Rebat M. Halder

Aberrations in T lymphocytes and natural killer cells in vitiligo: A flow cytometric study

Twenty-five patients with vitiligo and twenty-five healthy control subjects were evaluated with the use of flow cytometry to compare percentages of peripheral T lymphocytes and natural killer cells. The percentages of total T lymphocytes, helper T cells, suppressor T cells, and natural killer cells were evaluated with the use of OKT3, OKT4, OKT8, and Leu-7 monoclonal antibodies, respectively. Mean total T lymphocytes and helper T cells were markedly depressed; mean natural killer cells were markedly elevated and mean suppressor T cells were moderately elevated in patients with vitiligo in comparison with control subjects. These results indicate that cell-mediated immunity is subject to some defect in regulation in patients with vitiligo. It remains to be determined whether these abnormalities are a direct cause or a result of vitiligo. Antibody-dependent cytotoxicity, utilizing killer cells with recently reported antimelanocyte antibodies found in patients, may be responsible for pigment cell destruction in vitiligo. Helper T cells may be reduced because of low levels or faulty production of T lymphocyte-stimulating factors in patients or because of a serum factor in patients that is toxic to helper T cells. The presence or absence of autoimmune and/or endocrine disease in patients with vitiligo had no effect on lymphocyte populations. There seemed to be a trend toward lower levels of helper T cells in patients having vitiligo for the shortest amount of time. In summary, the data indicate immunologic abnormalities in patients with vitiligo.

New and emerging therapies for vitiligo.

Vitiligo is a common skin disease; however, it still remains a difficult disease to treat. Not all patients respond to current forms of treatment. There are several new treatments, surgical and nonsurgical, and immunologic, that appear to either have higher success rates than past therapies or have potential as future developments for therapy of vitiligo.

Skin cancer and photoaging in ethnic skin

Skin cancer prevalence in ethnic skin is low. Squamous cell carcinoma, hypopigmented mycosis fungoides, and acral lentiginous melanoma are the most serious types of skin cancer noted in the darker-skinned population. Photoaging occurs less frequently and is less severe in ethnic skin.

Structure and function of ethnic skin and hair

Differences have been found among blacks, whites, Asians, and Hispanics in various areas of skin structure and function. Among them is the stratum corneum lipid (ceramide) content, which is highest in Asians, then Hispanics, then whites, and lowest in blacks. Melanosomal packaging and percutaneous absorption rates for specific compounds also vary among the different races. Reports supporting the occurrence of difference in TEWL, tyrosinase levels, skin elasticity, and water absorption rates between blacks and whites, and reaction to skin irritation have been conflicting. No significant differences in corneocyte size, skin thickness, and skin biomechanics have been reported.

Ocular disturbances in vitiligo

One hundred fifty-six patients with vitiligo were examined for ocular abnormalities. A 2:3 ratio of white to black patients allowed us to evaluate the role of race in the occurrence of ocular disturbances. A large percentage (40%) of all patients showed some degree of fundal pigment disturbance including pigment clumps, focal hypopigmented spots, and choroidal nevi. Although racial variations were found in the incidence of choroidal nevi (p = 0.001) and iris transillumination (p = 0.0012), these variations were believed to reflect normal differences found in patients without vitiligo.

Determination of optimal topical photochemotherapy for vitiligo

The efficacy of topical 8-methoxypsoralen (8-MOP) in varying concentrations and vehicles was assessed in 73 vitiligo patients. The response rates in different anatomic sites were also assessed. Seven patients (9%) had 100% repigmentation; 26 (36%) had 50% or greater repigmentation, 29 (40%) had some degree of pigment return, but less than 50%; 11 (15%) had no repigmentation. Results suggest that neither concentration of drug nor vehicle is a crucial factor for inducing repigmentation of vitiliginous patches on the face, trunk, and extremities. Low-dose 8-MOP (0.1%) was as effective as high dose 8-MOP (0.5%, 1%), while causing fewer side effects. However, when treating recalcitrant areas (distal extremities), 1% 8-MOP may be the most efficacious preparation for topical photochemotherapy. A phototoxic response preceded repigmentation in all cases. The following responses were obtained for the various anatomic sites treated: 56% of facial lesions; 35% of trunk areas; 36% of the extremities, and 13% of the recalcitrant areas had greater than 50% repigmentation.

