Podiatry

Fungal infections of the feet are commonly associated with dry, cracked skin surrounding the plantar surface and heel fissures. Hyperkeratosis can have various etiologies, and chronic conditions are often quite difficult to treat. Moccasin tinea pedis is typically resistant to topical antifungal therapy when used as sole therapy, because the scale on the plantar surface of the foot impedes or limits the absorption of the antifungal agent. However, one study showed a 100% cure rate was achieved in 12 patients with confirmed moccasin tinea pedis who were treated with topical 40% urea cream and antifungal cream concomitantly for 2 to 3 weeks.

Cutis. 2004 May;73(5):355-7.. The use of 40% urea cream in the treatment of moccasin tinea pedis..

The following article concludes: “Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.”

BMJ. 1998 Jan 31;316(7128):333-8.. Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs..

The following article reports “The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure.”

Pharm Res. 1996 Jan;13(1):168-72.. Percutaneous absorption of ketoprofen from different anatomical sites in man..

Various synergistic combinations are used for antifungal therapy. Research points to the practicality “of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug’s antifungal and anti-inflammatory properties.”

J Med Microbiol. 2000 Sep;49(9):831-40.. Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species..

Neuropathic pain includes a variety of conditions such as diabetic neuropathy, phantom limb pain, reflex sympathetic dystrophy (RSD or Complex Regional Pain Syndrome), and pain caused by blunt trauma or crushing injuries. Symptoms of neuropathic pain may not be evident for weeks to months after the injury. Optimal treatment may involve not only the use of traditional analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, but may also include medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA antagonists. Combination therapy is frequently the only effective approach for managing the complex array of chemical mediators and other contributors to the individual pain experience.

Advanced Studies in Medicine 2003 July;3(7A):S639. .

As topical formulations are developed, they provide hope for more effective drug combinations, with fewer systemic adverse drug effects and drug-drug interactions. For example, research has shown that topically applied ketoprofen provides a high local concentration of drug below the site of application but decreases systemic exposure and significantly reduces the risk of gastrointestinal upset or bleeding. When properly compounded into an appropriate base, tissue concentrations of ketoprofen were found to be 100-fold greater below the application site (knee) compared to systemic concentrations.

Pharmaceutical Research (1996) 13: 1; 168-172. .

Sever disease is the most common cause of heel pain in pre-pubertal children. A case report described the use of topical ketoprofen 10% gel as an adjunct to physical therapy to relieve pain and inflammation.

Phys Ther. 2006 Mar;86(3):424-33. .

The following testimonial appeared in the December 1999 issue of Neuropathy News, a patient newsletter:

“My local [compounding pharmacist] has created a cream to help alleviate the pain of foot neuropathy. It reduces the burning and sharp, needle-like pain. All you need is a very thin coat. The directions call for using it four times a day, but I find it particularly helpful at night. [The formulation contains] 2% amitriptyline and 2% baclofen in a transdermal gel.”

“Compounding pharmacists have the unique training and ability to create medications that address the individual needs of patients. One of the most helpful products they use are transdermal gels that allow for the passage of medication directly through the tissue into the area of pain. Many of the medications typically prescribed for neuropathy patients such as amitriptyline, lidocaine, mexilitene, ketamine and [gabapentin] can cause significant side effects when taken orally. Transdermal gel minimizes systemic side effects and maximizes local pain relief. Compounding pharmacists have many resources that offer relief from neuropathic pain.”

In Diabetes Interviews, January 2000, Neil A. Burrell, DPM, CDE, of Beaumont, Texas, writes “We have a very high success rate using amitriptyline and baclofen mixed in a gel component. This compound is applied to the feet three times per day, and offers immediate relief… [For] recalcitrant neuropathic pain, many times we use a combination of tramadol, gabapentin and amitriptyline.”

At our compounding pharmacy, we work together with physicians and patients to prepare formulations containing the medications and doses that are most appropriate to meet each patient’s specific needs. Let us know how we can be of service.

Diabetes Care. 2004 Jan;27(1):284-5.. Improvement of temperature and flow in feet of subjects with diabetes with use of a transdermal preparation of L-arginine: a pilot study..

Topical doxepin could be an alternative and relatively safe treatment in alleviating neuropathic pain in the diabetic patient, especially when the use of systemic treatment is contraindicated. In the following case study, the soles of the patients feet were treated with topical doxepin 5% twice daily for four weeks. The patient responded dramatically with loss of the severe burning sensation and no side effects reported.

Wounds 15(8):272-276, 2003.. Burning Feet Due to Diabetic Neuropathy.

Resistant warts and molluscum contagiosum have been treated successfully with compounded topical medications, avoiding discomfort associated with freezing, scraping, electrocautery and laser therapy.

The following study found that 5% KOH aqueous solution proved to be as effective and less irritating when compared to the 10% KOH solution. This trial also emphasizes the effectiveness of topical KOH in the treatment of molluscum contagiosum, sparing affected children from more aggressive physical modalities of treatment.

Pediatr Dermatol. 2000 Nov-Dec;17(6):495.. Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum..

