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San Francisco—Recent advances in dermatology include progress toward gene therapy; better treatment for AIDS-induced skin disorders, hemangiomas, and skin cancers; new lasers for use on pigmented lesions and for skin resurfacing; and improvements in soft tissue–augmentation surgery.
Leading investigators in dermatology's main specialty areas reviewed major progress and outlined new directions for research and treatment at the annual meeting of the American Academy of Dermatology (AAD) here in March.
Better understanding of basic immunology has generated important insights into the mechanism of carcinogenesis, said Richard Granstein, MD, of Cornell University's Weill Medical College, speaking for the Society of Investigative Dermatology. A number of immune cell derangements induced by ultraviolet radiation, he said, allow an incipient skin cancer to arise and grow. "This is certainly true if you're a mouse," he added, "and almost certainly true if you're a human." Work is in progress, he said, to develop strategies to increase host immunity against malignant tumors.
Molecular genetic medicine holds great promise, Granstein said, despite recent setbacks. New studies show that injection of a gene associated with hair follicle development into the skin of mice that were genetically altered not to develop mature hair follicles prompted hair growth within a few days. Many important genodermatoses are single-gene defect disorders. Since the skin is accessible, Granstein said, it is an ideal site for experimentation.
The explosion of new drugs and widespread use of herbal remedies in recent years has triggered new inflammatory diseases, said Jean Bolognia, MD, of Yale Medical School, who represented the Medical Dermatology Society. Some cases of erythema multiforme and most cases of toxic epidermal necrolysis, she noted, are drug eruptions. Lithium can exacerbate psoriasis. Cephalosporins and anticonvulsants can cause pustular drug eruptions. The universal use of nonsteroidal anti-inflammatory drugs has produced pseudoporphyria cutanea tarda. Other technological advances bringing new dermatologic diseases, she said, include renal dialysis, heart valve replacement, and stem cell/bone marrow transplantation.
Some "new" diseases may have existed but were not recognized, Bolognia said, although new viruses continue to appear. Human immunodeficiency virus (HIV), for one, has a long list of dermatologic consequences, including exacerbations of common diseases such as psoriasis and seborrheic dermatitis, deep bacterial infections, oral candidiasis, Molluscum contagiosum, chronic herpes simplex, and verrucous forms of herpes zoster. The incidence of many of these diseases is now decreasing, thanks to improved HIV therapies. "As the world shrinks," Bolognia said, "differential diagnoses expand."
"It would be nice to know at the bedside if a patient has an infectious disease," Bolognia said, predicting that handheld instruments will soon be available to sample tissue, do multiple parallel polymerase chain reaction assays, and identify the responsible organisms within minutes. Bolognia's therapeutic wish list for the future includes a wart vaccine and an effective antipruritic.
Hope for hemangiomas
Research in angiogenesis may benefit treatment of hemangiomas, the most common tumor of infancy and among the most common birthmarks, said Ilona Frieden, MD, of the University of California, San Francisco, School of Medicine (UCSF), speaking for the Society for Pediatric Dermatology.
While involution of true hemangiomas almost always occurs, she said, some hemangiomas leave permanent scars. In the mid-20th century, x-rays were widely used to treat hemangiomas, Frieden said, but once their natural course became clear, such treatment was viewed as a shameful episode in medical history.
An anti-interventionist movement from the 1960s to 1980s stifled research on which hemangiomas should be treated. In 1960s, systemic corticosteroids serendipitously were found to be effective, and they are still the mainstay of treatment for multiple and extensive hemangiomas, despite their potential adverse effects. In the 1990s, interferon alfa, initially thought beneficial, proved to have central nervous system toxicity that caused permanent spastic diplegia in as many as 20% of treated infants. Interferon alfa now is reserved for serious or life-threatening hemangiomas that are corticosteroid-resistant.
Current research aims to find ways to achieve a local effect on hemangiomas without a systemic effect. Investigators are trying to find biologic markers, Frieden said, to predict which hemangiomas will stay small and which will cause functional disease or disfigurement. They also seek to understand the biologic switch that sends hemangiomas into involution, a phase now thought to be governed by apoptosis. "If a discrete switch exists and could be manipulated," she said, "that would bring a true biologic therapy of hemangiomas."
