Page 886 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Bullous Diseases of the Skin and

Mucous Membranes

Adela Rambi G. Cardones, Russell P. Hall III

PEMPHIGUS In the early 1960s, investigators found IgG antibodies bound
to the epithelial keratinocyte cell surface in the skin of patients
Pemphigus is a group of cutaneous autoimmune blistering diseases with PV and showed that the serum of these patients contained
characterized by intraepidermal blistering of the skin and mucous IgG antibodies that bound in an identical pattern to normal
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membranes. Pemphigus comprises four distinct conditions: human skin. These findings demonstrated that PV is an
pemphigus vulgaris (PV), pemphigus foliaceus (PF), paraneo- autoimmune disease directed against a normal component of
plastic pemphigus, and immunoglobulin A (IgA) pemphigus. stratified squamous epithelium.
Pemphigus Vulgaris Pemphigus Foliaceus
The most common and most severe form of pemphigus, PV is PF is characterized by blisters within the epidermis, resulting in
still a rare disease, with an incidence estimated at 0.5–1.6 per superficial erosions with scaling and crusting (Fig. 63.3). In
1-3
100 000. PV presents most often in the fourth to sixth decades contrast to patients with PV, patients with PF rarely develop
but can occur at any age. PV is characterized by the presence of mucous membrane lesions. Because the blisters are superficial,
flaccid blisters and erosions of the skin and mucous membranes many patients present with erythematous, scaling, and crusted
(Fig. 63.1). Virtually all patients with PV develop oral erosions plaques, which occur principally on the head, neck, and trunk
at some point during the course of their disease. Most present (Fig. 63.4). The prognosis for patients with PF is markedly better
with oral erosions, and for many, these are their only disease than that for patients with PV, although patients with severe PF
manifestation for months to years (Fig. 63.2). These erosions do occasionally die as a result of infections and/or the side effects
are often persistent and shaggy; they can involve all areas of the of therapy.
oral mucosa and extend into the esophagus. In severe cases, the An unusual variant of PF is the endemic form of the disease,
conjunctiva, nasal, anal, cervical, or urethral mucosae may be fogo selvagem (FS) (which is the Portuguese term for “wild
affected. fire”). Although clinically identical to the sporadic form of PF,
PV blisters are flaccid and easily ruptured; they can occur on FS only occurs in certain rural areas of South America and North
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inflamed or noninflamed skin. Once broken, these blisters leave Africa. The epidemiology suggests an infectious etiology, and
large, nonhealing erosions. Blisters can occur on any area of an arthropod vector may be involved in spreading the disease.
skin, most often beginning on the head, neck, or trunk. General- Pemphigus erythematosus, or Senear-Usher syndrome, is
ized blistering is not uncommon, especially if diagnosis and/or another PF variant. These patients have typical features of PF
treatment have been delayed. with additional characteristics suggestive of systemic lupus
Pemphigus vegetans is an unusual variant of PV, in which erythematosus (SLE) (Chapter 51), such as malar involvement
lesions develop mainly in the axilla, groin, and other flexural and antinuclear antibodies. The clinical course tends to parallel
areas. The characteristic lesions are plaques of hypertrophic that of PF, and most patients do not develop SLE. The patho-
granulation tissue with occasional pustules. These can occur de genesis of this form of PF is poorly understood.
novo or after healing of PV lesions. The etiology of this unusual PF can also be associated with drugs. The most common
clinical presentation is unknown. agents that induce pemphigus are D-penicillamine and
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Before the advent of glucocorticoids, PV was almost uniformly angiotensin-converting enzyme inhibitors. Although these drugs
fatal, with patients developing large areas of denuded skin and can induce a PV-like picture, the clinical manifestations are most
dying from overwhelming sepsis. Since the introduction of often similar to PF. Patients with drug-induced pemphigus have
systemic glucocorticoids, the mortality rate has fallen to approxi- autoantibodies directed against the keratinocyte cell surface; the
mately 10%. The residual mortality is largely due to the side mechanism(s) causing these antibodies are unknown, but reactive
effects of the high doses of glucocorticoids required to treat the sulfhydryl or amide groups on the drugs are thought to be
disease, particularly in debilitated or older patients. 4 responsible. 7
Histologically, PV is characterized by intraepithelial blisters, Histological examination of PF blisters reveals intraepidermal
with acantholysis (breaking apart of the suprabasilar portion of blisters with acantholysis of the most superficial portion of skin
the epidermis). Biopsy of early PV lesions shows that basal (the granular cell layer), resulting in blisters with an epithelial
epidermal cells remain attached to the dermis, forming a “row base rather than the basal cell layer as seen in PV.
of tombstones,” with loss of attachment of individual keratinocytes The immunohistological features of PF are indistinguishable
to each other, resulting in intraepidermal blisters. from those of PV (Fig. 63.5). Cell-surface IgG deposits are present,

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