Pediatr Clin North Am 1999;46:945-963

Int J Dermatol 1995 Jun;34(6):434-7
Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.

Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK
Department of Dermatology, State University of New York, College of Medicine, Brooklyn, USA.

Click here to access the PubMed abstract of this article.

J Dermatol 1996 Apr;23(4):243-6
Topical spironolactone reduces sebum secretion rates in young adults.

Yamamoto A, Ito M
Department of Dermatology, Niigata University School of Medicine, Japan.

Click here to access the PubMed abstract of this article.

Children pose many challenges when it comes to medication: they may resist having to take a medication, dislike the taste or texture, have difficulty swallowing solid dosage forms, and are fearful of injections.

The limited pediatric market for most drugs may be the leading reason for the lack of investment in drug development for this population by the pharmaceutical industry. Most medications are not labeled for pediatric populations, and when a medication is not approved for use in infants and children, it usually is not available in a suitable pediatric dosage form. Fortunately, our compounding pharmacy is able to help. We can compound oral medications into pleasantly flavored suspensions, solutions, concentrates, freezerpops, “gummy bears” or lozenges, in colors that entice the child to take the medication. A palatable formulation is more likely to improve compliance and minimize spillage or waste during administration. Lollipops are an ideal alternative to “swish and swallow” medications that need to be retained in the mouth for a prolonged period of time. Most drugs can be compounded into transdermal gels that can easily be applied to an appropriate site, such as the child’s wrist, for absorption through the skin.

Professional compounding is not just diluting existing medications, or mixing powders with bases. We must consider physical and chemical properties of each active and inactive ingredient in order to prepare an effective and safe customized medication with the desired taste, color, fragrance, viscosity, uniformity, texture, and stability. The efficacy of any compounded medication is influenced by the technique and equipment used in preparing the formulation, the purity and quality of the ingredients, choice of vehicle (base), and proper use of additives such as penetration enhancers.

• Alpha Lipoic Acid cream
• “BLT” gel (benzocaine, lidocaine, and tetracaine)
• Cholestyramine ointment
• 2-Deoxy D-Glucose (2-DDG) in various dosage forms such as creams, lip balms, and oral rinses
• Dapsone cream
• Ivermectin – oral or topical
• KOH solution – 5% and 10%
• Kojic Acid, Hydroquinone, Retinoic Acid gel
• Pseudocatalase cream
• Tamoxifen topical
• Trichloroacetic Acid/Lactic Acid/Azelaic Acid topical solution
• Urea 40% ointmen

Because of cantharidin’s potential for toxicity, the FDA has proposed that cantharidin should be limited to “topical use in the professional office setting only.” Severe blistering can result from improper use, and ingestion, especially by children, can be fatal. Treatment of mucous membranes is contraindicated and placement of cantharidin near the eyes and eyelids should be avoided to prevent scleral erosion.

Caution: The treatment of plantar warts with cantharidin is NOT recommended and may have a higher rate of significant complications including lymphangitis and refractory lymphedema.

Arch Dermatol. 2001;137:1357-1360
Click here to access the PubMed abstract

J Am Acad Dermatol. 2000;43:503-507
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Squaric Acid Dibutylester (SADBE) for Cutaneous Warts in Children

Warts are a common pediatric skin infection and clearance may be enhanced by contact sensitizers, such as squaric acid dibutylester (SADBE). Contact immunotherapy with SADBE is relatively safe and an effective alternative in the management of multiple and resistant cutaneous warts in children.

J Am Acad Dermatol. 2000 May;42(5 Pt 1):803-8
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Pediatr Dermatol. 2000 Jul-Aug;17(4):315-8
Click here to access the PubMed abstract

J Am Acad Dermatol. 1999 Oct;41(4):595-9
Click here to access the PubMed abstract

Vitiligo is a spontaneous irregular depigmentation of skin. Patients with vitiligo have low catalase levels in their epidermis with high levels of hydrogen peroxide. Pseudocatalase cream is an externally applied UVB-activated product that can lead to recovery of the oxidative damage in the epidermis and remarkable repigmentation.

Skin Pharmacol Appl Skin Physiol 1999 May-Jun;12(3):132-8
Click here to access the PubMed abstract

J Pathol 2000 Aug;191(4):407-16
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J Investig Dermatol Symp Proc 1999 Sep;4(1):91-6
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Dermatology 1995;190(3):223-9
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Topical Phenylalanine

Melanocytes may still be present in long-standing (>25 years) depigmented skin of patients with vitiligo. L-phenylalanine uptake and turnover in the pigment forming melanocytes is vital for initiation of melanogenesis. Phenylalanine hydroxylase activities increase linearly with inherited skin color yielding eightfold more activities in black skin compared to white skin.

