|Year : 1992 | Volume
| Issue : 1 | Page : 5-14
What`s new in paediatric dermatology
E James Rasmussen
E James Rasmussen
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rasmussen E J. What`s new in paediatric dermatology. Indian J Dermatol Venereol Leprol 1992;58:5-14
| 1. Photoprotection|| |
Certainly the most important trend in paediatric dermatology over the past decade has been a growing awareness that early exposure to sunlight is responsible for many long-term sequelae. Now both laboratory and clinical studies have shown that much of the actinic damage that becomes manifest after the age of 40 years actually has its genesis in the first two decades of life.
In North America both physicians and the public have become increasingly aware that increased exposure to ultraviolet light because of latitude, outdoor work, a generally sunny climate, leisure time activities, and fair skin are all associated with a significant number of long-term side effects. We commonly think of skin cancer, as being a disease of older adults, but Hansen and his colleagues  recently reported a case of a documented basal cell carcinoma in a 12 year-old child. The patient lived in Arizona, a section of the United. States that is notable for its intense, year-round sunlight. This patient had no other risk factors such as xeroderma pigmentosa or the basal cell naevus syndrome.
Many countries around the world are noting an increase in melanoma. Several of these studies have focused on the occurrence of melanoma and a prior history of acute over-exposure to the sun before the age of 20. A significant number of sunburns (3-5) before 20 years of age is associated with a two to four times increased risk of melanoma than the same number of sunburns obtained after 30 years of age. 
In an interesting study from Australia, public health officials noted that those who immigrated to Australia before 20 years of age very rapidly approached the number of actinic keratoses exhibited by native Australians by the time they reached 5070 of age. Those who immigrated to Australia after 20 years of age never caught up with their native, fair-skinned Australians. 
These and other studies suggest that sun exposure before the age 20 is a critical factor in the development of skin cancers, actinic keratoses, and naevi. Less well documented has been the association of sun exposure and skin wrinkling, yet publicizing this development has produced greater focus on the public health problem than prior concern about skin cancers.
A recent article in Paediatrics highlighted the relationship between sunburn, melanoma, and the paediatrician.  The article advised early counseling for avoidance, protective clothing and sun screens. This obviously varies with appropriate focus on skin types and concludes with a note that photoprotection should begin in childhood. Another recent publication documents the effectiveness of instructions which are begun very early in childhood.
| II. The Accutane Alert.|| |
Isotretinoin (Accutane) has been available in North America for the past seven years.
It is clearly the most effective agent ever introduced for the treatment of severe nodulocystic acne. Related compounds have also shown substantial efficacy in psoriasis and other keratinizing disorders. Although the drug has side effects in 100 % of acne patients, its efficacy is so profound that most patients and physicians are willing to accept these minor hazards.
Accutane poses particular perils for women who may conceive. It is well-recognized that Accutane is a potent teratogen, although its relative short half-life compared to other retinoids does not prevent a woman from bearing normal children several months after the drug has ben discontinued. Dermatologists, the Food and Drug Administration, and patient advocacy groups have been alarmed at the number of unintended pregnancies occurring in women on Accutane. A substantial percent of these patients have spontaneous abortions, or live births that result in deformed offspring. Most of these defects are incompatible with long life and normal development.
The Boston University of Public-Health conducted a survey of Accutane use in women nothing that in the United States greater than 80,000 per year use this drug. Based on a partially unpublished survey of 5,000 women, they found five pregnancies, a 0.1% rate of conception while on the drug. In the litigious society present in the United States, Accutane awards have exceeded $ 1 million. Consequently, physicians who wish to use this drug should adhere to very strict guidelines which have been proposed by the manufacturer. Tere should be a written, informed consent, and the effective use of contraception. The patient should have a negative serum pregnancy test and start treatment on day two to three on the next menstrual period. Visits should be on a monthly basis with a pregnancy test done before renewing the prescription. Contraception and pregnancy tests should continue one month after therapy. The reader should note that this is not a review of the general Accutane side effects but only those that pertain to women.
