Search

We hypothesized that a substantial portion of the mutagenic alterations produced in the basal layer of human skin by sunlight are induced by wavelengths in the UVA range. Using laser capture microdissection we examined separately basal and suprabasal keratinocytes from human skin squamous cell carcinomas and premalignant solar keratosis for both UVA- and UVB-induced adduct formation and signature mutations. We found that UVA fingerprint mutations were detectable in human skin squamous cell carcinomas and solar keratosis, mostly in the basal germinative layer, which contrasted with a predominantly suprabasal localization of UVB fingerprint mutations in these lesions. The epidermal layer bias was confirmed by immunohistochemical analyses with a superficial localization of cyclobutane thymine dimers contrasting with the localization of 8-hydroxy-2'-deoxyguanine adducts to the basal epithelial layers. If unrepaired, these adducts may lead to fixed genomic mutations. The basal location of UVA--rather than UVB-induced DNA damage suggests that longer-wavelength UVR is an important carcinogen in the stem cell compartment of the skin. Given the traditional emphasis on UVB, these results may have profound implications for future public health initiatives for skin cancer prevention.

Epidermal melanin reduces some effects of UV radiation, the major cause of skin cancer. To examine whether induced melanin can provide protection from sunburn injury, 65 subjects completed a trial with the potent synthetic melanotropin, [Nle4-D-Phe7]-α-melanocyte-stimulating hormone ([Nle4-D-Phe7]-α-MSH) delivered by subcutaneous injection into the abdomen at 0.16 mg/kg for three 10-day cycles over 3 months. Melanin density, measured by reflectance spectroscopy, increased significantly in all [Nle4-D-Phe7]-α-MSH-treated subjects. The highest increases were in volunteers with lowest baseline skin melanin levels. In subjects with low minimal erythemal dose (MED) skin type, melanin increased by an average of 41% (from 2.55 to 3.59, P<0.0001 vs placebo) over eight separate skin sites compared with only 12% (from 4.18 to 4.70, P<0.0001 vs placebo) in subjects with a high-MED skin type. Epidermal sunburn cells resulting from exposure to 3 MED of UV radiation were reduced by more than 50% after [Nle4-D-Phe7]-α-MSH treatment in the volunteers with low baseline MED. Thymine dimer formation was also shown to be reduced by 59% (P=0.002) in the epidermal basal layer. This study has shown for the first time the potential ability of a synthetic hormone that augments melanin production to provide photoprotection to people who normally burn in direct sunlight.Journal of Investigative Dermatology (2006) 126, 1869–1878. doi:10.1038/sj.jid.5700317; published online 8 June 2006 [ABSTRACT FROM AUTHOR]

Background: Chromomycosis is frequently resistant to systemic and local therapies, and advanced bulky disease can compromise limb function. Methods: A man developed extensive chromomycosis of the left arm, refractory to multiple systemic and local treatments. Regional chemotherapy with the isolated limb infusion (ILI) technique using melphalan and actinomycin D markedly reduced disease bulk and greatly improved function of the arm over the next 2 months. Repeat ILI was performed 10 months later, again with good improvement in mobility of the elbow and significant debulking of disease. At the present time, there is some persistent but stable disease, which is controlled by heat therapy with disposable pocket warmers. The patient declined any further systemic therapy. Conclusion: ILI rapidly reduced disease bulk, restoring the limb to normal function within a few weeks. Although not curative, ILI could be an effective adjunctive treatment for severe chromomycosis in patients resistant to or intolerant of other therapies. [ABSTRACT FROM AUTHOR]

Background: Severe psoriasis vulgaris can be extremely difficult to treat in some patients, even with the newer biological therapies available today. Case presentations: We present two patients with severe chronic plaque psoriasis who received numerous systemic anti-soriatic therapies with varied results. Both responded well to initial treatment with efalizumab (anti-CD11a), but then experienced a flare of their disease after missing a dose. However, after disease stablization, both patients responded well to re-introduction of efalizumab, one patient requiring concurrent treatment with infliximab (anti-TNF-á). Conclusion: These cases are presented to characterize this "flare" reaction, and to inform health care providers that efalizumab can still be administered after disease flare, and again may be a successful therapy. [ABSTRACT FROM AUTHOR]

Presents a clinical review of childhood atopic eczema. Complexity of the condition in children; How four in five children with atopic eczema have IgE mediated allergy to inhalants or foods; Exacerbation by food allergy in less than ten percent of cases; Suggestion that to reduce the need for admission to hospital children with severe eczema can be treated with topical or oral immunusuppression.

