Takeshi Hariya

Regulation of the cutaneous allergic reaction by humidity

Humidity is 1 of the environmental factors which regulate skin conditions. Effects of humidity on the cutaneous immune reaction were examined. Contact hypersensitivity to 2,4,6‐trinitrochlorobenzene was elicited in C57BL/6 mice. The reaction was greater in mice housed under low humidity conditions (about 10%) for 2 days, at either the induction or elicitation phase, than in mice housed under rather high humidity conditions (80%). After housing under controlled humidity for 2 days, the number of I‐A positive cells was 16% higher in the epidermis exposed to the dry condition. The increased population of FITC‐positive cells were in regional lymph nodes after painting of FITC during housing under lower humidity. Our study demonstrated that the cutaneous immune reaction is regulated by environmental humidity and suggested 2 possible mechanisms, i.e., increase in Langerhans cells and increased penetration of allergen with low humidity.

In vivo microscopic approaches for facial melanocytic lesions after quality-switched ruby laser therapy: time-sequential imaging of melanin and melanocytes of solar lentigo in Asian skin.

BACKGROUND The quality‐switched ruby laser (QSRL) has been widely used for the treatment of pigmented lesions, but clinical evaluations in most studies have been conducted on macroscopic skin color observation comparing the laser‐treated skin with its nontreated surrounding area. A few investigations examined skin changes after laser therapy at a cellular level, but almost none did so noninvasively. OBJECTIVE To elucidate the dynamic changes after QSRL irradiation of facial solar lentigo using noninvasive optical techniques. MATERIALS AND METHODS Time‐sequential imaging of Japanese female patients with a clinical diagnosis of solar lentigo was performed using ultraviolet photography, high‐magnification videomicroscopy, and reflectance‐mode confocal microscopy to examine pigmentary change after QSRL irradiation. RESULTS The present study showed that remaining melanocytes were visible in the solar lentigo of all subjects when crusts peeled off, despite hardly observable skin pigmentation to the naked eye. Moreover, noninvasive confocal imaging revealed that pigmented melanocytes varied in each solar lentigo after QSRL treatment, as indicated by melanin reflection level. CONCLUSIONS Optical techniques facilitate the evaluation of the in vivo dynamics of epidermal–melanocytic changes in solar lentigo after QSRL therapy and may be useful for monitoring outcomes after laser irradiation. The authors have indicated no significant interest with commercial supporters.

A cross-reaction between piroxicam-photosensitivity and thiosalicylate hypersensitivity in lymphocyte proliferation test

We examined the cross-reaction between photosensitivity to piroxicam (PXM) and contact sensitivity to thiosalicylate (TOS) by a lymphocyte proliferation test (LPT) in guinea pigs. The lymph node cells (LNCs) plus peritoneal exudate cells (PECs) from guinea pigs contact-sensitized with TOS remarkably cross-proliferated to PXM under UVA (4 J/cm2) irradiation. On the other hand, the PXM-photosensitized LNCs+PECs also cross-proliferated to TOS. From these results, the reciprocal cross-reaction between TOS-hypersensitivity and PXM-photosensitivity was reconfirmed by the in vitro LPT, indirectly indicating that the PXM-photosensitivity is a cell (probably T cell)-mediated PXM photoallergy in its nature. The TOS-primed LNCs+PECs did not cross-proliferate to UVA (4 J, 180 J or 500 J/cm2)-pretreated PXM (UVA-PXM) although it is supposed to contain several photoproducts of PXM. Furthermore, the TOS-primed LNCs developed a remarkable proliferative cross-response to the PECs pulsed with PXM under UVA (4 J/cm2) irradiation (photo-PXM-modified PECs), but not to the PECs pulsed with PXM or UVA-PXM. Therefore, it is presumed that the cross-reactive molecule, which is easily formed from PXM under UVA irradiation, is unstable, and that the formation of complete antigen by the generation of this molecule and its photobinding needs the coexistence of PECs, PXM and UVA irradiation at the same time in the culture.