In spite of these well-publicized precautions, many physicians continue to be too casual with their use of this drug. This continued high rate of pregnancy will result in further pressure from governmental, medical, and consumer advocacy groups to have this valuable agent removed from our pharmacy.
| III Cyclosporine.|| |
Childhood dermatomyositis is one of the worst problems facing the paediatric dermatologist. Although some effective therapies exist, in general the disease has a rather relentless progression toward muscle atrophy and severe cutaneous poikiloderma. Standard therapies include corticosteroids, methotrexate, Imuran, Cytoxan, and plasmapheresis. A recent study describes the use of cyclosporine in juvenile dermatomyositis.  Fourteen children, who were not fully responsive to parenteral steroids and immunosuppressants were treated with cyclosporine 2.5 - 7.5 mg/kg per day. Muscle strength improved greater than 90%, and the use of systemic corticosteroids could be reduced to an average of 3 mg per day. Six of the fourteen patients no longer required the use of systemic corticosteroids and all fourteen patients improved substantially. Of note, is the fact that no patients had severe side effects.
B. Atopic Dermatitis
Cyclosporine has been shown to be effective when given by mouth as studied by several groups of authors. Unfortunately, underlying infections may flare while on this drug. One author has reported that cyclosporine is effective topically although several other studies have been unable to reproduce these results.
| IV. The Changing Etiology Of Impetigo|| |
Prior to the last decade, conventional teaching suggested that impetigo could be conveniently divided into two types based on clinical and bacteriological classification. Non-bullous impetigo was composed of yellow adherent crusts, and was caused by group A beta haemolytic streptococci. Bullous impetigo was seen as thin bullae, or superficial erosions, and was always caused by phage group 2 Staph aureus. But now multiple studies from around the world have clearly shown both the etiology, and consequently the therapy of this disease, have changed substantially. Barton and Friedman studied 44 patients with a variety of impetigo, and found that S. aureus was the dominant organism in all types of lesions.  Strep was only isolated from two patients in pure culture, and from only 19 patients in mixed culture, primarily from the lower extremities. Maureen Rogers studied 243 cases of mixed impetigo from Sydney, Australia.  86% of the cultured specimens yielded S. 6ureus, and in 69% of the cases S. aureus was the only pathogen isolated. Rogers also noted that only 50% staph were sensitive to erythromycin, a finding which has been found in varying degrees from many other countries. These and other studies suggest that all varieties of impetigo are caused primarily by S. aureus and therapy should be directed towards them. Erythromycin is still a useful drug where S. aureus remain sensitive. Penicillinase-resistant antibiotics should be considered the drugs of choice.
The recent introduction of topical 2% mupirocin has substantially changed the way impetigo is treated in many countries. This antibiotic was originally isolated from Pseudomonas fluorescens. It works by inhibiting bacterial RNA synthesis and has virtually no toxicity when applied topically. It is not related to other topical or systemic antibiotics, and is not known to be a cutaneous sensitizer. Multiple studies have shown that mupirocin is effective in the topical treatment of impetigo. It has been shown to be substantially more effective than its vehicle, more effective than currently-used topical antibiotics, particularly those which contain neomycin, and as effective as oral erythromycin in the treatment of Impetigo.
A study in 1990 evaluated 54 children with impetigo.  The patients received either oral erythromycin and a topical placebo, or an oral placebo and 2% mupirocin. Both groups of patients noted cure rates slightly greater than 90%.
Even in the presence of methicillin resistant S. aureus, mupirocin remains effective.
| V. Drug-Drug Interactions|| |
A. Erythromycin - Theophylline
Erythromycin - theophylline interactions have been known for about ten years although they have not been well-publicized in the community of paediatric dermatologists. In a study the authors studied patients who had been maintained on theophylline, and they were given erythromycin.  Their theophylline clearance decreased by 22% , and serum theophylline levels increased by 28%. These and other studies have indicated that it is not appropriate to use erythromycin in patients who are taking theophylline. Theophylline toxicity can easily be produced in such a situation.
B. Erythromycin-Carbamazepine Interaction
An article described the association of heart-block when erythromycin and carbamazepine were given concurrently.  Carbamazepine is a commonly-used anticonvulsant in North America, and it has substantial interaction with erythromycin.
When erythromycin is given systemically, carbamazepine levels increase precipitously, and the patients may develop C.N.S. toxicity as well as the far more serious consequence of complete heart block with shock. I have personally seen such a case.
