Autoimmune Disorders

By | March 15, 2016

Pemphigus complex

  • the pemphigus complex comprises a group of rare autoimmune diseases described in dogs and cats
  • the diseases are vesiculobullous ulcerative disorders of the skin and often the mucous membranes
  • autoantibody is directed against the epidermal intercellular cement substance and may be demonstrated by direct immunofluorescence testing
  • histologically the pemphigus complex is characterized by acan-tholysis (loss of cohesion between individual epidermal cells)

Pemphigus foliaceus

  • the most common of the autoimmune diseases
  • dogs and cats
  • no age, breed or sex predisposition

Clinical features

  • often begins on the face, nose and ears as a vesiculobullous or exfoliative pustular dermatitis ()
  • footpads are frequently involved with hyperkeratosis
  • mucocutaneous lesions are uncommon

Diagnosis

  • history
  • physical examination
  • histological examination: subcorneal acantholysis leading to the development of a cleft. Within the cleft there are neutrophils and eosinophils
  • direct immunofluorescence may reveal intercellular deposition of immunoglobulin throughout the epidermis

Differential diagnosis

  • bacterial folliculitis
  • dermatophyte infection
  • seborrhoea
  • systemic lupus erythematosus
  • discoid lupus erythematosus
  • subcorneal pustular dermatosis
  • zinc-responsive dermatosis
  • dermatomyositis
  • neoplasia

Treatment

  • glucocorticoids are key drugs and prednisolone is the drug of choice. The dose suggested () is 4.4 mg/kg orally, which may cause unacceptable polyphagia, polydipsia and polyuria
  • in order to reduce these side-effects the following combination protocols are suggested:
  • glucocorticoid therapy and gold salt therapy (chrysotherapy) may be more successful in some cases (). Aurothioglucose (Solganol, Schering) or sodium aurothiomalate (Myocrisin, May and Baker) is given at a test dose of 1 mg intramuscularly initially, then 2 mg a week later; subsequently 1 mg/kg at weekly intervals
  • the addition of chrysotherapy may permit lower doses of glucocorticoids or abolish their need altogether
  • glucocorticoids and azathioprine (Imuran, Wellcome). Azathioprine is given at a dose of 2 mg/kg once daily and then on alternate days. When remission is achieved, it may be possible to reduce the dose of prednisolone, gradually phasing it out completely while maintaining the azathioprine
  • azathioprine is not recommended in cats
  • side-effects may occur with the above therapy (principally blood dyscrasias) and therefore complete blood counts and platelet counts are recommended at monthly intervals
  • without treatment the prognosis is poor. With treatment the prognosis is fair

Pemphigus vulgaris

  • dogs and cats
  • no age, breed or sex predisposition
  • the most severe form

Clinical features

Dogs
  • vesiculobullous, ulcerative, erosive lesions of the oral mucosa and mucocutaneous junctions (lips, nose, eyelids, prepuce, vulva, anus) and the skin (particularly the axilla and the groin). There may be involvement of the nail-bed, leading to onychomadesis
  • oral cavity lesions occur in approximately 90% of dogs
  • intact bullae are rarely seen due to the thin epidermis and self-trauma
  • the dog may be anorexic, depressed or febrile
Cats
  • vesiculobullous disorder of the oral mucocutaneous junction, involving the lips, hard palate, gums and planum nasale

Diagnosis

  • history
  • physical examination
  • biopsy; acantholysis occurs just above the stratum germinativum of the epidermis, leading to cleft formation. The basal epidermal cells adhere to the basement membrane (‘tombstones’)
  • Nikolsky sign: digital pressure can slip the epidermis
  • immunofluorescence: positive for IgG, occasionally complement within the epidermis
  • direct smears from intact vesicles or recent erosions may show numerous acantholytic keratinocytes

Differential diagnosis

  • bullous pemphigoid
  • drug eruption
  • systemic lupus erythematosus
  • mycosis fungoides
  • toxic epidermal necrolysis
  • erythema multiforme
  • candid iasis
  • other causes of stomatitis

Treatment

  • as discussed under pemphigus foliaceus
  • often fatal unless treated

Pemphigus erythematosus

  • dogs and cats
  • no age, breed or sex predilection
  • may be a benign form of pemphigus foliaceus

Clinical features

  • similar to pemphigus foliaceus but localized to the head and neck
  • there may be nasal depigmentation with resultant secondary photodermatitis

Diagnosis, differential diagnosis and treatment

  • This is as for pemphigus foliaceus.

Pemphigus vegetans

  • dogs
  • least common form — extremely rare
  • no age, breed or sex predisposition
  • may be a benign form of pemphigus vulgaris

Clinical features

  • verrucous vegetation and papillomatous proliferation, especially over the dorsum and trunk

Diagnosis and treatment

  • This is as for pemphigus foliaceus.

