Cicatricial Pemphigoid Workup

The histologic findings, DIF results, and IDIF results of cicatricial pemphigoid, BP, and EBA are similar; differentiation between these 3 entities depends on the clinical presentation.

Criteria for the diagnosis of cicatricial pemphigoid include an appropriate clinical presentation, histology demonstrating a subepidermal blistering process (as described below), and DIF results showing continuous deposits of any one or the combination of the following along the epithelial basement membrane zone: IgG, IgA, and/or C3. DIF study can be used to categorize the process as an autoimmune blistering disease, but it cannot be used to discriminate between cicatricial pemphigoid, BP, or EBA.

IDIF study of patients' sera depicts circulating antibasement membrane zone specific for IgG in 20% of patients, and, when present, it usually has a low titer (1:10-1:20).

• For evaluation of the upper airway or the esophagus, CT scans, barium swallows, or other imaging studies may be helpful. In patients with antiepiligrin cicatricial pemphigoid, imaging may be required as part of malignancy search.

• DIF study should be performed on noninvolved perilesional skin or mucous membrane. Patients with cicatricial pemphigoid typically demonstrate linear deposits of complement and IgG at the dermal-epidermal junction. The most commonly assayed complement component is C3; however, C4, properdin, and other complement components have been described. Linear deposits of IgG are detectable in 25% of patients. Linear deposits of IgA, in addition to IgG, have been reported in 20% of patients in one series. This pattern of DIF is also seen in patients with BP and EBA, and DIF assay cannot be used to differentiate among these disorders. Conjunctival specimens have been reported to be less sensitive than biopsy specimens of oral mucosa on DIF results.
• IDIF assay detects the presence of circulating antibodies directed against normal epithelial basement membrane in the sera of patients who are affected. In patients with cicatricial pemphigoid, IDIF assay reveals circulating IgG in 20% of patients, typically a low titer. When healthy human skin preincubated in 1 mol/L sodium chloride (salt-split skin) is used as a substrate, autoantibodies in patients with cicatricial pemphigoid associated with reactivity to BPAG2 bind to the epidermal roof. IDIF results demonstrate a similar localization in patients with BP. Patients with autoantibodies associated with epiligrin have circulating autoantibodies that bind to the blister floor, similar to that in patients with EBA. One laboratory has reported an increased sensitivity by IDIF study by concentrating serum samples prior to assay.
• Immunoblot (Western blot), immunoprecipitation, and immunoelectron microscopy are investigational tools used to better define target antigens. By immunoblot (Western blot) and immunoprecipitation, patients with cicatricial pemphigoid can have autoantibodies directed against BPAG2 (180 kd), BPAG1 (230 kd), and epiligrin (a chain of laminin-5). Enzyme-linked immunoassays using recombinant target antigens may ultimately be available to characterize autoantibody reactivity.
• Routine laboratory studies are not helpful in establishing the diagnosis of cicatricial pemphigoid. Most hematologic studies are within the reference range. Laboratory values that may be elevated include immunoglobulins, erythrocyte sedimentation rate, and acute phase reactants.

Biopsy of the edge of an early blister typically reveals a noninflammatory, subepidermal blister. When present, the inflammatory infiltrate localizes to the dermal-epidermal junction and the perivascular areas. This histologic feature can also be seen in other autoimmune subepidermal blistering diseases, including cell-poor BP, EBA, and linear IgA bullous dermatosis. The histologic features of porphyria cutanea tarda and variegate porphyria may also resemble cicatricial pemphigoid.