Pediatric Dennatology Vol. 9 No. 4 390-3%

What's New in '92—The Past Decade of Pediatric Dermatoiogy James E. Rasmussen, M.D. The subjects of Pediatric Dennatology that are new all begin with the letter d: drugs, diseases, diagnostic methods, devices, DNA, and diseaseoriented patient support groups. DRUGS Retinoids No other group of compounds has had such a major impact on pediatric dermatology as the retinoids. We are all aware of the significant advance in the treatment of acne with 13-cis retinoic acid. No other agent can transform mutilating nodulocystic acne into a prolonged remission after such a short period of therapy. Together with this benefit, however, has come the knowledge that it is probably one of the most teratogenic medications available. At least in the United States, desire to prevent damage to the unborn fetus, as well as concern over potential litigation, has directed an unprecedented amount of effort toward preventing pregnancies in women taking retinoic acid. Million-dollar awards are mentioned in publications such as the Wall Street Journal, and some attempt has been made to regulate the availability of this drug because of its effects on fetuses. It is currently the standard in the United States to require written, informed consent before prescribing this drug. In addition, pregnancy tests must be performed before the institution of therapy, as well as during and after treatment. If we are to continue to have access to 13-cis retinoic acid, it is our duty as pediatric dermatologists to warn other physicians about its hazards. Fortunately, other serious side effects have proved quite uncommon. Also of interest is the recent awareness that vitamin A may be useful in ameliorating some of the more severe signs and symptoms of measles. This is particularly pertinent because measles is increasingly frequent in many parts of North America. Large epidemics (several thousand cases) have

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been reported from major cities where inner-city poor have limited access to health care. Epidemics have also occurred among migrant farm workers and recent immigrants to the United States. Several publications (N Engl J Med 19W;323: 160-164) documented the efficacy of vitamin A 200,000 IU/day for two doses versus placebo in children with measles treated within five days of the onset of the rash. Most of these studies came from countries where dietary intake of vitamin A may be substantially less than in the United States, and transferring these results from one continent to another may not be justified. Nevertheless, patients treated with vitamin A had fewer days of pneumonia (6.3 vs 12.4), fewer cases of croup (13 vs 27), and fewer deaths (2 vs 10) than a comparable group of 27 children given placebo. It was the conclusion of the authors that all children with severe measles should be given vitamin A supplementation. Similar studies have been reported from the subcontinent of India. A recent paper (Pediatr Infect Dis J 1992; 11:203209) demonstrated that vitamin A increases specific antimeasles IgG and lymphocyte counts. This prospective, blinded, controlled trial of vitamin A in South African children with measles used 100 to 200,0(X) IU on days 2 and 8 versus placebo. Recovery was substantially quicker in the vitamin A group, and both specific antimeasles IgG and total lymphocyte counts were substantially higher, suggesting that they may be involved in the process of improvement. Acyclovir Although an effective varicella vaccine is available, it is not currently used in North America. Consequently, the publication of several controlled trials of acyclovir in the treatment of varicella have captured the ititerest of pediatricians and others involved in the management of this disease. The most recent of these (N Engl J Med 1991 ;325:1539L-I544)

Rasmussen: What's New in '92 391 studied acyclovir (Zovirax) 20 mg/kg four times a day for five days, starting within the first 24 hours of the onset of varicella. The 367 patients in the acyclovir group were compared with 357 patients in the placebo group. Patients treated with acyclovir had fewer lesions (294 vs 386), fewer patients had greater than 500 lesions (21.3% vs 38.4%), a smaller percentage were febrile at day 3 (10% vs 30%), fewer patients had new lesions at day 3 (4% vs 33%), and both groups had almost identical serologic results at 28 days (1:213 vs 1:240). An accompanying editorial in the journal noted that if the estimated 4 million children with chicken pox were treated with this drug at $32.00 per patient, the total cost would be $128 million. Zovirax is approved for the treatment of varicella by the Food and Drug Administration in the United States, and it is available in 800-mg tablets, as well as a 200mg suspension to facilitate delivery in the pediatric population. Cyclosporine A It is common to think of cyctospwrine for the management of cardiac, liver, renal, and bone marrow transplantation, but the drug's use has expanded significantly to include several dermatologic disorders. Dermatomyositis is often a disabling, destructive, indolent process that responds relatively poorly to systemic corticosteroids, azathioprine, methotrexate, antimalarials, plasmapheresis, and other modalities. A report in Lancet (1989; 1:10631066) describes the use of cyclosporine in juvenile dermatomyositis. In this paper, 14 children "not fully responsive" to steroids or immunosuppressants were treated with cyclosporine 2.5 to 7.5 mg/ kg/day. The need for oral steroids fell substantially, and muscle strength improved by 40% to 60%. Six patients were able to discontinue all use of corticosteroids. The authors noted, "all 14 patients improved" and none had severe side effects from cyclosporine. Although not considered first-line therapy, cyclosporine also improves psoriasis (JAMA 1986; 256:3110-3116). This double-blind, vehicle-controlled trial of 14 mg/kg/day showed that 10 of 11 patients cleared or markedly improved in four weeks versus none of 10 patients in the vehicle group. To my knowledge, no other agent is so rapidly effective. Many subsequent studies showed that a dosage of between 2 and 5 mg/kg is satisfactory for most patients, although the response rate is not as high. Unfortunately, cyclosporine does not produce long-term remissions.

