HEALTH HORIZONS : MEDICINE : Shedding New Light on the Skin : AFTER YEARS AS A MEDICAL BACKWATER, THE STUDY AND TREATMENT OF THE SKIN HAS BECOME A HOT AREA OF MEDICINE. DERMATOLOGY IS NOW ONE OF THE MOST COMPETITIVE MEDICAL SPECIALTIES
Years ago, I met a doctor who had started out as a dermatologist but soon after switched to orthopedics, a very different specialty that involves muscles, bones and joints. “It wasn’t that I wasn’t making enough money,” he explained. “It was just that medically, dermatology was so frustrating.
“Sometimes the treatments worked, and I would be a hero in the patient’s eyes. Other times, when I was confronted by precisely the same ailment--maybe even in the same patient--the treatment didn’t help at all. I was a failure in the patient’s eyes, and I felt totally exasperated.”
If my friend were practicing dermatology today, he would surely have second thoughts about leaving the field. After years as a medical backwater--whose practitioners were dismissed as “cos-medics,” caretakers of the complexions of wealthy matrons--the study and treatment of the skin has become a popular, groundbreaking area of medicine.
Not only are the nation’s 6,000 dermatologists finding themselves busier than ever, but more young doctors are knocking at the profession’s door. “Dermatology has become one of the most competitive medical sub-specialties,” says Dr. Bruce Wintroub, chairman of the dermatology department at the UC San Francisco Medical School, “and it’s attracting some of our best young graduates.” At that institution, the number of dermatology residents has increased fivefold in the last decade.
“Ten years ago, we worried that there wasn’t going to be enough business for people trained in dermatology,” Wintroub says. “Now, with the changing lifestyle of many Americans, especially in outdoor activities, and with increased exposure to the sun, we’re seeing more and more skin cancer. There is also more concern about aging skin, and a general increase in the incidence of skin diseases.”
In the past, skin doctors had to rely on hit-or-miss treatments for many skin ailments. Now they have many innovative drugs, ranging from medications for severe acne and psoriasis--the two most common reasons that Americans consult dermatologists--to anti-wrinkle creams that appear to make the skin a little smoother and a widely advertised compound that has raised hopes and, to a modest extent, hairs on younger balding pates. While hardly a cure, the drug minoxidil is considered the first medical step in the battle against baldness. “Better things are sure to come along,” Wintroub says. Even a problem as annoying as dandruff is finally succumbing to new medications, in the form of anti-fungal agents.
Equally impressive are new “transdermal” drug-delivery systems, in which drugs such as nitroglycerin (for heart disease), estrogen (for hormone replacement) and scopolamine (for motion sickness) are absorbed into the body through the skin from a patch, eliminating the need to take them orally or by injection. Doctors hope eventually to provide insulin to diabetics and pain-reducing peptides to the chronically injured by similar methods.
Technology also has brought hope for the treatment of so-called “port wine stains,” such as the birthmark on Soviet President Mikhail Gorbachev’s forehead. These markings, caused by an abnormal concentration of blood vessels in the skin, can be permanently removed by tiny, powerful lasers. The lasers’ precisely aimed pulses of light are selectively absorbed by the blood’s hemoglobin molecules, heating up and destroying the blood vessels without damaging the skin around them. “Some of the happiest patients we have are older people who have had these port wine stains all their lives and now are getting rid of them,” Wintroub says. “They feel absolutely blessed.”
As remarkable as the new treatments are, however, they represent just a portion of dermatology’s current success story. Much less publicized are the recent strides in understanding the skin and clarifying its role in human health. Although the skin is our largest organ, the one that defines us to the outside world, it traditionally has been dismissed as simply the body’s wrapper, an inert membrane.
We are learning that the skin is extremely vital to a person’s well-being. Thanks to techniques that allow researchers to cultivate and study living skin cells in a test tube, doctors have come to realize that the skin is a key factor in metabolic processes, as important in its own way as the liver and kidneys are in the active processing of drugs, enzymes and other substances.
The skin also appears to be an integral part of the immune system, helping the body ward off disease and dangerous chemicals. It may play a role in AIDS, a disease that often first manifests itself as a skin disorder. Revelations are emerging so rapidly from laboratories that doctors must scramble to keep up with the reports. Dr. Albert A. Kligman, a University of Pennsylvania dermatologist who has pioneered in the treatment of acne and aging skin, may not be exaggerating when he says: “A doctor who doesn’t read the medical journals for one year is 20 years behind.” His Pennsylvania colleague, Dr. James J. Leyden, adds: “Skin and science have found each other.”