Bullous pemphigoid

  • dogs
  • no age or sex predilection but collies, Shetland sheepdogs and Dobermanns may be predisposed

Clinical features

  • vesiculobullous lesions that may affect the oral cavity, mucocutaneous junctions or skin
  • about 80% of dogs have oral lesions
  • cutaneous lesions occur most commonly in the axillae or groin
  • there may paronychia, ulceration of the pads or onychomadesis
  • severely affected dogs may be anorexic, febrile and depressed and clinically indistinguishable from pemphigus vulgaris

Diagnosis

  • history
  • physical examination
  • biopsy: subepidermal cleft and vesicle formation
  • immunofluorescence: positive IgG, IgM or IgA and usually complement (C3) at the basement membrane zone
  • the above tests should be performed on intact vesicles or bullae, and it may be necessary to hospitalize the dog to wait for the development of these lesions, as they are transient
  • microscopic examination of direct smears from intact vesicles or bullae does not reveal acantholytic keratinocytes

Treatment

  • as for pemphigus foliaceus
  • prognosis guarded, may be fatal without treatment. Other cases appear relatively benign and localized

Cold agglutinin disease

  • dogs and cats
  • rare
  • associated with cold-reacting erythrocyte antibodies (especially IgM), which are most active at o-4°C
  • type 2 hypersensitivity
  • most cases are idiopathic, some cases in dogs have been associated with lead poisoning and in cats with upper respiratory infections

Clinical features

  • erythema, purpura, necrosis and ulceration
  • sites affected include the paws, tips of the ears and tail, and the nose
  • lesions are exacerbated by cold

Diagnosis

  • history
  • physical examination
  • Coombs’ test at 4°C using reagent with activity against IgM
  • autohaemagglutination of blood on a slide may occur if the blood is cooled from room temperature to o°C. This reaction is reversible on warming the slide to 37°C

Differential diagnosis

  • dermatomyositis
  • vasculitis
  • frost-bite
  • disseminated intravascular coagulation
  • systemic lupus erythematosus

Treatment

  • correction of the underlying cause if possible
  • immunosuppressive drugs such as glucocorticoids or azathioprine
  • avoid cold

Discoid lupus erythematosus

  • dogs
  • uncommon; affects principally the nose and other parts of the face
  • reported in collies, German shepherd dogs, Shetland sheepdogs and Siberian huskies
  • no age or sex predilection

Clinical features

  • early lesions are depigmentation, erythema and scaling of the planum nasale ()
  • subsequently there may be crusting, erosive or ulcerative lesions which spread to the bridge of the nose, and less frequently the periorbital region, ears and distal limbs
  • the condition is exacerbated by sunlight

Diagnosis

  • history
  • physical examination
  • biopsy: hydropic or lichenoid interface dermatitis, with hydropic degeneration, lymphocytic infiltration and thickening of the basement membrane zone
  • direct immunofluorescence: deposition of immunoglobulin or complement or both at the basement membrane zone

Differential diagnosis

  • demodicosis
  • dermatophyte infection
  • nasal pyoderma
  • pemphigus foliaceus
  • pemphigus erythematosus
  • subcorneal pustular dermatosis
  • dermatomyositis
  • contact hypersensitivity
  • Vogt-Koyanagi-Harada-like syndrome

Treatment

  • avoid sunlight
  • prednisolone i mg/kg orally b.i.d.
  • vitamin E 400 IU b.i.d. orally
  • vitamin E may be used in conjunction with glucocorticoids. It has a 4- to 8-week lag period before clinical benefit

Systemic lupus erythematosus

  • uncommon
  • dogs and cats
  • autoantibodies are directed against many tissues
  • the pathogenesis is unclear; there may be genetic, infective, immunological (lack of suppressor T-cell activity), endocrine and drug factors. Drugs such as chlorpromazine, hydralazine, isoniazid and phenytoin may be implicated
  • sunlight exacerbates the cutaneous lesions
  • no age or sex predilections in dogs or cats
  • in dogs, the collie, Shetland sheepdog and German shepherd dog may be predisposed

Clinical features

  • non-cutaneous; possibilities include:
  • polyarthritis
  • glomerulonephritis
  • pyrexia anaemia
  • peripheral lymphadenopathy
  • oral ulceration
  • pericarditis
  • polymyositis
  • pleuritis
  • neurological disorders
  • cutaneous; diverse possibilities include:
  • mucocutaneous ulcerative lesions
  • alopecia
  • seborrhoea
  • refractory pyoderma
  • facial dermatitis
  • footpad lesions (ulceration, hyperkeratosis)

Diagnosis

  • history
  • physical examination
  • on the basis of major and minor criteria ()
  • Major signs include:
  • non-infective polyarthritis
  • cutaneous lesions with supportive histopathological findings and positive immunofluorescence at the dermoepidermal junction
  • Coombs’-positive anaemia
  • Thrombocytopenia (platelet count below 50000/mm3) with or without a positive platelet function 3 test
  • Glomerulonephritis with proteinuria
  • Neutropenia
  • Polymyositis Minor signs include:
  • Fever
  • Central nervous system signs, e.g. seizures, meningitis, polyneuropathy
  • Pleuritis
  • Definitive diagnosis of systemic lupus erythematosus requires the presence of two major signs or one major and two minor signs with supporting serological evidence.

Serological evidence

  • positive antinuclear antibody test (ANA). Record the titre and compare with the normal for the laboratory performing the test
  • positive lupus erythematosus cell preparation

Cutaneous biopsy

  • inflammatory changes at the dermal — epidermal junctions; hydropic degeneration of the basal layer of the epidermis
  • direct immunofluorescence reveals deposition of immunoglobulin or complement or both at the basement membrane zone

Differential diagnosis

  • many dermatoses; systemic lupus erythematosus has been called the great imitator

Treatment

  • glucocorticoids: prednisolone 2 mg/kg orally b.i.d.
  • glucocorticoids and cytotoxic drugs: as described for pemphigus foliaceus
  • other drugs which have been tried with varying benefit include: aspirin, chlorambucil orally at a dose of 0.2 mg/kg once daily, and levamisole at a dose of 2.5 mg/kg every 48 hours
  • splenectomy (in some cases with severe haemolytic anaemia or thrombocytopenia)
  • the prognosis is guarded although some dogs and cats may go into drug-free remission

 

Selections from the book: “Skin Diseases in the Dog and Cat”. D. I. Grant, BVetMed (1991)