Deadly dermatoses (Proceedings)

Deadly dermatoses are defined as

1. Lethal diseases for the pet.

2. Diseases of the pet that lead to extreme owner frustration, leading to euthanasia of the pet.

3. Extreme owner expense, leading to euthanasia of the pet.

4. A decreased quality of the pet's life.

5. Treatment side effects that ultimately lead to euthanasia of the pet.

Auto-immune skin diseases

Any auto-immune skin disease can ultimately become a deadly dermatosis based on the criteria listed above. Examples include pemphigus foliaceus, pemphigus vulgaris and systemic lupus erythematosus.

Pemphigus Foliaceus is the most common of our auto immune skin diseases. The term pemphigus comes from the Greek word for blister, and all pemphigus diseases are blistering diseases. The hallmark of pemphigus diseases is acantholysis. Acantholysis is the process where keratinocytes lose their later cellular attachments, leading to intraepidermal clefting. Initially, it was thought that neutrophils and their mediators caused the clefts but we now realize that neutrophils invade the vesicle, leading to pustule formation. Many breeds of dogs are predisposed to pemphigus foliaceus including Akitas, Dobermans, Chow-Chows, Shar-peis and Dachshunds. Pemphigus foliaceus is typically found in middle aged dogs with a mean age of 4.2 years. Clinical signs of pemphigus foliaceus include facial crusts, ulcers and often depigmentation of the planum nasale. There are usually large, intact pustules on the trunk and face. Footpad hyperkeratosis and ulcerations are often noted, as are fevers and anorexia. Laboratory signs include a leukocytosis with neutrophilia and hyperglobulinemia are often seen with cases of pemphigus foliaceus. In addition, pets may have anemia of chronic disease or nonregenerative anemia. Cytologies of intact pustules may reveal hypersegmented neutrophils and acantholytic to lytic cells.

     • Dermatopathology shows intraepidermal pustular formation with acantholysis and neutrophils and/or eosinophils.

     • Treatments for pemphigus foliaceus include corticosteroid therapy such as Prednisone 2-4mg/kg, Imuran (azathioprine) 1-2/mg/kg EOD, Leukeran 0.1-0.2mg/kg EOD, Cyclosporine 5-10mg/kg.

Pemphigus Vulgaris is a more rare form of pemphigus and shows deeper clefting. Pemphigus vulgaris patients almost always (greater than 90%) have oral ulcerations. The erosions that are seen are more severe than with pemphigus foliaceus, and this is a much more difficult pemphigus to treat, often requiring much higher doses of steroid therapy initially to suppress the immune response.

     • Clinical signs include mucocutaneous erosions to ulcerations, severe crusting of the footpads and these ulcerations often lead to lameness.

     • Dermatopathology of pemphigus vulgaris shows intradermal pustule formation with acantholysis and neutrophils with a super basilar clefting leading to the classic row of tombstones appearance.

Cutaneous and systemic lupus erythematosus is another group of auto-immune skin diseases in our group of deadly dermatosis. Systemic lupus erythematosus is a multi-systemic disease often with mucocutaneous lesions, polyarthritis, immune-mediated thrombocytopenia, auto-immune hemolytic anemia and protein losing nephropathy. This disease is also known as the great imitator, due to the multitude of clinical signs that may be present. Systemic lupus erythematosus is a result of a type III hypersensitivity reaction. Antibodies to nucleic acid are a diagnostic hallmark for SLE (ANA positive). In one study of 75 cases of systemic lupus, the most common clinical signs are polyarthritis in 91% of the cases, renal disease in 65% of the cases and mucocutaneous skin disorders in 60% of the cases. Auto-immune hemolytic anemia was rare.

     • Diagnoses is made through a multitude of testing include ANA titers, urinalysis and urine protein/creatinine ratio, COOMBS positive test, joint fluid analysis, cytologies and skin biopsies. Skin biopsies show an interface dermatitis with a vacuolated dermal/epidermal junction and a thickened membrane zone.

     • Treatments are similar to the pemphigus cases, with corticosteroids such as Prednisone, Imuran, Leukeran and Cyclosporine.

