The epidermis and blistering disorders: pemphigus

Published on May 4, 2014   57 min
0:00
The epidermis and blistering disorders. This lecture is on pemphigus.
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Pemphigus vulgaris usually presents on oral and genital mucosa, and may also involve skin. The lesions are fragile bullae that lead to shallow erosions that heal very slowly. Biopsy shows acantholytic suprabasal cleft. Direct immunofluorescence of biopsy reveals epidermal deposits of IgG and complement in the intercerllular space. Indirect immunofluorescence of serum demonstrates so-called "intercellular" antibodies reacting with the cell membrane of stratified squamous epithelium.
0:44
Prior to the introduction of an effective therapy with oral coritcosteroids in the 1950s, the disease had a dismal natural course, with approximately 50% mortality rate at two years and about 100% mortality rate by five years after the onset of the disease. The mortality rate now is estimated at about 5%, and death is almost invariably due to complications of immunosuppressive therapy.
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Prognosis of pemphigus. Complete and long-lasting remissions, such as no evidence of the disease and no systemic therapy required for at least six months, can occur in about 25%, 50%, and 75% of patients 2, 5, and 10 years after diagnosis, respectively. Patients with mild or moderate disease and diagnosis are twice as likely to enter a long-lasting, complete remission than those with severe disease. Patients who respond rapidly to treatment are over twice as likely to enter a long-lasting, complete remission than those with a slower response. If not promptly and aggressively treated, pemphigus hardens, providing the opportunity for the spreading of epitopes and rendering the disease significantly more difficult to control.
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Let us talk about clinical and pathological correlations of pemphigus.
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Very early, small lesions in the patient's mouth. Lesions are non-healing erosions that occur on non-inflamed mucosa and show an irregular shape. Gingival involvement, probably due to irritation while brushing the teeth, inner lower lip involvement, a lesion on genital mucosa in a woman. First skin lesions most commonly appear on the head and might be related to the repetitive irritation of the skin due to daily hair combing. More spreading lesions involve abdominal skin, and it's important to appreciate the colorate of the lesions that are hanging freely on the borders of the lesion, as well as intact blisters in the periphery. When pemphigus is not treated, it may eventually involve the entire skin, which would lead to death, before corticosteroids were introduced. Large lesions are most commonly seen in the dependent area due to irritation by rubbing skin against hard surfaces, like in this patient on the back.
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The other histological term that's used to describe the split within the epidermis in pemphigus is known as acantholysis. This term was introduced by Doctor Auspitz in 1880 to describe the loss of intercellular bridges and cohesion between epidermal cells that are responsible for blister formation in pemphigus.
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On H and E, in pemphigus vulgaris, one can clearly see a suprabasal detachment, and the basal cells remain attached to the underlying dermal tissue, and they appear to look like tombs. And that is why the term used to describe the appearance of the basal keratinocytes in the lesions of pemphagus vulgaris is tombstoning.
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By electromicroscopy, one can see detachment of neighboring cells, showing an increase in intercellular space. This slide shows slightly shrunk basal cells and shedding of the membrane parts that contain desmosomes in the intercellular space.
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This is a fully developed acantholysis, where one can see that the cells round up and detach from each other, but not from the basal membrane.
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In contrast to pemphigus vuglaris, in pemphigus foliaceus the split is more superficial, and it is usually at the granular layer.
4:60
Consistently with the superficial split in the epidermis, the lesions in pemphigus foliaceus patients are more superficial and rarely present as an intact blister, because the thin roof is easily destroyed and slough from the skin.
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The epidermis and blistering disorders: pemphigus

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