Pearl E. Grimes

Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma.

Despite new technologies, few studies have assessed the histologic alterations in patients with melasma. Using current technologies, the present study was designed to re-evaluate the light microscopic, immunohistochemical, and ultrastructural changes of the hyperpigmented and adjacent normal skin of patients with melasma. Twenty-one patients were included in this study. Two millimeter punch biopsies were taken from the hyperpigmented and adjacent normal skin of the face. The integrity of the epidermis and dermis was assessed by light microscopy, computer-assisted image analysis, immunohistochemistry, and electron microscopy. Stains included hematoxylin-eosin and Fontana-Masson for melanin detection. Immunostaining was performed using Mel-5 antibody and CD1a antibody as markers for melanin and Langerhans cells, respectively.However, mild lymphohistiocytic infiltrates were present in 75% of the hyperpigmented areas. The areas of hyperpigmentation showed increased deposition of melanin in the epidermis and dermis of all cases. There was a statistically significant increase in the content of epidermal melanin. There were no quantitative increases in melanocytes in the hyperpigmented areas of skin. However, the melanocytes in the hyperpigmented areas were larger, intensely stained cells with very prominent dendrites. Electron microscopy revealed more melanosomes in keratinocytes, melanocytes, and dendrites in the involved skin in comparison to the uninvolved skin. The results of this study suggest that melasma is a consequence of specific hyperfunctional melanocytes that cause excessive melanin deposition in the epidermis and dermis.

A global survey of the role of ultraviolet radiation and hormonal influences in the development of melasma.

Background It has been generally believed that the four main causes of melasma are pregnancy, hormonal contraception, family history and sun exposure; however, there are few published comprehensive studies that confirm these assertions. The Pigmentary Disorders Academy – an international group of experts in pigmentary disorders – designed and conducted a global survey of women to investigate the effect of these factors on onset and chronicity of melasma and the course of the disease in order to gain a better understanding of the causative factors associated with this disorder, with a particular focus on hormonal factors and UV exposure in females.

Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method

BACKGROUND The Melasma Area and Severity Index (MASI), the most commonly used outcome measure for melasma, has not been validated. OBJECTIVE We sought to determine the reliability and validity of the MASI. METHODS After standardized training, 6 raters independently rated 21 patients with mild to severe melasma once daily over a period of 2 days to determine intrarater and interrater reliability. Validation was performed by comparing the MASI with the melasma severity scale. The darkness component of the MASI was validated by comparing it with the difference between mexameter scores for affected versus adjacent normal-appearing skin. The area component of the MASI was validated by comparing it with the area of each section of the face determined by computer-based measurement software. RESULTS The MASI score showed good reliability within and between raters and was found to be valid when compared with the melasma severity scale, mexameter scores, and area measurements. Homogeneity assessment by raters showed the least agreement and can be removed from the MASI score without any loss of reliability. LIMITATIONS Patients were limited to Hispanic, African, and Asian backgrounds. CONCLUSION The MASI is a reliable measure of melasma severity. Area of involvement and darkness are sufficient for accurate measurement of the severity of melasma and homogeneity can be eliminated.

T cell profiles in vitiligo

The purpose of our investigation was to quantitatively assess T cell profiles in vitiligo and to correlate any aberrations in these findings with the spectrum of clinical disease. Twenty randomly selected vitiligo patients and sixteen healthy matched control subjects were studied. The immunofluorescence and complement-mediated cytotoxicity assays were used to determine the percentages of total T (OKT3), helper (OKT4), and suppressor (OKT8) cells in the peripheral blood of patients and controls. Both assays gave comparable results. Patients with vitiligo had a statistically significant decrease in helper cells and helper/suppressor ratios in comparison with control subjects (p less than 0.01). In addition, there was a statistically significant decrease in helper cells among patients with a disease duration of less than 1 year (p less than 0.01) and in patients who produced serum autoantibodies (p less than 0.05). These findings tend to suggest that aberrations in cell-mediated immunity may be operative in the pathogenesis of vitiligo.

The Efficacy of Afamelanotide and Narrowband UV-B Phototherapy for Repigmentation of Vitiligo

BACKGROUND Vitiligo is characterized by depigmented patches of skin due to loss of cutaneous melanocytes. Many recent studies have demonstrated defects in the melanocortin system in patients with vitiligo, including decreased circulating and lesional skin levels of α-melanocyte-stimulating hormone (α-MSH). Afamelanotide is a potent and longer-lasting synthetic analogue of naturally occurring α-MSH. OBSERVATIONS We describe the preliminary results of 4 patients with generalized vitiligo who developed repigmentation using afamelanotide in combination with narrowband UV-B (NB-UV-B) phototherapy. Patients were treated 3 times weekly with NB-UV-B and starting in the second month received a series of 4 monthly implants containing 16 mg of afamelanotide. Afamelanotide induced faster and deeper repigmentation in each case. All patients experienced follicular and confluent areas of repigmentation within 2 days to 4 weeks after the initial implant, which progressed significantly throughout treatment. All patients experienced diffuse hyperpigmentation. CONCLUSIONS We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo. The combined therapy of NB-UV-B and afamelanotide appears to promote melanoblast differentiation, proliferation, and eumelanogenesis. Further studies are necessary to confirm these observations.