Drug eruptions include a full spectrum of diseases from simple drug eruptions to more severe erythema multiforme to the most severe which is toxic epidermal necrolysis. Drug eruptions like systemic lupus can be a great imitator and mimic many diseases, especially autoimmune diseases. The most common drugs that are implicated in canine drug eruptions include sulfonamides and cephalosporins. Drug eruptions are often targetoid lesions (bulls-eye) but can also be papular, vesicular and crusting.

     • Diagnosis of drug eruptions are made with thorough history. Histopathology can be quite variable. In many cases, they appear like a classic pemphigus case. Many cases have single cell keratinocyte necrosis to even full thickness epidermal necrosis as seen in TEN.

     • Treatment for drug eruptions include drug removal and supportive therapies such as IV fluid therapy and Silvadene Creams. Antibiotics may or may not help. Corticosteroid therapy is not recommended. Cyclosporine may be beneficial in erythema multiforme.

Toxic epidermal necrolysis (TEN) is the rarest of the drug eruptions but the most lethal. In the widespread necrosis of the skin, patients often have pyrexia, anorexia, lethargy and pain.

     • Toxic epidermal necrolysis (TEN) should always be given with a poor prognosis.

     • Treatment is to remove inciting drug/cause if possible and supportive care.

Necrolytic migratory erythema (Hepatic Cutaneous syndrome) is a syndrome that is usually seen in older animals. Hepatopathy, pancreatic or liver neoplasia are usually associated with NME. Diabetes Mellitus is often seen, especially later in the course of NME. Secondary staph and/or malassezia infections are often present. Necrolytic migratory erythema patients exhibit erythema, erosions, ulcerations and crusting often in the mucocutaneous syndromes with footpad hyperkeratosis and ulcerations often leading to lameness.

     • Diagnosing NME: Dermatopathology is diagnostic with often talked of the red, white and blue pattern seen by the pathologist. Ultrasound of the liver will often show a swiss cheese type of appearance.

     • Treatment for necrolytic migratory erythema should be based on amino acid intravenous supplementation. Amino acids are given weekly to biweekly usually through a central line to improve skin lesions. Concurrent antibacterial and antifungal drugs are used as needed. Contrary to logic, sometimes glucocorticoid therapy will be helpful in NME cases.

Demodicosis can be a lethal disease due to extreme expense or extreme frustration of the owner. Demodicosis is seen in 2 populations of canine patients. The younger genetic cases of demodicosis and older populations secondary to an immune-suppressing disease. Sometimes demodicosis can be secondary to chronic allergic diseases due to long term steroid use and even immune dysfunction from the chronic allergic disease.

     • Diagnosing demodicosis is done through skin scrapings, hair plucks and occasionally dermatopathology.

     • Treatment for demodicosis involves long-term antibiotic therapy for the secondary pyoderma, treating the underlying systemic diseases if possible.

     o Mitaban (amitraz) dips weekly to biweekly usually done in hospitals due to possible owner issues handling the dip.

     o Ivermectin 300-600mcg/kg daily orally. Ivermectin should not be used in herding breeds unless MDR1 genotyping has been shown that the patients will tolerate it. This is typically done through Washington State University's laboratory.

     o Doramectin? Promerus?

Cutaneous Neoplasias

1. Mass cell tumors

2. Squamous cell carcinoma

3. Mucoid Cutaneous melanoma

4. T-Cell lymphomas

Cutaneous T-Cell lymphoma is a proliferation of T-lymphocytes that have an epidermal affinity often leading to micro abscesses in the epidermis called Pautrier's micro abscesses. Many forms of T-cell are seen in the dog including a generalized erythema scaling, mucocutaneous depigmentations with erosions, crusting plaques, nodules to frank tumors.

     • Diagnosing neoplastic skin diseases involve dermatopathology.

     • Treatment for cutaneous T-cell lymphoma is often difficult with a variable prognosis and usually best treated through a medical oncologist. CCNU appears to be the treatment of choice but Prednisone, Safflower oil, Accutane and other vitamin A analogs have also been used to treat cutaneous T-cell lymphoma.

Paraneoplastic alopecia is a recently described syndrome in older cats that have a rather classic shiny skin with exfoliated alopecia. These cats often have weight loss and/or anorexia and ultrsonographic examination will usually reveal pancreatic carcinoma.

     • Treatment options are poor for this syndrome and usually involve supportive care but a grave prognosis should be given to the owners.