Cyclosporine also is remarkably effective in alopecia areata, pyoderma gangrenosum, chronic urticaria, oral lichen planus, and a variety of other dermatologic conditions. Mupirocin

The etiology of impetigo has changed substantially in the past decade. Numerous studies from around the world showed that the once ubiquitous streptococci have yielded to Staphylococcus aureus, which is becoming increasingly resistant to commonly used antibiotics. In addition, many of the streptococci currently being isolated no longer respond to erythromycin. Mupirocin has been studied extensively, and clearly is more effective than its vehicle and any currently existing topical antibiotic. One study (J Pediatr 1990,117:827-829) discussed 54 children with impetigo who were treated with erythromycin 40 mg/kg/day and a topical placebo four times a day for 14 days, or an oral placebo and 2% mupirocin four times a day for 14 days. At the end of this time, using a variety of clinical and cultural variables, 91% of patients in the mupirocin group and 92% in the oral erythromycin group were considered cleared. This is the first time that a topical antibiotic has been as effective as a systemic antibiotic in the treatment of impetigo. Obviously, patients with systemic signs and symptoms, or those at risk of secondary complications should be given systemic antibiotics. Widespread impetigo is also not as easily treated topically as it is systemically. On a costeffectiveness basis, mupirocin competes extremely well against systemic antibiotics. EMLA

£utetic mixture of the /ocal anesthetics (lidocaine and prilocaine), or EMLA, represents a significant advance for the relief of pain of minor procedures such as laser therapy and destruction of warts. A 1988 paper (Acta Dennatol Venereo! 1988;68:I49153) describes the analgesic effect of this EMLA cream in treating 55 children age 3 to 14 years whose molluscum were curretted. After 60 minutes of occlusive therapy, 76% of children reported no pain following curretting the molluscum, and only 6% reported the pain as moderate (4%) or severe (2%). I have used this agent extensively in the treatment of port-wine stains with pulsed dye laser, and believe that it takes approximately 50% to 75% of the sting out of the procedure. Unfortunately, analgesia is not complete, and there are subst^itial re-

392 Pediatiic Dermatology Vol. 9 No. 4 December 1992 gional variations in response, with the drug being almost completely ineffective over the eyelids and lips. NEW USES FOR OLDER DRUGS Beta Carotene and Retinoifis in Cancer Prevention and Chemoprophyiaxis

Beta carotene and topical and systemic retinoids have drawn increasing attention for their uses in cancer prevention and treatment. Kramer et al (N Engl J Med 1988;318:1633-1637) treated five patients with advanced xeroderma pigmentosum who had been developing skin cancers for a number of years. At a dosage of 2 mg/kg/day for two years, the patients had a 65% decrease in tumors. Unfortunately, after discontinuing the drug, there was an 8.5 times rebound increase in skin cancer formation, but nevertheless, the principle has been firmly established. At this dosage, isotretinoin is not suitable for long-term use except when the benefits outweigh the risks. These and other papers describing prevention of malignancies have caused many pediatric dermatologists to focus their attention on the role of sunlight in the development of skin cancers. A substantial amount of work has gone into studying the epidemiology of skin cancers, most of it focused on sun protection. It is now recognized that skin cancer is rising at a more rapid rate than any other type of malignancy, and this is particularly true for melanoma. Increasing numbers of patients have been seen with basal cell carcinomas who are not in the traditional 40 to 70 year age range. A 12-year-old boy without underlying xeroderma pigmentosum or basal cell nevus syndrome was reported to have a documented skin cancer. In addition to this emphasis on skin cancer from sunlight, pediatric dermatologists have focused on the relationship among sun, nevi, and melanomas. Large studies clearly show the relationship between overexposure to sunlight and the subsequent development of melanoma. Several cooperative trials also demonstrated that the distribution of nevi is tremendously influenced by exposure to sunlight. Examination of any patient with a large number of nevi will show that they are almost nonexistent on the buttocks and underarms compared with other body sites. Of most importance to us as pediatric dermatologists is the realization that skin cancer actually begins in the first 20 to 25 years of life. This was tiicely demonstrated in a study by Marks et al (Med J Aust

