RECENT UPDATE ON SELECTED AUTOIMMUNE AND IMMUNE MEDIATED DISEASES

PETRA BIZIKOVA MVDr PhD Dip ACVD, Dip ECVD

This veterinary webinar focused on autoimmune diseases of the basement membrane asking the question .

‘Can we tell them apart?’

It then went on to discuss Cutaneous Lupus Erythematosus in terms of what is new. Finally the diseases Erythema multiforme, Stevens -Johnson Syndrome and Toxic Epidermal Necrolysis (TEN) were discussed posing the question: –

‘Drug reaction or not?

The webinar began with an excellent diagram of the basement membrane zone clearly demonstrating the basement membrane proteins that can be targeted by autoantibodies. Those diseases described including in brackets their prevalence according to reports (77) in the veterinary literature were: –

Mucous Membrane Pemphigoid MMP           (48%)

Epidermolysis Bullosa Acquisita EBA             (20%)

Bullous Pemphigoid                                         (10%)

Acquired Junctional Epidermolysis Bullosa     (6%)

Mixed ASBDS                                                   (4%)

Pemphigoid of Gestation                                  (1%)

Diagnostic approach to differentiate autoimmune subepidermal blistering diseases (ASBD)

As there is no commercially available immunological test the key component is the clinical examination

Important information is derived from the breed and age of the dog, the distribution of the lesions (mucosal versus haired skin) and whether the disease leads to chronicity and scarring

Histopathological examination focuses on the concurrent inflammation and its type, and on the depth of the dermo-epidermal separation

Ultimately as Petra put it the clinician has to ‘play the odds’ taking into consideration the above and the prevalence of the different types of ASBDs

Regarding the first two diseases in this group (and the most common) the following is known: –

Breed disposition

MMP the German shepherd dog featured in 32% of cases

EBA   the Great Dane featured in 55% of cases

Age Predisposition

MMP Median is 5 years

EBA   Median is 1.2 years

Lesion distribution

MMP                                                                           EBA

Mucosal and/or mucocutaneous      100%                   95%

Footpads and haired skin                   15%                    100%

Genital                                                40%                    5%

Bullous Pemphigoid                                                 Acquired Junctional EBA

Haired skin                                                                    Similar to EBA

There are variations in histological findings, which are not diagnostic in themselves, but may be helpful when considered alongside the clinician’s findings.  For example in EBA 100% of cases demonstrate a neutrophilic inflammation

Collagen 1V staining is useful, as the site of the stain (above or below the blister) varies between the diseases. These were dealt with in detail and will be particularly of interest to pathologists. Very clear clinical pictures of the various diseases followed.

The next diseases described were:

Cutaneous lupus erythematosus.  This is divided into: –

Discoid Lupus erythematosus (DLE) and the newly described variant Generalised Discoid Lupus Erythematosus followed by

Vesicular Cutaneous lupus Erythematous (VCLE)

Exfoliative Cutaneous Lupus Erythematosus (ECLE) and finally

Mucocutaneous Lupus erythematosus (MCLE), which also has only just been described and, at the time of the webinar, an article detailing the condition was in press.

Clinical pictures followed, along with the typical histopathological findings and treatment. Only two cases of the generalised form of Discoid Lupus Erythematosus have so far been documented in the literature. Lesions consisted of annular plaques, erosions and scarring. Histopathological findings were lymphocyte rich interface dermatitis with basal cell death.  One case was treated with hydroxychloroquine and the other with cyclosporine and ketoconazole.

Exfoliative Cutaneous Lupus Erythematosus

This is a disease exclusively described in German shorthaired pointers. The mode of inheritance is autosomal recessive, with the candidate gene on chromosome 18.

Clinical Findings

The disease is one of young dogs and there is usually excessive scaling, alopecia, and erosions followed by systemic signs including fever, nephritis, and arthritis

Histopathological signs are interface dermatitis with follicular involvement and sebaceous adenitis, accounting for the generalised scaling.

Treatment

Various treatments have been tried including glucocorticoids, cyclosporine, and hydroxychloroquine. Response has in general been poor with the best that can be hoped for a reduction in severity of the signs and a slowing of the disease progression. Most cases have been euthanised.

Vesicular cutaneous lupus erythematosus

This disease affects collies and shelties with annular, polycyclic erythema, erosions and ulcers affecting the glabrous skin of the ventral abdomen and axilla

On histopathological examination there is interface dermatitis with a particularly prominent vesiculation and vesicle formation. Current treatment providing the best outcome is cyclosporine with topical steroids or tacrolimus.

Mucocutaneous lupus erythematosus

This is a newly described disease exclusively affecting mucocutaneous junctions with spread into the surrounding skin. Some cases in the past may have been diagnosed as mucocutaneous pyoderma.

Clinically there are erosions, ulcers, and hyperpigmentation in the areas mentioned.

Diagnosis is by clinical signs and histopathological examination demonstrating interface dermatitis.

Response to immunosuppressive does of glucocorticoids has been good but 50% of cases relapsed on stopping treatment

The final part of this webinar dealt with:

Erythema multiforme (EM), Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).

There was a brief outline of the conditions in people. One notable difference is that EM in people tends to have well defined target lesions whereas in dogs defined target lesions have not been described. Also in dogs drugs do not usually trigger EM, although there is some confusion in the literature regarding this statement and further studies are needed.  Certain drugs, cephalexin, levamisole, carprofen, some flea dips containing d-limonene for example have been incriminated as a trigger for SJS and TEN.

Diagnosis of these diseases is on clinical grounds predominantly. Excellent clinical pictures were shown demonstrating the relatively mild erythematous patches seen in EM to the bright red and ultimately necrotic lesions seen in SJS and TEN. In these latter two diseases the affected dogs are sick, febrile, and in tremendous pain from the skin separation that may occur-particularly with TEN. They are amongst the few incidences of true dermatological emergencies.

Histopathological examination cannot reliably differentiate between the three conditions. For this the clinician is the key person. The character of the lesions and their severity are important features.

Reviewer’s comments

This webinar along with the one on Pemphigus Foliaceus manages to encapsulate everything that is currently known about these important autoimmune skin diseases. Although, as Petra says, the diseases in the second webinar are ‘super rare’ (based on a compilation of 77 cases in the world literature compiled by Thierry Olivry,) more cases are bound to be seen, with our increased ability to recognise them. Throughout the presentations are clear, methodical and will benefit everyone from those wanting to know more about dermatology, to students and residents, through to specialists seeking a concise update. All are catered for. Thoroughly recommended.

 

 

 

 

 

 

 

 

 

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