Protective role of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand for arylhydrocarbon receptor, in chronic mite-induced dermatitis.

BACKGROUND: Chronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments, phototherapy is recommended for patients with extensive lesions. Although immunosuppression is believed to explain its primary effectiveness, the underlying mechanisms of phototherapy remain unsolved. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ). FICZ is known to be a potent endogenous agonist for aryl hydrocarbon receptor (AHR); however, the biological role of FICZ in chronic eczema is unknown. OBJECTIVE: To investigate the effect of FICZ on chronic eczema such as atopic dermatitis. METHODS: We stimulated HaCaT cells and normal human epidermal keratinocytes (NHEKs) with or without FICZ and then performed quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, and siRNA treatment. We used the atopic dermatitis-like NC/Nga murine model and treated the mice for 2 weeks with either Vaseline® as a control, FICZ ointment, or betamethasone 17-valerate ointment. The dermatitis score, transepidermal water loss, histology, and expression of skin barrier genes and proteins were evaluated. RESULTS: FICZ significantly upregulated the gene expression of filaggrin in both HaCaT cells and NHEKs in an AHR-dependent manner, but did not affect the gene expression of other barrier-related proteins. In addition, FICZ improved the atopic dermatitis-like skin inflammation, clinical scores, and transepidermal water loss in NC/Nga mice compared with those of control mice. On histology, FICZ significantly reduced the epidermal and dermal thickness as well as the number of mast cells. Topical FICZ also significantly reduced the gene expression of Il22. CONCLUSION: These findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.

An occlusive dressing containing betamethasone valerate 0.1% for the treatment of prurigo nodularis.

INTRODUCTION: Prurigo nodularis is a distressing condition characterized by the presence of multiple nodules associated with intense pruritus. OBJECTIVE: To assess the clinical efficacy and safety of betamethasone valerate 0.1% tape and a moisturizing itch-relief cream in prurigo nodularis. METHODS: Twelve patients were enrolled in this pilot comparison of betamethasone valerate 0.1% tape versus a moisturizing itch-relief cream containing feverfew. The study period was 4 weeks. Clinical evaluation was performed weekly. RESULTS: Eleven subjects completed the 4 weeks of therapy. The mean visual analogue scale (VAS) for pruritus at baseline was 8.75 for both sides of the body. The side treated with betamethasone valerate 0.1% tape showed a higher clinical response (VAS score at week 4: 3.9; p < 0.005) compared with the side treated with moisturizing itch-relief cream (VAS score at week 4: 5.6; p < 0.005). CONCLUSION: Both treatments were effective. However, the occlusive dressing enhanced the efficacy of the treatment, preventing scratching.

Low-level laser therapy in the treatment of mucous membrane pemphigoid: a promising procedure.

BACKGROUND: Mucous membrane pemphigoid is a heterogeneous group of autoimmune, subepithelial, blistering diseases. A combination of topical and systemic steroid treatment is often used when managing patients with mucous membrane pemphigoid. The use of systemic steroids presents an increased risk of adverse side effects. Consequently, effective alternative modalities of therapy should be considered, such as the application of low-level laser therapy (LLLT). METHODS: A patient presented with mucous membrane pemphigoid and was successfully treated with the application of local corticosteroids and LLLT using an 810-nm diode laser. The lesions were treated by LLLT over a period of 7 days using a continuous waveform for 40 seconds and an energy density of 5 J/cm(2). RESULTS: After treatment, a significant improvement in tissue color and consistency was observed. The patient was followed every month for a period of 12 months, and the lesions healed uneventfully. CONCLUSION: The results reported in this case show that the healing of mucous membrane pemphigoid was achieved when LLLT was used as an adjunct to the application of a local corticosteroid.

