A growing number of families use herbal preparations to manage dermatologic problems. Are you familiar with what the literature shows about their effectiveness and safety?
A growing number of families use herbs to manage dermatologic problems, including acne, minor wounds, fungal infections, herpes, and poison ivy. Are you familiar with what the literature shows about the effectiveness and safety of herbal preparations?
The use of complementary and alternative medicine (CAM) is rising rapidly in the pediatric population. Approximately 20% to 30% of general pediatric patients have used CAM.1 Anywhere from 30% to 70% of pediatric patients with chronic conditions, such as cancer, asthma, rheumatoid arthritis, and cystic fibrosis, have tried CAM treatments.2 Parents of hospitalized children report a keen interest in providing CAM to their children, but often have not discussed their interest in or use of CAM with their child's physician.3,4 If pediatricians want to know what patients and families are using or considering trying, they need to ask.
Herbs and other dietary supplements, such as fish oil and vitamin E, are the most popular CAM therapies. These products are readily available without a prescription in pharmacies and grocery stores and over the Web. They are often perceived as naturaland therefore safeand are used as part of a cultural tradition or home remedy. Physicians can't possibly ask patients about all of the more than 20,000 herbal products available. But they can and should be familiar with those herbs and dietary supplements most likely to be used by patients suffering from specific illnesses.
In the pediatric population, herbs are frequently used for dermatologic conditionseverything from acne vulgaris, the most prevalent skin problem among adolescents, to poison ivy, the leading cause of contact dermatitis in the United States. In this article, we review the herbs used most often for common dermatologic problems and provide resources to help answer additional clinical questions.
Nearly 90% of teenagers develop acne, with a peak prevalence at 18 years of age. The four primary causes of acne are stimulation of sebum production by steroid hormone (androgen, for example), plugging of hair follicles by sebum and desquamated cells, infection of the plugs with bacteria (Propionibacterium acnes), and inflammatory reaction to the plugging and infection. Conventional medical treatments are aimed at one or more of these four factors, and include oral contraceptives, retinoic acid, benzoyl peroxide, and topical antibacterial agents. [Editor's note: For more on the pathophysiology and management of acne, see "Acne vulgaris: A treatment update" in the December 2000 issue, also accessible at www.contpeds.com .]
Although mainstream acne treatments are effective and can often be purchased inexpensively without physician consultation or prescription, some patients prefer what they consider a more "natural" approach. Most of these patients are interested in lifestyle factors that they hope will mitigate acne symptoms (cleansers, diet, exercise). Some, recognizing the relationship between stress and more severe outbreaks, want to pursue stress management techniques. And a few are interested in herbal remedies such as tea tree oil.
Tea tree oil comes from the leaves of the Australian tree Melaleuca alternifolia. It can be found as a pure oil and as an ingredient in skin creams and gels, toothpaste, dental floss, mouthwash, deodorant, shampoos, and even toothpicks. It is a topical antibiotic and antifungal remedy for infections of the skin and mucous membranesthe mouth, for example. (Table 1 lists the actions of herbs discussed in this article.) Besides its popularity as a treatment for acne, tea tree oil is used for cradle cap, dandruff, cold and canker sores, gingivitis, insect bites, head lice, scabies, and warts. It is also used as a douche for nonspecific vaginitis.
Tea tree oil is a complex mixture of more than 100 components. The main ones are terpenes (pinene, terpinene, and cymene), cineol, and sesquiterpenes. The terpenes kill Staphylococcus bacteria that most often cause skin infections, acne-causing Propionibacteria, and even Candida, as well as other organisms. In a single-blind, randomized, controlled study of 124 Australian teenagers with mild to moderate acne, 5% tea tree oil gel was as effective as 5% benzoyl peroxide in reducing open and closed comedones. Although the tea tree oil took longer to work, those who used it experienced fewer side effects, such as dryness, irritation, stinging, burning, itching, and redness, than the benzoyl peroxide group.5
When taken internally, tea tree oil can cause systemic symptoms. In two cases, for example, toddlers became confused, uncoordinated, and sleepy 30 minutes after ingesting less than 10 cc of tea tree oil.6 When used topically, tea tree oil may produce local reactions. Severe allergic reactions of the skin have developed in cases in which the oil was used to treat ringworm and acne.7 (Table 2 lists the side effects of various herbs.)
