CONTINUING EDUCATION

Published through an educational grant from WYETH-AYERST LABORATORIES
TRENDS IN PHARMACY AND PHARMACEUTICAL CARE

An ongoing CE program of The University of Mississippi School of Pharmacy and DRUG TOPICS

The University of Mississippi School of Pharmacy is approved by the American Council on Pharmaceutical Education as a provider of continuing pharmaceutical education. Accredited in every state requiring CE. ® ACPE # 032-999-01-011-H01

This lesson is no longer valid for CE credit after 12/31/03.

CREDIT:

This lesson provides two hours of CE credit and requires a passing grade of 70%.

OBJECTIVES:

Upon completion of this article, the pharmacist should be able to:

• List typical topical podiatric diseases the pharmacist might encounter in practice
• List the incidence, etiology, clinical features, and complications associated with these topical diseases
• Counsel patients on the proper use of prescribed and over-the-counter medications used to treat these diseases
• Provide information to patients and care- givers on non-drug measures to treat these diseases
• Educate patients and caregivers about the natural history and prognosis of these diseases

GOAL:

• To provide information about common podiatric diseases and promote the interaction between the pharmacist and the podiatrist to effect positive outcomes in foot care

Podiatry and pharmacy:
Working together

By Robert W. Martin III, M.D. Chairman, Department of Dermatology, Arnett Clinic, and Clinical Assistant Professor, Department of Dermatology, Indiana University School of Medicine and Kent S. Martin, D.P.M. Martin Foot Specialists, Sheffield, Ala. and Nicholas G. Popovich, Ph.D., R.Ph. Professor and Associate Head, Department of Pharmacy Practice Purdue University School of Pharmacy and Pharmacal Sciences

These are exciting times for pharmacists as the profession grows into interdisciplinary health care. Beyond the important role of dispensing medications and counseling patients, pharmacists are becoming increasingly involved in disease state management. In a recent position paper, the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) stated, "Given the changing role of pharmacists and pharmacy automation, physicians need to be proactive and find new ways of working with pharmacists to enhance patient safety and care." This is a tremendous affirmation and commitment toward interdisciplinary care, and pharmacists must "seize the moment" to provide this in conjunction with all healthcare professionals.

Brief anatomy review

The foot at birth has 35 joints, 19 muscles, and over 100 ligaments that ultimately develop into 26 bones. The maturity of the foot is achieved in males between 15 and 21 years of age and in women between 14 and 16 years. Women notice changes in their feet during their fourth decade of life; men see changes during their fifth decade, when the feet begin to broaden and flatten after years of bearing the weight of the body. Constant daily pressure on the feet causes ligaments to stretch and bones to shift position. Thus, the potential for the development of adverse foot conditions increases with each year of life.

Standing, the foot is designed to help reduce pressure by redistributing weight to three points. Half of the body's weight is placed on the heel, one-quarter on the big toe joint, and the remainder on the four metatarsal heads located across the ball of the foot.

Many joints within the foot provide mobility and flexibility. Ligaments hold these joints in place and provide necessary stability. Some ligaments also function to maintain the arch of the foot. The muscles of the sole of the foot also help maintain the arch and allow standing on uneven ground. The movements of the foot follow from the contraction of muscles that originate in the leg and whose tendons insert onto the foot. Thus, each step results from complex and coordinated effort by leg and foot muscles.

It has been estimated that over a lifetime a person will walk about 115,000 miles, almost half the distance to the moon. Although the feet will grow and change in size and shape until early adulthood, as a person gets older, the feet will lose their natural resilience and may increase a size or two. Thus, a good exercise program and foot hygiene help prevent injury and pain to the feet from daily stress and trauma. However, when good preventive health measures are not observed, foot problems are more likely to result.

Foot conditions are in general nonthreatening, except to patients with diabetes and peripheral vascular disease. The pharmacist has a key role in counseling patients with foot conditions that are amenable to self-care. At the same time, it is important that the pharmacist and podiatrist work together for the benefit of patients. The following information on typical foot conditions is intended to broaden the perspective of the pharmacist and to explain the foot conditions that might be encountered in practice.

Noninfectious inflammatory disorders

• Pompholyx. Pompholyx (Fig. 1), an episodic blistering eczema affecting the palms and soles of adolescents and young adults, occurs most commonly in the spring and summer. Occlusive footwear, hyperhidrosis (excessive sweating), and atopic dermatitis may be associated with its development. Clinically, itching precedes onset of symmetrical, small, easily ruptured, plantar vesicles, which last several weeks and frequently recur. Treatment includes wet soaks, compresses, topical steroids, and bland applications such as a zinc cream or lotion. Topical antibiotics (e.g., mupirocin, Bactroban) that cover Streptococcus sp. and Staphylococcus sp. should be used if secondary infection coexists.

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• Palmoplantar pustulosis. PPP (Fig. 2) presents as crops of symmetrical, asymptomatic to slightly burning/pruritic 2- to 4-mm pustules with surrounding erythema on the medial/lateral foot, instep, and/or sides or back of the heel. Aging pustules turn yellow, then dark brown, and are shed in one to two weeks. PPP is more common in women between the ages of 20 and 60 and in patients with a family history of psoriasis. The disorder has been associated with psoriasis, lithium therapy, tonsillitis, smoking, thyroid disease, diabetes, various arthropathies, and seasonal factors such as high humidity and high temperature.

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PPP is difficult to treat. Potent topical glucocorticoids under occlusion, topical or systemic PUVA (i.e., psoralen [P] and UV radiation of 320 to 400 nm wavelength [UVA]), dithranol, methotrexate, acitretin, cyclosporine, and colchicine have variable success. Systemic glucocorticoids are not recommended because of rebound flare. Although spontaneous remission may occur, PPP is more often characterized by slow spread or extension. The disease tends to pursue a chronic course, with remissions lasting from a few months to years.

