Topical metronidazole maintains remissions of rosacea.

BACKGROUND: Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred. OBJECTIVE: To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea. DESIGN: A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study). SETTING: Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers. SUBJECTS: One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel. INTERVENTIONS: Subjects were evaluated monthly for up to 6 months to determine relapse rates. MAIN OUTCOME MEASURES: Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed. RESULTS: In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%). CONCLUSION: In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel.

Effect of desonide ointment, 0.05%, on the hypothalamic-pituitary-adrenal axis of children with atopic dermatitis.

Desonide ointment has demonstrated a good safety and efficacy profile during the many years it has been used in treating dermatoses. However, there have been no controlled clinical trials to evaluate its systemic safety when used in treating children. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis can occur after repeated application of topical corticosteroids. In general, the degree of suppression of the HPA axis function is related to the daily dosage of steroid given, the duration of its administration, the extent of body surface covered, and the potency of the corticosteroid. This study sought to determine the comparative effects of 0.05 percent desonide and 2.5 percent hydrocortisone ointments on the HPA axis of children with atopic dermatitis. There was no suppression of early morning cortisol in either treatment group. The ACTH-stimulated mean cortisol values after four weeks of treatment were not significantly different from the baseline values for either treatment group. We conclude that neither 0.05 percent desonide ointment nor 2.5 percent hydrocortisone ointment compromised the HPA axis of children with atopic dermatitis treated topically for four weeks.

Physiology of the vellus hair follicle: hair growth and sebum excretion.

The growth of vellus hair and the secretion of sebum from vellus hair follicles were measured on the forehead, cheek, chest, shoulder and back of healthy men and women aged 15-30 years. Hair growth was assessed by computerized image-analysis of photographs and sebum excretion by the use of Sebutape followed by image analysis. The density of vellus hairs and the percentage of growing hairs were higher on the face than on the thorax (439 hairs/cm2 with 49% growing hairs on the forehead compared with 85 hairs/cm2 with 31.5% growing hairs on the back). The rate of growth ranged from 0.03 mm/day on the forehead to 0.13 mm/day on the back. The maximum length of vellus hair significantly decreased with age; otherwise hair growth was not affected by age or sex. Some variations in hair growth and sebum secretion were observed over a period of 3 months, but no consistent rhythms were detected. There was no obvious link between vellus hair growth and sebum excretion.

Effect of chronic sun exposure on human Langerhans cell densities.

This study evaluated the Langerhans cell density in chronically sun-exposed skin (hand) and non-exposed skin (buttock) in subjects that were divided into 4 age groups (20-40; 41-60; 61-80; greater than 81 years). Two markers (OKT-6 and anti-HLA-DR) were used to identify the Langerhans cells (LC), and their count was performed either on epidermal sheets (52 individuals) or skin sections (43 individuals). Three major findings result from this study: 1) there are more LC in the non-exposed skin than in the chronically sun-exposed area; 2) there were no age-related changes in LC counts, and 3) LC co-express the T6 and HLA-DR antigens.

Further evidence for the self-reproducing capacity of Langerhans cells in human skin.

The limited number of Langerhans cells (LC) in the epidermis is one of the main reasons for the technical difficulties in resolving the question of LC kinetics. In the present paper, we describe a method to evaluate the LC replication potential in epidermis. The procedure is based on the specific incorporation of bromodeoxyuridine (BrdU), a thymidine analogue, into the DNA during the S-phase of the cell cycle. Mice, bearing human skin grafts, were injected s.c. every 6 h for up to 17 days with BrdU. At different times, the incorporated BrdU as well as the human epidermal LC were revealed on skin sections using anti-BrdU and OKT-6 monoclonal antibodies, respectively. After 6 h, 4.9% of the LC were labeled with BrdU. Then, the number of OKT-6(+) BrdU(+) cells increased in a linear manner and achieved 34% at 120 h, 67% at 240 h, and 94% at 400 h during the course of continuous labeling procedures. Based on this result we calculated a total cell cycle time of 392 h (16.3 days) and 12 h for the S-phase for human epidermal LC. Applying this technique, we were able to show also that 48 h after local treatment with 12-O-tetradecanoylphorbol-13-acetate or after stripping, the number of BrdU-labeled LC was considerably increased. Furthermore, after i.p. injection of colchicine in the nude mouse, human epidermal LC undergoing mitosis were evidenced by electron microscopy in the graft. From these results we conclude that the LC are actively cycling--therewith a self-reproducing cell population in human epidermis.

Class II MHC antigen expression by human keratinocytes results from lympho-epidermal interactions and gamma-interferon production.

Human peripheral blood lymphocytes were co-cultured with either allogeneic, autologous or purified protein derivative of tuberculin (PPD) pulsed autologous epidermal cells. In these mixed skin cell-lymphocyte culture reactions (MSLR), lymphocytes are stimulated to proliferate by epidermal cells. The supernatants of MSLR were examined for their capacity to induce class II MHC antigen expression on separately cultured epidermal cells. It is shown that supernatants from allogeneic and PPD pulsed autologous MSLR contained the factor(s) which stimulated HLA-DR antigen synthesis and expression by 30-40% of cultured epidermal cells. Kinetic analysis revealed a production rate maximum between 72 and 96 h of lympho-epidermal co-cultures. The factor mediating the induction of HLA-DR antigen expression on epidermal cells is thought to be gamma-interferon, because it was sensitive to pH 2 as well as heat incubation. Furthermore, anti-gamma-interferon monoclonal antibody abolished its activity. It is proposed, that HLA-DR antigen expression by keratinocytes observed in vivo in different dermatological inflammatory disorders originates from lympho-epidermal interactions and local gamma-interferon production as documented here in experiments in vitro.

Functional and phenotypic analysis of isolated human Langerhans cells and indeterminate cells.

In the mixed skin cell lymphocyte culture reaction (MSLR), epidermal cells induce the proliferation in vitro of peripheral blood lymphocytes. Using monoclonal antibodies (MCAB) OKT6 specific for Langerhans cells among epidermal cells and an anti HLA-Dr, we analysed which epidermal cells are necessary in MSLR in man. Inhibition and reduction of the proliferative responses in MSLR conducted respectively with 'anti HLA-Dr and complement' and 'OKT6 and complement'-pretreated epidermal cells suggested that not only Langerhans cells but also other HLA-Dr bearing cells play a major role. Immuno-electron microscopic studies of either HLA-Dr (+) or OKT6 (+) enriched and depleted epidermal cells suspensions: (I) were well correlated with results in MSLR; (2) indicated that Langerhans cells express both T6 and HLA-Dr determinants while indeterminate cells express only the HLA-Dr. No other epidermal cells were found to be either OKT6 or HLA-Dr (+). The data strongly suggest that not only Langerhans cells but also OKT6 (-) HLA-Dr (+) indeterminate cells play a major role in lympho-epidermal interactions.