Diseases of the footpads (Proceedings)

Zinc responsive dermatosis

Zinc responsive dermatosis is a nutritional skin disease that can be categorized as syndromes I or II. Syndrome I is a disease primarily seen in Siberian huskies and Malamutes. Lesions develop in these breeds despite having adequate zinc in their diets and most commonly occur in young dogs (1-3 years of age). It has been shown in malamutes that they have a decreased ability to absorb zinc from the intestines. About half of these patients are pruritic. Clinical signs include hyperkeratosis of the foot pads and sometimes claw disease (onychomalacia). Other common areas affected are perioral, periocular, pinnal, chin, mucocutaneous junctions (prepuce, vulva, and anus), elbows, and hocks. Lesions begin as erythema, then progress to alopecia, crusting, scaling/hyperkeratosis, and suppuration. The coat may be dull and excessive sebaceous secretions are common.

Syndrome II occurs in rapidly growing pups or young dogs that are fed a diet deficient in zinc or with large amounts of components such as calcium or phytates that bind zinc. Lesions are very similar to syndrome I.

Serum or hair zinc levels may or may not be normal and due to inherent difficulties in zinc analysis, this is not recommended. Diagnosis is made by history, exam, and skin biopsy. Treatment involves changing the diet in syndrome II dogs and zinc supplementation in syndrome I dogs. Treatment of secondary bacterial and Malassezia infections is essential. There are many forms of zinc that can be used but zinc methionine is the form of choice (1.7 mg.kg.day). Pruritic dogs may benefit initially with corticosteroids to decrease inflammation and pruritus as well as to enhance absorption of zinc from the intestines.

Necrolytic migratory erythema (hepatocutaneous syndrome, superficial necrolytic dermatitis, metabolic epidermal necrosis)

This is a condition that has been recognized in the dog and the cat, but it is exceedingly rare in the cat. The pathogenesis is ill-defined, but the skin lesions are due to degeneration of the keratinocytes and the foot pads are almost always affected and are often the first skin lesions to occur. At least 90% of dogs with NME have a hepatopathy with the remaining cases associated with pancreatic neoplasia (functional glucagonomas). Existing theories on the mechanism of the skin lesions are a direct cytotoxic effect on the keratinocytes from the excessive circulating glucagon, a profound deficiency in amino acids (hypoaminoacidemia) leading to epidermal protein depletion and necrosis, concurrent hypoalbuminemia resulting in a lack of ability to carry zinc and fatty acids to the skin, and an induction of eicosanoid production resulting in skin inflammation.

Hyperkeratotosis of the foot pads with resultant fissuring is the hallmark clinical feature. Over time, there is often scaling and alopecia of the feet as well. Other skin lesions start as erythema then progress to papules, plaques and crusts with occasional vesicles or bullae. Other regions affected are the mucocutaneous junctions, elbows, hocks, perineal region, axillae, groin, nose, and pinnae. The oral cavity is rarely affected.

Dogs with hepatocutaneous syndrome should have elevations in ALP and ALT, and often leukocytosis, anemia, and hypoalbuminemia . Concurrent diabetes mellitus is common. The vast majority of patients have an abnormal ultrasound with a characteristic "swiss cheese" or "honey-comb" look to the liver. I have seen some cases of chronic, severe, hepatocutaneous syndrome without abnormal liver enzyme changes at the time of presentation, but previously these enzymes had been elevated. In these cases, there are not even enough functional hepatocytes to release excessive ALT .Dogs with glucagonomas generally have hyperglycemia and mild to moderate (sometimes normal) elevations in ALT and ALP. An ultrasound may or may not be able to identify a pancreatic mass.

The diagnosis of NME can be confirmed with a skin biopsy as there are characteristic findings histologically. Impression smears should be performed to identify secondary infection with yeast and bacteria. There is almost always secondary infection interdigitally and this creates a large amount of pruritus and pain for these patients.

Treatment is aimed at controlling the infections and supporting the patient nutritionally. Intravenous amino acids (8.5 – 10% Aminosyn, Abbott Labs) are often used to correct the hypoaminoacidemia. These are ideally delivered through a central line due to phlebitis (25 ml/kg/bw or 500 mls total) once per week for 4 weeks, then as needed thereafter. Response should be seen with the first 2 treatments. Another method is to give these treatments for three days in a row and note response. Supplementation with fatty acids and zinc is also recommended. Before the advent of using IV amino acids, feeding egg yolks (1 yolk/4.5 kg) was thought to be helpful. Nutritional support of the liver (SAME, etc) may also be beneficial.