• Juvenile plantar dermatosis. This is a symmetrical painful red, dry, fissured "glazed" dermatitis on the ball and toe pads (sparing the instep and interdigitale areas) of children three to 14 years old. The exact cause is unknown, but barefoot sporting activities and friction from occlusive footwear (i.e., trainer shoe, rubber boot) with nonabsorbent synthetic socks that create hot, humid conditions with maceration from sweat retention may be contributive. Exacerbations in both winter and summer have been reported, and an allergic contact dermatitis may be associated with it. Skin scrapings to exclude fungus and patch tests to exclude footwear allergy are sometimes necessary. Most cases usually clear spontaneously, but the condition may persist until adolescence. The child should wear 100% cotton socks and leather shoes or sandals. Various topical products such as urea preparations, zinc oxide paste with salicylic acid (Lassar's Paste), white soft paraffin, or tar may be applied. In severe cases, bed rest may be needed. It is estimated that allergic contact dermatitis contributes to this condition in up to 10% of cases.

• Allergic contact dermatitis. Allergic contact dermatitis (Fig. 3) to shoe materials occurs in up to 3% of patients with foot dermatitis. The condition is more common in humid environments and/or poor working conditions. Shoe contact dermatitis is most commonly due to a rubber component allergy, usually mercaptobenzothiazole (MBT), a thiazole rubber accelerator; and, less frequently, thiurams (four closely related chemicals used as accelerators in rubber production). The dermatitis is usually limited to the area of contact in the rubber shoe (e.g., tennis shoes) or to leather shoes with rubber insoles, box toes, linings, or adhesives used to hold various shoe components together.

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The clinical appearance depends on the specific sensitizing agent. Typically, the dermatitis begins on the dorsal (top) portion of the foot (e.g., the big toe), spreading to the bottom (i.e., dorsa) of the foot and the other toes while sparing the interdigital spaces. Usually it involves both feet, although unilateral involvement may be seen. Dermatitis on the heels corresponds to the heel-cap of the shoe, while dorsal foot dermatitis corresponds to the tongue of the shoe. Plantar involvement is usually only on weight-bearing areas, although the instep may be involved if the athletic shoes have molded soles. Boots produce a dermatitis that extends to the backs of the calves. Furthermore, with wear, allergens frequently leach from the offending shoe component and spread to other areas of the shoe.

In addition to rubber chemicals (i.e., MBT and thiurams), leather (potassium dichromate), rubber, glues (p-tert-butylphenol formaldehyde resin), dyes (in shoes and socks), or impregnated linings are potential sensitizers. In many cases, the exact nature of the allergen remains unknown. In suspected cases, patch testing should be performed.

Treatment includes avoidance of allergens. Patients with chromate sensitivity or adhesive allergy may have to wear, respectively, shoes of synthetic material or fabric or stitched leather shoes. Plastic boots as well as plastic, cork, and charcoal insoles are also available. Hyperhidrosis is a common concomitant problem in shoe dermatitis. Thus, natural fiber (i.e., cotton) socks should be worn. Prescribed topical aluminum chloride hexahydrate (Drysol) or iontophoresis can control sweating. Iontophoresis utilizes the application of a D/C generated 15-18 mA electrical current to the soles of the feet, which are immersed in an electrolyte solution for 20 minutes. This costly and time-consuming procedure is repeated daily for the first several weeks; the schedule may be eventually stretched out to once weekly or every other week. Iontophoresis for the treatment of hyperhidrosis is more successful in patients with light to moderate hyperhidrosis.

• Irritant dermatitis. Irritant dermatitis of the foot can result from remedies for athlete's foot (tinea pedis), antiseptics and antiperspirants, cement, and other chemicals. Treatment is directed at identifying the cause and removing it.

• Lichen planus. LP is an inflammatory disorder of the skin and nails, affecting 1% of the population. On the skin, the characteristic pruritic purple, polygonal, planar papules (i.e., the five Ps ) usually occur on the extremities. Palmoplantar LP occurs in 26% of the patients with LP—more commonly in men between their third and fifth decade. Clinically, itchy, red, scaly and/or hyper-keratotic plaques with well-defined edges are located on the internal plantar arch. Spontaneous remission in six to 18 months is characteristic, but the course can be abbreviated with judicious use of mid- to high-potency topical corticosteroids tapered over time.

Infectious inflammatory disorders

BACTERIAL

• Microbial eczema of the feet. Microbial eczema of the feet (Fig. 4) is a distinctive pattern of eczema that mainly affects the interdigital spaces on the dorsum of the medial toes in patients with poor hygiene, hyperhidrosis, and/or heavy footwear. Staphylococcus sp. or Streptococcus sp. can be cultured, and lesions respond to topical mupirocin or oral, first-generation cephalosporins or macrolides. In children, the condition must be distinguished from juvenile plantar dermatosis.

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• Ingrown toenail (onychocryptosis). Ingrown toenail is the embedding of one or both of the toenail borders into the flesh due to an improperly trimmed nail, particular nail shapes, ill-fitting footwear, and trauma in athletically active young people. Distorted weight-bearing positions due to abnormalities in gait, hyperhidrosis, and overuse of foot baths may also contribute. Secondary bacterial infections are frequent. Treatment is surgical removal of the nail border (including associated matrix) and administration of systemic antibiotics (e.g., cephalosporins, second-generation macrolides).