One major result of this union is the discovery of the skin’s astonishing chemical complexity. “It’s a veritable enzyme factory,” says Dr. Peter Elias, head of the dermatology department at the Veterans Administration hospital in San Francisco and a professor at UC San Francisco. “The outer layer of the skin is by far the most metabolically active tissue of the body.”
A primary object of this activity is to meet the changing conditions of a frequently hostile world. Sensitive to the changes in heat, pressure, water and other environmental factors, the skin’s ever-vigilant network of nerve cells is constantly exchanging messages with the brain for instructions on how to react. Even so, the skin can respond with remarkable autonomy. “When you eat a high-fat meal,” Elias says, “your liver will stop making lipids (fats) because it is getting enough from the diet.” But, Elias says, that isn’t true of the skin. “If you eat a high-fat meal, (the skin) keeps right on cranking out lipids.” That’s because it requires the water-repelling molecules to act as a life-supporting barrier. “And you need that barrier whether you’re starving or bloating,” Elias says.
The skin almost never rests. “It is being assaulted all the time from the outside--by ultraviolet light, excess oxygen, all sorts of dangerous chemicals,” Elias says. These threats require more than lipids, however. They must be met by a much more sophisticated chemical weaponry--enzymes, essential proteins of the immune defense. Many of these enzymes are manufactured by the skin itself. “When the skin becomes stressed,” he says, “as when it is attacked by solvents or detergents or is subjected to unusually low humidity, the factory begins to crank up.” The stressed region is flooded with enzymes, which attack invading substances, until the threat passes.
But for all the protection the skin offers, it requires a measure of care that it doesn’t always get. Though Americans spend billions of dollars a year on skin products, they often mistreat their skin, exposing themselves to excessive sun, abusing their hair (considered part of the skin) with harsh treatments, neglecting warts and other growths with cancerous potential and working in environments hostile to the skin.
Diet also can affect the health of the skin. While it has long been known that many foods can cause hives or skin rashes, new studies show that poor eating habits can provoke or worsen many skin conditions, including oral ulcers, a heightened sensitivity to the sun and outbreaks of psoriasis and eczema. In addition, nutritional deficiencies in such trace elements as zinc, selenium and chromium have been linked to an increased susceptibility to skin cancer.
Though historic long-term figures are not available, one of three Americans experiences a skin disorder, making skin problems a common reason people seek out physicians, according to the American Academy of Dermatology. The academy also cited a recent study showing that 20% to 40% of job-related illnesses reported in the United States are the result of skin diseases caused by substances encountered in the workplace.
Because seemingly innocuous blemishes sometimes are symptoms of much more severe ailments, the skin is becoming increasingly important as a diagnostic tool. Dr. Neil A. Fenske, a dermatologist at the University of South Florida, notes, for example, that brownish-red hives, swelling or scaling on a patient’s chest, armpits or shoulder blades can be the initial signs of Hodgkin’s disease, a potentially fatal cancer of the lymph nodes that can be cured if detected and treated in time. Other skin lesions may signal the early stages of diabetes and syphilis.
Although the skin needs a certain amount of sunlight to manufacture Vitamin D for healthy bone development, it is becoming more and more evident that sunlight, particularly in the form of invisible rays called ultraviolet B (UVB), is the skin’s archenemy. Those with fair skin are especially vulnerable--though dark-skinned people are not entirely immune from the sun’s worst effects, particularly if the reduction in the atmosphere’s ozone shield continues.
During tanning, the skin produces an above-normal amount of melanin, a protective pigment that accounts for the skin’s coloration. Unfortunately, as studies by Dr. D. Martin Carter of Rockefeller University have shown, by the time the pigment reaches the skin’s surface, where melanin can absorb the sun’s harmful rays, the skin already has been damaged--as indicated by redness.
“People who like to tan simply refuse to take sunburn seriously,” Carter says. “The redness represents injury--damage that will accumulate over the years. This is why skin cancer is the most common of malignancies.” And it’s why dermatologists are almost uniformly opposed to tanning parlors. They strongly recommend the use of sunscreens--especially between the hours of 10 a.m. and 2 p.m., when the sun is at its highest and the UVB component of its light at its strongest. “Sunscreens are another important advance,” Wintroub says. “They do a terrific job”--along with sunglasses, hats and other protective clothing.
