Pemphigus:

Question 1

Pemphigus:

The condition known as pemphigus represents four related diseases of an autoimmune origin:

Answer 1

1. Pemphigus vulgaris

2. Pemphigus vegetans
3. Pemphigus erythematosus
4. Pemphigus foliaceus

Only the first two of these affect the oral mucosa

• Pemphigus vegetans is rare; most authorities now feel it represents simply a variant of pemphigus vulgaris

Question 2

Pemphigus:

There are two subtypes of pemphigus vulgaris:

Answer 2

• the mucosal-dominant type, with mucosal lesions but minimal skin involvement
• the mucocutaneous type, with extensive skin blisters and erosions in addition to mucosal involvement

Question 3

Pemphigus:

Etiology:

Answer 3

• Due to an abnormal production, for unknown reasons, of autoantibodies that are directed against the epidermal cell surface glycoproteins, desmoglein 3 and desmoglein 1
• These desmogleins are components of desmosomes and the autoantibodies attach to these desmosomal components, effectively inhibiting the molecular interaction that is responsible for adherence
• As a result of this immunologic attack on the desmosomes, a split develops within the epithelium, causing a blister to form

Question 4

Pemphigus:

Clinical Features:

Answer 4

1. The initial manifestations often involve the oral mucosa, typically in adults
2. The average age at diagnosis is 50 years
3. No sex predilection
4. More common in persons of Mediterranean, South
5. Asian, or Jewish heritage
6. Patients usually complain of oral soreness, and
7. examination shows superficial, ragged erosions and ulcerations distributed haphazardly on the oral mucosa
8. Affect virtually any oral mucosal location
9. The palate, labial mucosa, buccal mucosa, ventral tongue, and gingivae are often involved
10. Positive Nikolsky sign

Question 5

Pemphigus

Oral involvment:

Answer 5

• Patients rarely report vesicle or bulla formation intraorally, and such lesions can seldom be identified by the examining clinician, probably because of early rupture of the thin, friable roof of the blisters
• More than 50% of the patients have oral mucosal lesions before the onset of cutaneous lesions, sometimes by as much as 1 year or more
• Eventually, however, nearly all patients have intraoral involvement

Question 6

Pemphigus:

Skin lesions:

Answer 6

• The skin lesions appear as flaccid vesicles and bullae that rupture quickly, usually within hours to a few days, leaving an erythematous, denuded surface
• Infrequently ocular involvement may be seen, usually appearing as bilateral conjunctivitis
• Unlike cicatricial pemphigoid, the ocular lesions of pemphigus typically do not cause scarring and symblepharon formation

Question 7

Pemphigus:

Histo- pathologic Features:

Answer 7

• Biopsy specimens of perilesional tissue show characteristic intraepithelial separation, which occurs just above the basal cell layer of the epithelium
• The cells of the spinous layer of the surface epithelium typically appear to fall apart, a feature that has been termed acantholysis, and the loose cells tend to assume a rounded shape
• A mild-to-moderate chronic inflammatory cell infiltrate in the underlying connective tissue

Question 8

Pemphigus:

Diagnosis:

Answer 8

• The diagnosis of pemphigus vulgaris should be con- fresh perilesional tissue firmed by direct immunofluorescence examination of fresh perilesional tissue
• The blood of patients with pemphigus contains IgG
• antibodies that bind to the surface of normal keratinocytes; this binding is shown with the use of immunofluorescence
• Immunofluorescence staining also shows IgG antibodies on the surface of the keratinocytes in biopsy specimens of the skin from patients with pemphigus

Question 9

Pemphigus:

Treatment:

Answer 9

• A diagnosis of pemphigus vulgaris should be made as early as possible because control is generally easier to achieve Treatment consists primarily of systemic corticosteroids (usually prednisone), often in combination with other immunosuppressive drugs (so-called steroid-sparing agents), such as mycophenolate mofetil or azathioprine
• Rituximab, a monoclonal antibody that targets B-lymphocytes, represents another promising approach to managing this disease
• Initially high doses of systemic corticosteroids to clear the lesions, and then attempt to maintain the patient on as low a dose of corticosteroids as is necessary to control the condition.
• Monitor the titers of circulating autoantibodies using indirect immunofluorescence, because disease activity frequently correlates with the abnormal antibody levels