Pemphigus foliaceus (PF) is an autoimmune disease, with IgG and occasionally IgM antibodies targeting intercellular (transmembrane) proteins that hold the epidermal cells together. While in people this targeted protein is usually desmoglein-1, this is only the target protein in a minority of dogs.¹ In dogs the target is another protein, desmocollin-1.² The target protein(s) in cats has not been identified.

PF usually presents in one of two forms, a mucocutaneous and encrusted pustular disease starting on the nasal planum, periocularly and the foot pads, and a generalized and encrusted (often pruritic) dermatosis.³ This latter form is more common in Chow Chows, Retrievers, Setters, and cats, and often associated with systemic signs such as fever or lethargy. Pruritus is variable, but is frequently noted in cats. Crusts may also occur around the nipples, particularly in cats, and can appear on the pinna, mimicking squamous cell carcinoma in white cats. Cats will also often present with paronychia (crusts and inflammation of the claw bed). Certain dog breeds appear at risk, such as Chow Chows, Bearded Collies, Schipperkes, Akita, and others.

Histopathology of PF reveals subcorneal pustules filled with neutrophils (sometimes eosinophils) and acantholytic cells.

Drug-related pemphigus (RxP) Antibiotics, particularly trimethoprim-sulfa are the most common drugs reported causing this condition in small animals.^8-13

A topical anti-flea product containing metaflumizone and amitraz (now off the US market) has been documented as causing drug-related PF.¹⁴ More recently, another topical anti-flea medication, containing fipronil, amitraz and S-methoprene, has been implicated in causing PF.^14a

Pemphigus vulgaris (PV) is a rare disease reported in both dogs and cats - the author sees a case about once every 5 years! As in people, IgG antibodies to desmoglein 3. German Shepherd dogs and Collies may be at risk. Clinical signs are mucocutaneous and mucosal ulcers; there may be a nasal planum/muzzle variant as well. Histopathology shows a suprabasal cell layer cleft with occasional acantholytic and inflammatory cells.^16-18

Paraneoplastic pemphigus (PNP) is another rare skin disease - only three dogs and one cat are reported in the literature.^17,19,22,22a As its name implies, the disease is secondary to a neoplastic, usually malignant, condition. Clinically the disease resembles PV.

Treatment

The primary drug utilized in the treatment of the pemphigus foliaceus (or other forms of pemphigus) is some form of short-acting oral glucocorticoid. Usually this is prednisolone, started at a dosage of 1 mg/kg given twice daily. This dosage is reduced slowly over the course of six to eight weeks to an every 48 hour regimen, ideally at 0.5 mg/kg. Dogs that have severe polyuria/polydipsia may be switched to oral methylprednisolone at similar dosages. Pulse therapy of glucocorticoids has been reported previously with intravenous dosing,^23a and more recently using oral prednisolone^23b. Regimens approximate to 10 mg/kg once daily for 3 days, then 1–2 mg daily. In one study, this reduced mortality as well as the need to use other immunosuppressive drugs.^23b Prednisolone is therefore the initially recommended glucocorticoid to be used in cats. Alternatively, triamcinolone at 0.5–1.0 mg/kg may be very effective.

Only approximately 10–20% of the dogs and cats with autoimmune skin disease in the author's practice are well controlled on glucocorticoids alone. In most cases of pemphigus other drugs must be utilized. In dogs, the author's first choice is azathioprine, at a dosage of 2.2 mg/kg, given orally once daily for one month, then every 48 hours thereafter. Azathioprine is a purine analog that functions as an antimetabolite, and also has antiinflammatory effects. Azathioprine has a lag phase of four to six weeks before it reaches its full potential as an immunosuppressant drug. It is not good at inducing remission but rather at maintaining remission. Therefore, it is given concurrently with a glucocorticoid but eventually allows the veterinarian to lower the dose (i.e., it is a "steroid-sparing" drug). Azathioprine occasionally causes vomiting (less than 10% of dogs treated) and has been linked to blood dyscrasia (thrombocytopenia) and liver disease.

Azathioprine should not be used in cats, due to the bone marrow suppressive effects of the drug; leukopenia can be significant.

In cats, the preferred adjunctive therapy to glucocorticoids is chlorambucil. This drug, an alkylating agent, is similar to cyclophosphamide but does not cause the hemorrhagic cystitis so often seen with the latter drug. Its cost in the USA limits its use to cats and small dogs. Its dosage is 0.1–0.2 mg/kg/day until there is at least 75% improvement in clinical signs. At this point, every other day administration of chlorambucil is initiated. Chlorambucil is usually not good at inducing remission, therefore a glucocorticoid must be given concurrently; however, in some cats, the corticosteroid may be discontinued and the chlorambucil used alone once remission is achieved.