VIRAL

•Plantar warts. Plantar warts (Fig. 5) are common ailments occurring in 6% of children and adolescents, 17% of HIV-infected men, and immunocompromised patients. Clinically, warts start as small shiny papules, which enlarge into well-defined round hyperkeratotic papules/plaques on weight-bearing areas—heel, metatarsal heads, toes. Plantar warts are caused by human papilloma virus (HPV). Solitary small warts are caused by HPV-2, HPV-4, and HPV-57. HPV-1 causes a large myrmecia (domed-surface) wart. HPV-2 results in a mosaic wart with, as the name implies, a coalescing of smaller warts. HPV-60 is associated with plantar epidermic cysts and well-demarcated, flat, hyperkeratotic, hyperpigmented warts located on the plantar arch or other non-weight-bearing areas of the sole. Small warts are usually asymptomatic. However, larger warts may cause pain in walking. The life duration of a plantar wart is variable, with spontaneous regression more common in children.

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Initial treatment of plantar warts with topical salicylic acid plasters, Trichlor-/bichloracetic acid, or cryotherapy may cure up to 70% of common hand and foot warts within three months. Other treatment modalities include intralesional bleomycin, topical retinoids, laser destruction, oral cimetidine, photodynamic therapy, imiquimod therapy, and immunotherapy with squaric acid and diphencyprone (DPC).

• Herpes simplex. Although uncommon, herpes simplex (herpetic whitlow) of the toe has been reported in infants and adults. The most likely mode of transmission is autoinoculation, although a proposed neural transmission from sacral ganglia (in the case of genital herpes) to the toe has been proposed. Clinically, pain, swelling, vesicle formation, and erosion/ulceration occur. Because of the rarity of this entity, HSV is not often considered initially unless classic vesicles of an erythematous nature are present. Diagnosis is with Tzank stain and/or viral culture. Treatment includes acyclovir as early as possible.

• Papular-purpuric gloves and socks syndrome. PPGSS is a rare eruption affecting young, otherwise healthy adults in spring and summer. It is characterized by pruritic/painful, well-defined red, edematous, small, flat papules in a symmetrical gloves-and-socks distribution, rapidly progressing to petechia/purpura. Fatigue, anorexia, and sudden onset of fever can accompany the rash. A small mucous membrane eruption (enanthem) with small vesicles and erosion may be seen. PPGSS has been associated with parvovirus B19, cytomegalovirus, measles virus, Coxsackievirus B6, and HHV-6.

FUNGAL INFECTIONS

• Tinea pedis. Tinea pedis (athlete's foot) is an exogenously transmitted dermatophyte (fungal) infection (Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum) of the feet that affects 10% of the population. It most commonly occurs during the summer months or in hot, humid climates. Occlusive shoes, hyperhidrosis, and communal baths/ pools predispose one to infection.

There are four clinical variants of tinea pedis. The intertriginous type is characterized by fissuring, scaling, and maceration in the lateral toe webs, spreading to the sole or instep. The papulosquamous variant is a patchy or diffuse moccasin-like scaling over the soles, caused by T. rubrum. The third variant is the blistering/pustular form observed in the instep and mid-anterior plantar surface (vesicular or vesiculobullous type) caused by the T. mentagrophytes var. interdigitale. Lastly, the ulcerative variant demonstrates maceration and ulceration of the sole of the foot and is often complicated by a secondary bacterial (often gram-negative) overgrowth.

Tinea pedis is transmitted by contact with infected dead skin scales on bath or pool floors as well as on clothing. Associated hyperhidrosis is controlled with the application of talcum powder or antifungal powders (undecylenic acid or tolnaftate powders), absorbent socks, nonocclusive shoes, and/or topical 20% to 25% aluminum chloride hexahydrate.

The decision to treat topically or systemically depends on the extent of infection and symptoms. Topical azoles (miconazole, clotrimazole) and undecylenic acid are more efficacious than tolnaftate. Topical allylamines (naftifine HCl, terbinafine HCl) are slightly more efficacious than topical azoles, but more expensive. If the infection is widespread, fails to respond to topical drugs, or is recurrent or chronic—or when the condition is more severe, as in moccasin tinea pedis—the use of an oral agent should be considered by the clinician. Oral agents are more popular, with terbinafine HCl demonstrating better rates of cure than systemic itraconazole (Sporanox) or topical clotrimazole.

Maceration, erythema, or denudation of skin may be treated with soaks (Domeboro; saline; acetic acid [vinegar]). Secondary bacterial infection must be treated with systemic antibiotics.

• Tinea unguium/onychomycosis. Tinea unguium (Figs. 6, 7) is a fungal infection of the nail plate caused by T. rubrum, T. mentagrophytes var. interdigitale, and E. floccosum. Nondermatophytic fungi and molds and Candida albicans can also be cultured from dystrophic, infected nails but are not considered the primary cause of this problem. Table 1 shows the classification of onychomycosis.

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Topical agents for onychomycosis are of little benefit. Historically, griseofulvin was the drug of choice but often required 10-18 months of continuous therapy to demonstrate mycologic cure rates between only 3% and 38%. Currently, itraconazole and terbinafine have been approved for the treatment of distal subungual onychomycosis (DSO), which is also known as tinea unguium.

Itraconazole is a broad-spectrum imidazole that persists in the nail six months after discontinuation of therapy. Itraconazole has been approved for DSO at a daily dose of 200 mg orally for 12 weeks. Drug interactions involving drugs metabolized by the liver (e.g., diazepam, theophylline) and liver toxicity are potential problems. Alternatively, itraconazole pulse therapy is utilized in a recommended dosing regimen of two (for fingernail involvement only) to three pulses (for toenail involvement with or without fingernail involvement). Each pulse consists of 200 mg twice daily (400 mg/day) for one week with a three-week drug-free period. Then, the next pulse is repeated.