1990; 152:62-67) that evaltiated 1232 native Australians for the presence of actinic keratoses, and compared them with two groups of British immigrants who migrated before or after 20 years of age. Immigrants who arrived in Australia before 20 years of age had similar involvement with actinic keratoses as their native Australian counterparts. Those who immigrated after 20 years of age, however, never equaled their Australian counteiparts in number of lesions. These and other studies suggest that the genesis of premalignant and malignant tumors begins early in life, and that efforts at prevention should be focused here. This has given rise to a tremendous industry in North America with respect to sunscreen products, skin cancer detection and prevention programs, sun awareness, public service announcements, as well as "sun" clothing. A drug that originally was marketed for the treatment of acne, topical tretlnoin has clearly been shown to be the first and only drug available to reverse photoaging. Whereas I realize that photoaging is not of great concern to pediatric dermatologists, the fact that it begins in childhood, and involves a drug originally used for the treatment of acne in adolescents, makes it of interest to us all. Weiss et al (JAMA 1988;259:527-532) were the first to show that topical tretinoin improves photoaged skin in a double-blind study. This 16-week trial using halfbody treatment versus vehicle control showed that fine wrinkling improved in 70% with retinoic acid, and in otily 30% of those using the vehicle. Coarse wrinkling was not significantly improved by either treatment modality. Retinoic acid also is useful in the treatment of liver spots (N Engl J Med 1992;326:368-374). According to Rafal et al, these actinically induced signs of photoaging were substantially improved in 60 patients over 40 weeks in a blinded trial of 0.1% tretinoin. Although not documented in the study, these results suggest that the agent might be useful in managing the disfiguring but benign cosmetic problems seen in patients with xeroderma pigmentosum. Sulfasalazine

Guttate and plaquetype psoriasis in children is usually quite easy to treat with ultraviolet light, topical steroids, coal tar, and anthralin, but an occasional patient fails to respond to inpatient and outpatient therapy. The choice of systemic agents for such a patient with severe, disabling, or disfiguring psoriasis is relatively limited. Etretinate, because of its

Rasmussen: What's New in '92 393 long half-life, and teratogenicity, would not be considered a reasonable choice, at least in women. Methotrexate, cyclosporine, and corticosteroids also have long-term side effects. Vitamin D3 may be useful topically and systemicaliy in the future, but it is not currently available in North America. Consequently, the pediatric dennatology community was interested in a report by Gupta et al (Arch Dennatol 1990;126:487-493) noting that suifasalazine improves psoriasis. This eight-week double blind trial of suifasalazine (23 patients) versus placebo (23 patients) used a maximum dosage of 3 to 4 g/day. Approximately 20% of patients terminated the study because of gastrointestinal or allergic side effects. Those who remained noted a substantial improvement. Marked or complete clearing was seen in two-thirds of the patients who finished the eightweek course, which was substantially better than those treated with placebo. I have used this drug in approximately 15 patients with resistant pediatric psoriasis, and have been impressed with its results. Allergic reactions can, however, be severe. NEW DISEASES Lyme Disease, Protein C Deficiency In the past decade, the number of cases of Lyme disease in the United States had increased 100-fold, with over 4572 reported in 1989 (MMWR 1989;38: 668-672). The spirochetal etiology of this disease has been defined, as has the full clinical range of features. It is now realized that borreliosis existed in Europe for at least 100 years prior to its description in North America under the heading "Lyme disease." The disorder has become an obsession in North America, with national news magazines carrying pictures of gigantic ticks, and many nationally advertised products claiming that their use prevents the bite of the tick that carries the disease. The etiology of purpura fulminans and its relationship to protein C deficiency (in neonates) and coumadin necrosis in adults also has been recently defined. In protein C deficiency, the absence of a naturally occurring anticoagulant (protein C) allows the uninhibited progression of naturally occurring vascular thromboses. When seen in the homozygous state (neonatal period), infants have thrombosis of major internal vessels as weli as widespread infarction of the skin. Biopsy specimens show bland thrombi, but unfortunately, by the time the diagnosis is made, therapy is usually too late to be of benefit.