In a recent report, cyclosporine was shown to be as effective as methylprednisolone in a small cadre of cats.³²

Finally, it should be mentioned that the author has seen several dogs whose PF worsened upon excessive exposure to sunlight. Thus sun-avoidance should be a part of any PF treatment regimen.

Discoid Lupus Erythematosus

Discoid lupus erythematosus (DLE) is common in dogs.¹ It is most common in the long nose breeds (the author has never seen it in a bulldog). This is also a disease of young to middle aged-dogs. Clinical signs are usually limited to the face and most commonly involve depigmentation and ulceration of the nasal planum, the lips, the periocular area, membrana nictitans, and oral cavity. Silver to grey well-circumscribed scaling areas may be seen on the inner pinna. In general, discoid lupus is more likely to show depigmentation and less likely to be encrusted, compared to pemphigus foliaceus. Diagnosis is based on biopsy which reveals an interface dermatitis, similar to SLE. An ANA test is negative.

The author's first choice to treat DLE has utilized the combination of doxycycline (5 mg/kg q 12 h) and niacinamide (called nicotinamide in Europe) at 500 mg/dog q 8 h (if the dog is less than 10 kg, this dosage is reduced to 250 mg). A lag phase exists before full effect, usually four to eight weeks. However, these drugs will induce as well as maintain remission. Once control of the disease is achieved the drugs may be reduced in some dogs to twice a day or even once a day therapy. Some dogs may need topical corticosteroids, such as 0.1% betamethasone BID to SID, or low doses (0.25 mg/kg every other day) of prednisolone for maximum control. The overall success rate in discoid lupus with this combination of niacinamide and tetracycline is 65–70%.³ Side effects of this regimen are uncommon but vomiting, diarrhea, anorexia and lethargy have been noted, usually due to the niacinamide. Very rare cases in dogs have been seen with hepatotoxicity or neurologic signs (hindlimb weakness/inability to rise). It should be emphasized that in many dogs, restriction to sun exposure is helpful.

A topical treatment for DLE that the author has been impressed with in a small number of cases is tacrolimus 0.1% ointment (Protopic: Fujisawa), applied initially twice daily, then reduced to daily or every other day frequency depending upon response. In a number of cases this may be the only treatment necessary. This is an expensive product in the USA. It seems to be very well tolerated in the dog, with few if any adverse effects.

Exfoliative Cutaneous Lupus Erythematosus

Exfoliative cutaneous lupus erythematosus (ECLE) (a.k.a. lupoid dermatosis of German Short-haired Pointers) is a hereditary disease which usually occurs within the first year of life.^6,7 Thus far it has only been described in German Short-haired Pointers, many of which are related; initial inspection of pedigrees is suggestive of an autosomal recessive mode of inheritance. Affected dogs present with localized to generalized scale (sometimes with follicular casting) and alopecia. The disease may be progressive or may wax and wane. Pruritus is minimal. Rare dogs may have blood dyscrasias or joint disease. Histology shows hyperkeratosis, basal cell degeneration and apoptotic epidermal cells. Often sebaceous adenitis and/or a lack of sebaceous glands are noted. Treatment has not usually been successful - cyclosporine, HCQ, and adalimumab have been used without notable success.⁸ The author is aware of one dog that initially responded to niacinamide and tetracycline, and another to prednisolone and azathioprine.

Vesicular Cutaneous Lupus Erythematosus

Vesicular cutaneous lupus erythematosus (VCLE) (a.k.a. ulcerative dermatosis of Collies and Shetland Sheepdogs). This is an ulcerative dermatitis seen primarily in the Shetland Sheepdog and Rough Collie Dog, and their crosses.^9,10 An adult onset disease, seen more often in the summer months (UV light exacerbation/triggering?), lesions are annular, polycyclic and serpiginous ulcerations distributed over sparsely haired areas of the body. Axilla and inguinal areas especially are affected. Histology shows a lymphocyte-rich interface dermatitis and folliculitis, with vesiculation at the dermal-epidermal junction. Treatment varies, as does its success: some dogs do well on the niacinamide/tetracycline regimen noted above, some to cyclosporine, and some to the prednisolone/azathioprine regimen as with SLE. Unfortunately, some dogs do not respond at all to treatment. One report describes successful treatment using cyclosporine.¹¹

References

References are available upon request.