No child goes through life unscathed by minor traumas such as burns, bruises, abrasions, and lacerations. Traditional assessment and care for minor wounds include pain control, hemostasis, removal of foreign bodies, debridement of nonviable tissue, irrigation and cleansing, surgical closure, bandaging, topical or systemic antibiotic coverage, and tetanus immunization. Parents often elect to treat milder injuries at home with their own over-the-counter remedies, such as herbal gels, salves, compresses, and creams. Examples include aloe vera, calendula, and chamomile.
Aloe vera gel is an active ingredient in hundreds of skin lotions, sun blocks, and cosmetics. It first gained popularity in the United States in the 1930s with reports of its success in treating X-ray burns. Recently, aloe extracts have been used to treat sun burns, rashes, and other skin conditions.
Aloe gel is 99% water with a pH of 4.5. It contains an emollient polysaccharide, glucomannan. The major carbohydrate fraction in the gel, acemannan, is a water-soluble, long chain, mannose polymer that accelerates wound healing, modulates immune function (particularly macrophage activation and cytokine production), and demonstrates antiviral effects in vitro and in animals. The gel also contains magnesium lactate, which helps prevent itching, bradykininase and salicylic acid, and other antiprostaglandin compounds that relieve inflammation.
Both animal and in vitro studies have demonstrated aloe's effectiveness as a wound healer (vulnerary), due to its antimicrobial effects, its effects on collagen linking, and its anti-inflammatory and emollient properties. Aloe gel is either bacteriostatic or bactericidal against a variety of common wound-infecting bacteria: Staphylococcus aureus, Streptococcus pyogenes, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhosa, and Mycobacterium tuberculosis.8 In animal studies, aloe sped wound healing from burns, frostbite, electrical injuries, caustic chemicals, and surgery, and improved scar strength compared with topical antibiotic medications.9
In clinical trials in humans, aloe has significantly accelerated healing from burns, abrasions, frostbite, flash burns of the conjunctiva, and even canker sores.10-12 In a study of 27 adults with partial thickness burns, for example, those treated with aloe healed an average of six days faster than those treated with petroleum jelly gauze.13 Only one study has shown an opposite effect; that is, aloe-treated surgical wounds healing by secondary intention took longer to heal than comparison wounds.14 Despite the conflicting research, some dentists and otolaryngologists use aloe gel to promote healing in injured tissues in the mouth, nose, sinuses, and ear, and many parents keep it on hand in the kitchen as a home remedy.
Side effects to topical use of aloe are uncommon and usually mild. Contact dermatitis has been reported rarely. Occasionally, the gel stings a bit when first applied and, in rare cases, can aggravate irritated or surgically abraded skin. Topical use may enhance absorption of hydrocortisone. Acute toxicity associated with ingestion of the aloe's leaf lining, which contains potent cathartic compounds, is largely gastrointestinalsevere cramping, diarrhea, and nausea.
Calendula. Cultivated by the Egyptians, Greeks, Hindus, and Arabs, calendula has been used medicinally in Europe since the 12th century. The flowers were made into balms and salves and applied directly to the skin to help heal wounds and to soothe inflamed and damaged skin. Nowadays, teas made from calendula are used as eye washes, gargles, and compresses to treat conjunctivitis, pharyngitis, aphthous stomatitis, gingivostomatitis, diaper rashes, and other inflammatory conditions of the skin and mucous membranes.