If present, surgical removal of the pancreatic neoplasia is the treatment of choice. If this is not possible or there are metastases, a somatostatin analogue, ocetrotide that inhibits glucagon release has been shown to be effective in a few cases. This therapy may also prove to be beneficial in liver-asociated cases as well.

Pemphigus Foliaceus (PF)

PF is an autoimmune disease characterized by auto-antibody formation against the keratinocyte desmosome. Desmosomes are the intercellular adhesion molecules that hold the keratinocytes together. When these are disrupted, acantholysis occurs and an intraepidermal pustule is formed. This is the first lesion followd by rupture of the pustule and then a crust formation. PF is one of the most common immune mediated skin diseases in the dog and it is the most common in the cat. The mean age of onset in dogs is 4.2 yrs.

PF often involves the foot pads and claw bed, but it often begins on the face and ears. In early cases, pustules of the foot pads may be seen, but these are very transient and result in hyperkeratosis of the pads. There may be associated lameness as well as secondary bacterial infection. In cats, the clawbed is often affected and a purulent to caseous discharge with crusting will be seen around the nails. Diagnosis is through skin biopsy and cytology. Treatment involves immunosuppressive medications such as corticosteroids, azathioprine, chlorambucil, leukeran, chrysotherapy (gold salts), cyclosporine, and other medications. The goal of treatment is to obtain remission with more potent medications and dosing regimens, and then slowly transition to safer, preferably non-steroid based, maintenance protocols.

Epitheliotropic (T-Cell) Cutaneous Lymphoma (Mycosis Fungoides)

This is an uncommon cutaneous malignancy in dogs and cats. The malignant lymphocytes have a strong affinity for the epidermis and hair follicle epithelium. The initial stage of this disease manifests as an exfoliative erythroderma. At this stage it can greatly mimic atopic dermatitis. It is often in the early stages that the footpads become hyperkeratotic. Later, plaque-like tumors form followed by nodules. Depigmentation of the nasal planum and lips are common. The diagnosis is made via skin biopsy and immunohistochemistry. Impression smears of early plaques or fine needle aspirates of tumors can be supportive.

Treatment response to standard chemotherapy protocols for B-cell lymphomas have been disappointing. A more effective chemotherapy is lomustine (CCNU), an alkylating agent, at a dose of ~60 mg/m2 PO q 21-30 days. Neutropenia is common and is most likely to occur 1-2 weeks after dosing. Thrombocytopenia and hepatotoxicity can also be seen. Retinoids such as isotretinoin (1-8 mg/kg/day) have shown to be effective in some cases. High dose linoleic acid (safflower oil 3 ml/kg twice per week) was shown to be effective in 7 out of 10 dogs, but I have not seen success with this therapy in 5/5 cases.

Canine Distemper

Caused by a paramyxovirus that is easily vaccinated against, this is a rare dermatosis in the United States. Hard-pad disease is the classic skin manifestation of distemper. Dogs develop foot pad and nasal hyperkeratosis of variable severity and the pads are very hard to the touch. These patients are systemically ill. Skin biopsy and identification of inclusion bodies or viral particles via immunohistochemistry confirms the diagnosis.

Feline Plasma Cell Dermatitis

This is a condition of unknown pathogenesis, yet is thought to be immune mediated. Plasma cells infiltrate the foot pads causing very large swellings primarily of the metacarpal and metatarsal pads. There is usually more than one foot pad affected and the swelling is usually painless. In one study, 50% of cats affected had concurrent FIV infection. The diagnosis can often be made by physical examination alone. Fine needle aspiration can be supportive, and skin biopsy confirmative. Corticosteroids at immunosuppressive doses are effective in most cases followed by a slow taper. Doxycyline has also shown to be beneficial although response time is slow. In difficult cases, chrysotherapy or surgical excision of the fatty pad may be necessary.

Eosinophilic Granulomas

A reaction pattern in the skin usually associated with underlying allergies to fleas, food, or atopy. If lesions occur on the feet, they generally affect the interdigital skin with some footpad involvement possible.

Viral Papillomas

One syndrome in dogs involving infection with papillomavirus is the development of multiple warts on the footpads. This is a different type of papillomavirus than what causes warts in the mouth and lips. These warts can be significant cause of lameness in dogs, especially if they involve the larger pads. They may self resolve, although treatment options include, surgical excision, treatment with topical imiquimod (Aldara), or injectable interferon.

Footpad Hyperkeratosis

Familial footpad hyperkeratosis has been recognized in the Dogue de Bordeaux and the Irish terrier. The hyperkeratosis is severe and is obvious within the first 6 months of life. There is no cure for this disease. Symptomatic therapy with daily 50% propylene glycol soaks may be beneficial.