Terbinafine HCl (Lamisil), an allylamine, fungicidal agent effective against dermatophytes and some molds, has been approved for the treatment of DSO (250 mg daily for 12 weeks for toenail infection) with a complete cure rate in 82% of cases. Therapeutic levels of drug persist in the nail for three to six months after therapy is discontinued.

Chemical (using 40% urea) or surgical removal of the nail combined, with topical agents and oral agents, may be necessary in some nondermatophytic fungal infections. For those patients who cannot take or are reluctant to take an oral medication, an antifungal agent (e.g., terbinafine HCl) can be prepared in a pharmaceutical grade DMSO and applied topically. Also, Penlac Nail Lacquer (ciclopirox, 8%) can be used with some success.

Mechanical abnormalities

• Foot ulcers. Ulceration of the lower limb affects 1% of the adult population and 3.6% of people older than 65 years. Almost one-third of all ulcers of the lower extremity occurs on the foot, developing earlier in men. Ulcers result from breaks in the dermal barrier, with subsequent erosion of underlying subcutaneous tissue (Fig. 8). In severe cases, the breach may extend deeper into muscle and bone. The major causes for foot ulceration include vascular disease (especially arterial disease), musculoskeletal abnormalities, and neuropathy.

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Loss of protective sensation due to peripheral neuropathy is the most common cause of ulceration. People with normal sensation change their foot strike when they feel discomfort in their feet, but patients with neuropathy do not compensate for plantar pressure by changing gait pattern to avoid injury.

Ischemia (lack of oxygen) due to vascular disease reduces oxygen supply, nutrients, and soluble mediators involved in the repair process. Venous ulcers occur above the ankle; arterial ulcers affect the toes or areas over pressure points; and neuropathic ulcers occur on the sole over pressure points. Altered foot biomechanics, limited joint mobility, and bony deformities (e.g., deformities of the metatarsal heads and the forefoot and dislocation or atrophy of plantar fat pads) increase the risk of ulceration and subsequent amputation. Abnormalities in foot biomechanics result in a dysfunctional gait along with damaging structural changes in the foot.

Vasculitic ulcers are most commonly associated with rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, and diabetes. Blood dyscrasias such as sickle cell disease, thalassemia, thrombocythemia, and polycythemia rubra vera can lead to leg ulceration. Neuropathy can be due to poliomyelitis, syringomyelia, tabes dorsalis, and, most commonly, diabetes.

Foot ulcers affect up to 15% of all patients with diabetes at some point in their lifetime. Many ulcers are preventable. The diabetic foot has many predisposing risk factors for ulceration, including neuropathy (sensory, motor, and autonomic), impaired wound healing, accentuated plantar arches, hammertoes, interdigital maceration (with associated bacterial and fungal infection), immune compromise, peripheral vascular disease, and infection. Superficial foot ulcers with cellulitis infected with Staphylococcus sp. or Streptococci sp. are usually non-limb threatening, while polymicrobial (gram-positive and gram-negative), deeper ulcers can extend into the subcutaneous tissue/bone and are limb-threatening and can be gangrenous. Diabetics are also more prone to tinea pedis, verrucae, callus formation, hyperhidrosis and cutaneous infections, and blister formation. Inadequate footwear and biomechanical anomalies contribute to providing areas of overload in the feet.

Management of the ulcerated foot depends on the etiology and includes combinations of complete rest; sharp or surgical debridement of the necrotic tissue or bone; total contact casting (a molded walking cast to take pressure off of the ulcerated area); control of concurrent medical conditions (e.g., hyperglycemia, renal failure, and nutritional deficits); topical dressings; becaplermin gel; orthotic devices; antibiotic therapy; pentoxifylline; arterial reconstructive surgery; split-skin, rotation flaps, pedicle flaps, or amputation; and most important, patient education.

• Callosities, corns, and calluses. A callus is an ill-defined waxy, yellow hyperkeratosis with loss of dermatoglyphic markings typically over the metatarsal heads caused by repeated friction and/or pressure usually on the ball of the foot. Structural bony deformities that lead to increased stresses on the soft tissue of the sole of the foot contribute to these hyperkeratotic plaques. A corn is a sharply demarcated, painful, "glassy," kernel-like callus typically between the fourth and fifth toe or over a bony prominence on top of the toes.

About half of all podiatrist visits are for treatment of corns. Calluses and corns result from changes in the function of the foot exacerbated or caused by structural abnormalities and/or unsuitable footwear (e.g., narrow toe box, high heels). Corns are hard, soft, vascular, or neurovascular. Hard corns usually occur over the dorsal interphalangeal joints or on the great toe's interphalangeal joint. Soft corns arise exclusively interdigitally, typically in the fourth web space that is deeper and retains moisture to a greater degree than the other toe spaces.

Various foot abnormalities such as prominent condylar projection, malunion of a fracture, claw/hammer/mallet toes, a short first metatarsal or plantar-flexed metatarsal (a metatarsal below the plane of the other metatarsals), and deformity of the calcaneous bone position of the heel predispose one to callosities. The aims of treatment are to provide symptomatic relief, determine and relieve abnormal mechanical stressors by conservative means, and utilize surgery if these fail.

Careful and regular paring, a toe separator (felt, foam, or silicone) and salicylic acid (10%-20%) keratolytic preparations can be of some help. Because some patients will not use it properly or misapply it, topical salicylic acid therapy is not preferred by some podiatrists. Salicylic acid products are directed to help relieve pain and discomfort. Shoes should have extra width in the toe box. Orthotics, which are custom-molded arch supports, may also help to straighten the deformities by redistributing the mechanical forces. Surgical correction of toe deformities and resection of prominent condyles may be necessary.

