Chapter 055. Immunologically Mediated Skin Diseases (Part 6) pdf

Chapter 055. Immunologically
Mediated Skin Diseases
(Part 6)

Linear IgA Disease
Linear IgA disease, once considered a variant form of dermatitis
herpetiformis, is actually a separate and distinct entity. Clinically, these patients
may resemble individuals with DH, BP, or other subepidermal blistering diseases.
Lesions typically consist of papulovesicles, bullae, and/or urticarial plaques
predominantly on central or flexural sites. Oral mucosal involvement occurs in
some patients. Severe pruritus resembles that seen in patients with DH. Patients
with linear IgA disease do not have an increased frequency of the HLA-B8/DRw3
haplotype or an associated enteropathy and hence are not candidates for treatment
with a gluten-free diet.
The histologic alterations in early lesions may be virtually indistinguishable
from those in DH. However, direct immunofluorescence microscopy of normal-
appearing perilesional skin reveals linear deposits of IgA (and often C3) in the
epidermal basement membrane zone. Most patients with linear IgA disease
demonstrate circulating IgA anti-basement membrane autoantibodies directed
against neoepitopes in the proteolytically processed extracellular domain of
BPAG2. These patients generally respond to treatment with dapsone, 50–200
mg/d.
Epidermolysis Bullosa Acquisita
EBA is a rare, noninherited, polymorphic, chronic, subepidermal blistering
disease. (The inherited form is discussed in Chap. 357.) Patients with classic or
noninflammatory EBA have blisters on noninflamed skin, atrophic scars, milia,
nail dystrophy, and oral lesions. Because lesions generally occur at sites exposed
to minor trauma, classic EBA is considered to be a mechanobullous disease. Other
patients with EBA have widespread inflammatory, scarring, and bullous lesions
that resemble severe BP. Inflammatory EBA may evolve into the classic,
noninflammatory form of this disease. Rare patients present with lesions that

predominate on mucous membranes. The HLA-DR2 haplotype is found with
increased frequency in EBA patients. Recent studies suggest that EBA is often
associated with inflammatory bowel disease (especially Crohn's disease).
The histology of lesional skin varies depending on the character of the
lesion being studied. Noninflammatory bullae show subepidermal blisters with a
sparse leukocytic infiltrate and resemble those in patients with porphyria cutanea
tarda. Inflammatory lesions consist of neutrophil-rich subepidermal blisters. EBA
patients have continuous deposits of IgG (and frequently C3 as well as other
complement components) in a linear pattern within the epidermal basement
membrane zone. Ultrastructurally, these immunoreactants are found in the
sublamina densa region in association with anchoring fibrils. Approximately 50%
of EBA patients have demonstrable circulating IgG anti-basement membrane
autoantibodies directed against type VII collagen—the collagen species that
comprises anchoring fibrils. Such IgG autoantibodies bind the dermal side of 1 M
NaCl split skin (in contrast to IgG autoantibodies in patients with BP). Recent
studies have shown that passive transfer of experimental or patient IgG directed
against type VII collagen can produce lesions in mice that clinically,
histologically, and immunopathologically resemble those seen in patients with
inflammatory EBA.
Treatment of EBA is generally unsatisfactory. Some patients with
inflammatory EBA may respond to systemic glucocorticoids, either alone or in
combination with immunosuppressive agents. Other patients (especially those with
neutrophil-rich inflammatory lesions) may respond to dapsone. The chronic,
noninflammatory form of this disease is largely resistant to treatment, although
some patients may respond to cyclosporine, azathioprine, or IV immunoglobulin
(IVIg).
Cicatricial Pemphigoid
Cicatricial pemphigoid (CP) is a rare, acquired, subepithelial
immunobullous disease characterized by erosive lesions of mucous membranes
and skin that result in scarring of at least some sites of involvement. Common sites

of involvement include the oral mucosa (especially the gingiva) and conjunctiva;
other sites that may be affected include the nasopharyngeal, laryngeal, esophageal,
and anogenital mucosa. Skin lesions (present in about one-third of patients) tend to
predominate on the scalp, face, and upper trunk and generally consist of a few
scattered erosions or tense blisters on an erythematous or urticarial base. CP is
typically a chronic and progressive disorder. Serious complications may arise as a
consequence of ocular, laryngeal, esophageal, or anogenital lesions. Erosive
conjunctivitis may result in shortened fornices, symblephara, ankyloblepharon,
entropion, corneal opacities, and (in severe cases) blindness. Similarly, erosive
lesions of the larynx may cause hoarseness, pain, and tissue loss that, if
unrecognized and untreated, may eventuate in complete destruction of the airway.
Esophageal lesions may result in stenosis and/or strictures that may place patients
at risk for aspiration. Strictures may also complicate anogenital involvement.
Biopsies of lesional tissue generally demonstrate subepithelial
vesiculobullae and a mononuclear leukocytic infiltrate. Neutrophils and
eosinophils may be seen in biopsies of early lesions; older lesions may
demonstrate a scant leukocytic infiltrate and fibrosis. Direct immunofluorescence
microscopy of perilesional tissue typically demonstrates deposits of IgG, IgA,
and/or C3 in the epidermal basement membrane of these patients. Because many
of these patients show no evidence of circulating anti-basement membrane
autoantibodies, testing of perilesional skin is important diagnostically. Although
CP was once thought to be a single nosologic entity, it is now largely regarded as a
disease phenotype that may develop as a consequence of an autoimmune reaction
against a variety of different molecules in epidermal basement membrane (e.g.,
BPAG2, laminin 5, type VII collagen, and other antigens yet to be completely
defined). Recent studies suggest that CP patients with anti-laminin 5
autoantibodies have an increased relative risk for cancer. Treatment of CP is
largely dependent upon sites of involvement. Due to potentially severe
complications, patients with ocular, laryngeal, esophageal, and/or anogenital
involvement require aggressive systemic treatment with dapsone, prednisone, or

the latter in combination with another immunosuppressive agent (e.g.,
azathioprine, mycophenolate mofetil, or cyclophosphamide) or IVIg. Less
threatening forms of the disease may be managed with topical or intralesional
glucocorticoids.