Piroxicam has at least two epitopes for contact photoallergy

We have demonstrated previously in guinea pigs that the induction of photocontact sensitivity to piroxicam (PXM) also induces a state of cross-reactive contact hypersensitivity to two compounds having structurally related elements, thimerosal (TMS) and thiosalicylate (TOS). The present study was conducted to determine whether oral administration of TOS would desensitize guinea pigs previously photosensitized with PXM. At the same time, the spectrum of reactivities against these compounds and against tenoxicam (TXM) which resembles only piroxicam was assessed by appropriate sensitizing and eliciting protocols. As expected, animals photosensitized to PXM developed reactivities against all four compounds, PXM and TXM (photosensitivity) and TMS and TOS (contact sensitivity). By contrast, photosensitization with TXM induced cross-reactivity only against PXM. Moreover, the induction of contact sensitivity against TMS or TOS induced photosensitive cross-reactivity to PXM, but not to TXM. Finally, the oral administration of TOS produced a transient desensitization only for TMS and TOS. These results suggest that photosensitization with PXM induces two distinct reactivities. The first reactivity cross-reacts with TMS and TOS and is suppressible with orally administered TOS. The second cross-reacts only with TXM and is not suppressible with oral TOS. We conclude that PXM acquires at least two distinct immunogenic epitopes when exposed to UVA irradiation.

Allergenicity and tolerogenicity of amlexanox in the guinea pig

Amlexanox (AMLX), an anti‐allergic agent, is available in Japan as Elics® opthalmic solution, Solfa® nasal douche and Solfa® tablets. Cases of allergic contact dermatitis induced by Elics® ophthalmic solution, which contains 0.25% AMLX, were reported within a year of its introduction. We therefore examined the contact sensitizing potency of AMLX. Guinea pigs sensitized to 0.25% AMLX exhibited a strong positive patch test reaction. Further, AMLX‐sensitized animals developed rashes following oral and systemic challenge with AMLX. This animal model reflected the clinical experience of systemic contact dermatitis due to AMLX. The non‐responsiveness induced by oral administration of AMLX to AMLX‐induced animals was transient, and clinical prophylaxis by desensitization with oral AMLX may only increase the risk of systemic contact dermatitis. On the other hand, there have been few reports of drug eruption from oral Solfa® tablets in spite of their wide use. Therefore, we also examined the induction of tolerance by oral administration of AMLX. Oral administration of AMLX before sensitization resulted in complete non‐responsiveness. It seems likely that a substantial reduction in the risk of AMLX sensitization by Elics® may be achieved by prior oral administration of Solfa® tablets containing AMLX.

Antigenic characterization in ampiroxicam-induced photosensitivity using an in vivo model of contact hypersensitivity

Ampiroxicam (APX), a prodrug of piroxicam (PXM), has been reported to induce photosensitivity. Antigenic characterization of these photosensitivities, however, is still insufficient. The purpose of the present study was to elucidate further mechanism of photosenstivity induced by APX and PXM using an in vivo model of contact hypersensitivity in guinea pigs. Animals sensitized with ultraviolet-A (UVA)-irradiated 1% APX showed positive reaction in the patch testing to UVA-irradiated 1% APX and 1% thiosalicylate (TOS), while they were negative in challenge with UVA-irradiated 1% PXM, non-irradiated APX and PXM, whereas none of UVA-irradiated or non-irradiated APX and PXM showed positive patch test reaction in animals sensitized with UVA-irradiated 1% PXM or control vehicles. Animals sensitized with 1% TOS were successfully challenged by 1% TOS and cross-reacted with UVA-irradiated 1% APX; however, they failed to react with UVA-irradiated PXM, non-irradiated APX and PXM. Indeed, the in vitro study revealed that the concentration of APX was easily reduced by the increase of UVA irradiation dose, as compared with that of PXM. Interestingly, absorption spectrum of UVA-irradiated APX was similar to that of TOS, which is thought to be an active hapten of PXM. In the present study, we succeeded in the development of a novel animal model reflecting the clinical observations. Furthermore, these results suggested that contact hypersensitivity induced by UVA-irradiated APX is developed by photoproducts of APX itself, but not by the biotransformation of APX to PXM.