SUMMARYWe present an immunocompetent man with extensive warts on the hands, refractory to a number of conventional treatment modalities and causing substantial morbidity and impairment of normal function. Isolated limb infusion (regional intra-arterial chemotherapy) with melphalan and actinomycin D was performed, with substantial clearing of the warts within 2 months. Treatment-induced morbidity was limited to mild local erythema and oedema which resolved within 3 weeks. After 9 months’ follow up, the patient had only a few residual warts and was able to resume normal activities. [ABSTRACT FROM AUTHOR]

SUMMARYA multicentre, prospective, randomized, double-blind, parallel group study was undertaken to compare the efficacy and tolerability of topical terbinafine with topical clotrimazole in the treatment of interdigital tinea pedis. Patients were randomized to receive either terbinafine 1% cream twice daily for 1 week, followed by a similar placebo cream for 3 weeks, or clotrimazole 1% cream twice daily for 4 weeks. Outcome measures were: (i) mycological cure (negative culture); (ii) effective treatment (negative culture plus a symptom score of 2 or less out of a maximum score of 18); and (iii) complete cure (negative culture and a symptom score of 0); measured at 1, 4, 8 and 12 weeks after the commencement of the study. One hundred and four of the 217 patients randomized had a culture-confirmed dermatophyte infection at baseline. In these patients, 84.6% in the terbinafine group were culture negative after 1 week, compared with only 55.8% in the clotrimazole group. Both agents were well tolerated. The study showed that terbinafine achieves mycological cure more rapidly than clotrimazole. This may result in improved compliance and better control over transmission of infection. [ABSTRACT FROM AUTHOR]

This study investigates the influence of skin colour and minimal erythema dose (MED) on the in vivo determination of sunscreen sun protection factors (SPFs). The MEDs of groups of 10–20 subjects were measured on the lower back with a 1000-W solar-simulated xenon arc lamp. Five sunscreens, with commercially measured SPFs ranging from 4 to 30 + were then tested on the different groups, and their SPFs were correlated with volunteers' MEDs. We found that the sunscreens had higher SPF values when tested on subjects with lower MEDs and paler skin. The SPF values obtained with our ultraviolet (UV) source were lower than the SPF values reported with commercially used solar simulators. We conclude that while SPF tests with artificial UV sources and pale-skinned volunteers can and should be used to rank the efficacy of various sunscreens in preventing sunburn, they should not be interpreted as measures of a sunscreen's absolute level of sun protection. Factors such as the differences in skin colour and MED between subjects used for SPF testing and the general population, the spectral differences between sunlight and artificial UV, as well as the tendency of the public to apply only small amounts of sunscreen and to re-apply it infrequently, mean that laboratory and sunlight SPFs may be markedly different. [ABSTRACT FROM AUTHOR]

This study compares the ability of two ultraviolet (UV) B-absorbing sunscreens, 2-ethyihexyl p-me- thoxycinnamate (2-EHMC) and 2-ethylhexyl p-ami- nobenzoate (Padiniate O), and two physical sun- screens, microfine titanium dioxide (MTD) and zinc oxide, to protect the skin immune system from chronic (4 weeks) solar-simulated UV irradiation. Mice were exposed to suberythemal doses of UV before assessing local and systemic immunosuppression and tolerance to a contact sensitizer. Using a UV protocol that induced local but not systemic immunosuppression or tolerance in BALB/c mice, it was shown that Padimate O made the immunosuppression worse, whereas 2-EHMC and MTD protected the immune system. When the cumulative dose was increased by 12.7%, causing systemic immunosuppression and tolerance, none of the sunscreens protected from inimunosuppression, but 2-EHMC provided partial, and MTD gave complete protection from tolerance. To examine this apparent lack of protection from systemic immunosuppression, C3H/HeJ mice were used. These mice had a minimal erythema dose similar to that of the BALB/c mice but were systemically immunosuppressed, with only 44% of the UV dose required to immunosuppress BALB/c mice. 2-EHMC provided some protection, whereas MTD provided complete protection from systemic immunosuppression in C3H/HeJ mice. Hence, sunscreens can protect from local and systemic immunosuppression, although this protection is limited and is not related to the sun protection factor of the sunscreens or the minimal erythema dose of the mouse strain. Instead, protection seems to be related to the sunscreens' having a broad absorption spectrum. [ABSTRACT FROM AUTHOR]

Focuses on the efficacy of sunscreen to prevent immunosuppression. Use of sunscreens to protect from erythema; Assessment on the immunoprotective ability of sunscreens; Dependency of immune protection of the sunscreens upon absorption of ultraviolet-A and -B.

Pyoderma gangrenosum at the site of sternal marrow aspirate was observed in a patient with acute myeloproliferative disease characterized by a high peripheral blood basophilia. Lesions with a similar appearance were also seen on the palate. No other disease known to be associated with pyoderma gangrenosum could be demonstrated. A review of the literature suggests that myeloproliferative disease should now be recognized as occurring in association with pyoderma gangrenosum. [ABSTRACT FROM PUBLISHER]

Retinoids provide sonic protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of inimunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immuno-suppressed upon application of a contact sensitizer to irradiated or unir-radiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression. [ABSTRACT FROM AUTHOR]