How to deal with the difficult immune mediated diseases (Proceedings)

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How to deal with the difficult immune mediated diseases (Proceedings)

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Nov 01, 2010

A variety of different diseases are in the category of what are referred to as autoimmune or immune mediated dermatologic diseases. The diseases typically have differing etiologies though a significant component in there pathogenesis is an abnormal or deleterious immune response that affect normal cutaneous structures, such as epidermal keratinocytes, basement membranes, blood vessels or adnexal structures. There is a wide variation in what is "wrong" with the immune system as well as what initiated the response. In some cases infectious agents such as bacteria or viruses may be the inciting etiology or the reaction may be in response to a drug. Some diseases, such as discoid lupus erythematousus and pemphigus erythematosus, are known to have a percentage of the cases photoaggraveted and control to UV exposure may alleviate or diminish the lesions and failure to control exposure may decrease the response to therapy. Therapies for autoimmune and immune mediated skin diseases often require immunonosuppressive or immunomodulating drugs. These drugs often effect different aspects of the immune response or function by different mechanisms. The differences between the diseases and treatments lead to variable responses to therapy with these drugs. There is no one routinely effective treatment and many different drugs and combinations of drugs may be used to manage these cases. The variable responses to treatment, expense of the drug or required monitoring and potential adverse effects all contribute to the treatment selected for each patient.

A specific diagnosis as possible should be made when using immune suppressive drug regimens. Even with a specific diagnosis there appears to be some controversy for some of these diseases regarding treatment success and the ultimate long-term prognosis of many of these disorders. For example in canine pemphigus, pemphigus vulgaris (PV) tends to be a more aggressive disease and more difficult to treat and manage than other forms of pemphigus. When pemphigus vulgaris occurs some cases are controllable but when it occurs as a result of a paraneoplastic syndrome it usually is non responsive and a fatal disease. Pemphigus foliaceus (PF) tends to warrant a better prognosis than pemphigus vulgaris but there is still variation in reported success. One report of 43 cases 39.5% were alive at the end of a 6-year study period. Of the dogs that had died 92% were dead by one year into treatment. Of these cases, 87% were euthanized due to drug side effects. These results are different from another report. Another study evaluated 91dogs with PF and had treatment follow up for 88 dogs with an average follow up of 18months. Only 12.5% had died while 46 were in remission and 31 significantly improved and one dog was completely tapered off drugs and stayed in remission. Eleven dogs were euthanized with 4 for refractory disease, 4 for unrelated problems, 2 for drug side effects and one the reason was unknown.

Since many patients are euthanized prior to reaching an acceptable level of improvement, the goal of therapy should not just be to stop the destructive immunologic response. Instead, the primary objective is to stop the inflammation and immunological destruction without causing side effects that the patient and client will not tolerate. This goal dictates how to approach the treatment of immune mediated skin disease and led to the following key principles of treatment as adapted for treatment of pemphigus from Griffin and Newton, 2011.

Key principles for treatment of immune mediated skin disease:

  • Avoid doses of drugs that result in unacceptable side effects.
  • Unacceptable side effects are partly determined by the client and the client's family.
  • Severe cases initially need to be treated more aggressively.
  • Combination drug therapy is generally more effective and has fewer side effects than monotherapy.
  • Benefits are additive but differing side effects are not.
  • Often not selected as the initial treatment because it is more costly than glucocorticoids alone.
  • Mild or localized cases may initially be treated less aggressively.
  • May mean relying on more topical therapy.
  • Monotherapy with low immunosuppressive dose of glucocorticoids.
  • When known, avoid triggering factors such as drugs or UV radiation.
  • Persistent focal mild lesions should be acceptable only if their resolution requires higher drug doses that create more side effects or greater expense of therapy.
  • Clients should be advised that some dogs may be cured or reach long-term remission, depending on the cause and even when no cause if found there may be some chance for cure, though controlled studies providing prognostic statistics are lacking for most immune mediated diseases.
  • Three phases of treatment are typical for most immune mediated skin diseases:

      1. Induction of remission
      2. Transition
      3. Maintenance

Induction phase

The initial therapy used in treating pemphigus is selected to stop the inflammation and suppress the immunologic response against the epidermis. Higher doses of drugs are usually needed for this phase of therapy. If the induction therapy is not effective in a timely manner for the chosen class of drugs, then the induction treatment should be immediately changed. For example, if 2.2 mg/kg q12h of prednisolone is not effective within 7-10 days, then a different induction treatment should be selected. Patients treated with azathioprine alone should show a good response within four weeks. Good response during the induction phase is characterized by drying and resolution of erosions with no development of new pustules or erosions; crusts may still be present but generally are found in the hair rather than at the skin surface. Also, patients that start treatment depressed, febrile, or otherwise systemically ill should show great improvement in attitude during the initial induction phase.