There are numerous case reports of calendula-based ointments being used to speed wound healing. Anecdotal accounts report decreased pain and inflammation in postmastectomy patients and in children with chronic suppurative otitis media. Studies in rats also support calendula's use in treating minor wounds and lacerations. Among adults suffering from leprosy, an ointment containing 10% calendula extract helped heal chronic skin sores and prevented additional infections.15 It is not clear, however, whether enhanced healing was due to calendula or to other ingredients in the salve.
Allergic reactions to calendula are rare. No reports of acute toxic exposures have been made to poison control centers. No studies have specifically evaluated calendula's safety during pregnancy, lactation, or childhood. Based on its widespread use in OTC cosmetics and skin creams, however, it is presumed safe for topical use.
Chamomile. The name "chamomile" comes from the Greek words meaning "ground apple" and refers to the herb's apple-like smell. Chamomile is used both internally and externally to treat a variety of conditions, including minor wounds, mastitis, hemorrhoids, diaper rash, chicken pox, poison ivy, and conjunctivitis. In Europe, oncologists use a chamomile mouthwash called Kamillosan M to treat mouth sores caused by chemotherapy. The German Commission E (Germany's equivalent to the United States Food and Drug Administration) has approved chamomile for external use for inflammation of the skin, mucous membranes, and urogenital area, for bacterial skin diseases including those of the oral cavity and gums, and for respiratory tract inflammation.
No less than 120 chemical constituents have been identified in chamomile, including terpenoids, chamazulene, flavonoids (apigenin and luteolin), coumarins (umbelliferone), and a-bisabolol. Chamomile's anti-inflammatory effects are well documented in animal studies but have not been evaluated extensively in humans. In a randomized trial of 24 healthy adult volunteers, chamomile was less effective than 1% hydrocortisone in treating experimentally induced dermal inflammation. No studies have evaluated chamomile's anti-inflammatory effects in children.
The in vitro antimicrobial effects of chamomile have been well documented. The essential oil has antimicrobial effects in vitro against Staphylococcus and Candida. Chamazulene, a-bisabolol, flavonoids, and umbelliferone have antifungal properties against Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans. No studies in humans have evaluated chamomile's clinical effectiveness as a topical antimicrobial agent.
Chamomile has demonstrated wound healing properties in animals, but results of clinical studies in humans are mixed. In a double-blind, placebo-controlled trial of 14 adults with weeping wounds following dermabrasions of their tattoos, those treated topically with chamomile had a statistically significant decrease in the weeping wound area and increased drying of the wound compared with the placebo group.16 In contrast, a double-blind, randomized, placebo-controlled study of 48 women receiving radiation therapy for breast cancer found that those treated topically with chamomile cream did not have significantly less radiation-induced skin irritation than those treated with placebo.17 No clinical trials have evaluated chamomile's wound healing properties in children.
Allergic reactions to chamomile are rare, and the herb has been shown to have low toxicity in animal studies. No drug-herb interactions have been reported. No formal clinical studies have assessed the safety of chamomile in pregnant and lactating women or in children.
Ten percent of children in Western countries are plagued by eczema. The recurring, dry, and itchy rash of eczema usually appears at 2 to 3 months of age and often persists for years. Factors contributing to symptoms include familial predisposition, climate changes, allergens, sensitivity to certain foods, irritating substances, sweat, microbes, and stress.
When eczema flares up, mainstream therapies include anti-inflammatory agents, antihistamines, and antimicrobials. Parents often become frustrated with conventional medical treatments, which require multiple daily administrations and do not provide a cure. Some parents are convinced that skin symptoms are only the tip of the atopic iceberg and that eczema will manifest as asthma unless systemic treatments are used. Many parents therefore turn to complementary therapies such as evening primrose oil, chamomile, and complex mixtures of Chinese herbs.
Evening primrose was first used medicinally by Native American healers as a treatment for coughs, bruises, and upset stomachs. Nowadays, evening primrose oil (EPO) is used orally to treat a variety of ailments, ranging from eczema to diabetic peripheral neuropathy to cyclic mastalgia. American naturopathic physicians regularly recommend EPO supplements for eczema and other inflammatory diseases, such as asthma, allergies, arthritis, and lupus, and for the troublesome symptoms of menopause. Other uses of EPO include treatment of premenstrual syndrome, inflammatory bowel disease, chronic fatigue syndrome, Raynaud's phenomenon, and multiple sclerosis.