Camacho and Mazuecos performed an uncontrolled retrospective survey of a group of 193 patients (171 participants after screening) with evolving vitiligo who were treated with oral (50 or 100 mg/kg daily) and topical (10% gel) phenylalanine plus sun exposure . When the study closed, 100% repigmentation was achieved in 122 patients on the face, 35 on the trunk, and 33 on the limbs. Patients who were treated during the months of high solar radiation (and therefore also used the topical phenylalanine) achieved greater repigmentation. No side effects were reported.

Arch Dermatol. 1999;135:216-217
Click here to access the PubMed abstract

J Drugs Dermatol 2002 Sep;1(2):127-31
Click here to access the PubMed abstract

Mol Genet Metab 2005 Dec;86(4):27-33
Click here to access the PubMed abstract

Click here to access the PubMed abstract of this article.

Dermatology 2001;203:141-147

Click here to access the PubMed abstract of this article.
Arch Dermatol. 2005;141:43-46
Topical tacrolimus ointment combined with 6% salicylic acid gel for plaque psoriasis treatment.

Carroll CL, Clarke J, Camacho F, Balkrishnan R, Feldman SR.
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

Salicylic acid has been used alone as a treatment for psoriasis, but is most commonly used to increase the penetration of other topical preparations, primarily corticosteroids. In this small study, the use of 6% salicylic acid gel in conjunction with tacrolimus ointment showed statistically significant improvement for the treatment of plaque psoriasis compared with the use of salicylic acid alone.

“For patients with localized psoriasis, and for many of those with moderate psoriasis as well, the mainstay of treatment is still topical therapy. The quality of life is greatly affected in such patients, and they often express high levels of dissatisfaction with current treatment options. Safe, convenient, and effective topical regimens, such as combination therapy with topical tacrolimus and salicylic acid, can be of great benefit in this large population.”

Click here to view the abstract or FREE FULL TEXT of this complete article.

J Cutan Med Surg 2001; 299-302
Management of psoriasis vulgaris with methotrexate 0.25% in a hydrophilic gel: a placebo-controlled, double-blind study.

“Methotrexate has been used as an effective systemic chemotherapeutic drug for psoriasis by dermatologists for over 30 years. Nevertheless, pharmacokinetic data indicate that oral methotrexate can cause a decrease in red and white blood cell and platelet counts and can also cause severe liver damage, diarrhea, and stomach irritation, as dose-related drug-induced side effects. Such indications have limited its prescription by physicians. However, [Syed and Nordstrom of the Department of Dermatology, University of California-San Francisco, and researchers from three other locations note that] if its incorporation in a gel as a topical agent, in a proper dosage. imparts better results without the cited side effects, then such a formulation appears to justify a clinical evaluation. Furthermore, published data have indicated that 70% of patients prefer topical therapy for treating psoriasis.”

This article concludes: “methotrexate 0.25% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a patient-applied topical medication to treat psoriasis vulgaris.”

Click here to view the PubMed abstract for this article.

J Dermatol 2004 Oct;31(10):798-801
Topical 0.25% methotrexate gel in a hydrogel base for palmoplantar psoriasis.

This article concludes: “Methotrexate 0.25% in a hydrophilic gel is well tolerated but is not very effective in controlling the lesions of psoriasis on the palms and soles; however, a higher concentration in a different base with better penetration could possibly provide better results.”

Click here to access the PubMed abstract of this article.

Int J Dermatol. 2003 Feb;42(2):157-9
Topical methotrexate delivered by iontophoresis in the treatment of recalcitrant psoriais–a case report.

Tiwari, Kumar, et al. published a case report of topical methotrexate delivered by iontophoresis for the treatment of recalcitrant palmoplantar psoriasis. In a 46 y.o. male with well-defined bilateral palmar plaques of 6 years duration which were resistant to several therapies, the right palm was treated, as it had more severe lesions. Iontophoresis was performed using cotton gauze soaked in 4 to 6 ml of methotrexate disodium solution 10 mg/ml, once a week for four weeks. The researchers reported 75% improvement after four weeks of therapy. Iontophoresis allows high concentrations of drug to be delivered to a limited area, and may offer a method of reducing total drug accumulation and reduced side effects.

Click here to view the citation for this article.

