Vesiculopustular - Subepidermal

 

Aka subepidermal blistering dermatoses

There are congenital and acquired diseases

 

General causes

 

Acquired diseases

Phototoxic - Porphyria

Autoimmune subepidermal blistering dermatoses (AISBD)

Dermatomyositis

Severe subepidermal edema

Severe spongiosis

Contact hypersensitivity

Cutaneous vasculitis

 

Subacute Cutaneous Lupus (Ulcerative dermatosis of collies and shelties)

 

Cutaneous form of SLE

Not a true BP like disease

 

Auto-immune subepidermal blistering dermatoses (AISBDs)

 

Classified according to their target and clinical features

Olivry T. An autoimmune subepidermal blistering skin disease in a dog? The odds are that it is not bullous pemphigoid.

Vet Dermatol. 2014; 25: 316-318.

 

 

 

Linear IgA dermatosis (BP 180 (HD type XVII collagen)

 

Olivry T1, Dunston SM, Fahey M, Nguyen N, Marinkovich MP. Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180) define a canine homologue of linear IgA disease of humans. Vet Pathol. 2000 Jul;37(4):302-9.

 

transmembrane type XVII collagen (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA autoantibodies that target LAD-1, the processed extracellular form of type XVII collagen

 

Pressure points especially

Looks like BP

Antigen is a processed form of collagen 17

 

Bullous pemphigoid (BP 180, 230)

 

Vet Pathol 32: 388

oral, groin and axilla

subepidermal

Target is collagen 17 which links to keratin intermediate filaments of keratinocytes

Disease results in vesicle with BM left attached to dermis

Location – ear esp, 30% involve mucous membranes

Often have neutrophils or eosinophils as sources of protease to destroy BM

 

Uveodermatologic syndrome VKH

Zarfoss MK, Tusler CA, Kass PH, Montgomery K, Lim CC, Mowat F, Thomasy SM. Clinical findings and outcomes for dogs with uveodermatologic syndrome. J Am Vet Med Assoc. 2018; 252: 1263-1271

Epidermolysis bullosa acquisita (EBA)

Bizikova P, Linder KE, Wofford JA, Mamo LB, Dunston SM, Olivry T Canine epidermolysis bullosa acquisita: a retrospective study of 20 cases. Vet Dermatol. 2015; 26: 441-e103.
Great danes and males
most dogs have IgG to the NC1 domain of collagen VII
Generalized disease
Frictional areas – mouth, nasal planum, ears, axillae, groin and especially foot pad
Neutrophilic disease
Split is above collagen IV, so use anti collagen IV to show normal layer beneath vesicle
most dogs with this disease have
detectable circulating immunoglobulin G (IgG) autoanti-
bodies that also bind to the NC1 domain of collagen VII.
most dogs with this disease have
detectable circulating immunoglobulin G (IgG) autoanti-
bodies that also bind to the NC1 domain of collagen VII.
most dogs with this disease have
detectable circulating immunoglobulin G (IgG) autoanti-
bodies that also bind to the NC1 domain of collagen VI
Great Danes – 57%
German short haired pointers (20%)

Junctional EBA (JEBA)

Mucous membrane pemphigoid (MMP)

Multiple targets/Ag
Most common AISBD in dogs

Olivry T, Dunston SM, Schachter M, Xu L, Nguyen N, Marinkovich MP, Chan LS. A spontaneous canine model of mucous membrane (cicatricial) pemphigoid, an autoimmune blistering disease affecting mucosae and mucocutaneous junctions. J Autoimmun. 2001 Jun;16(4):411-21.
Circulating autoantibodies recognize epitopes on basement membrane proteins such as collagen XVII or laminin- 5/6
Most common blistering disease of dogs
German shepherds, huskys
Eyes, mouth, scrotum
No inflammatory cells
Epithelial slough is common, rarely see vesicles

