Diagnostic evaluation of patients with suspected bullous pemphigoid or mucous membrane pemphigoid

BP: bullous pemphigoid; MMP: mucous membrane pemphigoid; DIF: direct immunofluorescence; IIF: indirect immunofluorescence; BMZ: basement membrane zone; BP180: bullous pemphigoid antigen 180; BP230: bullous pemphigoid antigen 230; ELISA: enzyme-linked immunosorbent assay; IgG: immunoglobulin G; IgA: immunoglobulin A; EBA: epidermolysis bullosa acquisita; SLE: systemic lupus erythematosus.
* Clinical features that indicate BP or MMP include tense blisters and erosions without another identifiable cause and unexplained, pruritic, eczematous eruptions or urticarial plaques, mucositis, or desquamative gingivitis.
¶ The preferred biopsy site for histopathology includes a blister edge and adjacent tissue. Skin biopsy specimens for DIF testing should be taken from an erythematous or urticarial area adjacent to a blister (ie, perilesional skin). Mucosal specimens for DIF should be taken several millimeters away from the edge of a lesion. DIF is considered the standard test for the diagnosis of BP and MMP and should be performed whenever feasible. If biopsy cannot be performed on a patient with suspected BP or MMP, we recommend obtaining serum for IIF testing on human BMZ-split skin substrate and BP180 and BP230 ELISA. The combination of these tests can be useful for supporting a clinical diagnosis.
Δ Common histopathologic findings in BP include eosinophilic spongiosis, subepidermal blister formation, and a superficial dermal inflammatory cell infiltrate with lymphocytes, eosinophils, and neutrophils. Common findings in MMP include subepithelial separation and a mixed submucosal inflammatory cell infiltrate with lymphocytes, histiocytes, neutrophils, eosinophils, and plasma cells. DIF findings in BP specimens include linear IgG and/or linear C3 localization along the BMZ. DIF findings of MMP include linear IgG and/or linear IgA and/or linear C3 staining along the BMZ.
◊ The term "human basement membrane zone-split skin" is interchangeable with "human salt-split skin."
§ Additional biopsy specimens for DIF testing increase the sensitivity of DIF for the diagnosis of MMP and may be of value for patients with suspected MMP.
¥ Antibody deposition on the "roof" is also referred to as an "epidermal pattern." Antibody deposition on the "floor" is also referred to as a "dermal pattern."
‡ Primarily, IgA BMZ deposition is supportive of linear IgA bullous dermatosis. Refer to UpToDate content on linear IgA bullous dermatosis for further information.
† EBA may not be distinguishable from bullous SLE with this testing (similar IIF and IgG type VII collagen ELISA findings could be found in either). Refer to ** footnote.
** Refer to UpToDate content on the diagnosis of EBA, anti-p200 pemphigoid, bullous SLE, and anti-laminin 332 pemphigoid for information on the diagnostic evaluation of these diseases. Laboratory testing to confirm anti-laminin 332 MMP and anti-p200 pemphigoid is not widely available.
¶¶ Clinical correlation is needed because up to 7% of individuals unaffected by pemphigoid, including patients with other immunobullous diseases, have increased IgG BP180 and/or IgG BP230 antibody levels by ELISA.
ΔΔ Diagnostic possibilities include seronegative BP/MMP, BP/MMP with BMZ antibodies to targets other than BP180 and BP230, EBA, bullous SLE, and other blistering diseases. Review of IIF findings on monkey esophagus and type VII collagen ELISA may be helpful. Negative IIF on human skin but IIF on monkey esophagus showing IgG BMZ deposition may occur in BP/MMP with BMZ antibodies to targets other than BP180 and BP230, EBA, bullous SLE, anti-p200 pemphigoid, or anti-laminin 332 MMP. Positive type VII collagen ELISA supports a diagnosis of EBA or bullous SLE. Refer to UpToDate content for information on the diagnostic evaluation of these diseases.
◊◊ BP180 and BP230 ELISA can be negative in patients with BP or MMP. The sensitivity of serum testing is lower for MMP than for BP. In particular, MMP may be associated with autoantibodies to BMZ antigens other than BP180 and BP230.