bubble_chart Overview

Pemphigus is a severe type of skin disease characterized by thin-walled, easily ruptured blisters. Histopathology reveals intraepidermal blisters caused by acantholysis, with distinctive immunological findings.

bubble_chart Etiology

Pemphigus is an autoimmune disease. Antibodies against intercellular substances of keratinocytes are present in the blood circulation of patients with various types of pemphigus, and the antibody titer correlates with the severity of the condition. When pemphigus patient serum is added to epidermal organ cultures, acantholysis can be observed above the basal cells within 48 to 72 hours. The occurrence of acantholysis may be related to proteases produced after antigen-antibody binding. It has been confirmed that pemphigus antibodies binding to keratinocytes can cause epidermal cells to release plasminogen activators, which then activate the plasmin system, leading to acantholysis. The pemphigus antigen is located in the desmosomes of keratinocytes and is a glycoprotein. The antigen in pemphigus vulgaris has a molecular weight of 210,000 u (Daltons), while the antigen in pemphigus erythematosus is desmoglein, with a molecular weight of 160,000 u.

bubble_chart Pathogenesis

The basic pathological change is acantholysis of epidermal prickle cells, leading to intraepidermal clefts and bullae. The bulla fluid contains acantholytic cells, which are large, spherical, with large and deeply stained nuclei, and uniformly basophilic cytoplasm.

The site of acantholysis varies among different types. In pemphigus vulgaris, acantholysis occurs above the basal layer, hence the bullae form above the basal layer. In pemphigus vegetans, the site of acantholysis is the same as in pemphigus vulgaris, but there is marked acanthosis and papillomatous hyperplasia, along with intraepidermal abscesses composed of eosinophils. In pemphigus foliaceus and pemphigus erythematosus, acantholysis occurs in the granular layer or upper spinous layer, resulting in the most superficial bullae. In pemphigus herpetiformis, acantholysis occurs in the middle of the spinous layer, with eosinophils or neutrophils present in the bullae.

bubble_chart Clinical Manifestations

Pemphigus can be divided into four types: vulgaris, vegetans, foliaceus, and erythematosus. In recent years, pemphigus herpetiformis, which has been reported more frequently in China, is likely a subtype of pemphigus.

(1) Pemphigus vulgaris: This is the most severe and common type. Most patients develop oral mucosal blisters or erosions 4–6 months before skin lesions appear. The skin lesions consist of varying-sized serous bullae with thin, flaccid walls that easily rupture, forming erosions that rarely heal spontaneously. The blisters often appear on normal-appearing skin. Gentle pressure or rubbing on the blisters or normal skin can cause the blister walls to expand, enlarge, or lead to epidermal detachment or blister formation shortly after friction, known as the Nikolsky sign.

Initially, only a few blisters may appear, commonly on the chest or back, but they gradually increase and may spread across the body. Due to their thin walls, the blisters rupture easily, forming large erythematous erosions. Secondary infections may lead to pustules and crusts with foul-smelling discharge. Without timely treatment, the blisters and erosions continue to expand, leading to significant fluid loss, constitutional weakness, hypoalbuminemia, and potentially fatal outcomes due to pulmonary infections, sepsis, or cachexia.

(2) Pemphigus vegetans: This is a rare, benign variant of pemphigus vulgaris, typically affecting young individuals with stronger immunity. Lesions commonly occur in intertriginous areas such as the axillae, inframammary folds, groin, genitalia, perianal region, and nasolabial folds. Initially, thin-walled blisters rupture, forming erosions that gradually develop papillomatous granulation tissue. New blisters often appear at the edges, expanding the lesions. The warm, moist environment of intertriginous areas predisposes to bacterial and Candida infections, often accompanied by a foul odor. Older lesions become drier and papillomatous. The course is chronic, with a better prognosis.

(3) Pemphigus foliaceus: Early lesions often present as a few flaccid blisters on erythematous bases on the scalp, face, upper chest, or back, with a positive Nikolsky sign. The blister walls are even thinner than in pemphigus vulgaris, rupturing easily to form erosions covered with yellowish-brown crusts. Oral mucosa is rarely involved. The lesions slowly progress, eventually covering most of the body with scaly, dirty crusts resembling fallen leaves. Bacterial decomposition of secretions under the crusts often produces a foul odor. The course is chronic, and patients may die from exhaustion or secondary infections.

(4) Pemphigus erythematosus: This is a benign form of pemphigus foliaceus, with patients generally in good health. Lesions mainly affect the head, face, and upper chest or back, usually sparing the mucosa. Early lesions often manifest as facial erythema with grade I exudation, scaling, and grade I crusting, beneath which superficial erosions are visible. Lesions on the scalp, chest, and back appear as scattered erythematous blisters 0.5–2.0 cm in diameter with crusts. Primary lesions may persist for years, occasionally spreading systemically and transforming into pemphigus foliaceus or vulgaris.