EPO is one of best natural sources of linoleic acid (an essential fatty acid) and its derivative, gamma linolenic acid (an omega-6 fatty acid). It serves as a precursor to gamma linolenic acid (GLA) and from there is metabolized to dihomo-gamma linolenic acid (DGLA), to arachidonic acid (AA), and, finally, to a series of prostanoids that modulate immune and inflammatory reactions. Some eczema patients have a biochemical defect preventing the conversion of linolenic acid to GLA, leading to low levels of DGLA and the prostaglandin precursors required for normal immune function; treatment with EPO can normalize DGLA levels.18
In numerous double-blind, placebo-controlled, randomized trials in dogs and cats, EPO effectively treated eczema and allergic skin rashes. The clinical outcomes in humans, however, have been mixed. At 1east three randomized, controlled clinical trials in adults with eczema have failed to document benefits of EPO or GLA- rich borage oil; in one of these studies, a mix-up apparently occurred in the administration of EPO and placebo. In a placebo-controlled trial of 60 children with steroid-dependent eczema who were treated with EPO, both groups had similar improvements over 16 weeks of follow-up.19
In contrast, several controlled trials have reported modest but significant benefits of EPO and other GLA-rich oils as treatments for eczema. An open trial of EPO supplementation (3 g daily) in infants with chronic atopic dermatitis showed gradual improvement over one month of therapy in terms of excoriations and lichenification, as well as decreased need for antihistamines.20 In a double-blind, controlled trial of EPO in children with eczema, high doses of EPO (typically 7.5 g EPO daily for eight weeks for children weighing 35 pounds) significantly improved symptoms.21 A meta-analysis of studies evaluating EPO's effects on eczema concluded that, overall, both doctors and patients rated improvements seen in the EPO groups significantly better than those seen in the placebo groups, particularly for itching.22 With adults, effective treatment requires at least four to six grams of EPO per day for at least four to six weeks.
In randomized trials, the incidence of side effects was no greater in the active treatment groups than among patients who received placebo vegetable oils. Nausea, diarrhea, and headache have been the only reported long-term side effects, and they are seldom severe enough to discontinue treatment. EPO is nonteratogenic in animal studies; GLA is normally present in breast milk.
Chamomile. In a clinical trial in Germany, 161 patients with eczema on their hands, forearms, and lower legs who had been initially treated with 0. 1 % difluocortolone valerate (a glucocorticoid) were treated with either Kamillosan cream (a chamomile cream), 0.25% hydrocortisone, 0.75% fluocortin butyl ester (a glucocorticoid), or 5% bufexamac (a nonsteroidal anti-inflammatory). During the three- to four-week maintenance therapy, the Kamillosan cream was as effective as hydrocortisone; it was superior to fluocortin butyl ester and bufexamac.23
Chinese herbs. Several randomized trials were undertaken following case reports that drinking tea made of a complex mixture of Chinese herbs was very effective in adults who have severe eczema. Two of these trials reported significant benefits for both adult and pediatric eczema sufferers who drank the Chinese herbal mixture,24 but a recent placebo-controlled trial in adults did not report any significant improvements.25
Concerns about contamination of 30% or more of Chinese herbal products with compounds such as steroids, heavy metals, and misidentified herbs, and numerous reports of serious cardiovascular, hepatic, and renal toxicity, have led us to counsel patients against using Chinese herbal remedies to treat eczema.26-28 Also, parents report that it is difficult to get children to drink the teas because of poor palatability.
