Displaying One Session

CVMA Sessions
Moderators
Room
Hall 718
Date
07/16/2019
Time
10:20 AM - 11:10 AM
Presentation Type
Level 1: Requires little or no prior knowledge or experience of the areas covered
Session Description
Session Sponsored by Hill's

Common immune-mediated dermatologic diseases

Lecture Time
10:20 AM - 11:10 AM
Authors
Room
Hall 718
Date
07/16/2019
Time
10:20 AM - 11:10 AM

Abstract

Abstract Body

COMMON IMMUNE MEDIATED DERMATOLOGIC DISEASES
Dr Charlie Pye BSc, DVM, DVSc, DACVD
Atlantic Veterinary College
550 University Avenue
Charlottetown
Prince Edward Island
cpye@upei.ca


Overview of the Issue
An immune mediated disease is defined as a condition that lacks a definitive etiology but is characterized by inflammatory pathways resulting from, or triggered by, a dysregulation of the normal immune response.

Objectives of the Presentation
1. To review common immune mediated dermatologic diseases
2. To review diagnosis and treatment options

Pemphigus Foliaceus

Pemphigus foliaceus (PF) is the most common disease that is part of the pemphigus complex. The complex is characterized by acantholysis; breakdown of intercellular desmosomal components between keratinocytes1. In PF the major antigen targeted within the desmosome was originally thought to be Desmoglein-1. More recently studies have shown that Desmocolin-1 may also be a major autoantigen in PF2. PF can be triggered by an adverse drug reaction and there is also evidence to suggest that chronic skin disease, such as atopic dermatitis, can predispose to PF3.

Clinical signs include large, multi-follicle pustules and intense crusting. A facial presentation is the most common seen with PF including lesions on the nasal planum, dorsal muzzle, periocular region and the pinnae. Lesions are most often symmetrical1. Occasionally the footpads can become hyperkeratotic and fissure. In cats, lesions are commonly noted around the nail beds as a sterile paronychia. The areolar region and the legs are more commonly affected in cats compared to dogs. A more generalized pustular form of the disease has also been documented. Pruritus with PF has been found to be variable depending on the individual1.

Diagnosis

Cytology should be performed to diagnose any secondary infections. Acantholytic cells can be found on cytology but one must be aware that these cells are not pathognomonic for PF. Skin biopsy can provide a definitive diagnosis if lesions are selected appropriately. If pustules are found on examination, these should be submitted as samples. Histopathology will reveal intra/subcorneal or intragranular pustules with acantholytic keratinocytes, “fresh” neutrophils and eosinophils1. Fungal stains will be negative and should be pursued to rule out Trichophyton.

Treatment

The mainstay of treatment with PF is glucocorticoids administered at immunosuppressive dosages. These can then be tapered to the lowest effective dose that keeps clinical signs under control. If doses cannot be tapered or patients do not respond to glucocorticoids, then a second immunosuppressive agent should be added to the therapeutic regimen. Azathioprine (dogs), chlorambucil (dogs/cats) or mycophenolate mofetil (dogs) have been sown to be effective1,3. Cyclosporine is another treatment option. In this author’s opinion cyclosporine therapy is more effective in cats than dogs when treating PF. The prognosis for PF is fair. In a retrospective study by Gomez et al, the case fatality rate was 60.5%. Treatment times lasting more than 10 months correlated significantly with survival as did the use of concurrent antimicrobials during initiation of immunosuppressive treatment3.

Discoid Lupus Erythematosus

Discoid Lupus (DLE), is one of the forms of cutaneous lupus. This disease tends to be localized to the face and more specifically the nasal planum. In DLE, autoantibodies to antigens on epidermal basal cells are created leading to immune complex deposition at the level of the basal membrane4.

The age of onset for this disease is young to middle aged and no sex predilection has been documented. Dolichocephalic breeds are affected and some breed predispositions have been noted (German shepherd, Akita, Husky etc)4.

Dogs can present with depigmentation of the nasal planum followed by a loss of cobblestone architecture, erythema, scaling, erosion and ulceration. Leions can extend up the dorsal muzzle and can sometimes affect the periocular region or the ear pinnae. Footpads are rarely affected4.

Diagnosis

Cytology in cases of DLE is unrewarding. Histopathology will show a lymphocyte rich interface dermatitis with hydropic degeneration of basal cells and pigmentary incontinence. Both DLE and mucocutaneous pyoderma (MP) have overlapping histopathological changes so MP should be ruled out prior to beginning therapy for DLE4.

Treatment

DLE carries a good prognosis. Sunlight should be avoided to prevent UV damage to the skin. Treatment options can include systemic glucocorticoids, topical 0.1% tacrolimus, tetracycline/niacinamide and Vitamin E. Cyclosporine has been shown to be effective in some cases4.