C. Erythromycin - Cyclosporine Interaction
In 1988, an article described the adverse interaction between erythromycin and cyclosporine.  Two renal transplant patients taking cyclosporine were treated with erythromycin for systemic infection. Both patients' blood cyclosporine levels rose substantially along with concurrent increases in blood pressure and signs of renal deterioration. Both of these side effects were reversible when the erythromycin was discontinued. The mechanism for this interaction has been reasonably well worked out, and involves the cytochrome P-450 system in the liver. Erythromycin forms a relatively insoluble complex with this enzyme which is , no longer able to clear cyclosporine from the blood.
| VI. Rhus Hypersensitivity|| |
The problem of allergic contact dermatitis in children due to Rhus (Poison ivy) sensitivity is particularly prevalent in the United States. This allergen exists in plants around the world, however. Other than avoidance, there have been no effective ways of preventing this disease. Many topical agents have been tried but all have been found wanting. Now a study by Francis Storrs and her colleagues notes the efficacy of topical cream composed of linoleic acid dimers (Stokoguard). 14 She. proved the efficacy of this compound in an experimental trial involving patients known to be highly sensitive to the rhus antigen. Stokoguard was applied and then the patient was exposed to either light or heavy amounts of rhus antigen. The rhus was then washed off in either 15 minutes, 2 hours, or 24 hours. Protection ranged from 90-100% in the lightly exposed group and from 60-80% in the heavily exposed group depending upon the amount of time the antigen was allowed to remain on the skin. It is thought that the rhus antigen forms complexes with the linoleic acid dimers preventing its absorption through the stratum corneum.
| VII. New Products For The Treatment Of Head Lice And Scabies|| |
Lindane has been receiving a substantial amount of adverse publicity because of its potential for neurotoxic reactions. Although these reactions are exceptionally rare and have almost invariably occurred in the setting of misuse or ingestion, physicians and patient advocates have clearly welcomed the arrival of permethrin. Permethrin is effective when used as a rinse for the treatment of head lice and when used as a cream for the treatment of scabies. Permethrin are synthetic pyrethrins which originally were extracts of a type of chrysanthemum. They work as insecticidal neurotoxins, but have no known significant toxicity in humans. Although absorbed ' - in small quantities (approximately 0.5%), they are rapidly metabolized into inert compounds. The drug has been well studied in blind, controlled experiments, and has been shown to be more effective than its vehicle, and much more effective than lindane when used as a single application. Although the drug is more expensive than lindane, it is convenient for patients as It only has to be used on a one-time basis.
There has also been a considerable interest in the use of nit combs in the United States and several public health agencies have adopted a no-nit policy before allowing children to return to school. Even the most effective nit comb, however, will not completely remove nits from the scalp. Consequently, physicians in North America were interested to see the development of an 8% formic acid cream rinse (Step 2) as a nit remover. Prior to this time, no product had been successfully shown to remove nits from the scalp. Formic acid helps to dissolve chitin, the natural adhesive that insects use to cement nits to the scalp hair. In 1990 study Step 2 was shown to significantly increase the nit-removing potential of a More than 90% of nits were removed after the use of Step 2 and five minutes of nit combing compared to only about 25% of nits removed with nit-combing alone.
| VIII. Measles - Rubeola|| |
In spite of the long-term existence of an effective vaccine, measles continues to be a major health problem throughout North America. Patients are often the inner-city poor and migrant farm workers. Both are groups for whom routine medical care is not readily available. Several epidemics have been reported comprising hundreds of cases and multiple deaths. A 1989 outbreak in Chicago involved 2,400 confirmed cases, and eight deaths. 
sub Consequently, an article on the efficacy of vitamin A in children with severe measles has been widely discussed.  This study was conducted in South Africa where vitamin A deficiency is much more common than it is in the United States, and so it is not certain if the results can be directly transferable to our country. Nevertheless, the South African authors noted that the use of 20,000 I.U. vitamin A daily time two doses in patients with measles substantially reduced the incidence or duration of pneumonia, diarrhea, croup and deaths. The 97 patients treated with placebo had five times as many deaths (10 versus 2).