Yeast and dermatophyte infections are among the most common reasons for trips to the pediatrician. Yeast infections in the diaper area are usually preceded by maceration and friction and possibly by contact with urine and the presence of fecal enzymes. Traditional treatment recommendations for diaper dermatitis include dressing the infant in soft, clean clothes, changing diapers frequently, washing with water only, and exposing the affected skin to the air. Barrier ointments (petroleum, lanolin), drying agents (zinc oxide), and antifungal creams (imidazoles) are the conventional choices for tougher bouts.
Four major types of dermatophyte infections occur in children: tinea capitis, tinea corporis, tinea pedis, and onychomycosis. Tinea capitis is treated medically with a systemic antifungal agent like griseofulvin. Adjunctive treatment can include sporicidal topical medications like selenium sulfide and antibiotics for superinfection. (No herbal remedies are effective in treating tinea capitis, for which only systemic antifungal therapy is known to work.) Imidazole cream is first-line treatment for tinea corporis; systemic antifungal medications are typically used for widespread or deep-seated infections. Treatment for tinea pedis is similar to that for tinea corporis. Onychomycosis requires long courses of systemic antifungal therapy and surgery.
Many parents turn to alternative remedies for both yeast and dermatophyte infections because they are so common and stubborn to cure and they often recur. Typical home remedies include aloe, calendula, chamomile (see previous discussions for these three herbs), and tea tree oil.
Tea tree oil. Although tea tree oil is effective in ameliorating clinical symptoms of fungal infections such as tinea corporis, athlete's foot, and jock itch, it is less effective than standard antifungal medications in clearing the infection itself. For example, in a randomized, double-blind trial, 104 patients with tinea pedis were treated with either 10% tea tree oil cream, 1% tolnaftate cream, or placebo cream. The tea tree oil and tolnaftate groups showed significant improvement in clinical condition compared with the placebo group, but significantly more patients treated with tolnaftate (85%) than treated with tea tree oil (30%) or placebo (21%) converted to negative cultures at the end of therapy.29
In a double-blind, multicenter, randomized, controlled trial at two primary care centers and one podiatrist's office that included 117 patients with distal subungual onychomycosis proven by culture, the efficacy of 1% clotrimazole solution was compared with that of straight tea tree oil applied daily. After six months of therapy, culture cure and clinical resolution were comparable for the two groups. Three months later, about half of each group reported continued improvement or resolution.30 No studies have evaluated the effectiveness of tea tree oil in treating onychomycosis in children.
Tea tree oil can be quite toxic if taken internally and can also be irritating to broken or irritated skin. We do not recommend straight tea tree oil as a treatment for neonatal diaper rashes.
Herpes simplex virus types 1 and 2 causes recurrent gingivostomatitis and genital lesions. HSV infection is probably the most frequent culprit for stomatitis in children age 1 to 3 years, and painful HSV cold sores cause anguish for many children and adolescents. All sexually active teens are at risk for genital herpes.
HSV infects epithelial cells, then travels up local sensory or autonomic nerve axons and settles in sensory ganglia; when reactivated, it returns down the nerve and causes the skin to flare up again. Triggers for reactivation include stress, trauma, ultraviolet light exposure, and immunodeficiency. Standard treatments include antiviral medications (acyclovir, valacyclovir, famciclovir) to decrease frequency and severity of outbreaks, but no therapy is curative. Many patients, particularly in Europe, seek relief from herbal remedies such as lemon balm, aloe, and chamomile.
Lemon balm is native to southern Europe and is commonly planted in gardens to attract bees. Systemically, it has been used to treat insomnia, anxiety, depression, neuralgia, migraine, nausea, anorexia, colic, chronic fatigue, shingles, coughs, irregular menstrual periods, toothache, heart conditions, nervous palpitations, and high blood pressure. Lemon balm is used topically to treat wounds, skin irritations, and insect bites. In Europe, lemon balm cream is applied at the first sign of a herpes flare-up or regularly for prevention.
