Vulvar pemphigus

　　First, the cause of the disease

　　The occurrence of vulvar pemphigus requires a triggering factor, and certain drugs and foods can induce pemphigus. Recent research suggests that infection factors may be another triggering factor for pemphigus. Drugs that can induce pemphigus include: thiolytic drugs such as penicillamine, thiopropyl alanine, thalidomide, and brain new; antibiotics such as penicillin, rifampicin, isoniazid, and cefoperazone; pyrazolone drugs such as aminopyrine, butazolidine, etc.; and others such as digoxin, IL-2, beta-interferon, nifedipine, etc. The number of pemphigus caused by thiolytic drugs accounts for about 80% of the total amount of drug-induced pemphigus. Circulating pemphigus antibodies can be detected in the blood of patients with drug-induced ordinary pemphigus. UV radiation can also worsen the condition, and there are reports that PUVA therapy for psoriasis can trigger pemphigus.

　　Many studies have shown that ordinary pemphigus may exist with genetic susceptibility. Serological methods suggest that the susceptibility of ordinary pemphigus in North European Asknezim Jews is related to HLA-DR4, and in non-Jews, it is related to HLA-DR4 and DR6. A study in Japan found that the susceptibility of pemphigus is related to HLA-DRBl*0406, *0403, and HLA-DRBl*1403, *1405. Although current research data suggest that the susceptibility of pemphigus is related to HIA, not all people with susceptibility-related genes develop the disease. It is currently believed that ordinary pemphigus is an autoimmune disease, and the basis for this is:

　　1. Direct immunofluorescence confirms that IgG-type pemphigus antibodies can be found between the stratum spinosum cells in the epidermis and oral mucosal epithelium of patients, and in the areas of desquamation, C3 deposition can also be seen.

　　2. Indirect immunofluorescence technique shows that 80% to 90% of patients with ordinary pemphigus can be detected with circulating pemphigus antibodies in their serum, and the antibody titer is proportional to the severity of the disease. Plasmapheresis can remove pemphigus antibodies from the patient's serum, which can alleviate the condition.

　　3. The addition of pemphigus patient serum to normal skin culture results in epidermal acantholysis.

　　4. Blisters develop on the skin of new mice injected with human pemphigus antibodies within 18-72 hours. Further studies have shown that IgG4 subclass of anti-epidermal intercellular material antibodies is a pathogenic antibody for pemphigus.

　　Second, Pathogenesis

　　The antigen for classical pemphigus is desmoglein 3 (Dsg3), with a molecular weight of 130 kd. It is a cell surface glycoprotein synthesized by keratinocytes and intercellular adhesion substances, belonging to the calcium-dependent adhesion molecule (cadherin) family. Dsg3 binds to the 85 kd desmoglein plaque protein in desmosomes, playing an important role in cell adhesion between epidermal cells. Therefore, when anti-epidermal intercellular material antibodies bind to Dsg3, they inhibit the function of desmosome-mediated adhesion of epithelial cells, leading to acantholysis, which is one of the pathogenic mechanisms. Additionally, when pemphigus antibodies bind to Dsg3, phospholipase C and 1,4,5-trisphosphate inositol mediate intracellular signal transduction, causing the epidermal cells to synthesize and release plasminogen activators. These activators convert plasminogen into plasmin, leading to the loss of adhesion ability of the prickle cells and causing acantholysis.

　　Approximately 60% of patients with vulvar and mucosal lesions may initially develop blisters in the mouth, with almost all cases involving the oral mucosa. In addition, the nose, pharynx, conjunctiva of the eyes, and esophageal mucosa can also be affected. The skin and mucosa of the genitalia, urethra, and anus are also common sites for pemphigus. The vulva is often affected by the labia majora and minora, vagina, and cervical mucosa. Mucosal lesions present with an initial sensory hyperesthesia and burning pain, followed by blisters in areas prone to friction. The blisters break quickly, with rare intact blisters, forming a painful erosive surface that is prone to bleeding on contact. Healing is slow, lasting for several weeks or months, and secondary bacterial or candidal infections are common. In some cases, ulcers may develop. Cervical lesions can occur early in the disease, leading to abnormal Papanicolaou smears and may be misdiagnosed as abnormal cervical epithelial hyperplasia. Some pemphigus cases are associated with malignant tumors.