Besides being blamed for a documented increase in skin cancer cases in recent years, excessive sunlight is a prime culprit in the development of the dry, leathery look known technically as photoaging and of the stigmata--”liver spots”--on the faces and hands of older people. In addition, too much sun accelerates the development of cataracts and can provoke allergic reactions to certain chemicals.
Sunburns also may have more sweeping effects on the body. In research at the University of Texas Southwestern Medical Center in Dallas, dermatologists have found that UVB not only causes direct damage to the skin but also impairs the immune response. Dr. Paul Bergstrasser, the lead researcher in the field, says: “I think that the skin not only provides immune protection for its own tissue but plays a role--a role we don’t understand very well--in protecting the whole body.”
Tantalizing clues as to how this defensive mechanism functions with the rest of the body have been uncovered. Researchers have found that the skin’s so-called Langerhans cells are able to seize invading microorganisms while calling upon the help of white blood cells known as T-cells to destroy them.
Other skin cells that work with the immune system--and may be considered part of it--are keratinocytes. As their name implies, they produce keratin, a family of tough, waterproof proteins that coat the body and are the basic component of hair and nails. But that’s apparently not all they do: Scientists have found that these cells produce a hormone that stimulates the growth and development of T-cells--the immune system cells that are the special target of the AIDS virus. Before this discovery, the production of T-cells was regarded as the exclusive responsibility of the thymus, a gland at the base of the neck that is crucial to the development of the immune system early in life. (Doctors have also found that the AIDS virus can lie dormant in Langerhans cells, which originate in the bone marrow and migrate to the skin, before any overt symptom of the disease appears.)
The surprisingly versatile keratinocytes also produce a substance called interleukin-1, which in turn stimulates the T-cells into making a related substance called interleukin-2--a material that triggers the manufacture of special T-cells called helper cells. One of the helper cells’ critical jobs is to mobilize still other components of the immune system to start churning out antibodies--proteins specifically designed by the body to latch onto the outer surfaces of invading materials and neutralize or destroy them.
Researchers are discovering that the skin’s chemical defenses deal with invading substances directly. When certain carcinogens enter the skin, they are attacked quickly by skin enzymes that render the invaders harmless. But not always; sometimes the skin’s enzymes hook up with ordinarily inoffensive substances, such as benzopyrene--a byproduct of the incomplete burning of heavy oil or coal--and turn them into carcinogens. In its transformed lethal state, benzopyrene is able to enter the nuclei of cells, damage their DNA and make them cancerous.
To counter such effects, scientists are exploring the enhancement of those enzymes that might offer protection against intruding chemicals and the weakening of those that increase the potency of the invaders. Dr. David R. Bickers of Case Western Reserve University in Cleveland says that it’s theoretically possible to create lotions that could increase the production of enzymes that would disable invading chemicals.
The chemical transformations wrought naturally by the skin are already proving helpful, as illustrated by the skin’s reaction to the steroid cortisone, often used to treat injuries. A relatively weak anti-inflammatory agent on its own, it works as a healing agent largely because chemical agents in the skin convert it into much more effective hydrocortisone.
Elias considers the creation of enzymes that will beef up the skin’s defenses “one of the great frontiers” of dermatologic research. “It’s not quite at the level of molecular biology,” Elias says, “but the cosmetic companies are interested in learning how these enzymes can be supplemented, boosted or provided externally to further protect the epidermis”--the skin’s outermost layer--against the ravages of photoaging.
The concoction of anti-aging lotions, however, won’t be easy. Elias notes that while the hands are most commonly subjected to harsh solvents and detergents, only 1% or 2% of the skin on the hands is composed of protective lipids by weight. Paradoxically, the sheltered skin of the abdomen is about 10% lipid. “It’s a good idea to put cream on the hands immediately after they’ve been exposed to water and detergents,” Elias says, “but what’s the right cream? Unfortunately, any old cream won’t work. The epidermis has a special array of lipids, special molecules that are not present in any other tissue of the body.” Thus, he says, the challenge in creating lotions is not only to pick the right molecules but to mix them in the right proportions. “If you screw up the ratio, you screw up the ability to form a membrane,” he says.
Despite their danger, even the sun’s rays, or artificial versions of them, can be used therapeutically. Administered under carefully controlled conditions, measured doses of ultraviolet light have turned out to be among the most effective treatments of psoriasis, a stubborn skin ailment characterized by patches of excessive skin growth. Usually patients take a medication, such as methoxsalen, beforehand to sensitize the skin to the ultraviolet light.