• Friction blisters. Friction blisters occur on the heel or sole following repeated shearing forces moving across the skin, resulting in midepidermal cell death. Heat, sweating, and maceration increase the risk of blistering, which frequently occurs in an individual who reinitiates an exercise program overzealously. Uncomplicated blisters heal rapidly. Appropriate care includes incision and drainage, then sterile removal of the roof of symptomatic large blisters by the podiatrist. Subsequent protection of the wound is achieved with doughnut moleskin or nonadherent dressing and protective padding such hydrocolloid dressings (e.g., Tegasorb, 3M; Cutinova hydro, Beiersdorf-Jobst; Dermatell, Gentell). Betadine soaks can also be employed as necessary.

Proper fitting of footwear, synthetic insoles to absorb frictional force, and acrylic or thin polyester socks under a thick, dense outer sock and mesh-top footwear can reduce blistering. Topical antibiotics (e.g., mupirocin, Neosporin, Polysporin) or oral systemic antibiotics (e.g., cephalosporins, macrolides) should be used if secondary infection is present. Other treatments may include drying the area first with a Betadine/salt soak that is antiseptic/antibacterial.

• Black heel. Black heel (talon noir, calcaneal petechiae) refers to suddenly appearing, asymptomatic, closely aggregated groups of small blue-black specks on the back or side of the heel in athletic adolescents. Shear-stress rupture of the papillary capillaries from repeated jumping and sudden stopping or twisting of the heel results in extravasation of red blood cells in the skin. The major concern is the distinction from melanoma of the heel. Paring the skin removes the hemorrhage. Prevention is achieved by wearing a second pair of socks and properly fitting shoes.

• Piezogenic pedal papules. These are soft, skin-colored, typically asymptomatic, medial heel papules and nodules that are noted in standing. Painful papules may be treated through avoidance of prolonged standing, weight loss, orthotics, and, when necessary, excision of the papules.

• Athlete's nodules. Collagenous nodules occurring at sites of pressure, trauma, and friction occur in surfers, boxers, marble players, and football players and can be treated with excision. Subsequent preventive measures include avoidance and additional padding/protection whenever applicable.

• Bunion. A bunion (Fig. 9) is a painful medial prominence of the metatarsal head of the great toe—an enlarged big toe joint—that causes the big toe to angle toward the outer toes. It is aggravated by the wearing of shoes with too high heels and/or too narrow toe boxes that force the side of the toe inward. As the prominence enlarges from continued pressure, a medial bursa forms over the head that can become inflamed and/or infected.

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It is estimated that 3% of all Americans (mainly women) and 7% of those over 65 years of age have bunions. Bunion sufferers should be instructed to wear properly fitted, roomy shoes. Self-adhesive cushioning can help to ease the pain caused by pressure and friction. A caution, however, is that too long a use of these cushions can cause the underlying skin to macerate. The macerated tissue could break down, leading to an ulceration and, potentially, bacterial infection.

• Onychogryphosis. Onychogryphosis (Ram's horn; Fig. 10) is a distorted, club-shaped, laterally deviated thickened opaque or discolored nail associated with onychomycosis, trauma, poorly fitting footwear, and failure to trim nails. The nail tip may pierce adjacent tissue, resulting in infection. Manual debridement and trimming help to relieve pressure, and because the nail is so large, temporary or permanent removal may be performed. In some instances, treatment may be directed to partial nail excision and could include administration of systemic antibiotics (e.g., cephalosporins, broad-spectrum macrolides, fluoroquinolones) to prevent secondary bacterial infection.

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Malignancies

• Squamous cell carcinoma. Verrucous carcinoma is a well-differentiated, slow-growing neoplasm with a tendency for local recurrence, but without a tendency to metastasize, occurring in the oral cavity (oral florid papillomatosis), the anogenital region (giant condyloma of Buschke and Lowenstein), and the plantar surface of the foot (epithelioma cuniculatum). Epithelioma cuniculatum (EC) is more common in men in their 50s. EC presents as a nonhealing, fungating, exophytic mass with numerous keratin-filled sinuses on the anterior weight-bearing sole; it is locally invasive and destructive. EC rarely metastasizes to regional lymph nodes and has a low mortality rate.

Treatment is wide local excision. In more serious cases, amputation of a toe or even a foot may be necessary; electrodesiccation, cryotherapy, and laser surgery often fail. Surgical curettage is sufficient in minor cases. EC should not be treated with radiation because this procedure can induce a more aggressive behavior pattern.

• Melanoma. Approximately 32,000 newly diagnosed cases of melanoma occur annually in the United States. Of these, approximately 6,700, or 20%, result in death. The prevalence of melanoma is increasing at a greater rate than any other malignancy. Currently, one in 105 Americans born in 1990 will have a malignant melanoma during their lifetime. Primary cutaneous melanoma is the most common malignancy of the foot.

Cutaneous melanomas are classified as superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM), nodular melanoma (NM), and acral lentiginous melanoma (ALM). Palmar or plantar ALM has specific epidemiologic characteristics. ALM is the most common melanoma of African-Americans, Hispanics, and Asians but is the least common of the four types of melanoma. Palmoplantar and subungual ALM occurs with a peak incidence in 61- to 70-year-olds.

The etiology of ALM is unknown. Survival of ALM and NM patients is significantly poorer than survival of LMM and SSM because the diagnosis of ALM is often delayed and tumor thickness is often greater compared with SSM or LMM. Treatment involves amputation for subungual/toe lesions and wide local excision with split-thickness grafting for plantar lesions. The depth of the melanoma determines the extent of amputation or excision.

If a patient confides to a pharmacist that there is a pigmented lesion on the foot, the patient should be immediately directed to consult his/her podiatrist. Usually, melanomas are asymptomatic and thus are not discovered until it is too late.