The role of retinoids in the management of cutaneous conditions in blacks

From the Department of Dermatology, Howard University College of Medicine. Reprint requests: Rebat M. Halder, MD, Department of Dermatology, Howard University Hospital, 2041 Georgia Ave., NW, Washington, DC 20060. (J Am Acad Dermatol 1998;39:S98-103.) Copyright

Management of dyschromias in ethnic skin

ABSTRACT:  Pigmentary disorders are one of the most common skin disorders among people of color. Dyspigmentation in the form of either hyperpigmentation or hypopigmentation is often psychologically devastating to patients with darker skin. There is marked contrast between normally pigmented hyperpigmented, hypopigmented or depigmented skin in people of color. Despite being common, pigmentary disorders remain difficult to treat.

Acne in ethnic skin

Acne is the most common disorder observed in ethnic skin. Clinical presentation is different than in white skin. Postinflammatory hyperpigmentation is a common sequelae of acne in darker skin. The management of acne in ethnic skin is based largely on the prevention and treatment of hyperpigmentation.

Pharmacokinetics of Dapsone Gel, 5% for the Treatment of Acne Vulgaris

BackgroundOral dapsone has been available for over 60 years and has been used to treat severe acne vulgaris; however, the oral formulation is known to cause dose-dependent haematological reactions and is currently indicated only for diseases such as dermatitis herpetiformis and Hansen’s disease. A gel formulation of dapsone was recently developed to treat acne vulgaris. As dapsone is administered topically, it was expected that systemic absorption would be considerably lower than that observed with oral dapsone therapy, thereby avoiding any adverse haematological effects.ObjectiveTo report the pharmacokinetic profile of topically applied dapsone gel, 5% in the treatment of acne vulgaris.Study participants and methodsThree prospective, open-label studies enrolled a total of 548 subjects with acne vulgaris: two phase I pharmacokinetic studies (crossover and drug interaction) and one phase III long-term safety study. In the crossover study (n = 18), topical dapsone gel applied twice daily for a total of 14 days to 22.5% of the body surface area was compared with a single dose of oral dapsone 100mg (the typical clinical dose). In the drug-interaction study (n = 24), oral trimethoprim/sulfamethoxazole monotherapy, topical dapsone gel monotherapy and the two in combination were used twice daily for 7, 21 and 7 days, respectively. In the long-term safety study (n = 506), topical dapsone gel was applied twice daily to acne-affected areas for up to 12 months. Blood samples were drawn at various timepoints in each study to assess drug and metabolite concentrations. Systemic concentrations of dapsone, N-acetyl dapsone, dapsone hydroxylamine, trimethoprim and sulfamethoxazole were determined, according to the study design.ResultsIn the crossover study, the mean area under the plasma concentration-time curve (AUC) from 0 to 24 hours for dapsone was 417.5 ng · h/mL after 2 weeks of dapsone gel therapy (n = 10), compared with an AUC from time zero to infinity of 52 641 ng · h/mL after a single dose of oral dapsone; this represents a 126-fold lower systemic exposure for dapsone gel at typical therapeutic doses. In the drug-interaction study, the AUC from 0 to 12 hours for dapsone was 221.52 ng · h/mL after 3 weeks of dapsone gel monotherapy compared with 320.3 ng · h/mL after 1 week of coadministration with trimethoprim/sulfamethoxazole. In the long-term safety study, the mean plasma dapsone concentrations ranged from 7.5 to 11 ng/mL over 12 months. Overall, total systemic exposures to dapsone and its metabolites were approximately 100-fold less for dapsone gel than for oral dapsone, even in the presence of trimethoprim/ sulfamethoxazole. There were no reports of any haematological adverse events.ConclusionsTopical application of dapsone gel in various settings ranging from 2 weeks to 12 months resulted in systemic exposures to dapsone and its metabolites that were approximately 100-fold less than those after oral dapsone at a therapeutic dose level. The concentrations of dapsone and its metabolites reached steady state and did not increase during prolonged treatment.