The effects of topical application of phytonadione, retinol and vitamins C and E on infraorbital dark circles and wrinkles of the lower eyelids.

Mitsuishi T, Shimoda T, Mitsui Y, Kuriyama Y, Kawana S.
Department of Dermatology, Nippon Medical School, Tokyo, Japan.

Click here to access the PubMed abstract of this article.
 

Protection and Reversal of Photodamage with Topical Antioxidants
 
Topical vitamins C and E, as well as topical selenium, protect skin against sunburn, suntan and skin cancer and also reverse the mottled pigmentation and wrinkles of photoaging. However, only certain forms of these antioxidants are stable and active after percutaneous absorption. Benefits of topical application are that the skin attains far higher levels of each antioxidant than can be achieved by taking these vitamins orally and topical application arms the skin with a reservoir of antioxidants that cannot be washed or rubbed off, protecting the skin for several days after application.
 
J Cosmet Dermatol. 2004 Jul;3(3):149-55 

Photodamage of the skin: protection and reversal with topical antioxidants.

Burke KE.
River Court, New York, USA.

Click here to access the PubMed abstract of this article.

Topical application of niacinamide (such as in a 2% cream) has a stabilizing effect on epidermal barrier function, seen as a reduction in transepidermal water loss and an improvement in the moisture content of the horny layer, and it may be used as a treatment adjunct in atopic dermatitis. In aging skin, topical application of niacinamide improves the surface structure and pigmentary disorders, smoothes out wrinkles and inhibits photocarcinogenesis.

Cutis 2006 Jan;77(1 Suppl):11-6.

Click here to access the PubMed abstract of this article.

Int J Dermatol 2005 Mar;44(3):197-202.

Click here to access the PubMed abstract of this article.

J Cosmet Dermatol 2004 Apr;3(2):88-93  

Click here to access the PubMed abstract of this article.

 
Niacinamide can be combined with other active ingredients such as DMAE, sodium hyaluronate, benzoyl peroxide, or metronidazole in a customized medication that can be used as anti-wrinkle or anti-aging therapy or to treat acne or rosacea

Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.

Br J Dermatol. 2003 Oct; 149(4): 841-9

Beitner H.
Department of Dermatology, Karolinska Hospital, 17176 Stockholm, Sweden.

Click here to access the PubMed abstract of this article.

Estrogen Therapy to Prevent or Reverse Skin Aging

Declining estrogen levels are associated with a variety of cutaneous changes, many of which can be reversed or improved by topical or systemic estrogen supplementation. Studies of postmenopausal women indicate that estrogen deprivation is associated with declining dermal collagen content, diminished elasticity and skin strength, loss of moisture in the skin, epidermal thinning, atrophy, fine wrinkling, and impaired wound healing. Keratinocytes, Langerhans’ cells, melanocytes, sebaceous glands, collagen content and the synthesis of hyaluronic acid are under hormonal influence. Estrogen may attenuate inflammation in psoriatic lesions. Alone or together with progesterone, estrogen prevents or reverses skin atrophy, dryness and wrinkles associated with chronological or photo-aging. Estrogen and progesterone stimulate proliferation of keratinocytes while estrogen suppresses apoptosis and thus prevents epidermal atrophy. Estrogen maintains skin moisture by increasing acid mucopolysaccharide or hyaluronic acid levels in the dermis, and accelerates cutaneous wound healing.

Low estrogen levels that accompany menopause exacerbate the deleterious effects of both intrinsic and environmental aging. Estrogens clearly have a key role in skin aging homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years.

At Yale University School of Medicine, the effects of long-term hormone replacement therapy (HRT) on skin rigidity and wrinkling at 11 facial locations was assessed using the Lemperle scale by a plastic surgeon who was blinded to HRT use. Skin rigidity at the cheek and forehead was measured with a durometer. Demographics including age, race, sun exposure, sunscreen use, tobacco use, and skin type were similar. Rigidity was significantly decreased in HRT users compared to nonusers at both the cheek and forehead. Average wrinkle scores were lower in hormone users than in nonhormone users. The study concluded that long-term postmenopausal HRT users have more elastic skin and less severe wrinkling than women who never used HRT, suggesting that hormone therapy may have cosmetic benefits.

   In another study, the dermal collagen of 15 postmenopausal women who had received systemic estrogen replacement was analyzed before and after using a topical 0.01% estrogen treatment. Epithelial and dermal thickness improved after topical estrogen therapy. Facial skin collagen significantly increased after 16 weeks of treatment. Systemic estrogen levels did not significantly increase after topical therapy. 

