Aaron B. Lerner

Vitiligo in patients with metastatic melanoma: A good prognostic sign

We have identified and studied twenty-seven patients with melanoma who also had vitiligo. Four patients had vitiligo before the diagnosis of melanoma, and twenty-three developed depigmentation after the diagnosis of malignancy. We also have reviewed published reports about twenty-four other patients with melanoma who developed vitiligo. The clinical course of the melanoma in the fifty-one patients was remarkably similar. Thirty-seven had a melanoma arising at a site which tends to carry a poor prognosis, for example, on the trunk, under the nail, or on the mucous membranes. Forty-nine patients had metastases in regional lymph nodes or at distal sites. Thirty-three patients survived 5 years, and twenty-five survived 10 years. These data suggest that the appearance of vitiligo in patients with metastatic melanoma portends a longer survival than expected. The patients with vitiligo are not necessarily cured and eventually may succumb to metastatic disease. We were unable to determine whether the vitiligo caused retardation of tumor growth or whether the melanoma caused vitiligo.

On the Etiology of Vitiligo and Gray Hair

Abstract From an analysis of the clinical features of vitiligo and of the chemicals that cause depigmentation, a melanocyte self-destruct hypothesis for the etiology of vitiligo and graying of hair can be derived. A melanin precursor, one that is either a phenol or a catechol derivative or the phenol-tyrosinase complex, is lethal for melanocytes. When the natural mechanism that protects against the precursor is lost, the melanocytes are destroyed.

The effect of vitiligo on sexual relationships

To study the effect of vitiligo on interference with sexual relationships, we surveyed 158 patients by questionnaire. Although a majority of patients reported a negative impact on sexual relationships, most patients felt embarrassment when showing their body or meeting strangers. The majority of patients who reported a negative impact on sexual relationships attributed the problems to their embarrassment. Those who were particularly affected were those with low self-esteem, men, those to whom appearance is important, and single persons. Dermatologists should be especially alert to the effects of disfigurement and should attempt to assist patients with this problem.

Psychological reaction to chronic skin disorders: a study of patients with vitiligo.

Diseases that cause physical handicaps can seriously interfere with the life of a patient. Some disorders such as vitiligo cosmetically disfigure patients without producing any physical disabilities. The effects of such diseases as vitiligo on the life of a patient have not been widely investigated. The investigation reported here utilized a questionnaire survey to focus on emotional disturbances caused by vitiligo and on the factors that differentiated patients who cope well from those who cope poorly with this stress. The results indicate that the cosmetic disfigurement of a seemingly inconsequential skin disease also can seriously disrupt the lives of a large number of patients. Those who cope well with their disfigurement have higher self-esteem than a matched control group without the disorder. Those who cope poorly have significantly lower self-esteem, which suggests that response to disfiguring diseases is affected by basic ego strength. Younger patients and those individuals in the lower socioeconomic groups show especially poor adjustment. A number of suggestions for better patient care are offered.

Tyrosinase activity and abundance in Cloudman melanoma cells

Rabbit anti-tyrosinase antibodies were used to study the abundance, processing, and degradation of tyrosinase in murine (Cloudman) melanoma cells. The polyclonal antibodies precipitated low-molecular-weight (68,000 and 70,000) and high-molecular-weight (78,000 and 80,000) tyrosinases that had a precursor-product relationship. Cells with high basal tyrosinase activity had high levels of newly synthesized tyrosinase. Cells with low tyrosinase activity synthesized less tyrosinase and degraded the enzyme at a faster rate than cells with high tyrosinase activity. Melanotropin (melanocyte stimulating hormone), dibutyryl cyclic adenosine monophosphate, and isobutylmethylxanthine caused an increase in the abundance of newly synthesized tyrosinase that was directly proportional to the increase in enzyme activity. This enzyme was not a phosphoprotein. Other changes in the culture conditions that increased the level of tyrosinase activity increased the abundance of newly synthesized enzyme. It is thus concluded that the level of tyrosinase activity in Cloudman melanoma cells is a direct reflection of the abundance of enzyme protein.