More recently, doctors have been using Vitamin D analogs, the immunosuppressant drug cyclosporine and various metabolites to treat particularly bad cases of psoriasis, although possible adverse effects on the kidneys and elevated blood pressure have delayed full acceptance of these agents. Until researchers actually discover the cause of the disease--which may be a genetically linked problem of the immune system--no cure is likely.
An intriguing offshoot of ultraviolet therapy is being tried against scleroderma, a much more serious condition caused by an inflammation of the connective tissue in and around tiny blood vessels and characterized by patches of shiny, uncomfortably taut skin. Instead of bathing the entire body in ultraviolet light, the usual approach with psoriasis, doctors remove some of the patient’s white blood cells, mix them with a photo-sensitizing drug and irradiate the combination externally. Then the cells and drug are returned to the body, with good results. “We find that patients respond to the mixture by showing improvement,” says Wintroub, whose department has been testing the treatment.
While the hunt for more effective treatments for psoriasis, scleroderma and other skin-related ailments continues, a major preoccupation of pharmaceutical houses remains the quest for “fountain of youth” drugs--those miraculous medications that will remove flaws and give the user’s skin a fresh, youthful glow. Although it’s hardly a life-saving matter, it has preoccupied people at least since the days of the ancient Egyptians. Any number of potions have been blended; yet those combinations that seem to work, dermatologists explain, usually do so by covering up blemishes rather than eliminating them.
Elias illustrates the point by citing the “secret” of the much-admired complexions of many Japanese women. “They put on an average of 10 different cosmetic products a day, far more than Western women,” he says. “They’re artists at it, but under those layers they have the same bad skin as you and I.”
If the art of cosmetics has a single, overriding goal, it’s the elimination of wrinkles. The myths about these facial lines abound. Mothers have warned their children not to frown or scowl lest the wrinkles freeze permanently into place. The truth is, in this instance at least, that mother doesn’t know best. No one really can explain what causes wrinkles--though, as we age, our skin certainly loses its elasticity. The interwoven fibers of collagen and elastin--the proteins that give the skin its firmness--become weaker and less resilient. In some places, there are complete collapses. These areas are visible as wrinkles.
No one has yet come up with a cream or lotion that can stop the clock. That’s why plastic surgeons and dermatologists--they sometimes step on each other’s turf--are doing a thriving business taking a tuck here or injecting squirts of collagen there to create smoother skin for patients. But while these procedures often can produce attractive results, the skin eventually begins to sag again--sometimes sooner than later--and nothing seems to help the patient. As with many chronic diseases, the best remedy is, alas, prevention. Keeping skin youthful-looking means staying out of the sun. It’s a message even teen-agers should heed, since photoaging quietly begins to take its toll in those years.
Something of an elixir against wrinkles has emerged from dermatological labs. For some time, doctors have been treating cases of severe acne with a drug called tretinoin, a Vitamin A derivative sold under the name Retin-A. A few years ago, doctors discovered that tretinoin produced some reduction of wrinkling in their acne patients’ skin.
The word that Retin-A was a wrinkle cure spread quickly, and women beseeched their doctors for the prescription drug, though, as with minoxidil, the results often fell short of patients’ expectations. “It seems to have a small but real effect in reversing the effects of sunlight,” Wintroub says, though he and his colleagues say that it can’t restore the apple cheeks of youth. Nor is it without side effects. “If you’re not careful,” he warns, “you can get a bad burn in the sunlight after being dabbed with Retin-A because it’s phototoxic.”
No one can explain how tretinoin works, although doctors suspect that the drug blocks the activities of collagenase, an enzyme that breaks down collagen and the fibers that anchor one layer of skin to another. Some support for this theory comes from a recent study in which doctors treated the forearms of two groups of women--one with tretinoin, the other with a placebo. Subsequent microscopic examination of the women’s skin showed that those treated with tretinoin had double the density of anchoring fibers.
“Dermatology has a lot of black magic in it,” Elias acknowledges. But, as he puts it, “it is no longer in the realm of quackery.” Invigorated by science, dermatology is finally revealing the skin in all its complexities, promising still more advances in skin care and giving lie to the old phrase: It’s only skin-deep. As we are learning, there’s nothing superficial about the skin.
