Current status of clinical diagnosis and treatment of pemphigus (part one)

Pemphigus is an autoimmune disease, including mucous membrane pemphigoid (MMP), bullous pemphigoid (BP), and pemphigoid gestationis (PG; Pregnancy herpes gestationis, HG). PG occurs during pregnancy or the postpartum period. It has prodromal symptoms of fatigue, nausea, headache and severe itching. The skin lesions are mostly erythema, blisters and wheal, distributed in the abdomen, limbs and buttocks, umbilical cord and other parts. Histopathology Epidermis blister, superficial eosinophilic and neutrophil infiltration, direct immunofluorescence (DIF) showed anti-basement membrane antibody IgA, complement C3 linear deposition. PG often develops rapidly after delivery and then usually resolves spontaneously within 3 months. Recurrence is common, and the disease can be aggravated by the next menstrual period or oral contraceptives. PG can be diagnosed by biopsy, immunofluorescence, and clinical procedures. MMP and BP are the more common types of pemphigus. The clinical manifestations of both were blisters, bullae, and Nissl's sign; histopathological examination showed subepidermal blister without acanthosis; DIF had IgG in the epidermal basement membrane zone (BMZ). C3 is deposited linearly. When there is no eye lesion, it increases the difficulty of identification of the two diseases and affects the treatment. This article aims to focus on the clinical progress of MMP and BP.

1 Mucosal Membrane Pemphigus

1.1 Mucosal Membrane Pemphigus Symptoms

MMP occurs in older women and is characterized by transient blisters, which quickly rupture, leaving erosions and scars. The course of the disease is slow, with an average of 3 to 5 years, and some can be extended for a lifetime. The majority of patients with primary lesions are located in the mucosa, mainly invading the oral cavity, conjunctiva, nose, throat, esophagus, urethra, vagina and anal mucosa, of which 85% involve the oral cavity and 64% to 89% involve the ocular mucosa. Mucosal damage manifests as erythema, blisters, erosions, ulcers, and scar formation after healing. Damage to certain special parts such as the throat, trachea, and esophagus can even be life-threatening. The clinical manifestations of conjunctiva are divided into four stages: (1) chronic conjunctivitis, subcutaneous fibrosis on the epiphyseal plate; (2) shortening of the eyelid; (3) eyelid and eyeball adhesion; (4) keratinization of the eye surface, adhesion of the gingival margin, and finally reduced secretion of the lacrimal gland Corneal opacity, ulcers, perforation, and eventually blindness. Skin lesions are seen in approximately 25% of patients, mainly in the form of generalized tension vesicles, similar to BP, with or without scarring after healing. There is also a skin manifestation called the Brunsting-Perry type, which has no mucosal damage, but has clustered blisters that recur on the erythema, usually invading the head and neck.

1.2 Laboratory Inspection

1.2.1 Histopathology: blistering under the epidermis, without acanthosis, the upper layer of the dermis may have fibrosis and scar formation.

1.2.2 Immunofluorescence: DIF: 80% to 95% of patients with linear IgG, C3 deposition in the basement membrane, a small number of IgA or IgM deposition. Indirect immunofluorescence (IIF): Anti-basement membrane antibodies can be found in approximately 20% of cases. Salt-split skin as a substrate for IIF examination: Most IIF-positive cases found circulating IgG deposited on the epidermal side of the basement membrane. DIF examination was performed with normal skin around the MMP lesions: IgG was deposited on the dermal side.

1.2.3 Immune electron-microscopy: IgG and C3 are mainly deposited in the lower dense plate at the lower part of the transparent plate, and the antibody binding site is deeper than BP.

2 Bullous Pemphigoid

2.1 Clinical manifestations

BP is common in the elderly, while also in young children, generally without gender differences. Tension bullae that occurs on the skin is characteristic. The prognosis is good and self-limiting, usually relieved within 5 years. The course of a child is usually 1 year or less. Skin lesions are more common, mainly involving the groin, ankle, torso, thigh and forearm flexion. It often manifests as non-specific skin lesions, such as eczema-like dermatitis, which often lasts for several weeks. A typical skin lesion occurs later, which is characterized by cherries to walnut blister on the erythema or normal appearance of the skin, the blister wall is thick and tense, not easy to break, the blister fluid is clear, a few are hemorrhagic, and the Nissl sign is negative. The blister is easy to heal after rupture, and generally does not spread to the surrounding area, leaving no scars. According to the area of ​​skin lesions, the degree of disease is graded: less than 10% of the total body surface area is mild, 10% to 50% is moderate, and 50% is severe. Oral mucosal damage is rare, accounting for about 10% to 20%, mainly as blister, small blister, like miliary. The blister is not easy to break, and the ulcer gradually heals and does not expand after the break, and the Nissl sign is negative. In addition to the oral cavity, other body and mucous membranes are rare.

2.2 Laboratory examination

2.2.1 Histopathology: epidermis bullae, no acanthosis, a small amount of eosinophils can be seen in the cavity.

2.2.2 Immunofluorescence: DIF is more sensitive than IIF. In the positive test, continuous linear immunofluorescence was distributed along the basement membrane. Almost 100% of patients are positive for DIF, most commonly with deposition of complement C3, and 80% of cases have IgG deposition with occasional IgA and IgM deposition. Salt-split skin is used as a substrate for IIF examination: IgG is observed in the epidermal layer. DIF examination of normal skin around salt cracked lesions: IgG was deposited on the surface and dermis.

2.2.3 Immune electron-microscopy: IgG and C3 are deposited on the basal cell membrane.

To be continued in part two…

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