The effects of ultraviolet light and certain drugs on Ia-bearing Langerhans cells in murine epidermis☆

Abstract Langerhans cells and indeterminate cells are immune macrophages of the epidermis and have Ia markers on their surface. Because of their position in the epidermis, they are subject to many environmental toxins like ultraviolet light. Also medications like cortisone applied topically to the skin could have important effects on these cells. We have used an anti-Ia serum and an indirect immunofluorescent technique to study Langerhans cells in epidermal sheets. We found that shortwave ultraviolet light (250–320 nm) and ultraviolet B (280–320nm) increased the density of Ia-bearing cells (Langerhans cells) in the skin. Psoralens and ultraviolet A (PUVA) (320–400 nm) depleted the skin of Ia-bearing cells, an effect which takes 2 weeks to produce but which persists for several weeks after stopping treatment. Triamcinolone acetonide administered topically or intraperitoneally also depletes the skin of Ia-bearing cells. These agents, light and steroids, either destroy the Ia-bearing cells or remove the Ia markers from the cellular surface.

Ocular Abnormalities Occurring with Vitiligo

One hundred twelve patients with vitiligo were examined for ocular abnormalities. Discrete areas of depigmentation with associated pigment hyperplasia clinically appearing to involve the choroid and retinal pigment epithelium were observed in 44 patients, and active uveitis was seen in nine patients. The changes observed suggest that the spectrum of diseases that includes Haradas disease and the Vogt-Koyanagi syndrome may be broader than previously appreciated. Patients with these syndromes may represent the most severe examples of vitiligo and uveal inflammation. The occurrence of symptoms of night blindness in 12 patients and a family history of retinitis pigmentosa in two of these may signify a possible malfunction of the retinal pigment epithelium. Further evidence for a pigment epithelium disorder is suggested by the high incidence of an unusually prominent choroidal pattern in these patients.

Pigment cell transplantation for treatment of vitiligo: A progress report

BACKGROUND Because available treatments for vitiligo generally provide unsatisfactory results, the search for viable therapeutic alternatives continues. OBJECTIVE Our purpose was to evaluate several transplantation procedures with cultured autologous melanocytes for their practicality in treating patients with vitiligo. METHODS Twenty-seven patients with stable or active vitiligo were treated after superficial dermabrasion with application of suspensions of autologous cultured melanocytes, melanocyte-keratinocyte mixtures, or epidermal sheets established in vitro. RESULTS Regardless of disease activity, use of each method resulted in repigmentation to a similar degree and without scarring in all patients. Melanocyte suspensions offer several advantages: They are easily prepared, can be applied in a controlled manner, permit coverage of large areas, and produce a homogeneous skin color that affords the best cosmetic restoration. The ultrastructure of transplant sites resembled that of uninvolved skin, with one exception: the melanocytes were located slightly higher than in uninvolved skin. CONCLUSION Application of cultured autologous melanocytes to lightly abraded skin is an advantageous addition to the treatments available for patients with vitiligo.

PANCREATIC DISEASES IN CHILDREN

The main congenital anomalies of the exocrine pancreas are reviewed, and several generalized and isolated hereditary pancreatic diseases are discussed. In contrast with adults, the most frequent causes of acute pancreatitis are viral infection, drug induction, and trauma. The dissimilarities between pediatric and acute and chronic pancreatitis are emphasized.

Normal murine melanocytes in culture

SummaryA major obstacle to applying the techniques of molecular biology to the genetics and cell biology of pigmentation has been our inability to grow normal murine melanocytes in culture. We report here the establishment and characterization of continuously proliferating cultures of cutaneous pigment cells from seven strains of mice. Melanocytes were grown from the dermis of newborn mice in medium containing 12-0-tetradecanoyl-13-phorbol-acetate; a substance, such as melanotropin, that raises intracellular levels of cyclic AMP; and an extract made from human placenta.