Successful and long-lasting treatment of solar urticaria with ultraviolet A rush hardening therapy.

BACKGROUND: Solar urticaria (SU) is a photodermatosis that is thought to be caused through the effects of mast cell mediators released because of an altered chromophore, possibly a photoallergen recognized by IgE. Phototherapy for SU to induce a tolerant state appears to be most effective, but is often time consuming and provides only short-lived remission. Ultraviolet (UV) A rush hardening has been successful and less time consuming in serum factor-negative patients with SU. However, the mechanism of action and long-lasting effects of UVA rush hardening therapy remain unclear. OBJECTIVES: We aimed to evaluate whether UVA rush hardening exhibits long-lasting therapeutic effects in serum factor-positive patients with SU and to examine the action mechanism of tolerance. METHODS: Two serum factor-positive patients with SU were exposed to multiple UVA irradiations at 1-h intervals per day for 2 or 3 days. Intradermal injection of their in vitro-irradiated autologous serum or compound 48/80 and a prick test for histamine were performed before and after UVA rush hardening. RESULTS: The two serum factor-positive patients with SU benefited greatly from UVA rush hardening, as documented by a marked increase in minimal wealing dose, and remained symptom free without using sunscreen in their daily life. Intradermal injection of in vitro-irradiated autologous serum induced wealing before hardening, but not in tolerized skin after hardening. The responses to compound 48/80 and histamine were unaltered. CONCLUSIONS: UVA rush hardening is an effective and long-lasting treatment even in serum factor-positive patients with SU. The mechanism of tolerance may involve continued blockade of photoallergen binding to IgE on mast cells, rather than depletion of mast cell mediators or histamine tachyphylaxis.

A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated pain.

We report the result of a randomized, controlled, open trial of anti-thrombin therapy for herpes zoster-associated pain. Fifty-five herpes zoster patients within 8 days after the onset of skin lesion were enrolled in the trial. Patients were treated with an optimal dose of oral acyclovir (4000 mg/day for 7 days) with or without intravenous administration of a specific anti-thrombin agent, argatroban (10 mg/day, three times a week). Administration of argatroban reduced pain intensity at the 4th through 21st day after the initiation of treatment as determined by visual analogue scale (Mann-Whitney U test, p < 0.05). It also shortened the median time to cessation of analgesic use (14 days vs. 24 days, p = 0.02, logrank test), although it did not significantly reduce the median time to cessation of pain (21 days vs. 43 days, p = 0.07, logrank test). None of the enrolled patients showed evidence of adverse effects including hemorrhagic diathesis. The results suggested that relatively low doses of argatroban are effective in reducing herpes zoster-associated pain. Up-regulation of prothrombin expression by the vascular endothelial and sweat gland epithelial cells in the active skin lesion and transient elevation of plasma thrombin-antithrombin III complex levels in a proportion of patients suggest a lesional generation of thrombin in herpes zoster. This may be relevant to the beneficial effects of the anti-thrombin treatment on the resolution of herpes zoster-associated pain.

Acute urticaria with elevated circulating interleukin-6 is resistant to anti-histamine treatment.

Histamine released from dermal mast cells plays a central role in the increased vascular permeability in acute urticaria, and administration of anti-histamines usually suppresses development of wheals. Acute idiopathic urticaria, particularly a severe case, occasionally presents with acute inflammatory reactions such as low-grade fever and leukocytosis and is resistant to anti-histamines. Considering the wide spectrum of proinflammatory cytokines and chemokines that can be released from activated mast cells, some of them might be involved in the pathogenesis of urticaria. We measured plasma levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in 16 cases of severe acute urticaria. None of them showed elevated plasma levels of IL-8 or TNF-alpha. Nine out of 16 acute urticaria patients showed elevated circulating IL-6 with concomitant increases in serum CRP levels. All such patients were resistant to conventional anti-histamine treatment and required systemic steroids for complete suppression of wheal development. After subsidence of the urticaria, their elevated IL-6 and CRP levels dropped to their normal ranges. In contrast, all but one patient without elevated circulating IL-6 was successfully treated with a H1 receptor antagonist, cetirizine. The data suggest involvement of IL-6 in the pathogenesis of severe acute urticaria that is resistant to anti-histamines.

Unilateral exophthalmos due to orbital metastasis from a contralateral intraocular melanoma.

Progressive, left exophthalmos developed due to a left, retrobulbar mass in a 76-year-old Japanese woman. An open tumor biopsy was carried out, and both macro- and microscopic findings of the mass confirmed that it was a malignant melanoma. Orbital melanomas usually result from distant metastasis of cutaneous melanomas or from secondary extension of ipsilateral intraocular melanomas. Thorough physical, laboratory, and radiological examination, however, did not disclose any primary cutaneous or visceral melanoma, nor had the patient any previous history of excision or spontaneous regression of a pigmented lesion. Histopathologically, the left retrobulbar melanoma was rich in sinusoidal vessels which were surrounded by melanoma cells, oriented in a perpendicular array, a histological feature more characteristic of uveal melanomas than of cutaneous ones. The ophthalmological examination excluded development of a primary intraocular melanoma on the left side. Fundoscopic examination of the right eye was not feasible because of the complete opacity of the right vitreous body which had resulted from previous episode of idiopathic vitreous hemorrhage. Unexpectedly, CT and MR studies depicted retrobulbar masses of non-homogeneous densities in the bilateral orbits. These radiologic studies indicated the metastatic nature of the left retrobulbar melanoma, while suggesting the development of a primary, intraocular melanoma on the right side, extension into the right orbit, and involvement of the right optic nerve. All these clinical, radiological, and histological data suggested the development of a primary melanoma in the right eye and subsequent metastasis to the left orbit producing exophthalmos. The mechanism of such a peculiar mode of metastasis remains entirely unknown. This is a rare case of metastatic orbital melanoma, without visceral involvement, which originated in the contralateral eye. Development of the right ocular melanoma remained unrecognized due to atrophic degeneration of the right eyeball and complete opacity of the right vitreous body, until the contralateral orbital metastasis grew massive enough to cause exophthalmos.