A somewhat similar study showed reduced mortality from measles in Indian children when given vitamin A and E on a weekly basis.  8,300 I. U. of vitamin A and 20 mg of vitamin E were compared with vitamin E alone. This study included mortalities from all causes, not just measles. Of 7,500 children, the control group suffered 80 deaths versus 37 deaths seen in the 7,700 patients who were given vitamin A and E combination. When evaluated for disease-specific mortality, the combination was shown to have a significantly beneficial effect in measles, seven deaths in Vitamin A and E combined versus 12 in the control group.
| IX. Latex Rubber Allergy|| |
Although immediate and delayed hypersensitivity to latex (natural rubber) has been known for a number of years, it has recently achieved a tremendous amount of publicity in the United States. The initial article announcing the severity of this problem appeared in 1989.  The author described acute rubber anaphylaxis in two children with spina bifida. This was followed by another article '+[ 20] which was a response from the New England Spina Bifida Association, a patient-oriented group. These individuals contacted their membership and of the 187 families with children with spina bifida who were surveyed, between 18-28% had noticed allergy in the form of rash, urticaria, or asthma, depending upon. how the problem was defined. These children were highly susceptible to rubber anaphylaxis because of their continued exposure to rubber medical objects such as gloves, catheters, and braces.
This was shortly followed by a Food and Drug Administration medical alert, noting that sensitivity to latex had been increasing among spina bifida patients. The article also noted a 6-7% incidence of rubber hypersensitivity among operating room personnel.
This was most recently followed by an article in the AMA News (Nov 11, 1991) under the heading `Latex Allergy'. They noted a survey of 26 hospitals throughout the United States in which 76 cases of latex anaphylaxis had been discovered in paediatric patients. They related this increase in part to the more widespread use of latex gloves and condoms to prevent spread of the HIV virus.
Medical personnel who are allergic to latex can find a wide list of latex-free products in any good text on allergic contact dermatitis.
| X. Iodochlorhydroxyquin Alert|| |
The Committee on Drugs in the American Academy of Paediatrics published a cautionary note on the use of iodochlorohydroxyquin in 1990. 1 This advisory group suggested abandoning the use of medications containing iodochlorohydroxyquin for use in the diaper areas. In the United States, these products are widely used as mildly anti-inflammatory and antibacterial agents. Consequently, they are often considered useful in a variety of diaper rashes.
The Committee on Drugs noted that recent animal studies showed 40% absorption of this drug in animals whose hind-quarters were occluded with plastic wrap. They made reference to the subacute myelo-optic neuropathy (SMON) which was noted extensively in Japan when these agents were found in adulterated cooking oil. Recent animal studies have shown that with transepidermal absorption, the mortality is 20%, and a further 20% become paralyzed.
The Committee of Drugs concluded that "Products containing these agents should not be used."
| XI. Transverse Limb Defects|| |
A report  described limb abnormalities after chorion villus sampling at 56 to 66 days of gestation. These authors surveyed 289 pregnancies who had undergone chorion villus sampling and subsequently noted a 1.7% incidence (6/ 289) of transverse limb reduction defects with oral-mandibular hypogenesis. Chorion villus sampling involves the insertion of a thin probe through the cervical mouth until it makes contact with the chorion of the placenta. A small snip biopsy is taken, and is used for genetic or enzyme analysis. The advantage of a chorion villus sampling over amniocentesis is that it can be done much earlier (8-13 weeks gestation versus 15-20 weeks gestation for amniocentesis), produces far more abundant material making cytogenetic and biochemical analysis available in very short periods of time (114 days versus 2-4 weeks for amniocentesis), is done transcervically versus transabdominally for amniocentesis, and appears to have less risk of foetal loss.
These transverse limb defects may produce agenesis of the distal phalanges with partial or complete onychia. The history of chorion villus sampling should be sought in any infant who presents with hypoplasia of the distal phalanges.
| XII. Pulse Oxymeter Burns|| |
Severe burns from a pulse oxymeter were described.  In this situation, the paediatric patient received a significant burn on the ear and finger at the site of the pulse oxymeter. Pulse oxymetry is becoming very common to monitor oxygen saturation of haemoglobin in premature infants or during operative procedures when general anaesthesia is used. The oxymeter works by being attached to a digit or an ear and by the use of red and infrared light, produces hyperemia from which the depth of penetration of red light can judge the amount of oxygenated haemoglobin. Burns can result from malfunction of the infrared source, or the use of incompatible electrical circuits thereby causing it to draw more current than is necessary.
| XIII. Other Iatrogenic Nursery Diseases|| |
A variety of technologies and machines have caused inadvertent or unexpected side effects. We have discussed burns from pulse oxymeters, and transverse limb defects from chorion villus sampling. Other potential causes of neonatal skin disease include amniocentesis scars, monitor marks, calcified nodules on the heels, and a variety of other problems. I sometimes refer to this as my biotechnology series.
