Niacinamide with tetracycline or doxycycline

Tetracycline is an antibiotic that also modulates the immune system by suppressing neutrophil chemotaxis and lymphocyte activation.⁶⁵ Tetracycline is used in combination with niacinamide for a variety of immune-mediated dermatologic conditions.

For dogs < 10 kg, 250 mg each of tetracycline and niacinamide are given orally every eight hours. For dogs > 10 kg, the dose is 500 mg of each every eight hours. Tetracycline and niacinamide are typically not used in cats because it is difficult to administer these larger-sized oral medications to most cats. Doxycycline has the advantage of needing less frequent dosing than tetracycline. It has been substituted for tetracycline and used at a dose of 5 to 10 mg/kg orally in dogs every 12 to 24 hours. However, there is no documentation of the benefit of doxycycline when it is substituted for tetracycline to treat canine pemphigus foliaceus.

Side effects include lethargy, anorexia, diarrhea, and increased risk of seizures. Lethargy and anorexia are especially associated with niacinamide. If the niacinamide needs to be discontinued, the tetracycline (or doxycycline) alone can continue to have immunomodulatory activity.

Other medications

A variety of other therapies have been used for pemphigus foliaceus, including cyclophosphamide, injectable gold salts, intravenous immunoglobulins, mycophenolate mofetil, and dapsone. Referral to a veterinary dermatologist is recommended before using these therapies. Referral is also recommended if treatment failure occurs with any of the medications discussed in this article.

MONITORING

No matter which medications are chosen to manage pemphigus foliaceus, frequent recheck examinations are important to assess clinical response and to determine when to taper medications. We recommend rechecking all pemphigus foliaceus patients within one or two weeks of starting medical management. A substantial improvement in clinical signs within 10 days of starting glucocorticoid therapy in dogs is a positive prognostic factor in the successful management of pemphigus foliaceus.⁵

Glucocorticoids are often used for pemphigus foliaceus treatment induction because of their rapid onset. If marked clinical improvement is noted, the glucocorticoid dose or frequency of administration should be tapered by about 25%. If clinical signs have stayed the same or worsened despite glucocorticoid therapy, the glucocorticoid dose should be increased or combination therapy should be started. Combination therapy should also be started if remission of the pemphigus foliaceus cannot be maintained when the glucocorticoid dose is tapered. We recommend rechecking patients before and after each change in medication type or dose to help monitor clinical signs.

Cutaneous side effects of immunosuppression such as a bacterial skin infection, demodicosis, or dermatophytosis can look clinically similar to a pemphigus foliaceus flare. It is important to rule out these conditions instead of assuming that any new dermatologic lesions are due to pemphigus foliaceus, otherwise lesions may worsen from immunosuppression, and refractory pemphigus foliaceus may be erroneously diagnosed. Skin scrapes and hair plucks should be performed on new areas of alopecia, and cytologic examination should be used to evaluate lesions for secondary skin infections.

Table 4: Principles of Treating Pemphigus Foliaceus in Dogs and Cats

The outcome of treating pemphigus foliaceus in dogs and cats is variable; 40%⁵¹ to 88%⁴ of dogs with pemphigus foliaceus have their condition managed successfully. Neither a younger age of onset nor a localized disease pattern correlate with improved survival times.⁵¹ The only factor that has influenced long-term survival time in dogs with pemphigus foliaceus is the concurrent use of antimicrobials with immunosuppressive medications, likely because the antimicrobials minimize the development of secondary bacterial skin infections and urinary tract infections. Prolonged remission after immunosuppressive therapy can occur in dogs and cats with pemphigus foliaceus.^15,67

Mortality from pemphigus foliaceus can occur because of disease progression, medication side effects, or client-requested euthanasia. Severe cases of pemphigus foliaceus can result in marked cachexia or sepsis secondary to infections. Adverse effects are common with most of the medications used for pemphigus foliaceus. Euthanasia accounted for almost 70% of deaths in pemphigus foliaceus dogs in one retrospective study.⁵¹ Reasons for client-requested euthanasia included not being able to control the pemphigus foliaceus, a perceived poor quality of life, and the development of adverse effects from medications. For all these reasons, pemphigus foliaceus should be considered a potentially fatal dermatologic condition. Consultation with a specialist or referral can be helpful when managing pemphigus foliaceus cases.

SUMMARY

Pemphigus foliaceus is a pustular and crusting autoimmune dermatologic condition. The prognosis for pemphigus foliaceus in dogs and cats is variable, and signs can wax and wane. A diagnosis is based on the patient's clinical history, a histologic examination of skin samples, and a diagnostic work-up that rules out other neutrophilic and pustular skin conditions. A variety of immunomodulatory medications can be used to manage pemphigus foliaceus. Frequent recheck examinations and client communication are important for managing pemphigus foliaceus. Because of the potential for severe medication side effects, medications should be selected and tapered based on the severity of clinical signs.

Kathy C. Tater, DVM, DACVD
Angell Animal Medical Center
350 S. Huntington Ave.
Boston, MA 02130

Thierry Olivry, DrVet, PhD, DECVD, DACVD
Department of Clinical Sciences
College of Veterinary Medicine
North Carolina State University
Raleigh, NC 27606

REFERENCES

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2. Koulu L, Kusumi A, Steinberg MS, et al. Human autoantibodies against a desmosomal core protein in pemphigus foliaceus. J Exp Med 1984;160(5):1509-1518.

3. Rock B, Martins CR, Theofilopoulos A, et al. The pathogenic effect of IgG4 autoantibodies in endemic pemphigus foliaceus (fogo selvagem). N Engl J Med 1989;320(22):1463-1469.

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6. Olivry T, Dunston SM, Walker RH, et al. Investigations on the nature and pathogenicity of circulating antikeratinocyte antibodies in dogs with pemphigus foliaceus. Vet Dermatol 2008;20(1):42-50.