• Cutaneous T-cell lymphoma. Mycosis fungoides (MF) refers to cutaneous T-cell lymphoma. MF moves from patches to plaques to tumor nodules. The patch phase presents with single or multiple red scaly, variably sized macules or papules on non-sun-exposed sites that last years. Plaques are sharply demarcated dusky red, hyper/ hypopigmented or poikilodermic, scaly, indurated lesions often coalescing into annular, arcuate, or serpiginous patterns. As MF progresses, large nodules with or without ulceration develop.

Diagnosis is by biopsy, immunoperoxidase staining, or T-cell receptor gamma gene rearrangement. Palmar/ plantar involvement occurs in approximately 11.5% of MF patients with age range of 13-69 years (mean: 55 years). Over half of these patients have their disease confined to the palms or soles. Clinically, the lesions are vesiculorpustules, hyperkeratotic/verrucoid plaques. Treatment includes PUVA, methotrexate, electron beam radiation, and/or topical corticosteroids.

Miscellaneous conditions

• Palmoplantar keratodermas. The PPKs (Fig. 11) are a heterogeneous group of disorders characterized by abnormal thickening of the palms and soles. They may be inherited or acquired. Autosomal recessive, X-linked, and dominant modes of inheritance as well as acquired forms have all been described. A complete discussion is beyond the scope of this article, and the reader is referred to appropriate texts and review articles.

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Clinically, three distinct clinical patterns of PPK may be identified. The diffuse pattern of PPK demonstrates uniform involvement of the palmoplantar surface. Focal (nummular) keratoses refer to localized areas of hyperkeratosis over pressure points. Punctate keratodermas feature tiny hyperkeratotic papules, nodules, or spicules on the palms and soles.

Clinical classifications of these diseases are often confusing, based upon eponymous case reports of individual families, with lack of uniform nomenclature. One simple working classification involves assessment of the following phenotypic characteristics in patients: (1) the specific morphology and distribution of palmoplantar hyperkeratoses; (2) the presence of associated cutaneous and noncutaneous ectodermal disease in sites other than the palms and soles; and (3) the presence or absence of histological epidermolysis.

Acquired PPK can be associated with AIDS, hypothyroidism, mycosis fungoides, arsenic, menopause, eczema, warts, Reiter's syndrome, lichen planus, Norwegian scabies, internal malignancy, psoriasis, or tinea pedis.

Treatment includes surgically paring the excess callus, keratolytics (Whitfield's ointment, lactic acid), retinoids (topically and systemically), systemic antibiotics/antifungals (for secondary infections), and rarely skin grafting.

General foot care

Prevention of foot problems begins with daily foot hygiene. Every day, the feet should be washed with soap and warm water. They should be pat-dried, including the soles and between the toes. Then the feet should be inspected for any roughened skin areas, dry skin, and/or local irritations.

For those who are overweight and/or suffer from arthritis, a handheld mirror is very useful to observe the feet. When inspecting the feet, the patient should be instructed to run the hands over the skin and toes in an attempt to identify any dry skin and/or roughened areas. The skin texture of the feet should not be dry. Daily foot baths and/or the application of a moisturizing cream maintain appropriate skin texture and suppleness. A foot bath also helps to soften toenails for clipping and filing. The toenails should be periodically manicured and kept at proper length and trimmed straight across.

Any pain or irritation should be investigated as soon as possible. A new pair of shoes will likely cause an initial irritation. This, however, could result in the development of a corn, callus, or bunion. People should understand the need to gradually break in a new pair of shoes by limiting the daily time they are worn. For patients with diabetes, extra precaution is needed. For them, a persistent, slight irritation can lead to a serious and life-threatening infection.

If patients complain to the pharmacist about persistent, unusual feelings of numbness or tingling, burning, and/or fatigue of the feet and legs, they should be advised to contact their podiatrist. These could be early signs of poor circulation or neurological problems. If these patients do not have a podiatrist, the pharmacist should be able to recommend one.

Routine foot care is also critical for patients with arthritis. These patients should undergo periodic foot examinations and wear properly fitted shoes. Insoles also provide cushioning and protection for these patients' feet from the shock of hard surfaces.

When purchasing shoes, the patient should do so cautiously and err on the side of comfort and good fit versus style. The shoe should fit snugly but should not cause friction or irritation. And, if a pair of new shoes is worn continuously, the feet should be inspected periodically throughout the day. Foot inspection is especially important for patients with diabetes. Even a slight irritation from new shoes worn for less than an hour can have devastating consequences. Diabetes patients should be advised to purchase soft leather shoes for maximum comfort.

Consumers/patients need to know their specific type of foot structure, which might include a low arch (pronated or flat foot), normal arch, or high arch (supinated or cavus foot). The foundation on which a shoe is made is called the last; different lasts fit different arch types. Standing barefoot, consumers can determine which type of arch they have—whether the arch breaks down (flattens out) excessively or remains high. With age, the foot lengthens, widens, and flattens, so people should make adequate adjustment, always trying new shoes on both feet. Different types of bone abnormalities, hammertoes, bunions, and plantar-flexed metatarsals may predispose patients to corns, calluses, and foot ulcerations. If a patient's foot problem is in the forefoot area, a "tie shoe" may be preferred to a "slip on." Certain shoes or boots that are poorly ventilated and keep moisture in contact with the skin of the foot can also aggravate certain skin problems (e.g., hyperhidrosis, bromhidrosis, tinea pedis).

No one's feet should ache at the end of the day. If they do, shoe inserts/insoles can be used for support. Over-the-counter arch supports are good alternatives for certain types of foot problems, such as heel and arch pain. However, the support should be molded to the arch by the podiatrist so that there is no gapping, and the plastic should be cut to properly distribute pressure on the foot.