In distinction, coumadin necrosis is often seen in the face of heterozygous protein C deficiency. The production of coagulant and anticoagulant enzymes that are hepatically produced is inhibited by coumadin. The half-life of anticoagulant enzymes inhibited by coumadin is shorter than that of coagulant enzymes. In patients with heterozygous protein C deficiency, there exists a transient state shortly after beginning the use of coumadin when anticoagulant enzymes remain while protein C and others have been inhibited. This unopposed state of vascular thrombosis produces the areas of superficial purpura that are known as coumadin necrosis. Although this problem is serious, it does not usually result in the systemic morbidity seen in homozygous protein C deficiency. ADVANCES IN OLDER DISEASE Erythema Infectkisttni In the past decade the etiology of erythema infectiosum (slapped cheek, fifth disease) clearly was shown to be due to parvovirus B-19. While this in itself is a significant advance, many reports expanded the clinical spectrum of disease caused by this virus. It has a tropism for red cell precursors, and produces aplastic crisis in sickle cell anemia and other hemoglobinopathies. A similar response (severe anemia) occurred in a small group of patients with leukemias. The clinical features of erythema infectiosum are somewhat unique in that they occur after the viremia has resolved, and in fact may be due to some unusual immunologic response to it. In distinction, patients with aplastic crises still are viremic, and consequently represent an infectious source to exposed personnel, including those who care for them if hospitalized. This has brought increased awareness of the effect the virus has on the fetus. Several reports showed that mothers exposed to parvovirus B-19 may have hydropic fetuses. This is probably related to the anemia the virus produces, resulting in congestive heart failure and subsequent hydrops. Also expanding our knowledge were articles defining the incubation period of the disease and the clinical spectrum in adults. Adults may not have the typical appearance of slapped cheek, but instead develop moderate to severe myalgias and arthralgias, some of which may be subacute to chronic. Consequently, the Committee Of Infectious Diseases of the American Academy of Pediatrics (Pe-

394 Pediatric Dennatology Vol. 9 No. 4 December 1992 diatrics 1990;85:131-133) published a position papier on parvovirus, erythema infectiosum, and pregnancy. Cat Scratch Disease A series of wonderful articles clearly elucidated the etiology of cat scratch disease. Margileth and colleagues at the National Medical Institute in Bethesda, Maryland, began this chain of remarkable publications in Science (1983 ;221:1403-1404). In 34 of 39 lymph nodes, they were able to demonstrate a gram-negative bacterium in the walls of capillaries. Subsequent publications demonstrated that this organism could be cultured in blood agar, brain-heart infusion agar, and in the armadillo. A recent publication (J Clin Microbiol 1991;29:2450-2460) named this organism Afipiafelis, an acronym representing Armed Forces Institute of Pathology. Langerhans Cells Approximately 100 years ago, Paul Langerhans, a junior medical student, identified the dendritic epidermal cell that bears his name. Recently, the use of improved identification techniques such as monoclonal antibody immunostaining, enabled several groups of workers around the world to focus on the function of the Langerhans cell. It has become clear that this is an immunoregulatory cell with antigenpresenting capabilities. One recent and attractive etiologic theory of atopic dermatitis suggests that Langerhans cells induce an abnormal immunologic response in patients with atopic dermatitis. These CDI+ cells normally attract Thy-1 + T lymphocytes into immunologic reactions such as allergic eczematous contact dermatitis. In atopic dermatitis, Langerhans cells attract and stimulate Thy-2 + cells. These cells liberate the cytokine IL-4, which stimulates the production of mast cells and IgEproducing B cells. This shift toward these two cell types helps define the hyper-lgE and the "itch that rashes" that are so characteristic of atopic dermatitis. Interferon--y shifts the production of lymphocytes from Thy-2 to Thy-1. Several recent pai>ers focused on the use of interferon-7 as an outstanding means of treating even the most severe atopic dermatitis. Unfortunately, interferon does not produce long-standing remission, has significant associated toxicity, and is very expensive. AbscH-bent Gel Diapers and Stool Enzymes The most significant advance in diapering practices in the last decade has been the use of absorbent gel