Lemon balm contains numerous potentially active compounds, including caffeic acid and tannins, both of which have antiviral properties. In a multicenter open study of 115 adults with cold sore symptoms for less than 72 hours, topical application of 1% dried lemon balm extract up to five times daily resulted in complete healing in 60% of patients by the fourth day, 87% by the sixth day, and 96% by the eighth day.31 In a double-blind, placebo-controlled trial of 116 patients treated for five days, both physicians and patients judged Lomahephan cream (1% dried lemon balm extract) as significantly superior to placebo.31 In a double-blind, placebo-controlled, randomized trial of 66 patients with a history of recurrent herpes labialis, those treated with Lomahephan within four hours of prodromal symptoms had significantly better symptom scores than those treated with placebo cream.32
The Food and Drug Administration includes lemon balm on its Generally Recognized As Safe (GRAS) list. Contact dermatitis has been reported. People with thyroid problems such as Graves' disease should use lemon balm with caution because it may inhibit certain thyroid hormones. In animal studies, lemon balm increased the hypnotic effects of barbiturates. No human studies have evaluated potential drug interactions with lemon balm, and no clinical studies have assessed its safety in pregnancy, lactation, or childhood.
Aloe. In a randomized, controlled, double-blind clinical trial of 60 men suffering from an initial episode of herpes simplex infection, those treated with an aloe vera extract (0.5%) in a hydrophilic cream had a significantly faster healing time and a higher number of healed lesions than the placebo comparison group.33
Some 50% to 70% of the US population is sensitized to poison ivy. If the sap from this plant gets on a sensitized child and is not cleaned off within 10 minutes, oily substances called urushiols trigger a T-cell mediated response manifested by the well-known itchy rash. Conventional treatment is aimed at soothing this self-limited condition (cool compresses, calamine lotion, baths with oatmeal, oral antihistamines) and fighting the inflammation (topical or systemic corticosteriods).
Aloe, calendula, oatmeal, and other emollients are frequently used home remedies for relieving the symptoms of poison ivy and other itchy rashes. We were unable to locate any English language reports of clinical trials specifically evaluating the effectiveness of any of these home remedies in treating poison ivy. Because of their long historical use and safety, however, we support families who choose to use these home remedies.
Dermatologic problems are among the most frequent conditions seen in pediatric practice. The use of herbs and other dietary supplements to treat these conditions will no doubt grow as the use of CAM in general increases. Pediatricians need to be aware of the actions of the substances being used and what clinical studies have shown about their safety and effectiveness. Most herbs are safe when used topically. More research is needed, however, to evaluate their effectiveness, particularly in comparison, and in conjunction, with medications. Table 3 lists evidence-based resources you can consult for additional information.
1. Simpson N, Pearce A, Finlay F, et al: The use of complementary medicine in paediatric outpatient clinics. Ambulatory Child Health 1998;3:351
2. Grootenhuis MA, deGraaf-Nijkerk JH, Wel Mvd: Use of alternative treatment in pediatric oncology. Cancer Nursing 1998;21:282
3. Armishaw J, Grant CC: Use of complementary treatment by those hospitalised with acute illness. Arch Dis Child 1999;81:133
4. Sibinga E, Ottolini M, Duggan A, et al: Communication about complementary/alternative medicine use in children. Pediatric Research 2000;47:226A
5. Bassett IB, Pannowitz DL, Bametson RS: A comparative study of tea-tree oil versus benzoyl peroxide in the treatment of acne. Med J Aust 1990;153:455
6. Del Beccaro MA: Melaleuca oil poisoning in a 17-month-old. Vet Hum Toxicol 1995;37:557