Lifestyle footwear considerations

Women who wear high-heeled shoes are inviting problems with their knees and feet. A heel between 3/4 to 1 in. in height, however, can help reduce heel pain. Changing shoes during the day can provide much needed relief.

Obese individuals have an increased amount of stress on their weight-bearing joints. Typically, the ankle joint becomes very stressed, so the patient needs strong, supportive shoes. Those shoes with insufficient heels will compromise the overall balance of the patient and increase the chance for a foot and/or ankle injury. Because of the additional downward force during walking, obese individuals will need to replace their shoes more often. In this instance, the shoe heel loses its resiliency and shock-absorbing capacity much more quickly. Properly fitted insoles can be very beneficial for these individuals.

Recreational athletes should be advised to purchase sport-specific footwear that is comfortable and provides appropriate support. For example, tennis shoes have smooth soles and enough "give" in them that allow for side-to-side sliding. Basketball shoes offer needed extra ankle support for quick, sudden changes in movement and shock absorption. Jogging/running shoes have extra cushioning for shock absorption and adequate toe flex. Recreational athletes should have these shoes fitted properly to minimize the likelihood of injury, being sure to wear the appropriate hosiery at the time of fitting.

Pregnancy can contribute to foot strain by putting extra stress on foot ligaments. The patient's added weight and increased amount of female hormones can result in swollen ankles and feet that can aggravate any existing conditions and promote inflammation and irritation. These women should wear shoes with broad-based heels that provide good support and shock absorption. Insoles also help to protect the heels and arches against excessive shock.

Treatment

NONDRUG MEASURES

Nondrug measures include avoiding going barefoot, wearing cotton socks, and treating injuries such as blisters, lacerations, and abrasions promptly. Especially for the diabetic patient, the feet should be washed daily in mild soap and tepid water (ideally, 80^o F), making sure to check the water temperature before immersing the foot. And to avoid dry skin, an oil/water lotion should be applied, starting at the heel. The patient should make sure to avoid applying the lotion between the toes. A dusting powder can be applied lightly in order to prevent fungal infections, making sure to avoid overapplication and subsequent accumulation of powder between the toes.

DRUG THERAPY CONSIDERATIONS

The decision to treat a podiatric disorder with topical medication and/or systemic therapy is dictated by the extensiveness of the problem. For example, when the condition is widespread, fails to respond to topical drugs, is recurrent/chronic, and/or is more severe (e.g., moccasin tinea pedis), the use of oral medication should be strongly considered. Also, topical therapy may be ineffective for lack of penetration compared with systemically administered medications. The notable example is in the treatment of tinea unguium and onychomycosis in which penetration into the nail bed by topical medication can be difficult. Representative drugs mentioned in this article are listed in Table 2.

Alternatively, topical medication can be very useful in delivering the drug directly to the problem area. Also, topical medications usually have a lower adverse drug-reaction profile and are not prone to drug-drug interactions, as are systemic medications, if used properly.

The selection of topical drug delivery systems is very important. Table 3 highlights important points about each.

Patient consultation and education

The pharmacist is in an excellent position to complement the podiatrist's care of his/her patients. The pharmacist must become knowledgeable of the primary foot disorders and their treatments. Patient education and follow-up/monitoring are central features and tenets of pharmaceutical care that are intended to maximize patient adherence with the therapeutic plan. Pharmacists can advise patients (and their caregivers) on the proper use of prescribed medications, nonpharmacologic measures to alleviate symptoms and enhance therapy, and avoidance of factors that contribute to the development of certain conditions.

It is extremely important that the patient has an adequate amount of medication and understands the frequency of its application, the method of application, and the amount to be applied. Further, the patient should be encouraged to adhere to the prescribed medication(s) and know what the treatment endpoint will be. Adverse effects that might occur with therapy should also be shared with the patient. Coupled with all of this should be the appropriate timing of return visits to ensure successful therapy.

The pharmacist should monitor the patient's use of medications to ensure that the patient is realizing the maximum benefit. Further, the pharmacist should listen carefully to the patient/caregiver comments during follow-up visits to the pharmacy and decide if a referral to a physician or podiatrist is advisable. Patient misconceptions about therapy, its intent, and other features can be clarified. Indeed, if patient concern or problems are encountered that are too complex for the pharmacist to solve, it is important that the pharmacist share these confidentially with the podiatrist so that a suitable approach can be undertaken.

A central goal of the pharmacist is the education of patients and caregivers with respect to self-care. Certain patient types should not self-treat even minor foot problems. Most notably is the patient with diabetes. Diabetic patients should never use over-the-counter products to treat corns or calluses. The indiscriminate use of medicated pads for these conditions could cause the local tissue of the foot to macerate, then ulcerate and become infected. Because of vascular compromise, a severe infection could lead to the loss of a toe and/or limb.

The pharmacist should alert the diabetic patient to increased risks for ulceration: obesity, poor glucose control, current or recent foot trauma, inappropriate foot care, alcohol abuse, cigarette smoking, inadequate knowledge of diabetes management, and noncompliance with the diabetes management plan. The pharmacist should provide the diabetic patient with information on diabetes-specific foot care (see "Nondrug treatment," above). Feet should be examined daily for any irritation, cuts, abrasions, etc. Use of cotton socks, topical antiperspirants, antifungal powder, and appropriate footwear will also be a component of effective care. Toenail care and frequent visits to the patient's podiatrist should be stressed.

Overcoming communication barriers

It is very important that the podiatrist and pharmacist work collegially for the benefit of the patient. To begin, pharmacists should take the initiative to contact podiatrists to establish a communication link. In this, pharmacists can share the various types of services (e.g., disease management, extemporaneous compounding, self-care foot products) that are available to the podiatrist and his/her patients. Extemporaneous compounding can be particularly valuable, as there are some formulations that are not commercially available. For example, a topical ketoprofen gel may benefit the patient with tendinitis or plantar fasciitis. This and other formulations are listed in Table 4. Patients with diabetes who demonstrate neuropathy with a burning, radiating pain may benefit from a neurogel made up of different combinations as capsaicin, ketoprofen, amitriptyline, baclofen, and lidocaine.