(5) Pemphigus herpetiformis: The primary lesions are mung bean-sized or larger blisters. Although also intraepidermal, the blister walls are tense, and the Nikolsky sign is less evident. Lesions often arrange in annular or polycyclic patterns, predominantly on the chest, back, and abdomen. Patients are mostly middle-aged or elderly, experiencing varying degrees of cutaneous pruritus. The course is chronic with a good prognosis, though a few cases may progress to pemphigus erythematosus.

bubble_chart Diagnosis

The diagnosis is primarily based on clinical manifestations, histopathology of skin lesions, and immunofluorescence tests.

1. Clinical manifestations: The fundamental lesions of all types of pemphigus are flaccid, thin-walled bullae and erosions that are slow to heal, with a positive Nikolsky sign. Pemphigus vulgaris often begins with oral mucosal lesions.
2. Histopathology: Examination of fresh bullae reveals intraepidermal blisters caused by acantholysis.
3. Immunofluorescence: Direct immunofluorescence of perilesional skin shows intercellular fluorescence in the epidermis, due to deposits of IgG and/or C3. Indirect immunofluorescence using serum from patients with active disease can detect pemphigus antibodies.

bubble_chart Treatment Measures

1. Supportive therapy is very important. A high-protein, high-vitamin diet should be provided, with attention to water and electrolyte balance. Intravenous supplementation is necessary for those with difficulty eating, and small, frequent blood transfusions are required for those with systemic failure. Hygiene should be maintained, and bedsore prevention is essential.
2. Corticosteroids are the first-line drugs for treating this condition. Commonly used ones include prednisone and prednisolone. The initial dose should be high to control the disease as quickly as possible. Generally, prednisone is administered first: - For mild cases with lesions covering less than 10% of the body surface, 30–40 mg/day is given. - For moderate cases with lesions covering about 30% of the body surface, 60 mg/day is given. - For severe cases with lesions covering more than 50% of the body surface, 80 mg/day is given. After administration, the patient's condition should be closely monitored. If new blisters continue to appear after 3–5 days, the dose should be increased as appropriate until new blister formation is controlled and existing lesions subside. Maintain this dose for 10 days to 2 weeks before tapering. The initial reduction can be slightly faster, such as reducing the total dose by 10% weekly, but caution is required once the dose reaches 30 mg/day. If new blisters appear during tapering, the reduction should be paused. Once the condition stabilizes, gradually adjust to a maintenance dose for long-term use. Rapid tapering or abrupt discontinuation is a major cause of relapse.
3. Immunosuppressants can be combined with corticosteroids to reduce the steroid dose and avoid or minimize the side effects of high-dose steroids. Options include: - Root Leaf or Flower of Common Threewingnut glycosides (30–60 mg/day). - Azathioprine or cyclophosphamide (1–2 mg/kg/day, orally). - Methotrexate (10–25 mg, intramuscular injection, once weekly).
4. For severe cases where high-dose corticosteroids fail to control the lesions, plasma exchange therapy may be considered.
5. Local treatment for extensive erosions should follow grade II burn protocols, with strict disinfection and isolation measures during dressing changes. Maintain room temperature to avoid chilling. Clean the wound surface, remove purulent crusts, and treat erosions with: - 1:8000 potassium permanganate baths. - 1:2000 Coptis Rhizome solution rinses. - Topical antibiotics based on bacterial culture results. For oral erosions, in addition to antiseptic mouthwashes, applying 2.5% chlortetracycline glycerin can alleviate pain.
6. Precautions: Due to the high and prolonged use of steroids, close monitoring for side effects is crucial. Severe complications include gastrointestinal ulcer bleeding, pulmonary infections, diabetes, subcutaneous nodule activity, hypertension, and psychiatric symptoms. Appropriate measures should be taken if these occur. For concurrent infections, perform bacterial cultures and antibiotic sensitivity tests to select suitable antibiotics. For Candida infections, antifungal agents such as clotrimazole or fluconazole may be used. Patients on immunosuppressants should undergo regular blood tests and liver/kidney function monitoring.

bubble_chart Differentiation

1. Bullous pemphigoid: Mostly occurs in the elderly, with basic lesions being thick-walled, tense bullae or blood blisters that are not easily ruptured and heal readily after rupture. The Nikolsky sign is negative, and mucosal lesions are rare. Histopathological examination reveals subepidermal blisters. Direct immunofluorescence of skin lesions shows a linear fluorescence pattern in the basement membrane zone due to IgG and/or C3 deposition.
2. Dermatitis herpetiformis lesions: Polymorphic, grouped, tense blisters ranging from mung bean to cherry size with thick walls, and the Nikolsky sign is negative. Patients experience cutaneous pruritus. Histopathological examination shows subepidermal blisters. Direct immunofluorescence of skin lesions demonstrates granular IgA deposits in the dermal papillae.