Autoimmune Skin Diseases I PDF

AUTOIMMUNE SKIN DISEASES VCS 80610 – Small Animal Medicine I PAULO GOMES, DVM, DACVD COLLEGE OF VETERINARY MEDICINE CLINICAL ASSISTANT PROFESSOR OF VETERINARY DERMATOLOGY DEPARTMENT OF VETERINARY CLINICAL SCIENCES Outline Ø Pemphigus Complex ü Pemphigus foliaceous ü Pemphigus erythematosus ü P...

AUTOIMMUNE SKIN DISEASES VCS 80610 – Small Animal Medicine I PAULO GOMES, DVM, DACVD COLLEGE OF VETERINARY MEDICINE CLINICAL ASSISTANT PROFESSOR OF VETERINARY DERMATOLOGY DEPARTMENT OF VETERINARY CLINICAL SCIENCES Outline Ø Pemphigus Complex ü Pemphigus foliaceous ü Pemphigus erythematosus ü Pemphigus vulgaris Ø Discoid Lupus Erythematosus Pemphigus Complex Ø Autoimmunity is a condition characterized by a specific humoral or cell-mediated immune response against the component of adhesion molecules on keratinocytes Ø Three most common forms of Pemphigus ü Pemphigus foliaceous ü Pemphigus erythematous ü Pemphigus vulgaris Pemphigus Complex Ø Pathomechanism ü Antibodies (IgG) directed against adhesion molecules within the desmosomes ü Desmosomes • Epidermal intercellular structure that holds the cells together ü Targeted adhesion molecules • Desmoglein or desmocollin Pemphigus Complex Ø Pathomechanism ü The final result of IgG binding to desmoglein/desmocollin • Acantholysis (cells detach from each other) ü Acantholytic cells are detached immature keratinocytes that are the hallmark of pemphigus Pemphigus Complex Ø Forms of pemphigus ü Superficial – lesions are formed underneath the stratum corneum or inside the stratum granulosum • Pemphigus foliaceus • Pemphigus erythematous ü Deep – lesions are formed just above the basal cell layer • Pemphigus vulgaris Pemphigus Foliaceus Ø The most common autoimmune skin disease of dogs and cats ü Animals of any age, breed, or sex can be affected ü Akitas and chow chows seem to be over-represented Ø Usually idiopathic, but in some cases can be induced by drugs or chronic inflammation ü Acute onset ü Systemic signs are uncommon: lymphadenomegaly, limb edema, fever, anorexia, and depression Pemphigus Foliaceus Ø Primary lesions ü Pustules • Difficult to find because they rupture very easily • Obscured by the haircoat Ø Secondary lesions ü Crusts, scales, collarettes, alopecia, erosions, and erythema Ø Footpad hyperkeratosis Ø Pruritus and pain are variable Pemphigus Foliaceus Ø Distribution of lesions ü ü ü ü ü Nasal planum Ear pinnae Footpads Paronychia: often seen in cats Crusts on the nipple. Usually present in cats Ø Begins on the bridge of the nose, around the eyes, and pinnae before it becomes generalized Ø Oral lesions and mucocutaneous involvement are very rare and if present are minimal Pemphigus foliaceus: frequently starts on the face especially the dorsal aspect of the nose and the nasal planum. Pemphigus foliaceous: pinnae involvement. Pemphigus foliaceus: footpad hyperkeratosis. Pemphigus foliaceus: generalized – crusts, scales, alopecia, erosions, and erythema. Pemphigus foliaceus: crusts, scales, alopecia, erosions, and erythema on the bridge of the nose, head, and pinnae. Pemphigus foliaceus: Cat – hyperkeratosis of the footpads, and paronychia (inflammation of the nail fold). Pemphigus Foliaceus Ø Differential diagnosis ü Bacterial folliculitis ü Dermatophytosis ü Other immune mediated diseases • Pemphigus complex, SLE, DLE, bullous pemphigoid, dermatomyositis ü Drug eruption, zinc-responsive dermatitis, cutaneous lymphoma, superficial necrolytic dermatitis, demodicosis, and mosquito bite hypersensitivity in cats Pemphigus Foliaceus Ø Diagnosis ü Middle age adult dogs ü Acute onset and gradual progression of skin lesions ü Lesions on the nasal planum, ear pinnae, and footpads are characteristic of autoimmune skin disease ü Nasal depigmentation frequently accompanies facial lesion ü Cytology of pustules ü Dermatohistopathology ü Immunofluorescence or immunohistochemistry: usually not performed on a clinical setting ü Bacterial culture: if secondary infections are present Pemphigus Foliaceus Ø Diagnosis ü Cytology of a pustule • If pustule not present - collect sample from underneath a crust • Nondegenerated neutrophils, multiple acantholytic keratinocytes, +/- eosinophils, no bacteria Pemphigus foliaceus: Cytology – several acantholytic cells (arrow) and nondegenerated