Calcified nodules on the heels are usually seen in patients who have been in a neonatal intensive care unit, but can also be seen in those who have had multiple heel punctures without pre-existing severe illness.. The haematomas produced by multiple heel punctures in some patients produce small, calcific nodules over the base and ends of the heels and give the impression of small warts. These lesions resolve transepidermally, and are usually gone by the time the patient is two to three years old.
Amniocentesis marks are usually seen as grouped, depressed, dimple-like scars on the anterior chest. the amniocentesis needle has been improperly guided producing a traumatic lesion in the patient. Although these are usually cutaneous and of no great consequence, nerve injury and blindness has also been reported.
The PO2 and PCO2 monitors currently used in nurseries around the world work by heating the skin. The resultant hyperemia allows maximum flow of oxygen or carbon dioxide across the skin where its presence is detected by a small sensor. When these monitors are left in place too long, or when they heat the skin slightly above the desired temperature, small burns can result. We have seen numerous children with blisters, hyperpigmented lesions, and even scars on the chest, back and trunk where these monitors are usually placed.
| XIV. Sulfasalazine For Psoriasis|| |
Fortunately, psoriasis is not usually a common or severe problem in childhood. There are, however, a small number of children who do not respond to topical steroids, tar, ultraviolet light or.anthralin. In this situation, if the psoriasis is severe, pustular, or life-threatening, there are only five or six reasonable choices for a systemic therapy. PUVA, cyclosporine, methotrexate, retinoids, and systemic corticosteroids all have appropriate uses in the treatment of psoriasis. These drugs all have long term side effects which make their use in children difficult, if not impossible.
Gupta and his colleagues  conducted a double-blind controlled trial of sulfasalazine, and clearly showed a beneficial effect on psoriasis. 23 patients were given sulfasalazine in a maximum dose of one gram t.i.d. to q.i.d. versus a placebo in 23 patients. 82% of the patients who completed the trial had marked to moderate improvement versus only 4% of those given the placebo. It is important to appreciate that allergic rashes and G.I. intolerance are common in patients who are given this drug. Nevertheless, this agent represents a substantial choice for paediatric patients with psoriasis. It has no tendency to produce long term side effects as the previously mentioned drugs do. Although we have not conducted a blinded study such as the one done by Gupta, I have used sulfasalazine in ten paediatric patients (less than 16 years of age). In eight of these patients who had not been helped by hospitalization with Goeckerman therapy, the patients' psoriasis was moderately to markedly improved, enabling them to return to school and continue a reasonably normal life. Two patients had either no response, or had gastro-intestinal side effects. There were no allergic reactions seen in this small group of patients.
| XV. Varicella|| |
Although potentially useful vaccines against varicella are being developed in many countries, at the present time chicken pox remains one of the most common infectious exanthems of childhood. Several recent studies in both children and adults have shown that the disease can be substantially altered by the use of acyclovir. One of these  clearly showed that the treatment of varicella with acyclovir in otherwise healthy children was effective and without serious side effects. This was a prospective randomized double-blind trial of 105 children aged 5 to 16 years who were given 20 mg/kg of acyclovir for five to seven days at the first sign of the disease. Maximum number of lesions was reduced by approximately 33%, number of days of fever was also reduced by approximately 33%, as were complications. At one year post varicella, the antibody titers were similar in the groups treated with placebo and acyclovir. Its significant drawback remains, however, its cost.
A recent study  confirmed these reports in another group of normal children. It was also prospective and double-blind using at a dose of 20 mg / kg per day for five days given in the first 24 hours. These authors also noted a substantial decrease in maximum number of lesions, number of patients with greater than 500 lesions, and number of febrile days. Anti-varicella titers measured at 4 weeks post therapy were similar in treated and control groups.
A similar study evaluated 31 adults given a gram of acyclovir four times a day for five days at various times after the onset of the chicken pox.  Those patients treated within 24-48 hours had a substantial reduction in days of fever, days to crusting, and days lost from school/work, compared to those patients who were given either no treatment or were treated later than 48 hours.
These three studies pose considerable ethical dilemmas for physicians throughout the world. Should acyclovir be used to treat all patients with varicella even though we know the disease is mild and rarely produces morbidity or mortality? Should we target its use for those who are more likely to develop complications such as the ill, or those with pre-existing skin rashes such as atopic dermatitis? Should the drug be used in a prophylactic fashion when exposure is recognized? Should secondary cases within the household be targeted since it is known that these will be more severe than the primary case within a household, probably due to increased exposure?
