Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis.

BACKGROUND: A standardized instrument is needed to rate the overall severity of chronic hand dermatitis (CHD), in particular during clinical trials. OBJECTIVES: To design and validate a photographic guide. METHODS: Initially, five experts were asked to grade 50 photographs of CHD, first individually, then as a consensus-building group, in order to select the photographs included in the guide. Then, a validation session with 11 different dermatologists evaluating 28 patients was conducted to assess the interrater reliability and test-retest reproducibility of the assessment of disease severity, relying on the photographic guide, on two consecutive days. Patient order was randomized, and only diseased hands were visible to prevent any bias in evaluation. RESULTS: The experts reached a consensus for development of a photographic guide composed of five severity levels and four photographs per severity level. Results of the validation session showed a high level of interrater reliability and test-retest reproducibility. CONCLUSIONS: The photographic guide is a reliable tool for assessing the morphological severity of hand dermatitis, and can be used as part of a comprehensive evaluation of disease in international multicentre clinical trials.

Isotretinoin improves the appearance of photodamaged skin: results of a 36-week, multicenter, double-blind, placebo-controlled trial.

Photodamaged skin occurs as a result of long-term exposure to ultraviolet radiation. The incidence of photodamage in European and North American populations with Fitzpatrick skin types I, II, and III is estimated at 80% to 90%. We conducted a double-blind clinical trial to test the efficacy and safety of 0.1% isotretinoin versus vehicle cream in 800 patients with moderate to severe photodamaged skin. Patients applied either 0.1% isotretinoin or matching vehicle cream to the face, forearms, and hands once nightly for 36 weeks. Local irritation and adverse events were assessed, and plasma retinoid levels were measured before and during treatment. Treatment response increased throughout the 36-week treatment period and the overall appearance of photodamaged skin was significantly better than with the vehicle alone. Topical application of 0.1% isotretinoin is an effective and well-tolerated treatment leading to clinically apparent improvement in the appearance of photodamaged skin of the face, forearms, and hands.

An exploratory trial of two dosages of a novel synthetic thrombin inhibitor (napsagatran, Ro 46-6240) compared with unfractionated heparin for treatment of proximal deep-vein thrombosis -- results of the European multicenter ADVENT trial.

One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5th treatment day, as soon as the International Normalized Ratio was above 2. Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versus none in heparin-treated patients) and worsening in 4 napsagatran-treated patients (versus 2 in heparin-treated patients). The venographic Marder's score did not change among the treatment groups. New lung scan perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11%), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, respectively. There was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed and the rare minor bleedings occurred at a similar rate in the three treatment groups. In conclusion, the ADVENT trial has shown data that suggest comparable efficacy and safety of a synthetic, direct thrombin inhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserves further development in this field.

Negligible systemic absorption of topical isotretinoin cream: implications for teratogenicity.

The objective of the study was to assess the extent of systemic exposure of retinoic acid metabolites after excessive application of 0.1% isotretinoin cream in patients with photodamaged skin. This was a single-center, open-label, noncomparative, multiple-dose study of isotretinoin cream. Eighteen female patients with photodamaged skin received a 10 g topical application of isotretinoin cream once daily to a surface area of approximately 2,300 cm2 for 42 days. The patients were not allowed to have high vitamin A-containing foods, vitamin A supplements, or concomitant medications during the entire study period. Plasma levels of four retinoic acids (isotretinoin, tretinoin, 4-oxo-isotretinoin, and 4-oxo-tretinoin) were evaluated after 42 days of isotretinoin application and compared with baseline (pretreatment) levels. The mean area under the curve (AUC) in plasma increased by 48% (+/-SE 9.2) and 77% (+/-13) from the 24-hour pretreatment baseline level for isotretinoin and 4-oxo-isotretinoin, respectively, after treatment with excessive amounts of isotretinoin cream, suggesting systemic absorption of isotretinoin cream. This increase in systemic exposure of retinoic acids was less than that reported earlier after the U.S. recommended daily allowance of 5,000 i.u. of vitamin A supplementation (isotretinoin 141 +/- 19% and 4-oxo-isotretinoin 171 +/- 27%). The minimal systemic availability of isotretinoin cream compared with the U.S. recommended daily allowance for vitamin A supplements provides reasonable evidence for lack of its potential teratogenic risk.

Clinical panel assessment of photodamaged skin treated with isotretinoin using photographs.

BACKGROUND AND DESIGN: Evaluation of the treatment of photodamaged skin requires adequate efficacy criteria. This study tested the ability of five independent dermatologists to distinguish the effect of topical treatment with isotretinoin cream (0.05% for 3 months, then 0.1% for 6 months) in 326 patients compared with vehicle for 9 months in 325 patients using high-quality, reproducible photographic slides. Panelists were blinded to the patient's identity, treatment group, and time of the photograph (baseline or end of treatment). A computer randomly projected the baseline photograph to one side of a split screen and the end-of-treatment photograph to the other. OBSERVATIONS: Isotretinoin was significantly better than vehicle for overall appearance, fine wrinkles, and discrete pigmentation by multivariate analysis of the combined results for all panelists. Univariate analysis for each panelist also indicated statistically significant superiority of isotretinoin over vehicle for overall appearance (four panelists), fine wrinkles (five panelists), and discrete pigmentation (three panelists). CONCLUSION: The clinical panel detected significantly better improvement in photodamaged-skin treated with isotretinoin than in such skin treated with vehicle. The panel provided an independent assessment of the effects of treatment uninfluenced by physical findings during treatment or information provided by the patients treated.

Cutaneous response to ultraviolet radiation-induced erythema in patients with type A dysplastic nevi.