neutrophils Pemphigus Foliaceus Ø Diagnosis ü Histopathology • The most important test for a definitive diagnosis • Sub corneal or intraepidermal pustule with neutrophils, variable numbers of eosinophils and acantholytic cells Pemphigus foliaceus: histopathology - subcorneal pustule several acantholytic cells and nondegenerated neutrophils Pemphigus Foliaceus Ø Diagnosis ü Direct Immunofluorescence or immunoperoxidase • Intercellular staining of Immunoglobulins • Sample – skin biopsy • Immunofluorescence - Michel’s solution • Immunoperoxidase - Formalin • False negatives/false positives Pemphigus foliaceus: Immunofluorescence – intercellular staining of immunoglobulins Pemphigus Foliaceus Ø Diagnosis ü Indirect Immunofluorescence • Sample - serum • Usually low titer or negative results ü CBC, chemistry profile, UA • Usually normal • Inflammatory changes may be seen ü Antinuclear antibody (ANA): negative Pemphigus Erythematosus (PE) Ø Uncommon in dogs and rare in cats Ø Increased incidence: German shepherds, collies, and Shetland sheepdogs Ø Considered a benign form of pemphigus foliaceous or a crossover between pemphigus and lupus erythematosus Ø It does have some similarities with lupus erythematous ü ANA may be positive but not pathognomonic of PE ü Immunofluorescence similar to both, pemphigus (intercellular staining) and lupus (staining along basement membrane) ü Lesions are aggravated by UV light Pemphigus Erythematosus Ø Distribution of lesions ü Face (nasal planum and dorsal muzzle) and ear pinnae only ü Oral cavity is not involved Ø Histopathology ü Lesions characteristic of pemphigus foliaceus ü Lesions characteristic of lupus erythematosus • Basal keratinocyte vacuolization and presence of apoptotic cells in the basal layer ü Histopathology is the most important test for a definitive diagnosis Pemphigus erythematosus Pemphigus Vulgaris Ø Uncommon to rare Ø It is the ulcerative and most severe form of pemphigus Ø Autoantibodies against antigen in or near the epidermaldermal junction Ø Primary lesions ü Vesicles and bulla Ø Secondary lesions ü Erosions, ulcers, and occasionally crusts ü Most commonly seen Pemphigus Vulgaris Ø Distribution of lesions ü Mucocutaneous regions • Lips, nares, eyelids, mouth, anus, genitalia ü Nail beds, inguinal, and axillary areas ü Erosions, ulcerations, and rarely vesicle and bullae • Oral cavity affected in about 80% of the cases • Marked salivation and halitosis Ø Animals can become sick and present with anorexia, fever and depression Pemphigus Vulgaris Ø Differential diagnosis ü Bullous pemphigoid, systemic lupus erythematosus, erythema multiforme, toxic epidermal necrolysis, drug reaction, vasculitis, cutaneous epitheliotropic lymphoma, bacterial and fungal infections Pemphigus vulgaris: erosions and ulcerations in mucocutaneous areas Pemphigus vulgaris: erosion and erythema affecting oral mucosa Pemphigus vulgaris: erosion and ulcer on vaginal mucosa Pemphigus vulgaris: cytology - acantholytic cells and neutrophils Pemphigus Vulgaris Ø Cytology ü Acanthocytes and neutrophils Ø Histopathology ü Suprabasilar acantholysis and cleft forming a vesicle or bulla which will contain acanthocytes and neutrophils. Basal cells will have a “tombstone” appearance. Hair follicles may be involved Pemphigus Complex Ø Treatment ü Typically combination of therapies have been used to achieve remission and minimize adverse effects of any one therapy ü Oral glucocorticoids • Immunosuppressive doses • Once remission has been achieved - gradually decrease to low dose alternate day medication • Prednisone, prednisolone, dexamethasone, triamcinolone Pemphigus Complex Ø Treatment ü Recheck in 14 days ü About 50% respond to oral glucocorticoids alone ü Cytotoxic Drugs • Consider if no significant response after 10 to 14 days of glucocorticoids and/or severe side effects • Can be used initially with glucocorticoids • Dogs: Azathioprine, chlorambucil, dapsone • Cats: Chlorambucil Pemphigus Complex Ø Aggressive treatments with few studies documenting efficacy and safety ü Glucocorticoid pulse therapy • Very high doses for 3 days followed by reduced daily dose • Pulses are repeated as needed ü Mycophenolate mofetil ü Leflunomide Ø It is unclear if Cyclosporine is an efficacious treatment for canine pemphigus foliaceous