CICATRICIAL/MUCOUS MEMBRANE PEMHIGOID: CLINICAL FEATURES, HISTOPATHOLOGY & TREATMENT
Author: Sanketh DS, MDS
Cicatricial pemphigoid, now renamed as mucous membrane pemphigoid(MMP), is an auto-immune blistering disease affecting mucous membranes which may include oral cavity, conjunctiva, oro-pharynx, and skin of head and neck. The term “cicatricial” in cicatricial pemhigoid is derived from the word “cicatrix”, which means scar.
There are several types of cellular junctions, one group of which are called hemi-desmososmes. Hemi-desmosomes form the basement membrane and are composed primarily of three proteins: transmembrane proteins, cytoplasmic adapter proteins and cytoskeletal filament. In the hemidesmosomal junction Bullous Pemphigoid antigen 180 (BP 180) and α6β4 integrins form the transmembrane proteins, BP 230 and plectin form the cytoplasmic adapter proteins and intermediate filaments form the cytoskeletal proteins. Together with these proteins, constituents of the basal lamina, like laminin and type VII collagen otherwise called the anchoring fibrils help in attachment of the epithelium to the connective tissue.
The initiating factor for this condition could be a drug like furosemide or it could be due to the presence of HLA DQB1. This may cause T cells to recognise antigens of the basement membrane. MMP is a type II hypersensitivity reaction, where auto-antibodies target BP 180 mainly and less often target BP230, laminin 5, type VII collagen/anchoring fibrils or the β4 unit of α6β4 integrins. This results in severing of the hemi-desmosomal junction leading to a sub-epithelial split. It has been speculated that the T helper cells happen to recognize the hemi-desmosomal epitopes leading to B cell activation and antibody formation. These anti-bodies may cause complement mediated damage and leukotactic response leading to destruction of the antigens of the basement membrane.
MMP affects older adults aged between 50-60 years, and occurs twice as frequently in females than males. MMP may include patients with oral lesions alone, patients with involvement of other mucous membranes and skin (mostly head and neck).
Oral lesions are often the initial signs of the disease. It may start as vesicles and bullae in any site of the oral mucosa. It is common to see vesicles or bullae in pemhigoid, unlike pemphigus where blisters are rare because, the blisters formed in pemphigoid are sub-epithelial, which are thicker and stronger as compared to blisters of pemphigus which may rupture easily. However, the blisters in pemphigoid eventually rupture leaving raw, eroded and ulcerated surfaces. These lesions are painful and may persist for months if not treated.
MMP is one of the common causes of desquamative gingivitis, and is often the initial signs of the disease. It presents as widespread erythema of the gingiva, with soreness and burning sensations as well as loss of stippling.
Lesions in other mucous membranes
Other mucous membranes like those of the eyes, larynx, oesophagus, vulva, penis and anus may be affected. One of the most important complications of MMP is the ocular involvement, which may affect 40% of the patients. Ocular lesions begin as conjunctivitis and progresses to become inflamed and eroded. When these lesions attempt to heal, scarring occurs leading to adhesions between the bulbar and the palpebral part of the conjunctiva. These adhesions are called symblepharons. Progressive scarring makes the eyelids turn inward, called entropion. Inwardly turned eyelids, further result in eyelashes rubbing against the cornea, causing irritation. This is called trichiasis. Trichiasis causes cornea to produce keratin as a protective mechanism, which may cause blindness.
Involvement of the skin is rare and is restricted to the head and neck, axilla and extremities.
Microscopy reveals, a sub-epithelial split, ie, a split at the basement membrane level with mild chronic inflammatory infiltrate in the subjacent connective tissue.
Direct immunofluorescence shows linear deposits of IgG and C3 in the basement membrane zone. Indirect immunofluorescence is positive only in 5-25% of the cases.
Patients should maintain good oral hygiene and should have soft foods. Once the diagnosis is established, and if the patients have ocular lesions, they have to be sent to an ophthalmologist for examination of the conjunctiva. Patients with oral lesions alone can be controlled with topical application of corticosteroids many times a day. Triamcinolone acetonide 0.1–0.5% as an aqueous rinse or ointment or clobetasol propionate 0.05% could be used. Patients with gingival lesions alone may benefit immensely with good oral hygiene. If the patients have other mucous membranes involved too, systemic agents like dapsone, corticosteroids, methotrexate, thalidomide, mycophenolate mofetil and other immune modulating agents can be used.
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