Buster, a 2-year old castrated male Staffordshire bull terrier mix, presented to the Dermatology Service at Foster Hospital for Small Animals at Cummings School of Veterinary Medicine for a five-month history of generalized demodicosis with secondary bacterial folliculitis. The dog had been treated with ivermectin at a therapeutic dosage of 0.5mg/kg PO every 24 hours as well as cephalexin at 25mg/kg PO twice daily for the concurrent secondary infection for the past three months. The owners had also been bathing him with an over-the-counter baby shampoo. The owners reported that Buster initially seemed to improve; however, over the course of approximately six weeks, Buster’s skin condition had worsened. On physical examination, Buster had marked generalized erythema with pustules and crusting over his entire body and legs. He also had marked crusting of the footpads with fissuring at the junction of the haired interdigital skin and pads. The mucocutaneous regions, previously unaffected, also showed signs of alopecia and crusting. He also appeared to be lethargic.
Buster’s treatment regimen was on par with the current published guidelines for the treatment of demodicosis. What would cause his skin lesions to change and progress? What are your differentials for generalized crusting of the body, legs, mucocutaneous regions, and footpads? What further diagnostic tests would you recommend at this time?
Since the clinical description no longer fits with generalized demodicosis and the clinical signs had worsened, we felt it was important to reevaluate the current treatment plan and consider an alternative differential diagnosis.
Deep skin scrapings were repeated and no Demodex mites were visualized. Skin cytology performed using clear acetate tape showed only occasional coccoid bacteria. Biopsies were taken from 4 different skin sites; two, 6mm punch biopsies were taken from the lateral flanks and two, 6mm punch biopsies were taken from a distal hind leg. The histopathology showed subcorneal-intragranular pustular dermatitis with acantholysis. This is a classic histologic description for pemphigus foliaceus.
Pemphigus foliaceus is the most common immune-mediated skin condition reported in dogs. It is characterized by the production of IgG autoantibodies against primarily desmocollin-1, an intercellular adhesion molecule found in abundance in the uppermost layers of the epidermis. This results in the keratinocytes detaching from one another, causing acantholysis and pustule formation. These pustules are generally very fragile, and thereby their presence is often transient. Therefore, more classic clinical signs may include secondary crusting and erosions. Predilection sites include the nasal planum, dorsal muzzle, periocular skin, pinnae, and footpads, before the lesions become more generalized. Most cases are idiopathic and can occur in dogs of any age, breed, or sex. Some cases may be drug induced, or may rarely occur as a paraneoplastic syndrome.
Once a definitive diagnosis has been reached, immunosuppressive therapy may be implemented. Oral prednisone is often used as a first line option at 2mg/kg per day to help achieve remission rapidly. Although corticosteroids alone may be effective in maintaining remission, the dosages required may result in many undesirable adverse effects. A second non-steroidal immunosuppressive drug may be added, for example, azathioprine, cyclosporine A, or mycophenolate mofetil. The goal for any of these immunosuppressive agents is to taper the dosages to the lowest possible and least frequent to maintain remission long term. Regular lab work is important to monitor for adverse reactions.
Buster’s treatment plan was particularly challenging to manage because of his history of juvenile-onset generalized demodicosis, in which future treatment with any corticosteroid is contraindicated. However, after weighing the risks and benefits, he was eventually started on prednisone. Advantage Multi® (Bayer) was used concurrently at a once weekly interval as a precaution to prevent recurrence of demodicosis. Remission was achieved rapidly with no recurrence of demodicosis. The prednisone was eventually tapered and cyclosporine A was added as a steroid-sparing agent. Buster is doing well two years following his diagnosis of pemphigus foliaceus.
Figure 1. Marked crusting of the footpads and erythema of the interdigital spaces.
Figure 2. One pustule is noted in the granular layer of the epidermis. The brightly eosinophilic nucleated cells within the pustule are acantholytic cells.