Pemphigus Complex Ø Client education ü It is a controllable but not curable disease ü Multiple recheck visits will be needed until the ideal treatment protocol is determined ü Response to therapy is variable and unpredictable ü There are potentially severe side effects associated with the immunosuppressive treatment ü Complications: drug adverse effects, secondary bacterial infections, fungal infections, and demodicosis Discoid Lupus Erythematosus (DLE) Ø The second most common autoimmune skin disease after pemphigus foliaceous in dogs Ø Uncommon in cats Ø Only the skin is affected Ø No systemic signs Discoid Lupus Erythematosus Ø Hypothesis for the pathogenesis of skin lesions in genetically susceptible individuals ü Ultraviolet light (UVB/UVA) penetrates to the level of epidermal basal cells induces, on the keratinocyte surface, the enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and of autoantigens previously found only in the nucleus or cytoplasm ü Specific autoantibodies to these antigens, that are present in plasma and in tissues attach to keratinocytes and induce antibodydependent cytotoxicity of keratinocytes ü Injured keratinocytes release interleukin-2 (IL-2) and other lymphocyte chemoattractants, resulting in a lymphohistiocytic infiltrate. Inappropriate activation of keratinocyte apoptosis Discoid Lupus Erythematosus Ø Clinical Signs ü Lesions • Usually start as depigmentation and erythema of the nasal planum • Progress to erosions, ulcers, scaling and crusts • Lesions may heal with atrophic scars • Loss of normal cobblestone architecture of the nose • Lesions are exacerbated by sunlight ü Distribution • Most often limited to the nasal planum and dorsal muzzle Discoid Lupus Erythematosus: depigmentation, erythema, erosions, scaling, crusts, and loss of normal cobblestone appearance of the nasal planum Discoid Lupus Erythematosus: erosion on oral mucosa, and crust on ear flap (areas uncommonly affected) Discoid Lupus Erythematosus Ø Differentials diagnosis ü Nasal pyoderma, nasal solar dermatitis, pemphigus foliaceus, pemphigus erythematous, uveodermatologic syndrome, bullous pemphigoid, dermatomyositis, and mosquito bite hypersensitivity in cats Ø Cytology ü No significant findings Discoid Lupus Erythematosus Ø Histopathology ü Skin biopsy ü Interface dermatitis reaction ü Hydropic-vacuolar changes at the basement membrane zone and basal cell layer or lichenoid band-like infiltrate at the dermoepidermal junction ü Individual necrosis of keratinocytes in the lower epidermis; dermal infiltrates consisting of lymphocytes and plasma cells and pigmentary incontinence are additional findings Discoid Lupus Erythematosus Ø Direct immunofluorescence or immunoperoxidase ü Non-diagnostic ü Deposition of immunoglobulin or complement at the basement membrane ü Fluorescence at the dermoepidermal junction ü Do not rule out discoid lupus if the results are negative ü Michel’s solution - immunofluorescence ü Formalin – immunoperoxidase Ø Antinuclear antibody (ANA) ü Negative or very low titer Discoid Lupus Erythematosus: direct immunofluorescence – fluorescence at the dermoepidermal junction Discoid Lupus Erythematosus Ø Treatment ü Mild cases • Systemic vitamin E o 400-800 IU q12h PO • Tetracycline and Niacinamide o < 10 Kg: 250 mg of each TID o > 10 Kg: 500 mg of each TID • Topical steroids o Be aware of skin atrophy Discoid Lupus Erythematosus Ø Treatment ü All cases • Tacrolimus ointment o Protopic® 0.1% • Sunscreens with SPF 15 or higher ü Severe cases • Systemic steroids in conjunction with one or more of the medications recommended for mild cases • Once in remission, steroids should be given q48h Discoid Lupus Erythematosus Ø Treatment ü Severe cases • Many cases can be tapered off the systemic steroids and maintained on just tetracycline + niacinamide, topical steroids or tracrolimus, vitamin E and sunscreens • Oral cyclosporine (microemulsion) o Dose 5mg/kg/day o If given in conjunction with ketoconazole, reduce the dosage to half Discoid Lupus Erythematosus Ø Client education ü Prognosis is good ü Lifelong treatment is usually necessary ü Only the skin is affected ü Sunlight can aggravate the disease ü Squamous cell carcinoma is a possible complication ü Various treatments may be needed before the ideal maintenance regimen is found