The effects of an exposure to 6 times the minimal erythemal dose of ultraviolet radiation (UV) were studied using a visual scale and a tri-stimulus colorimeter in 12 sun-tolerant (skin types III and IV) patients with type A dysplastic nevus syndrome. In such individuals, the melanocytic system would be susceptible to neoplastic transformation induced by sunlight. The cutaneous response to a marked UVB erythema has been shown to identify the high-risk patients prone to light-induced skin cancer. This study indicates that the UVB cutaneous susceptibility of patients with type A dysplastic nevi is not significantly different from control subjects, in terms of erythemal and tanning response.

The effect of topical retinoids on the leukotriene-B4-induced migration of polymorphonuclear leukocytes into human skin.

Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pretreated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.

Intractable epidermolysis bullosa acquisita: efficacy of cyclosporin A.

We report the case of a 66-year-old man who presented with a spontaneous blistering involving both skin and mucous membranes, diagnosed as an inflammatory form of epidermolysis bullosa acquisita. During a 5-year course, the condition failed to respond to various therapies. Finally, only ciclosporin, together with a low dose regimen of prednisone, achieved a dramatic improvement with a total clearing within 6 months, persisting 1 1/2 years after discontinuation. Such results prompt us to propose such an association as a primary therapeutic scheme in an otherwise barely tractable disease.

Malignant angioendotheliomatosis. Reclassification as an angiotropic lymphoma.

A 70-year-old woman with chronic edema of the lower limbs was diagnosed as having a "malignant angio-endotheliomatosis," because histologic examination showed a strict intravascular location of a malignant proliferation. Immunochemical studies actually disclosed the lymphomatous origin of malignant cells. The recent literature regarding the nosology of this rare condition is reviewed.

Pyoderma gangrenosum in an allogeneic bone marrow transplant recipient.

We present the case of a 15-year-old boy who developed facial pyoderma gangrenosum following an allogeneic bone marrow transplantation for the treatment of a 'blast' crisis developing in the course of chronic myelogenous leukaemia. The lesion appeared 7 months before any evidence of relapse. The discussion is focused on both the presentation of pyoderma gangrenosum associated with myelo-proliferative disorders and its pathogenesis via the underlying immunosuppression.

Reaction to UV-induced erythema in young patients with basal cell carcinoma.

The effects of an irradiation 6 times the minimal erythemal dose of UVB were studied using a visual scale from 1 to 4+ in 12 patients aged under 45 years with a past medical history of basal cell carcinoma, and in 12 sex-, age- and skin-type-matched controls. Erythema was significantly more intense at days 15 (p less than 0.01) and 22 (p less than 0.001) in patients than in controls. Pigmentation was significantly weaker at day 22 than in controls (p less than 0.005).

A double-blind study of topical 1 alpha,25-dihydroxyvitamin D3 in psoriasis.

Several open studies with active forms of vitamin D3 have been reported to be effective in the treatment of psoriasis. We report a double-blind study of 1 alpha,25-dihydroxycholecalciferol in psoriasis using 0.5 microgram of active substance applied topically twice daily. In contrast to previous studies, the present investigation does not provide evidence of clinical efficacy for the drug at that dosage and with the vehicle that was used.

Surgical treatment of epidermolytic hereditary palmoplantar keratoderma.

We report the case of a man with epidermolytic hereditary palmoplantar keratoderma. After failure of topical and systemic therapy, excision and skin grafting of both hands was done in several steps. Attention must be given to the skin-repair procedures (split- or full-thickness grafting), and the exact setting of the suture lines in the fingers is important.

Successive legionellosis in the course of lymphomatoid granulomatosis.

A 75-year-old male presented with typical cutaneous lesions and pulmonary involvement due to lymphomatoid granulomatosis. A legionellosis was associated with this condition. Though the radiological findings in lymphomatoid granulomatosis are suggestive, they are not specific, and set a difficult problem in distinguishing the two conditions. Monoclonal antibody studies indicated the predominance of CD8 T lymphocytes in the infiltrate of the skin, as well as in the bronchoalveolar fluid.

[Herpes gestationis. Apropos of 2 cases]. / L'herpès gestationis. A propos de deux cas.

Herpes gestationis is an autoimmune disorder specific of pregnancy. The authors report two cases of this condition with distinctive clinical and immunological features. Both the pathogenesis and the nosologic connections between Herpes gestationis and Bullous pemphigoid are reviewed and discussed.

[Green hair: clinical, chemical and epidemiologic study. Apropos of a case]. / Les cheveux verts: étude clinique, chimique et épidémiologique. A propos d'un cas.

A 36-year-old blond woman suddenly developed green tinted hair following exposure to swimming pool water. This was the first green discoloration she noticed, although she had been an active swimmer for several years. Clinical examination showed green tinting toward the distal ends of the most superficial strands of hair. The copper content of plucked green hair measured by atomic absorption was elevated to 3,900 ppm and the copper concentration in water from the swimming pool implicated was 9.94 ppm. Following renewal, the latter value decreased to 107 ppb. Hair examination under polarizing light was normal, and a scanning electronmicroscopic study of hair samples showed a total loss of cuticle with micropits scattered over the hair shaft surface mimicking a "dead tree trunk". Epidemiological investigations showed that the increased copper content of swimming pool water was due to added algaecides without adequate replacement of the water. Hair damage resulting from repeated waving and/or bleaching of the hair turns out to be an important factor in the deposition of copper by inducing an increase in keratin content of cysteic acid and related anionic sulfonate groups which participate in copper adsorption. On the ocassion of this case-report, epidemiological data published by others, together with the chemical and therapeutic aspects of green hair are reviewed.