Although surgical excision is the most popular method for removing nails, the use of concentrated urea plasters applied under occlusion may be superior. The use of urea plasters has inherent advantages – they are inexpensive, several nails can be treated in one session, and the procedure is essentially painless. Various synergistic combinations and topical medications with penetrant enhancers can be compounded for antifungal therapy. Topical medications usually have a lower adverse drug-reaction profile than systemic medications.

Cutis. 1980 Jun;25(6):609-12.. Urea ointment in the nonsurgical avulsion of nail dystrophies--a reappraisal..

Cutis. 1980 Apr;25(4):397, 405.. Combination urea and salicyclic acid ointment nail avulsion in nondystrophic nails: a follow-up observation..

JAMA. 1979 Apr 13;241(15):1559, 1563.. Urea plasters alternative to surgery for nail removal..

Clin Exp Dermatol. 1982 May;7(3):273-6.. The treatment of fungus and yeast infections of nails by the method of 'chemical removal'..

Management of onychomycosis, a fungal infection of the fingernails and toenails, usually consists of systemic antifungal medications, topical therapy (e.g., urea ointment, desiccating solutions, keratolytics, vital dyes), or surgical intervention (e.g., nail plate avulsion, laser therapy). Topical prescription antifungal preparations, containing the active ingredient of your choice, may be less likely to cause the serious systemic side effects that can occur with oral antifungal therapy and can provide a more economical alternative, as lower doses are needed when the medication is applied topically at the site. Penetrant enhancers can be included in the preparation to improve the effectiveness of topical antifungals.

Trop Med Int Health. 1999 Apr;4(4):284-7.. Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream..

Phys Ther. 2002 Dec;82(12):1184-91.. Treatment of plantar verrucae using 2% sodium salicylate iontophoresis..

Wounds and pressure sores may heal more quickly if treated with topical phenytoin. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area.

Topical Phenytoin for Wound Healing

The stimulatory effect of orally administered phenytoin on gingival tissue prompted its assessment in wound healing. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Phenytoin has been used topically in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns.

Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations.

Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: “topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing.”

The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days). Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings.

The efficacy of topical phenytoin in the treatment of diabetic foot ulcers was evaluated in a controlled inpatient study. Fifty patients were treated with topical phenytoin, and 50 patients received dry sterile occlusive dressings. Both groups improved, but the ulcers treated with topical phenytoin healed more rapidly. Mean time to complete healing was 21 days with phenytoin and 45 days with control.

No study reported any significant adverse effects secondary to topical phenytoin therapy.

Ann Pharmacother. 2001 Jun;35(6):675-81.. Topical phenytoin treatment of stage II decubitus ulcers in the elderly..

Biochem Pharmacol. 1999 May 15;57(10):1085-94.. Role of phenytoin in wound healing--a wound pharmacology perspective..

Ann Pharmacother. 1996 Jul-Aug;30(7-8):768-75.. Phenytoin in wound healing..

Int J Dermatol. 1993 Mar;32(3):214-7.. Topical phenytoin in wound healing..

Zhonghua Yi Xue Za Zhi. 1997 Jan;77(1):54-7.. The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium..

Diabetes Care. 1991 Oct;14(10):909-11.. Topical phenytoin in diabetic foot ulcers..

Iontophoresis facilitates delivery of medications into the tissues beneath the skin by electronic transport of ionized drugs in solution. Acetic acid iontophoresis is effective in the treatment of heel pain. Iontophoresis of dexamethasone for plantar fasciitis should be considered when more immediate results are needed. Iontophoresis has also been used to successfully treat plantar hyperhidrosis.

Phonophoresis is a technique that combines topical drug therapy with ultrasound to achieve therapeutic drug concentrations in muscle and other tissues beneath the skin. Ultrasound gels can be formulated to contain medications such as anti-inflammatories and/or anesthetics.

J Am Podiatr Med Assoc. 1999 May;89(5):251-7.. Management of heel pain syndrome with acetic acid iontophoresis..

Am J Sports Med. 1997 May-Jun;25(3):312-6.. Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study..

Cantharidin in a collodion vehicle has been used by dermatologists as a treatment for molluscum contagiosum and warts since the 1950s. Cantharidin lost FDA approval in 1962 because its manufacturers failed to submit data attesting to cantharidin’s efficacy. However, in 1999, the FDA included cantharidin on its “Bulk Substances List” of drugs which although not available as commercial products, were approved for compounding on a customized basis for individual patients.

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 Oct;137(10):1357-60.. Cantharidin revisited: a blistering defense of an ancient medicine..

J Am Acad Dermatol. 2000 Sep;43(3):503-7.. Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients..

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.. Squaric acid immunotherapy for warts in children..

Pediatr Dermatol. 2000 Jul-Aug;17(4):315-8.. Use of squaric acid dibutylester (SADBE) for cutaneous warts in children..

J Am Acad Dermatol. 1999 Oct;41(4):595-9.. Contact immunotherapy with squaric acid dibutylester for the treatment of recalcitrant warts..