　　1. Skin Lesions

　　Typical skin lesions appear on normal-appearing skin, with a few on the base of erythematous plaques, presenting with fluid-filled blisters of varying sizes from pea to egg, which can be solitary or confluent. The blister fluid is clear early on, but may become cloudy or hemorrhagic later. The blister walls are thin, relaxed, and prone to rupture. The Nikolsky sign is positive, meaning that pressing on the intact top of a blister causes it to expand laterally; friction or pressure on the blister can cause erosion of the surrounding epidermis, leading to epidermal desquamation. After the blister wall breaks, a red erosive surface is formed with serous exudate, which gradually solidifies into a dirty crust with an unpleasant smell. The erosive surface continues to expand outward, merging into irregular shapes, with the edges showing annular separation of the epidermis. There is often no tendency to heal spontaneously, and post-healing hyperpigmentation may occur. Patients may experience a burning sensation or pain, which can be accompanied by systemic symptoms such as fever and anorexia. Large blisters can occur anywhere on the body, but are most common on the head, face, neck, back, axilla, and inguinal areas.

　　2. Vulvar and mucosal damage

　　About 60% of patients may initially develop blisters in the oral cavity, and almost all cases involve oral mucosa. In addition, it can also affect the nose, pharynx, conjunctiva of the eyes, esophageal mucosa, external genitalia, urethra, and anal skin and mucosa, which are also common sites of pemphigus. The vulva often involves the labia majora and minora, vagina, and cervical mucosa. Mucosal damage in the early stage is characterized by hypoesthesia and burning pain, followed by blisters in areas prone to friction. The blisters break quickly, complete blisters are rare, and painful erosive surfaces form, which are prone to bleeding upon contact. The erosions heal slowly, lasting for several weeks or months, and are susceptible to secondary bacterial or candidal infections. Sometimes, they can develop into ulcers. Cervical damage can occur early in the disease, leading to abnormal Papanicolaou smears and easy misdiagnosis as abnormal cervical epithelial hyperplasia.

　　The occurrence of vulvar pemphigus requires inciting factors, and certain drugs or foods can induce pemphigus.

      1. Prevention: Early detection, early treatment, and follow-up care.

　　2. Prognosis: There may be recurrence; the prognosis is poor when accompanied by malignant tumors.

　　Immunofluorescence examination:

　　1. Direct immunofluorescence:

　　Take a sample of normal skin around the skin lesions or newly formed lesions for examination, showing IgG and C3 deposited in a fishnet pattern between epidermal cells. Other components include C1q and C4. The positive rate is 80% to 95%, reaching 100% in active lesions, with a few antibodies being IgM or IgA.

　　2. Indirect immunofluorescence:

　　80% to 90% of patients can detect anti-intercellular substance antibodies, known as pemphigus antibodies, in their serum, mainly IgG, with a few being IgM, IgA. The titer of antibodies is highly correlated with the activity of the disease, but it can be false-negative in the early stage. Electron microscopy shows that early changes include the partial or complete dissolution of the intercellular matrix or glycocalyx of epidermal cells, widening of cell gaps, and separation of desmosomes. In the later stage, tensin filaments detach from the desmosome attachment plate, and desmosomes disappear.

　　I. Dietetic recipe for vulvar pemphigus

　　1. Chrysanthemum leaves and tangcao mung bean porridge

　　Ingredients: 10 grams of chrysanthemum leaves, 1.5 grams of tangcao, 1.5 grams of licorice, 30 grams of mung beans, 150 grams of glutinous rice.

　　Method: Cut chrysanthemum leaves, tangcao, and licorice into pieces and put them into a gauze bag. Add mung beans and glutinous rice, and boil them together with water for 30 minutes. Cook into porridge over low heat.

　　Effect: Clear heat and reduce fire, detoxify and heal sores.

　　Usage: Take in the morning and evening.

　　2. Frosting lotus flowers

　　Ingredients: 10 fresh white lotus flowers, 150 grams of sugar, a small amount of starch, refined flour, and osmanthus, 100 grams of peanut oil (50 grams consumed).