The speaker for the American Society of Dermatopathology, Antoinette Hood, MD, of Indiana University School of Medicine, predicted that the presence of fewer but larger laboratories will decrease training opportunities in pathology and lead to fewer dermatologists who read their own slides. It also may decrease physician-to-physician communication, she said, and lead to a less accurate perception of a laboratory's reliability.
Most textbooks in the field of dermatopathology are now written by pathologists, Hood said, and twice as many pathologists as dermatologists took the dermatopathology board examinations in the past 3 years. Although pathologists are in the forefront of research in areas such as three-dimensional imaging, dermatologists who are dermatopathologists, she asserted, offer the best bridge between the bedside and the laboratory.
Melanoma reduction goal
Charles McDonald, MD, of Brown University School of Medicine, Providence, RI, and immediate past president of the American Cancer Society (ACS), said the organization's major goals for the next 15 years include a 25% reduction in the incidence of malignant melanoma and a 50% reduction in melanoma mortality, along with comparable progress in colorectal, lung, breast, and prostate cancers. This is the first time in the history of the ACS, McDonald said, that skin cancer has achieved such prominence. Some 35,000 persons were diagnosed with melanoma in the United States in 1995 and 44,000 in 1999, he said, while the incidence as well as the mortality rate of nearly all other cancers declined.
Use of lymphoscintigraphy to determine lymph node drainage in melanoma, followed by biopsy of the sentinel node(s), permits prediction of an individual patient's prognosis, said Mary Maloney, MD, of the University of Massachusetts Medical School. Whether this procedure improves survival, she said, still is not known (JAMA. 2000;283:2223).
In removing melanomas, Maloney said, margins have narrowed, and better repair of surgical defects has improved cosmesis. Although more than 200 trials of immunotherapies have been conducted, she noted, overall clinical improvements remain elusive.
Excellent sunscreens and protective clothing are available, she said, although research should continue in these areas. Pools, playgrounds, and other recreational sites need more sun-protected areas, she said, urging dermatologists to campaign to boost sun-safe practices in their communities. Maloney also called for more research into the causes and effects of ozone depletion, more whole-body skin cancer screening, and continued public education about the risks of excessive exposure to ultraviolet light.
Addressing new directions in laser surgery, Richard Glogau, MD, of UCSF, said wavelengths are getting longer, pulse widths are getting wider, and biologic effects are getting deeper. At the same time, he said, lasers are becoming more gentle, faster, and more efficient. Lasers offer more control than traditional, cold steel surgery, he said, and provide a more elegant solution than any previously available treatment. Uses of lasers in dermatology include cutting, treatment of pigmented and vascular lesions, hair removal, and skin resurfacing.
As lasers continue to develop, Glogau said, speaking for the American Society for Dermatologic Surgery, they will be used to produce their desired biologic effect while sparing the epidermis. They will target selective parts of the dermis, with less morbidity and greater reliability. The pigmentary response in the patient's skin, however, remains difficult to predict.
In the area of soft tissue augmentation, Glogau said, the elegance of the effects of injection of botulinus toxin in the upper third of the face only highlights current limitations of tissue fillers in the lower third. "There is a tidal wave of soft tissue augmentation products about to enter the United States," he noted, adding that many are used extensively in South America, Europe, and Australia. Growing understanding of lipocyte pathophysiology, he said, will allow the use of autologous fat in a more predictable and efficient way than now is possible.
Not all soft tissue augmentation falls into the vanity area, he noted. Many persons with AIDS suffer facial lipoatrophy from the use of protease inhibitors. Although their illness is controlled well by multidrug therapy, he said, this form of disfigurement causes enormous emotional pain. Reconstruction is possible with implants that can be taken out later if the reason for this metabolic defect is found and a way to correct it is devised.
Lamberg L. New and Emerging Dermatologic Therapies Presented at Conference. JAMA. 2000;283(18):2377–2378. doi:10.1001/jama.283.18.2377-JMN0510-2-1
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