diapers. These gels bind water (urine) and keep it from being released back onto the infant's skin, resulting in documentary drier baby's bottoms. At first when they were introduced in the United States it was claimed that these gels were so efficient that they would actually suck water from the infant's skin and produce dehydration. Such concerns have proved completely unfounded, and the diapers are now regularly used around the world. The diapers also have stimulated much recent research in the etiology of diaper dermatitis. In a series of articles appearing in Pediatric Dennatology, a group of researchers at Proctor & Gamble clearly showed that the old ammonia theory is not dead. They demonstrated that urine by itself was not particularly irritating, even if left on the skin for long periods of time. When urine is mixed with feces, however, the irritation index increases substantially. Concomitant with this increase in irritation is an elevation of pH from about 6.0 to 8.0. The cause of this increased pH is the liberation of ammonia from urea by bacterial ureases that are normally present in stool. The elevated pH activates stool lipases and proteases, which are normally inactive at pHs of 5.0 to 6.0. It is hypothesized that this increase in enzyme activity is at least in part responsible for many cases of diaper dermatitis. Antibiotics, rapid stool transit times, and other factors are also probably responsible for activating these lipases. The efficacy of absorbent gel diapers in decreasing diaper dermatitis has been documented in several studies in the United States and abroad. Currently, the effectiveness of these superabsorbent diapers depends on their keeping the infant's skin drier and less susceptible to irritation. In addition, they keep urine from contact with stool so that the pH cannot rise, and Upases and proteases remain relatively inactive. DIAGNOSTIC METHODS Imaging Techniques Imaging techniques have changed substantially in the past generation. Ultrasound examination is commonly used to diagnose fetal abnormalities, and reveals to curious patients the sex of their unborn child. Of more practical use to pediatric dermatologists is the computerized axial tomographic (CAT) scan in divulging the relationship between cutaneous and spinal defects. Magnetic resonance imaging (MRI) is a good clue to the physiology of studied tissues. When used by Hernandez and colleagues to

Rasmussen: What's New in '92 395 evaluate muscles in dermatomyositis in four patients, it demonstrated increased density in inflamed muscles (J Pediatr 1990;l 17:346-350). This technique was much easier and less dramatic than muscle biopsy, was more sensitive than muscle enzymes for long-term follow-up, and gave a graphic representation that could easily be recognized. Obviously, MRI is substantially more expensive than most of the other techniques, costing $750.00 to $2000.00 in the United States. Chorionic Villus Sampling, Amniocentesis

Many prenatal dic^nostic techniques significantly advanced the field of pediatric dermatology; however, some generated new diseases. Firth et al reported limb abnormalities after chorionic vitlus sampling at 56 to 66 days' gestation (Lancet 1991; 337:762-763). Of 289 pregnancies that were subjected to villus sampling, 5 (1.7%) fetuses had transverse limb reduction defects and some had oromandibular hypogenesis. The advantage of chorionic villus sampling over amniocentesis is that it is much less traumatic, obtains a larger quantity of tissue for cytogenic and enzyme analyses, can be done much earlier in pregnancy, and yields diagnostic answers after less time. Thus, if termination or other intervention is desired, it can be performed earlier. There is some controversy as to whether chorionic villus sampling is a safer technique than amniocentesis. Its mechanism for producing transverse limbs defect has not been well defined. In contrast, amniocentesis also can result in "amniocentesis marks." Immunomapping

McCuaig and colleagues expanded the spectrum of epidermolysis bullosa acquisita to inciude the pediatric population. They described a child who since 3 months of £^e had a disease that was clinically and histopathologically considered to be epidermolysis bullosa dystrophica. Immunomapping, however, clearly disclosed this to be a form of epidermolysis bullosa acquisita, and therapy with corticosteroids and dapsone allowed this ciiild to resume a nearly nonnal life. Epidermolysis bullosa acquisita has now been described in a number of children. Monoclonal Antibodies

The explosion of monoclonal antibodies has enabled scientists to identify a dizzying array of celis, enzymes, and cytokines. It also generated a new

obsession with dis^ams filled with code names such as CD, BD, ELAM, ICAM, IL, IF, KLIF, MHC, LFA, TGF, TNF, and VCAM, to name a few. How many of these can you identify without a legend? DEVICES

Lasers Dye lasers have substantially changed the way that pediatric dermatologists think about patients with port-wine stains. We can now eradicate many of these lesions, particularly if treated early in life, when they are smaller and more amenable to therapy. The copper vapor laser shows much promise as a pigmented lesion laser, although it has yet to achieve the widespread popularity of the dye laser. Computers