7. Selvaag E, Eriksen B, Thune P: Contact allergy due to tea tree oil and cross-sensitization to colophony. Contact Dermatitis 1994;31:124
8. Robson MC, Heggers JP, Hagstrom WJ, Jr: Myth, magic, witchcraft, or fact? Aloe vera revisited. Journal of Burn Care & Rehabilitation 1982;3:157
9. Heggers JP, Elzaim H, Garfield R, et al: Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model. Journal of Alternative & Complementary Medicine 1997;3:149
10. Fulton JE, Jr: The stimulation of postdermabrasion wound healing with stabilized aloe vera gel polyethylene oxide dressing. Journal of Dermatologic Surgery & Oncology 1990;16:460
11. Heggers JP, Pelley RP, Robson MC: Beneficial effects of aloe in wound healing. Phytotherapy Research 1993;7:S48
12. Garnick JJ, Singh B, Winkley G: Effectiveness of a medicament containing silicon dioxide, aloe, and allantoin on aphthous stomatitis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, & Endodontics 1998;86:550
13. Visuthikosol V, Chowchuen B, Sukwanarat Y, et al: Effect of aloe vera gel to healing of bum wound: A clinical and histologic study. Journal of the Medical Association of Thailand 1995;78:403
14. Schmidt JM, Greenspoon JS: Aloe vera dermal wound gel is associated with a delay in wound healing. Obstetrics & Gynecology 1991;78:115
15. Kartikeyan S, Chaturvedi RM, Narkar SV: Effect of calendula on trophic ulcers. Lepr Rev 1990;61:399
16. Glowania HJ, Raulin C, Swoboda M: The effect of chamomile on wound healing: A controlled clinical-experimental double-blind trial. Zeitschriftfur Hautkrankheiten 1262;62:1262
17. Maiche AG, Grohn P, Maki-Hokkonen H: Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncologica 1991;30:395
18. Horrobin DF: Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr 2000; 71:367S
19. Hederos CA, Berg A: Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child 1996;75:494
20. Fiocchi A, Sala M, Signoroni P, et al: The efficacy and safety of gamma-linolenic acid in the treatment of infantile atopic dermatitis. J Intl Med Res. 1994; 22:244
21. Biagi PL, Bordoni A, Masi M, et al: A long-term study on the use of evening primrose oil (Efamol) in atopic children. Drugs Exp Clin Res 1988;14:285
22. Morse PF, Horrobin DF, Manku MS, et al: Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol 1989;121:75
23. Aertgeerts P, Albring M, Klaschka F, et al: Comparison of Kamillosan(TM) cream (2 g ethanolic extract from chamomile flowers in 100 g cream) versus steroidal (0.25% hydrocortisone, 0.75% fluocortin butyl ester) and nonsteroidal (5% bufexamac) dermatics in the maintenance therapy of eczema. Zeitschrift fur Hautkrankheiten 1985;60:270
24. Armstrong NC, Ernst E: The treatment of eczema with Chinese herbs: A systematic review of randomized clinical trials. Br J Clin Pharmacol 1999;48:262
25. Fung A, Look P, Chong L, et al: A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis. Int J Dermatol 1999;38:387
26. Kane JA, Kane SP, Jain S: Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut 1995;36:146
27. Ferguson JE, Chalmers RJ, Rowlands DJ: Reversible dilated cardiomyopathy following treatment of atopic eczema with Chinese herbal medicine. Br J Dermatol 1997;136:592
28. Lord GM, Tagore R, Cook T, et al: Nephropathy caused by Chinese herbs in the UK [letter] [see comments]. Lancet 1999;354:481
29. Tong MM, Altman PM, Barnetson RS: Tea tree oil in the treatment of tinea pedis. Australas J Dermatol 1992;33:145
30. Buck DS, Nidorf DM, Addino JG: Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. J Fam Pract 1994;3 8:601
31. Wolbling RH, Leonhardt K: Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25
32. Koytchev RH, Alken RG, Dundarov S: Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis. Phytomedicine 1999;6:225
33. Syed TA, Afzal M, Ashfaq Ahmad S, et al: Management of genital herpes in men with 0.5% Aloe vera extract in a hydrophilic cream: A placebo-controlled double-blind study. Journal of Dermatological Treatment 1997;8:99
Kathi Kemper, Paula Gardiner, Danny Coles. The skinny on herbal remedies for dermatologic disorders. Contemporary Pediatrics 2001;7:103.