The pharmacist should alert the podiatrist of recent events and/or conditions in the patient's life (lithium therapy, tonsillitis, and thyroid disease) that might predispose the patient to certain conditions (palmoplantar pustulosis). Indeed, the pharmacist can triage the patient to the podiatrist when certain complaints—a growth on the bottom of the foot, unexplained foot throbbing, or nonhealing ulcers/blisters—warrant professional intervention.

References are available upon request.

TEST QUESTIONS

Write your answers on the answer form appearing below (photocopies of the answer form are acceptable) or on a separate sheet of paper. Mark only one correct answer.

1. Which one of the following statements about the feet is true?

a. Tendons in the feet hold joints in place and provide necessary stability.
b. The foot is fully developed and mature by the time a person is 21 years of age.
c. The potential for foot problems decreases with age.
d. The feet disperse the body's weight exclusively to the heel.

2. Proper foot hygiene includes all of the following except:

a. Washing the feet on a daily basis with soap and warm water
b. Inspecting the feet at least one time per week
c. Applying a moisturizing cream
d. Periodically manicuring and trimming the toenails

3. All of the following patient types would be expected to demonstrate foot problems except a patient with:

a. Rheumatoid arthritis
b. Diabetes mellitus
c. Peripheral circulatory disease
d. Peptic ulcers

4. An episodic blistering eczema that affects the soles of the feet of adolescents and young adults typically in the spring and summer months is known as:

a. Athlete's foot
b. Juvenile plantar dermatosis
c. Palmoplanar pustulosis
d. Pompholyx

5. Palmoplantar pustulosis is:

a. Associated with lithium therapy
b. Common in patients with a family history of lupus erythematosus
c. Common in men between the ages of 20 and 60
d. Associated with winter climate conditions

6. Which of the following statements is true about allergic contact dermatitis?

a. About 10% of patients demonstrate foot dermatitis.
b. Working in a cool, dry environment causes exacerbations of the condition.
c. Chemical accelerators in rubber products have been implicated as a central cause.
d. Hypohidrosis is a common concurrent problem with this condition.

7. All of the following conditions predispose the patient to the development of foot eczema except:

a. Heavy footwear
b. Hyperhidrosis
c. Low environmental humidity
d. Poor hygiene

8. Ingrown toenails are caused by all of the following except:

a. Distorted weight bearing on the feet
b. Ill-fitting footwear
c. Physical trauma to the nail
d. Trimming the nail straight across

9. All of the following statements are true about plantar warts except:

a. They can occur in children and HIV-infected men
b. They are caused by herpes simplex virus (HSV-1)
c. If large enough, they can cause pain in walking
d. They can spontaneously regress, especially in children

10. Treatment methods for plantar warts include all of the following except:

a. Cryotherapy
c. Oral cimetidine
b. Infrared photocoagulation
d. Topical salicylic acid

11. Which of the following statements characterizes athlete's foot?

a. It is caused by human papilloma viruses.
b. Excessive foot skin dryness contributes to its development.
c. It is quite common in the pediatric population.
d. It can be acquired by walking barefoot in common areas.

12. Which of the following is a contributing factor to the development of athlete's foot?

a. The cold, dry climate of wintertime
b. Wearing shoes that promote ventilation
c. Hyperhidrosis
d. Wearing nonsynthetic cotton socks

13. Hyperhidrosis associated with an active case of athlete's foot can be controlled by all of the following except:

a. Wearing absorbent socks
b. Applying topical aluminum chloride hexahydrate
c. Applying topical talcum powder
d. Wearing heavy footwear with little ventilation

14. Which one of the following microorganisms is a primary cause of tinea unguium?

a. Candida albicans
b. Pseudomonas aeruginosa
c. Staphylococcus aureus
d. Trichophyton mentagrophytes

15. All of the following are examples of therapy for onychomycosis except:

a. Itraconazole, 400 mg daily every fourth week for nine weeks
b. Terbinafine HCl, 250 mg daily for 12 weeks
c. Griseofulvin ultramicrosize, 165-330 mg for six weeks
d. Surgical removal of the nail

16. Appropriate foot hygiene/precaution for a patient with diabetes mellitus should include which one of the following?

a. Selecting shoes that are slightly tight and snugly fitting
b. Inspecting the feet on a daily basis
c. Applying a moisturizing cream to the entire foot, including between the toes
d. Cutting the toenails periodically and tapering/rounding the edges of the nail

17. Diabetes mellitus patients are prone to develop which one of the following foot disorders?

a. Allergic contact dermatitis
b. Bunions
c. Cutaneous infections
d. Pompholyx

18. Which of the following is a true statement about corns?

a. Typically, they occur on the bottom of the toes.
b. Loose-fitting shoes are a contributing factor to their development.
c. Those that appear in the toe web between the fourth and fifth toe are known as soft corns.
d. Usually, they are asymptomatic, with little or no pain.

19. Which of the following is a true statement about calluses?

a. Typically, they occur on the arch of the foot.
b. Constant friction and/or pressure cause them.
c. They are described as painful and sharply demarcated in appearance.
d. They are perfused, with a rich supply of blood.

20. An acute or chronic inflammation and thickening of the bursa of the joint of the big toe, with lateral displacement of the toe, is known as a:

a. Bunion
b. Callus
c. Corn
d. Ingrown toenail

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Nicholas Popovich. Podiatry and pharmacy: Working together. Drug Topics 2001;11:43.