Exp Dermatol. 2004;13 Suppl 4:36-40

Exp Dermatol. 2006 Feb;15(2):83-94

Eur J Obstet Gynecol Reprod Biol. 2006 Jun 22

J Am Acad Dermatol. 2005 Oct;53(4):555-68; quiz 569-72

Fertil Steril. 2005 Aug;84(2):285-8

Am J Clin Dermatol. 2003;4(6):371-8

Am J Clin Dermatol. 2001;2(3):143-50

J Dermatol Sci. 2005 Apr;38(1):1-7

In the following study, the effects of topical 0.01% estradiol and 0.3% estriol compounds were measured in preclimacteric women with skin aging symptoms. After treatment for 6 months, elasticity and firmness of the skin had markedly improved; wrinkle depth and pore sizes had decreased by 61 to 100%; skin moisture had increased; and wrinkle depth decreased significantly.

Int J Dermatol 1996 Sep;35(9):669-74
Treatment of skin aging with topical estrogens.

Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A.
Department of Dermatology, University of Vienna Medical School, Austria.

Click here to access the PubMed abstract of this article.

A low-dose, topical gel form of diclofenac sodium has been developed in Europe for pain relief and reduction of redness after sunburn.

Eur J Dermatol. 2004 Jul-Aug;14(4):238-46

The efficacy and safety of low-dose diclofenac sodium 0.1% gel for the symptomatic relief of pain and erythema associated with superficial natural sunburn.

Click here to access the PubMed abstract of this article.

Topical Application of Phytonadione, Retinol and Vitamins C and E to Reduce Infraorbital Dark Circles and Wrinkles of the Lower Eyelids
 
 Infraorbital dark circles and wrinkles of the lower eyelids are cosmetic problems that worsen with age. Fifty-seven healthy adult volunteers with dark under-eye circles and wrinkles were enrolled in an open label study to determine whether a gel containing 2% phytonadione, 0.1% retinol and 0.1% vitamins C and E is effective in reducing dark under-eye circles and wrinkles of the lower eyelids. The gel formulation was applied twice daily to the lower eyelid site for 8 weeks. Hemostasis, pigmentation and wrinkles were evaluated by a physician and by the patients after 4 and 8 weeks of treatment. Topical application of the gel decreased not only hemostasis but also wrinkles after 8 weeks of treatment. Of 57 patients, 27 (47%) had reductions in hemostasis. However, pigmentation was not clearly removed by this gel.
 
J Cosmet Dermatol. 2004 Apr;3(2):73-5

The effects of topical application of phytonadione, retinol and vitamins C and E on infraorbital dark circles and wrinkles of the lower eyelids.

Mitsuishi T, Shimoda T, Mitsui Y, Kuriyama Y, Kawana S.
Department of Dermatology, Nippon Medical School, Tokyo, Japan.

Click here to access the PubMed abstract of this article.
 

Protection and Reversal of Photodamage with Topical Antioxidants
 
Topical vitamins C and E, as well as topical selenium, protect skin against sunburn, suntan and skin cancer and also reverse the mottled pigmentation and wrinkles of photoaging. However, only certain forms of these antioxidants are stable and active after percutaneous absorption. Benefits of topical application are that the skin attains far higher levels of each antioxidant than can be achieved by taking these vitamins orally and topical application arms the skin with a reservoir of antioxidants that cannot be washed or rubbed off, protecting the skin for several days after application.
 
J Cosmet Dermatol. 2004 Jul;3(3):149-55 

Photodamage of the skin: protection and reversal with topical antioxidants.

Burke KE.
River Court, New York, USA.

Click here to access the PubMed abstract of this article.

Topical application of niacinamide (such as in a 2% cream) has a stabilizing effect on epidermal barrier function, seen as a reduction in transepidermal water loss and an improvement in the moisture content of the horny layer, and it may be used as a treatment adjunct in atopic dermatitis. In aging skin, topical application of niacinamide improves the surface structure and pigmentary disorders, smoothes out wrinkles and inhibits photocarcinogenesis.

Cutis 2006 Jan;77(1 Suppl):11-6.

Click here to access the PubMed abstract of this article.

Int J Dermatol 2005 Mar;44(3):197-202.

Click here to access the PubMed abstract of this article.

J Cosmet Dermatol 2004 Apr;3(2):88-93  

Click here to access the PubMed abstract of this article.

 
Niacinamide can be combined with other active ingredients such as DMAE, sodium hyaluronate, benzoyl peroxide, or metronidazole in a customized medication that can be used as anti-wrinkle or anti-aging therapy or to treat acne or rosacea

Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.