Tham HL, Olivry T, Linder KE, Bizikova P. Mucous membrane pemphigoid in dogs: a retrospective study of 16 new cases. Vet Dermatol. 2016; 27(5):376-e94
Background – Mucous membrane pemphigoid (MMP) is a chronic autoimmune subepidermal blistering disease of dogs, cats and humans.
Objectives – The goal of this study was to describe the clinical, histological and immunological features and treatment outcomes of canine MMP.
Animals – Sixteen dogs were diagnosed with MMP based on the presence of mucosal- or mucocutaneous-predominant vesiculation and/or ulceration, histological confirmation of subepidermal clefting and an age of disease onset greater than 6 months.
Results – Six of 16 dogs (38%) were German shepherd dogs and their crosses. The median age of disease onset was 6 years (range: 1–10 years). At the time of presentation, the dogs exhibited erosions and ulcers in the oral cavity (11 of 16; 69%), nasal (nine of 16; 56%), periocular (eight of 16; 50%) and genital (six of 16; 38%) regions. Haired skin lesions were less frequent (six of 16; 38%) and involved mostly concave pinnae. Information on treatment outcome was available for 11 dogs (69%). A complete remission (CR) of lesions was achieved in 10 of 11 dogs (91%). The median time to CR was 33 weeks (range: 6–64 weeks). Treatment regimens varied widely but six of 10 (60%) dogs received a combination of tetracycline antibiotic and niacinamide alone, or with another drug, at the time of CR. Forty percent of the dogs in which CR had occurred experienced lesion relapse upon drug dose reduction.
Conclusions and clinical importance – Canine MMP is a chronic and relapsing disease requiring long term treatment. Combination therapy is often needed to achieve CR.

Bullous systemic lupus erythematosis

General characteristics

Olivry T, Bizikova P, Dunston SM, Bond R, Halliwell R, Loeffler A, Pucheu-Haston CM, Chen M, Marinkovich MP 2010 Clinical and immunological heterogeneity of canine subepidermal blistering dermatoses with anti-laminin-332 (laminin-5) auto-antibodies. Vet Dermatol 2010; 21: 345-357
ABSTRACT
Laminin-332 (laminin-5) is a basement membrane heterotrimeric protein composed of alpha-3, beta-3 and gamma-2 laminin chains. Laminin-332 polypeptides are targeted by auto-antibodies in human patients with mucous membrane (cicatricial) pemphigoid or, more rarely, subepidermal vesicular diseases that resemble epidermolysis bullosa acquisita (EBA) or bullous pemphigoid (BP). The objectives of this report were to characterize the clinical, histopathological and immunological characteristics of nine dogs with auto-antibodies targeting laminin-332. Immunological investigations consisted of direct immunofluorescence (IF), indirect IF with intact and salt-split canine gingival, and salt-split normal or laminin-332-deficient human skin, immunoblotting with purified human laminin-332 and immunoblotting with recombinant NC1 domain of human collagen VII. All dogs exhibited varying degrees of skin blistering and ulceration associated with microscopic subepidermal vesiculation with or without inflammatory cells. Indirect IF established that circulating IgG auto-antibodies bound the dermal side of salt-split canine lip and human skin. In five dogs, IgG variably recognized the basement membrane of laminin-332-deficient human skin (three dogs negative, two dogs positive). In all nine dogs, IgG auto-antibodies detected purified human laminin-332 by immunoblotting. In two dogs, additional targeting of collagen VII-NC1 was present. These observations establish laminin-332 as a novel basement membrane antigen in dogs with autoimmune blistering diseases with variable clinical phenotypes. The names 'acquired junctional epidermolysis bullosa', 'anti-laminin-332 mucous membrane pemphigoid (MMP)' and 'mixed auto-immune subepidermal blistering dermatosis' are proposed for dogs with clinical signs reminiscent of EBA, MMP or BP respectively.
Iwasaki ACVSc 2010

T. Olivry and S. M. Dunston (2010) Usefulness of Collagen IV Immunostaining for Diagnosis of Canine Epidermolysis Bullosa Acquisita Vet Pathol 2010 47: 565-568.
In dogs, autoimmune subepidermal blistering diseases (AISBDs) encompass several distinct entities that exhibit varying clinical signs, microscopic characteristics, prognosis, and response to treatment. The identification of targeted autoantigens is usually required to make the diagnosis, but immunological tests to determine these antigens are not commercially available. Epidermolysis bullosa acquisita (EBA) is an AISBD characterized by the production of autoantibodies against collagen VII in sublamina densa anchoring fibrils. This article reports on the usefulness of collagen IV immunostaining on paraffin-embedded skin biopsies as an aid to diagnose EBA in dogs. In this disease, collagen IV, which forms the fibrous 2-dimensional network of lamina densa, is detected more commonly above subepidermal vesicles than below. In other canine AISBDs, this is rarely the case. Collagen IV immunostaining therefore offers an inexpensive means to help making a suggestive diagnosis of EBA in the absence of serological determination of the targeted autoantigen.

Mucous membrane pemphigoid: symmetrical erosions and ulcers of several mucous membranes; responds to doxycyclin and niacinamide. Collagen IV on
Epidermolysis bullosa acquisita: blisters and erosion affecting friction areas and footpads: difficult to treat. Collagen IV above or on both sides of vesicles.
Bullous pemphigoid: eosinophil rich subepidermal vesicles. Collagen IV below vesicle
Linear IgA disease: Collagen IV below vesicle