Six-Month Safety Results of Calcium Hydroxylapatite for Treatment of Nasolabial Folds in Fitzpatrick Skin Types IV to VI

BACKGROUND Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin. OBJECTIVES This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin. METHODS This open‐label, nonrandomized, prospective, five‐center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25‐ to 27‐gauge needle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper‐ or hypopigmentation. If necessary, each subject was offered a touch‐up at the conclusion of the 6‐month visit. RESULTS No reports of keloid formation, hypertrophic scarring, hypo‐ or hyperpigmentation, or other clinically significant adverse events were recorded. CONCLUSIONS People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper‐ or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population. BioForm Medical, Inc. provided the products and equipment for this study. Drs. Marmur and Boyd are members of the Medical Education Faculty of Bioform.

Safety and effectiveness of hyaluronic acid fillers in skin of color

Objectives  To assess the safety and effectiveness of hyaluronic acid (HA) fillers in skin of color.

SKIN AND HAIR COSMETIC ISSUES IN WOMEN OF COLOR

Women of color comprise many phenotypically heterogeneous groups. Despite the general heterogeneity, however, there are unique skin and hair care issues and needs. These issues often present therapeutically challenging problems for the dermatologist and the skin and hair care industry.

A Four‐Month Randomized, Double‐Blind Evaluation of the Efficacy of Botulinum Toxin Type A for the Treatment of Glabellar Lines in Women with Skin Types V and VI

BACKGROUND Histologic differences (e.g., dermal thickness, collagen fibers) between Caucasian and other racial and ethnic groups may affect wrinkle formation and influence responses to treatment with botulinum toxin type A (BoNT‐A). OBJECTIVE To evaluate the degree and duration of efficacy of 20 and 30 U of BoNT‐A for the treatment of glabellar lines in African‐American women with skin types V and VI. MATERIALS & METHODS Women aged 18 to 65 with a glabellar rhytid score of 2 or more at maximum frown on an investigator‐rated 4‐point facial wrinkle scale (FWS; 0=none, 3=severe) were eligible for this study. Patients were randomly assigned to receive 20 U or 30 U of BoNT‐A in the glabellar region. Evaluations were conducted at baseline and days 30, 60, 90, and 120 postinjection. The investigator and patient graded the severity of wrinkles at maximum frown and repose on the same 4‐point FWS. BoNT‐A was administered at the assigned dose, divided between five equal intramuscular injections into the procerus muscle, each corrugator muscle, and a site above the midpupillary line on each side. RESULTS The percentage of responders at maximum frown did not differ significantly between the two groups. Although not statistically significant, the effect lasted somewhat longer in the subjects receiving the 30 U dose. No differences were evident between groups at repose through day 120. Adverse events were mild and transient and did not differ between the groups. CONCLUSION These results indicate that doses of 20 and 30 U of BoNT‐A demonstrate efficacy and safety in African‐American women with skin types V and VI. This phase 4 clinical trial study was underwritten by Allergan.

Natural cell-mediated cytotoxicity in vitiligo

Natural cell-mediated cytotoxicity was studied in 18 patients with vitiligo and 13 healthy age-, race-, and sex-matched control subjects. The 4-hour chromium51 (51Cr) release assay was used to determine the activity of natural killer (NK) cells in the peripheral blood against K562 and Molt-4 target cells. Patients with vitiligo had a 50%, 67%, and 60% decrease in the cytotoxic response with Molt-4 cells at effector-target ratios of 25:1, 50:1, and 100:1, respectively, in comparison with control subjects (p less than 0.001). This inhibition was consistent with an 80% decrease in the binding capacity of NK cells to Molt-4 target cells (p less than 0.005). In contrast, cytotoxic responses did not differ in patients and control subjects with K562 target cells. These results suggest that patients with vitiligo have a decreased capacity for effector cell recognition of Molt-4 target cells but not K562 target cells. Hence patients with vitiligo may have defective clones of NK cells that are incapable of initial recognition of Molt-4 target cells, a necessary prerequisite for target cell lysis. Perhaps this phenomenon occurs with other tumor cells, which would explain the association of vitiligo with certain internal malignancies.