Br J Dermatol. 2003 Oct; 149(4): 841-9

Beitner H.
Department of Dermatology, Karolinska Hospital, 17176 Stockholm, Sweden.

Click here to access the PubMed abstract of this article.

Estrogen Therapy to Prevent or Reverse Skin Aging

Declining estrogen levels are associated with a variety of cutaneous changes, many of which can be reversed or improved by topical or systemic estrogen supplementation. Studies of postmenopausal women indicate that estrogen deprivation is associated with declining dermal collagen content, diminished elasticity and skin strength, loss of moisture in the skin, epidermal thinning, atrophy, fine wrinkling, and impaired wound healing. Keratinocytes, Langerhans’ cells, melanocytes, sebaceous glands, collagen content and the synthesis of hyaluronic acid are under hormonal influence. Estrogen may attenuate inflammation in psoriatic lesions. Alone or together with progesterone, estrogen prevents or reverses skin atrophy, dryness and wrinkles associated with chronological or photo-aging. Estrogen and progesterone stimulate proliferation of keratinocytes while estrogen suppresses apoptosis and thus prevents epidermal atrophy. Estrogen maintains skin moisture by increasing acid mucopolysaccharide or hyaluronic acid levels in the dermis, and accelerates cutaneous wound healing.

Low estrogen levels that accompany menopause exacerbate the deleterious effects of both intrinsic and environmental aging. Estrogens clearly have a key role in skin aging homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years.

At Yale University School of Medicine, the effects of long-term hormone replacement therapy (HRT) on skin rigidity and wrinkling at 11 facial locations was assessed using the Lemperle scale by a plastic surgeon who was blinded to HRT use. Skin rigidity at the cheek and forehead was measured with a durometer. Demographics including age, race, sun exposure, sunscreen use, tobacco use, and skin type were similar. Rigidity was significantly decreased in HRT users compared to nonusers at both the cheek and forehead. Average wrinkle scores were lower in hormone users than in nonhormone users. The study concluded that long-term postmenopausal HRT users have more elastic skin and less severe wrinkling than women who never used HRT, suggesting that hormone therapy may have cosmetic benefits.

   In another study, the dermal collagen of 15 postmenopausal women who had received systemic estrogen replacement was analyzed before and after using a topical 0.01% estrogen treatment. Epithelial and dermal thickness improved after topical estrogen therapy. Facial skin collagen significantly increased after 16 weeks of treatment. Systemic estrogen levels did not significantly increase after topical therapy. 

Exp Dermatol. 2004;13 Suppl 4:36-40

Exp Dermatol. 2006 Feb;15(2):83-94

Eur J Obstet Gynecol Reprod Biol. 2006 Jun 22

J Am Acad Dermatol. 2005 Oct;53(4):555-68; quiz 569-72

Fertil Steril. 2005 Aug;84(2):285-8

Am J Clin Dermatol. 2003;4(6):371-8

Am J Clin Dermatol. 2001;2(3):143-50

J Dermatol Sci. 2005 Apr;38(1):1-7

In the following study, the effects of topical 0.01% estradiol and 0.3% estriol compounds were measured in preclimacteric women with skin aging symptoms. After treatment for 6 months, elasticity and firmness of the skin had markedly improved; wrinkle depth and pore sizes had decreased by 61 to 100%; skin moisture had increased; and wrinkle depth decreased significantly.

Int J Dermatol 1996 Sep;35(9):669-74
Treatment of skin aging with topical estrogens.

Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A.
Department of Dermatology, University of Vienna Medical School, Austria.

Click here to access the PubMed abstract of this article.

A low-dose, topical gel form of diclofenac sodium has been developed in Europe for pain relief and reduction of redness after sunburn.

Eur J Dermatol. 2004 Jul-Aug;14(4):238-46

The efficacy and safety of low-dose diclofenac sodium 0.1% gel for the symptomatic relief of pain and erythema associated with superficial natural sunburn.

Click here to access the PubMed abstract of this article.

Hu D, Hughes MA, Cherry GW
Department of Dermatology, Churchill Hospital, Headington, Oxford, UK.

Click here to access the PubMed abstract of this article.

Wozniacka A, Sysa-Jedrzejowska A, Adamus J, Gebicki J.
Department of Dermatology, Medical University, and the Institute of Applied Radiation Chemistry, Technical University, Lodz, Poland.

Click here to access the PubMed abstract of this article.