Symmetrical Lupoid Onychodystrophy

Claw disease as the only manifestation of disease is uncommon and in one study accounted for 1.3% of dogs presented to a veterinary hospital5. Symmetrical Lupoid Onychodystrophy (SLO) is a condition described in dogs. The exact cause and pathogenesis in unknown but based on response to therapy, an immune mediated basis is suspected.

The disease is generally noted in young to middle aged dogs with no sex predilection. Predisposed breeds include German Shepherd dogs and Gordon setters5. Another common breed presenting with this disease is the Rottweiler. In a study by Wilbe et al, DLA class II alleles have been found in Gordon setters indicating a possible genetic predisposition6.

Dogs are otherwise healthy. In a retrospective study of 30 dogs and literature review, 17% of dogs with SLO were also diagnosed with hypothyroidism7. It is thought that antithyroid antibodies could be binding to the claw matrix causing a lupoid reaction. Many patients in this study had well controlled hypothyroidism prior to developing SLO so the direct association is not clear. This author continues to recommend thyroid evaluation in SLO patients. In the above study, there was 1 dog with a confirmed cutaneous adverse food reaction (CAFR), so CAFR have also been proposed as a possible factor in development of SLO7. Dogs will show licking of the paws, dry/brittle claws, sloughing of claws, exudate from the claw bed, misshapen claws and pain (lameness). It is common for dogs to have secondary infections at the claw base. A feature of the disease is that multiple claws on multiple feet will become affected.

Diagnosis

Cytology of the claw beds should always be performed to assess for any secondary infections. If digits are swollen, radiographs should be taken to rule out a tumour or boney changes. Thyroid testing may be indicated as well as a complete bloodcount and serum biochemistry as a baseline for overall health and prior to treatment.

Most dermatologists will diagnose SLO based on clinical signs, history and examination. Very few diseases affect the claws and SLO should be at the top of your differential list if multiple claws are affected. The diagnosis of SLO can be confirmed via biopsy and histopathology if required. To collect a biopsy sample, the 3rd phalanx of an effected digit must be amputated so that the entire claw and base can be assessed. If possible a dewclaw should be selected for biopsy. Histopathology will show a hydropic and lichenoid interface dermatitis similar to that seen in cases of discoid lupus. There is, however, concern that these changes may be just a reaction pattern to an insult on the claw5.

Treatment

Treatment options include supplementation with omega 3 and 6 fatty acids, tetracycline and niacinamide, cyclosporine, pentoxifylline and glucocorticoids5,8. Patients should receive pain medications if required and claws should be trimmed every 2-3 weeks. Improvement is generally noted within 3-4 months at which time, medications can be tapered to the lowest effective dose. Each time the dose is tapered, no further adjustments should be made for at least 6-8 weeks. At rechecks, new claw growth should be assessed by looking at the base of the claw.

Summary including 5 KEY “TAKE HOME” POINTS:
1. Immune mediated disease is due to dysregulation of the immune response
2. Histopathology paired with clinical signs is the best way to diagnose an immune mediated skin disease
3. Treatment is often long term if a trigger factor cannot be identified
4. Treatment revolves around either topical or systemic immunosuppressive/immunomodulating agents
5. Most immune mediated dermatologic diseases are treatable

References/Suggested Reading

1. Miller WH, Griffin CE, Campbell KL. Muller and Kirk’s Small Animal Dermatology. 7th ed. Toronto, Ontario: Elsevier; 2013. pp. 438-448.
2. Bizikova P, Dean GA, Hashimoto T, Olivry T. Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus. Vet Immunol Immunopathol. 2012;149(3-4):197-207.
3. Gomez S, Morris DO, Rosenbaum MR, Goldschmidt MH. Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases (1994-2000). J Am Vet Med Assoc. 2004;224(8):1312-1316.
4. Miller WH, Griffin CE, Campbell KL. Muller and Kirk’s Small Animal Dermatology. 7th ed. Toronto, Ontario: Elsevier; 2013. pp. 453–461.
5. Miller WH, Griffin CE, Campbell KL. Muller and Kirk’s Small Animal Dermatology. 7th ed. Toronto, Ontario: Elsevier; 2013. pp. 731–739.
6. Wilbe M, Ziener ML, Aronsson A, et al. DLA Class II alleles are associated with risk for canine symmetrical lupoid onychodystropy (SLO) PLoS ONE. 2010;5:e12332.
7. Mueller RS, Rosychuk RA, Jonas LD. A retrospective study regarding the treatment of lupoid onychodystrophy in 30 dogs and literature review. J Am Anim Hosp Assoc. 2003;39:139–150.
8. Ziener ML, Nødtvedt A. A treatment study of canine symmetrical onychomadesis (symmetrical lupoid onychodystrophy) comparing fish oil and cyclosporine supplementation in addition to a diet rich in omega-3 fatty acids. Acta Veterinaria Scandinavica. 2014;56:66.




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