both the less sensitive photopatch and the potentially dangerous and/or bothersome technique of systemic photochallenge.     

Cellular aspects of phototoxic reactions induced by kynurenic acid. II. Fine structural analysis and cytochemistry on cultivated cells.

A recent report described the establishment of an experimental model for studying photo-oxidative damage inflicted by kynurenic acid on cultivated cells. Preliminary findings by scanning electron microscopy (SEM) were reported. For the present paper supplementary SEM studies were performed, and it was found that maximum cell damage appears 2 to 4 hours post irradiation. With low concentrations of kynurenic acid and brief UVA exposure, repair mechanisms seem to occur. Damage in the form of cellular swelling and plasma membrane alterations is most easily recognized by SEM, which is far more sensitive than ordinary light microscopy. Transmission electron microscopy (TEM) reveals morphologic alterations, consisting of an enhanced formation of endocytotic vacuoles from the plasma membranes, swelling with disruptions of the cell sap continuity, mitochondrial swelling, dilatation of the endoplasmic net, and vesiculation of some of the microvilli. Lysosomal damage, which was not seen until very late post irradiation and only for high concentrations of kynurenic acid and long-term UVA exposure, seems to be a secondary phenomenon. This hypothesis is further supported by the cytochemical analysis. The primary event thus seems to affect the plasma membrane level and originate in the binding of kynurenic acid to the plasma membrane on which subsequent UVA irradiation inflicts secondary intracellular alterations due to increased permeability and swelling.