No office- and home-based device wiU have as great an impact on the individuai practice of medicine as the computer. Various programs allow us to search hospital records and iaboratory reports, and to keep up more easily with the tremendous increase in medical knowledge. As preparation for this talk, I did a computer search on items related to pediatric dermatology and found over 16,000 entries during the past decade alone. No individual could possibly read and remember this huge amount of information. In the past decade we welcomed the arrival of three new journals, the Japanese Joumal of Pediatric Dermatology (editor Kazuya Yamamoto); Pediatric Dermatology (editors Lawrence Solomon and Nancy Esterly); and the European Journal of Pediatric Dermatoiogy (editor Ernesto Bonifazi). We have new text books, such as Pediatric dermatology by Schachner and Hansen; Pediatric dermatology by Maidonado, Parish, and Beare; Clinical pediatric dermatology by Sidney Hurwitz; Handbook of pediatric dermatology by Harper; Atlas of pediatric dermatology by Menegjni and Bonifazi; Pediatric dermatology by Wiiliam Weston; The color textbook of pediatric dermatology by Weston and Lane; The color atlas of pediatric dermatology by Verbov and Thoriey; Pediatric dermatology by Happie and Grosshans; The skin and systemic disease in children by Hurwitz; Vascular birthmarks by Mulliken and Young; Viral warts by Bunni; Pediatric dermatology for the primary care practitioner by Weinberg and Appleman; and The ichthyoses by Heiko Traupe. These are the Engiishtextbooks published in North America

396 Pediatric Dennatology Vol. 9 No. 4 December 1992 with which I have famiMarity. I am sure that there are many others. After the initial cost of the computer, accessing articles and journals is usually no more expensive than a long-distance phone call. In addition, computer-assisted graphics have made medical subjects that seemed to be dull and obtuse into more understandable Etnd enjoyable topics. DNA/RNA

In terms of its impact on medical practice, no area holds brighter promise for diagnosis and therapy than evaluation of the mysteries of DNA and RNA. This is best exemplified by the human genome project, an international cooperative undertaking that also involves the study of bacteria (Escherichia coli), yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans), and fruit fly {Drosophila melanogaster). This has given rise to an indication that there are over 4000 human genetic diseases. The implications for molecular diagnostics, gene therapy, and preventive medicine are far too staggering to be discussed here. DISEASE-ORIENTED PATIENT-PARENT GROUPS Beginning with the National Psoriasis Foundation, many disease-oriented patient groups have developed throughout the world. They are reliable sources of information for patients and physicians alike. They offer newsletters, counseling services, hotlines, and inexpensive sources of pharmaceutical supplies. In addition, they are very valuable in fundraising and lobbying. In the United States, many of these organizations have been singlehandedly responsible for the development of national research programs into diseases such as epidermolysis bullosa. THE FUTURE Now I am going to forecast for pediatric dermatology in the year 2000.1 begin with a prediction that I

knew would come true. That is. the 7th International Congress of Pediatric Dermatology in Buenos Aires would break the tradition of prior meetings held in cities ending in the letter O (Mexico City, Chicago, Monte Carlo, Tokyo, Milano, Toronto). The other more serious predictions address the lack of predictability of medicine. Very little research proceeds in a straight and uninterrupted line, and progress is usually slow. Much more likely to occur are the unpredictable and perhaps serendipitous discoveries that will open new horizons for medicine in general and pediatric dermatology in particular. These are most likely to be seen in gene therapy, gene replacement, fetal medicine, and infectious diseases, AIDS, Kawasaki disease, and atopic eczema. Other important progress will be made in the field of carcinogenesis where chemoprophylaxis will become a custom rather than the exception. We will have greater understanding of aging, and the use of vitamins, minerals, and anoxidants to prevent and counteract its effects. There will be substantial development in the field of new biologic agents such as antivirals and cytokines, but I doubt that there will be any major breakthroughs such as a cure for the common cold or AIDS. Increased emphasis on public health awareness will lead to less sun exposure, decreased smoking, increased emphasis on proper nutrition, cleaner sources of air, water, and food, and the development of biologies to retard and reverse the process of aging. If these predictions come true, by the year 2000 we may be able to recycle our geriatric patients into new groups of patients for pediatric dermatologists. Also expected is the resurrection of diseases once considered forgotten: measles, syphilis, and tuberculosis. The microorganisms in our environment will continue to outrace our ability to defend and prevent infection. I end with two predictions certain to be true in the year 2000—I will continue to show pictures of stunning orchids, and pediatric dermatologists will continue to have the most beautiful patients in the world.