Chapter 48 Immune-Mediated Dermatoses
Immune-mediated dermatoses are relatively uncommon diseases in domestic animals. This group may be divided into autoimmune and immune-mediated categories according to immunopathogenesis.
• Autoimmune diseases include the pemphigus complex, bullous pemphigoid, mucous membrane pemphigus, and uveodermatologic syndrome (Vogt-Koyanagi-Harada syndrome). These are characterized by a specific antibody-mediated or cell-mediated immune response directed against a normal component of the skin or body.
• Immune-mediated dermatoses include systemic lupus erythematosus and cutaneous (discoid) lupus erythematosus. In these diseases, antigen-antibody complexes are formed and then deposited in various locations (vessel walls, glomeruli of the kidney, or basement membrane zone of the skin). This deposition of immune complexes may then trigger an inflammatory response that results in tissue destruction.
PEMPHIGUS COMPLEX
The pemphigus complex of diseases includes pemphigus foliaceus, pemphigus erythematosus, pemphigus vulgaris, pemphigus vegetans, panepidermal pustular pemphigus, paraneoplastic pemphigus, and drug-related pemphigus.
• Pemphigus erythematosus is considered a variant of pemphigus foliaceus. It may have clinical and histopathologic features of lupus erythematosus and is therefore considered a “crossover” between the pemphigus and the lupus erythematosus complexes.
• Pemphigus vegetans is an extremely rare variant of pemphigus vulgaris that is distinguished clinically from the other autoimmune diseases by the production of lesions that are vegetative (i.e., proliferative) rather than pustular or ulcerative.
Etiology
The exact cause or stimulant for the production of the pemphigus antibody is unknown. Theories involve either abnormal immune regulation or abnormal antigen stimulation.
• A virus spread by an insect vector has been proposed as the initial stimulus. This theory gains support from an endemic form of pemphigus (fogo selvagem) in humans in South America.
• In humans, once formed, the antibody binds with components found in the core of the desmosome (desmoglein I or plakoglobin). Desmosomes function as attachment areas between keratinocytes of the skin. This binding stimulates plasminogen activators (i.e., serine proteases), which subsequently cause the conversion of plasminogen to plasmin.
• The production of plasmin causes the disruption of the desmosome attachments and therefore a loss of keratinocyte adhesion. This loss of adhesion between adjacent cells is called acantholysis, and the individual cells are termed acantholytic cells.
• All of the diseases in the pemphigus complex appear to have the same immunopathogenesis, but the target protein will vary depending on the type of pemphigus. The location of the bulla or separation within the epidermis differs; for example, pemphigus foliaceus has a more superficial bulla than pemphigus vulgaris.
Clinical Signs
Pemphigus Foliaceus
• Breeds that are predisposed include Akitas, chow chows, bearded collies, dachshunds, Doberman pinschers, schipperkes, and rottweilers.
• Lesions consist of erythematous macules that progress rapidly to a pustular phase and then appear as a dry, yellow crust. These lesions may be limited to the pinnal, perioral, periocular, dorsal muzzle, nasal planum, and/or nail bed regions, or they may be generalized. Although pustules are the primary lesions, these are uncommonly seen and the clinician is more typically presented with a crusting dermatitis.
• Animals may present with marked hyperkeratosis (scaling) or crusting of the foot pads with or without nail bed involvement. The nails usually are normal.
• Cats commonly exhibit a marked paronychia that appears as a thick “cheesy” core of exudate when the nails are extruded manually.
Pemphigus Erythematosus
• Collies appear to be at risk (this disease is one of several differential diagnoses for “collie nose”).
Pemphigus Vulgaris
• Ulceration of the oral cavity may be an initial presenting sign in over 50% of cases and is eventually present in 90% of cases. Drooling and difficulty in eating may be presenting signs.
Paraneoplastic Pemphigus
• Rare form of pemphigus recognized in association with canine lymphoma and one case of Sertoli cell tumor.
Diagnosis
Histopathologic examination of skin biopsies gives the most valuable diagnostic information. Obtain at least three biopsies of the freshest pustules, vesicles, or bullae or from the edge of an ulcerated lesion.
• In all of the pemphigus complex diseases, the complete blood count (CBC), serum biochemical profile, and urinalysis are non-diagnostic.
• Anti-nuclear antibody (ANA) tests are positive at low titers in 50% of pemphigus erythematosus patients, but in other forms of pemphigus the ANA tests are generally negative.
False-positive ANA titers may be seen in animals with pemphigus, rheumatoid arthritis, idiopathic thrombocytopenia, autoimmune hemolytic anemia, thyroiditis, endocarditis, cancer, hepatotoxicity, feline leukemia, feline infectious peritonitis, dirofilariasis, demodicosis, and flea allergy dermatitis; they even may be seen in clinically normal animals.
Pemphigus Foliaceus
• Direct smear of an intact pustule or surface beneath a thick crust reveals numerous acantholytic cells.
• Histopathologic findings include subcorneal and/or intragranular pustules with acantholytic cells.
• Direct immunofluorescent antibody (IFA) tests and direct immunoperoxidase staining (IPS) tests are positive, with intercellular staining of immunoglobulin and/or complement in the upper one-third of the epidermis.
• IPS is not very specific; positive results are obtained in 73% of animals with pyoderma, 67% with dermatophytes, 50% with demodicosis, and 100% with scabies. Also, IPS is positive with the immunoreactant immunoglobulin G in an intercellular pattern in biopsies obtained from normal canine planum nasale and foot pads. IFA is positive with the immunoreactant immunoglobulin M in a basement membrane zone pattern in 75% of normal canine nasal biopsies and 45% of biopsies of normal foot pads, thus yielding false-positive results.
Pemphigus Erythematosus
• Histopathologic findings include subcorneal and/or intragranular pustules, hydropic degeneration of the basal cell layer, and dyskeratotic cells.
Pemphigus Vegetans
• Histopathologic findings include intraepidermal acantholytic eosinophilic microabscesses with significant surface crusting and verrucous vegetations and papillomatous proliferations.
Paraneoplastic Pemphigus
• Histologic lesions appear to be a mixture of pemphigus foliaceus (PF), pemphigus vulgaris (PV), and erythema multiforme.
Differential Diagnoses
The major differential diagnoses for pemphigus foliaceus include the following.
Generalized Pustular Crusting
• Bacterial pyoderma (it is essential to rule out pyoderma before making a diagnosis of pemphigus foliaceus based on negative cytology, negative culture, and poor response to antibiotics)
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