These ethical questions will continue to be debated for many years, or at least until an effective vaccine becomes available.
| References|| |
|1.||Hansen R, Levine R, Joyman D. Basal Cell Carcinoma in a Twelve Year-Old. Peds 1990; 88: 480-2 |
|2.||Striker L, McMichaels E. Melanoma in Women and Sun Exposure Before 20. Peds 1989; 84: 199-204. |
|3.||Marks R, Bowen D. Childhood Exposure to Sunlight and the Development of Keratoses. Med J Australia 1990; 152 : 62-6. |
|4.||Williams M, Sagebel R. Melanoma and the Pediatrician. Peds 1990; 84: 381-2. |
|5.||Heckmatt A, Fitzpatrick T. Cyclosporine in Juvenile Dermatomyositis. Lancet 1990; 1 1063-6. |
|6.||Ellis CN, Gupta A, Griffiths CEM, et al. Cyclosporine Improves Psoriasis. JAMA 1986; 256: 3110-6. |
|7.||Eisen D, Ellis CN, Griffiths CEM. Cyclosporine Rinse in Oral Lichen Planus. New Eng J Med 1990; 323: 280-4. |
|8.||Barton J, Friedman L. Impetigo: a Reassessment of Etiology and Therapy. Ped Dermatol 1987; 4: 185-8. |
|9.||Rodgers M, VanKamp D. Impetigo in Sydney. Med J Aust 1987; 147: 63-5. |
|10.||Schwartz S, Steele R. Mupirocin Vs. Erythromycin in Impetigo. J Peds 1990; 117 827-9. |
|11.||Risey D, Ho C. The Effect of Erythromycin on Theophylline Pharmacokinetics. Amer Rev Resp Dis 1983:127: 581-4. |
|12.||Faulkner T, Sturgiss P, Pallu B. Erythromycin - Carbamazepine Interactions. Peds 1987; 80 951-3. |
|13.||Ben- Ari S, Levine B. An Unusual Reaction to Erythromycin. Peds 1988; 112: 992-3. |
|14.||Storrs FJ, Widenbach J, Vargo N. The Effect of Linoleic Dimers on Rhus Dermatitis. Arch Dermatol 1988; 122: 783-9. |
|15.||DeFelice J, Parrish L, Varom D. Studies of a Nit Removal System. Int J Dermatol 1989; 28: 468-70. |
|16.||Measles in Chigaco - 1989. MMWR 1990; 39: 317-21. |
|17.||Hussey V, VanVoorten C, Kanaba D, et al.. The Use of Vitamin-A in Children with Severe Measles. New Eng J Med 1990; 323: 160-4. |
|18.||Varnish S, Baumann S, Wolffe S, et al. Reduced Mortality from Vitamin A and E in Indian Children. New Eng J Med 1990; 323 : 929-35. |
|19.||Slater R. Rubber Anaphylaxis. New Eng J Med 1989; 320: 1126-30. |
|20.||Meropol J. Rubber Anaphylaxis. New Eng J Med 1990; 323: 1072. |
|21.||Committee on Drugs, American Academy of Pediatrics. lodochlorohydroxyquin (Vioform): Blindness and Neuropathy. Peds 1990; 88 787-8. |
|22.||Firth T, VanGorn J, Pegs L. Limb Abnormalities After Chorion Villus Sampling. Lancet 1990; 1337: 762-3. |
|23.||Murphy J, Santorini R, Howes L. Severe Burns from a Pulse Oxymeter. Aneth 1990; 73 : 350-2. |
|24.||Gupta A, Hamilton T, Ellis CN, et al. Sulfasalizine Improves Psoriasis. Arch Dermatol 1990; 127: 487-93. |
|25.||Balfour J, McCracken G, Steele R, et al. The Use of Acyclovir in Otherwise Normal Children with Varicella. J Pediat 1990: 116: 633-9. |
|26.||Dunkle H, Burton T, Levy M, et al. Acyclovir for Chicken Pox in Normal Children. New Eng J Med 1991; 325: 1539-44. |
|27.||Feder G, Ganglia L, Orion H. Adult Chicken Pox and Acyclovir. Arch Int Med 1990; 150 2061-5. |