Actualización terapéutica en alopecia areata / Update on the Treatment of Alopecia Areata

La alopecia areata es una alopecia no cicatricial telogénica de base autoinmune. Se estima que origina un 2 % de las consultas dermatológicas y puede aparecer a cualquier edad, aunque es más frecuente en pacientes jóvenes. Su tratamiento va a depender de varios factores, fundamentalmente de la extensión de la enfermedad, de la edad del paciente, así como de medidas locales y sistémicas. Mientras que los tratamientos locales tienen como objetivo conseguir el recrecimiento piloso, sin influir en la evolución de la enfermedad, los tratamientos sistémicos pueden interferir en la evolución de la misma, siendo ambos medidas paliativas. En este trabajo revisamos la mayoría de las opciones terapéuticas descritas en la literatura para la alopecia areata (AU)

Alopecia areata is nonscarring telogenic alopecia of autoimmune etiology. It is estimated to be the presenting complaint in 2 % of dermatologic consultations, and can appear at any age although it is more common in young patients. Treatment depends on several factors, such as extent of the disease and age, and may be local or systemic. Local treatments aim to achieve hair regrowth, but do not alter the underlying condition, whereas systemic treatments can modify the course of the disease. In neither case does treatment provide a cure. In this article, we review most of the therapeutic options described in the literature for alopecia areata (AU)

Comparison of Psoralen ultraviolet A (PUVA) photochemotherapy plus topical corticosteroids with PUVA plus bland emollients in the treatment of psoriasis.

BACKGROUND: Psoralen Ultraviolet A (PUVA) therapy is a well-established treatment of psoriasis. The objective of the study was to compare the clinical improvement in psoriasis with PUVA photochemotherapy + topical corticosteroids and PUVA + bland emollients. METHODS: Forty patients with chronic plaque type of psoriasis were divided into two equal groups each having 20 patients. PUVA therapy was given thrice weekly. In addition, patients of group-A were allowed to apply topical betamethasone 17-valerate 0.1% diluted 1 into 2 parts with plain vaseline twice daily. Patients of group-B were allowed to apply only plain vaseline over lesions twice daily. Clinical improvement in lesions was observed by decrease in the severity of erythema, scaling and plaque elevation. RESULTS: Clearance of psoriasis was achieved in 95%, of the patients treated with PUVA plus topical corticosteroids while clearance was achieved in 80% of patients treated with PUVA plus bland emollients (P = 0.0758). Median numbers of exposures for group-A were 16 & for group-B were 17.5 (p = 0.1029). Similarly, median cumulative dose in group-A was 64.5 J/cm2 & in group-B was 70.7 J/cm2 (p = 0.372). CONCLUSION: There is no significant difference in clinical improvement in psoriasis treated either by PUVA plus topical steroids or PUVA plus bland emollients.

[Allergic contact dermatitis to common ivy (Hedera helix L.)]. / Allergische Kontaktdermatitis auf Efeu (Hedera helix L.).

Common ivy (Hedera helix L.) is a ubiquitous plant in Europe whose major allergen falcarinol has moderate allergic potential. It is not related to poison ivy (Toxicodendron spp.). There are no cross reactions between the allergens of common ivy (falcarinol) and poison ivy (urushiol). Contact with common ivy or falcarinol may lead to sensitization and then a delayed hypersensitivity reaction. There are only few cases described in the literature. We report on a male hobby gardener with appropriate clinical history and positive patch test. The pathogenic mechanism is a type IV reaction following a sensitization exposure. Gardeners and landscape architects with frequent exposure to common ivy and thus a high risk of sensitization should wear appropriate protective clothing.

Clinical experience with topical calcitriol (1,25-dihydroxyvitamin D3) in psoriasis.

The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short-contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8-week period; however, the combination had a radiation dose-sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice-daily betamethasone, thereby achieving a corticosteroid-sparing effect. Finally, two studies confirm that calcitriol 3 microg g(-1) ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound.

Local anti-inflammatory activity and systemic side effects of NM-135, a new prodrug glucocorticoid, in an experimental inflammatory rat model.

The local anti-inflammatory activity and systemic side effects of NM-135 (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4-methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local anti-inflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the anti-inflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects.

Antipsoriatic therapies inhibit epidermal plasminogen activator activity.

