PEMPHIGUS FOLIACEUS-RECENT UPDATE ON THE PATHOGENESIS, DIAGNOSIS AND TREATMENT

PETRA BIZIKOVA MVDr PhD Dip ECVD, Dip ACVD NORTH CAROLINA STATE UNIVERSITY, COLLEGE OF VETERINARY MEDICINE

Petra began this veterinary webinar by emphasizing that Pemphigus foliaceus, (PF) is unique in autoimmune diseases because it is a pustular disease. The primary lesions are pustules that develop into erosions and finally crusts, involving keratinocytes.

Classically facial involvement is involved in more than 90% of affected dogs with between 40 and 80%(depending on what you read) involving footpads. In 120 cases accessed from the files of North Carolina state university, college of veterinary medicine, 80% had footpad involvement. Eventually these cases will generalise in approximately 66% of dogs. Clinical illustrations of the disease were shown and these were of the highest possible standard. Being able to view them on the computer screen in close up ensured a better appreciation of the clinical picture than would be possible in the lecture hall.

In addition very clear diagrams of the desmosome, which links keratinocytes, were used to illustrate the pathogenesis of this disease. In humans autoantibodies are directed against desmoglein 1 but only in 6% of dogs is this the case. In dogs desmocollin is the major target of the autoantibodies (75% of dogs). Experiments by Petra’s colleague, Thierry Olivry, have demonstrated that IgG from PF affected dogs is pathogenic to the skin of neonatal mice producing blistering and classic histopathological lesions of pemphigus.

DIAGNOSTIC APPROACH

The diagnosis of PF involves the clinician’s findings and the results of cytological and histopathological examination. From the clinical point of view it is necessary to rule out differential diagnoses. In particular, exfoliative superficial pyoderma and pustular dermatophytosis can look identical to PF in a biopsy. Thus it is important to use the laboratory tests as part of the diagnostic approach and not rely on any one test alone. This was a point emphasised throughout the two presentations that Petra made on autoimmune skin diseases.

TRIGGER FACTORS

There are known trigger factors associated with PF.  These have been incorporated into an acronym

PE Pesticides

M   Malignancy

PH Pharmaceuticals and hormones

I      Infections and Immunisation

G     Genetics

U     Ultraviolet light

For the purpose of this talk the focus was on pesticides and ultraviolet light.

PESTICIDES

Organophosphates have been reported in humans as trigger factors for PF. There are several theories as to the cause, including alteration of signaling pathways and chemical injury to the epidermis and release of hidden self-antigens.

There have been reports of pesticide induced PF in dogs.  Those involved:

Certifect (fipronil, S –methoprene, amitraz) in 21 dogs

Promeris Duo (metaflumizone, amitraz) in 22 dogs and

Vectra 3D (dinotefuran, pyriproxyfen, permethrin) in 3 dogs

Although amitraz is a constituent in two of the products incriminated it is not in the other. And of course amitraz has been very extensively used in the treatment of scabies and demodicosis without inducing PF so the precise cause of this problem is uncertain.

Clinically the reported cases have produced localised lesions in two thirds of the cases (pustules, erosions and crusts) with generalised lesions in the remaining third.  Most of the affected dogs have been large, (more than 20 kilos in weight) and in more than half of the dogs systemic signs such as lethargy, fever, anorexia, pain and lameness were reported.

Diagnosis

It is not possible to differentiate between natural PF and drug induced PF on cytological or histopathological signs. The history should help achieve this, as the lesions start at the site of application-sites where natural PF would not usually be expected.

Treatment

Pesticide induced PF appears to respond better to treatment than the naturally occurring disease.  Complete remission was obtained in 82% of cases reported with 64% achieving treatment discontinuation. Time to remission was variable, however, between a few weeks to a year.  Treatment comprised glucocorticoids, with or without azathioprine and cyclosporine.

ULTRAVIOLET LIGHT

Ultraviolet light is responsible for seasonal worsening of the signs of PF. The reason for this is not certain and there are several theories. For example it is thought that there is increased expression of inflammatory cytokines which results in altered signaling pathways in cell-cell adhesion. These theories were explored in some detail in the webinar.

Acantholysis is not a unique feature of PF. Thus finding acanthocytes cytologically or on histopathological examination does not make the diagnosis. For this the clinician’s judgment is required additionally. Excellent pictures of acanthocytes were shown for those new to the subject.

In some cases PF may be a diagnostic challenge for clinicians and pathologists alike. Occasionally cocci or hyphae (with special stains) may be seen in biopsy samples.

Clues that suggest a diagnosis of PF are the lesion localisation-predominantly facial and pedal, rarely on the trunk and usually bilaterally symmetrical. With superficial pustular dermatophytosis facial localisation is also common, but there is generally a lack of symmetry and there is a tendency to spread centrifugally.  Exfoliative superficial pyoderma commonly occurs on the trunk with the nasal planum and footpads not involved. Epidermal collarettes are common and there is a rapid expansion of lesions due to exfoliation caused by bacterial toxins.

Immunotesting of anti-keratinocyte and/or anti desmocollin IgG is currently a research option only.

Reviewer’s comments

Petra Bizikova is eminently qualified to speak on this subject, being a member of a world-leading academic team, with a PhD in the subject area and diplomas of both the American and European colleges of veterinary dermatology. The webinar is beautifully illustrated throughout and the content very clearly explained. I particularly liked that Petra has obviously considered her audience and explained terms that might not be familiar to all, when necessary.

This is a webinar for everyone interested in dermatology, from general practitioners, to students of dermatology and also as a useful update for specialists. You will not find a better source of up to date information.

 

 

 

 

 

 

 

Leave a Reply

Your email address will not be published. Required fields are marked *