MUCOUS MEMBRANE PEMPHIGOID
Mucous membrane pemphigoid goes by other names, including cicatricial pemphigoid, Brunsting-Perry pemphigoid, ocular pemphigoid, and benign mucous membrane pemphigoid. The last name should not be used because this is a chronic progressive, disabling disease with severe morbidity and mortality. The term cicatricial inherently states that the disease is associated with scarring, but this is not always the case. Hence, one patient without scarring may be referred to as having ocular pemphigoid and another with scarring may be said to have cicatricial ocular pemphigoid. Almost all patients will have some form of scarring, albeit very mild in some cases, if monitored for a long enough period. In reality, these are names given to a heterogeneous group of autoimmune blistering diseases that express a unique phenotype and have been shown to have small variances in the basement membrane zone autoantibodies they produce.
Clinical
Findings: Mucous membrane pemphigoid can be seen in any racial group and affects
females more often than males, in a 2
: 1 ratio. It is a disease of older persons and is most commonly seen in the
seventh and eighth decades of life. Mucous membrane pemphigoid is a severe,
chronic autoimmune blistering disease with grave consequences. It is a major
cause of morbidity and mortality, and therapy can be difficult. Up to one
quarter of these patients have eye involvement, which can lead to decreased
vision and blindness. Mucous membrane disease is typically the initial sign: Patients
present with painful erosions in the nasal passages, oropharynx, genitalia, and
pulmonary tree. Patients complain of pain and difficulty eating secondary to
severe discomfort. Erosions are the most common clinical findings, but vesicles
and bullae may also be seen. Pulmonary and esophageal involvement may lead to
strictures that result in difficulty with breathing or eating. Weight loss
typically ensues, as does malaise and fatigue.
The skin can
also be affected, leading to blister formation that heals with scarring and
milia. If blisters develop on the scalp, they heal with a scarring alopecia.
This form of the disease has been given the name Brunsting-Perry pemphigoid.
This term is typically reserved for only those cases involving the scalp and
skin that do not affect the mucous membranes.
Ocular
pemphigoid is a chronic symmetric disease. The initial symptoms are inflamed
conjunctiva, discomfort, pain, and increased tear production. Scarring soon
develops and forms fibrous adhesions between the palpebral and bulbar
conjunctivae. This scarring is termed symblepharon. The scaring is
progressive, and it may cause the eyeball to become frozen in place. Entropion
is common, and as it progresses, the eyelashes turn inward (trichiasis) and are
forced against the cornea, which causes severe pain, irritation, and corneal
ulceration. Patients cannot entirely close their eyelids because of the severe
scarring. The damaged cornea undergoes keratinization, leading to opacity of
the cornea and blindness.
Histology:
Subepidermal
blistering that heals with scar formation is the hallmark of this disease. The
blistering takes place just below the keratinocyte, within in the lamina
lucida. Immunohistochemical staining with collagen type IV shows that the
blister plane is above the level of the lamina densa. The immunostaining and
routine hematoxylin and eosin staining show a picture very similar to that of
bullous pemphigoid. Linear immunoglobulin G and complement C3 immunofluorescent
staining is present along the basement membrane zone.
Pathogenesis:
Autoantibody
formation against proteins of the basement membrane zone has been linked to
cicatricial pemphigoid. Many different antibodies against these proteins exist,
including antibodies against the laminins, bullous pemphigoid antigens 180 and
230, and many other proteins as yet unclassified. The heterogeneity in antibody
production likely accounts for the varying clinical phenotypes that are expressed.
Treatment:
Prednisone
is the drug used to treat the disease initially. After the disease is under
some control, the addition of a steroid-sparring immunosuppressant should be
attempted. Commonly used medications include azathioprine, methotrexate,
myco-phenolate mofetil, and cyclophosphamide. Dapsone and sulfapyridine, a similar
medication that can be used in place of dapsone, have had some success treating
this disease. Intravenous immunoglobulin (IVIG) has been used with success in
refractory cases.