Urokinase (UK, Mr 55,000) and tissue-type plasminogen activator (tPA, Mr 74,000) are serine proteinases involved in many biological processes, ie, cell migration, neoplastic transformation, and extracellular proteolysis. Cutaneous fibrinolytic activity (dependent on the activity of UK and tPA) was studied with the autohistographic fibrin film method in 40 patients affected by psoriasis vulgaris before and after topical (anthralin, betamethasone valerate, hydrocolloid occlusive dressing) or systemic psoralen-ultraviolet-light (PUVA) treatments. Autohistographic studies also were performed after apposition of monoclonal antibodies directed against the catalytic site of UK and tPA. Finally, UK and tPA were localized immunohistochemically in the psoriatic plaques and in controls using the immunoperoxidase procedure based on the biotin/avidin system. UK and tPA immunoreactivity was present in the cytoplasm and around the outlines of keratinocytes in the psoriatic patches before treatment and in the patches not cleared after treatment, while it was not detectable in normal epidermis, in the unaffected psoriatic epidermis, and in the cleared psoriatic skin. Cutaneous fibrinolytic activity was present in the cases in which UK and tPA were detected histochemically and, in the psoriatic epidermis, it was abolished by preincubation with anti-tPA but not with anti-UK antibodies. This study suggests that established topical and systemic treatments for psoriasis possess UK and tPA antagonist activity.

PUVA therapy of chronic actinic dermatitis.

Four men with long-standing chronic actinic dermatitis were treated with a modified PUVA regime which initially included generalized applications of topical steroids given immediately after PUVA exposure. All patients are now free of rash, no longer need protection from UV radiation, and are being maintained on twice monthly PUVA therapy (IO J/cm2).

The effect of percutaneously absorbed steroids on hypothalamic--pituitary--adrenal function after intensive use in in-patients.

Hypothalamic-pituitary-adrenal (HPA) axis function has been monitored in adults and children who required intensive treatment of their skin disease with topical corticosteroid preparations while in hospital. Evidence of mild suppression of the HPA axis was seen in adults when the more potent topical steroids were used, but recovery of function was rapid when the intensive treatment ceased. In children suppression was still present in twelve of sixteen cases on the 2nd day after treatment with 0-1% betamethasone 17-valerate ointment had stopped, yet in nine cases treated in a comparable manner with 1% hydrocortisone acetate ointment, there was no evidence of impaired HPA axis function.

A clinical study of the prophylactic use of betamethasone valerate and sodium cromoglycate in the treatment of seasonal allergic rhinitis.

The prophylactic use of betamethasone valerate and sodium cromoglycate in seasonal allergic rhinitis has been investigated in 20 patients in an open study. The subjective assessment of the symptoms recorded on a daily record card was significantly lower in the betamethasone valerate group compared with the sodium cromoglycate group. Patients' and physician's overall assessment of the treatment favoured the steroid aerosol. No clinically significant side effects were noted.

Betamethasone valerate in corticosteroid-dependent asthmatics. The integrity of the hypothalamic pituitary adrenal axis.

In a single-blind trial 29 patients with corticosteroid-dependent asthma reduced their daily dose of oral prednisolone by 1 mg/week while using a placebo inhaler until an unacceptable degree of asthma occurred. Betamethasone-17-vlaerate in a dose of 800 mug/day and if necessary 1600 mug/day was then substituted for the placebo inhaler and the reduction of oral prednisolone continued until the prednisolone was withdrawn completely or an unacceptable degree of asthma recurred. In 22 patients (76%) prednisolone was withdrawn completely, 11 on 800 mug and 11 on 1600 mug betamethasone-17-valerate. The mean reduction of prednisolone was 3-8 mg on placebo, 5-4 mg on 800 mug and a further 1-8 mg in patients requiring 1600 mug of betamethasone-17-valerate. The hypothalamic pituitary adrenal (HPA) axis was assessed by tetracosactrin and insulin stress tests at the start of the study and after withdrawal of oral prednisolone. The results indicate that an HPA axis which is completely suppressed by systemic corticosteroids can regain normal integrity when the systemic steroid is replaced by betamethasone-17-valerate in a dose of either 800 mug/day or 1600 mug/day. Candidiasis was observed, but will be reported later.

Intranasal betamethasone valerate in the treatment of seasonal rhinitis.

Betamethasone valerate aerosol given in doses of 100 mug into each nostril twice daily was compared with a placebo in a double-blind, cross-over trial involving thirty patients with seasonal rhinitis. Patients recorded symptoms of eye irritation and watering, sneezing, rhinorrhoea, and nasal blockage, on a diary card. Analysis of the symptom scores showed that nasal symptoms were significantly better on betamethasone valerate than on placebo (P less than 0.01) and that nasal blockage in particular was improved (P less than 0.001). The patients' preference was significantly in favour of the active compound (p less than 0.02) and no side-effects were noted. It is concluded that betamethasone valerate offers a safe and effective form of treatment for seasonal rhinitis.