　　Preparation: First, mix 50 grams of sugar, a small amount of osmanthus, starch, and refined flour together to form a thin paste. Slightly open a newly bloomed white lotus flower and dip it into the paste for use. Place a pot on the stove, add peanut oil, and fry the coated lotus flower until slightly golden yellow, then remove and arrange on a plate. Sprinkle with sugar and it's ready.

　　Effect: Clear summer dampness, stop bleeding. Suitable for hematemesis, bullous pemphigoid, and eczema, etc.

　　Usage: Take in the morning and evening.

　　2. Foods that are good for vulvar pemphigoid

　　1. Eat more vegetables and fruits.

　　2. Drink more tea or light beverages.

　　3. Foods that are good for cooling blood and detoxifying. Green beans, glutinous rice, cucumber, bitter melon, portulaca oleracea, green tea, etc.

　　3. Foods to avoid for vulvar pemphigoid

　　1. Avoid spicy and irritant foods: Spicy and irritant foods can affect the endocrine system in the body, causing skin itching and affecting treatment. Spicy and irritant foods include chili, pepper powder, horseradish, scallions, garlic, white wine, etc.

　　2. Avoid greasy foods: Greasy foods mainly refer to oils and fats. Excessive intake of these foods can promote the secretion of sebaceous glands, exacerbating the condition. At the same time, it is also necessary to eat less sweet and salty foods to facilitate skin recovery.

　　3. Avoid seafood and irritant, sensitizing foods when itching is severe.

　　1. Chinese medicine treatment formula:

　　25 grams of raw rehmannia, 25 grams of lonicera, 25 grams of salvia miltiorrhiza, 10 grams each of cortex moutan and peony root, 15 grams of fructus rubi, 12 grams of angelica sinensis, 15 grams of forsythia, 10 grams each of white thorn, fried apium, black mustard seed, umeboshi, bupleurum chinense, and schisandra chinensis, 6 grams of licorice.

　　Usage: Take one dose daily, decocted and taken as a decoction. The Western medical treatment method for vulvar pemphigoid includes: 1. Supportive treatment: Due to the large area of skin lesions in pemphigoid patients, with blisters, erosion, exudation, and desquamation, which leads to the loss of a large amount of protein and other nutritional components in the body, and often accompanied by systemic symptoms such as fever, active supportive treatment should be given. High-protein, high-calorie, and high-vitamin diet should be provided, attention should be paid to water and electrolyte balance. For patients with systemic failure, blood, plasma, or human serum albumin can be transfused, and secondary infection should be prevented.

　　2. Systemic treatment

　　1. Corticosteroids:

　　It is the most effective drug for treating bullous pemphigoid. It mainly inhibits the production of bullous pemphigoid antibodies and should be administered early, in sufficient dosage, and for a sufficient duration, with regular and correct dose reduction, maintaining the minimum dose for a long period. The drug dosage is determined based on the area of skin lesions and the severity of the condition. For patients with localized skin lesions, prednisone (Prednisone) at 0.5 to 1mg/kg can be administered, while for those with widespread lesions (area > 50%), the dosage is 1 to 2mg/(kg?d). If the treatment is ineffective after 4 to 5 days, the dose should be increased by 1/3 to 1/2 of the original dose. The dose should be maintained for 2 to 3 weeks to control symptoms, and then gradually reduced. Depending on the condition, dose reduction can be done every 1 to 2 weeks. When the dosage of hormones is high, the reduction can be faster and more extensive, approximately 1/6 to 1/10 of the original dose. Subsequently, as the dosage of hormones decreases, the reduction should be slower and less frequent. Particularly, when the dose of prednisone (Prednisone) reaches about 30mg, caution should be exercised. The maintenance dose is generally 10 to 15mg/d, and most patients require maintenance for several years. For severe and refractory cases, a high-dose pulse therapy can be used, which often achieves good efficacy. Methylprednisolone (Methylprednisone) injection at 0.5 to 1.0g can be administered intravenously for 3 days, followed by continued treatment with the original dose after 3 days.

　　2. Immunosuppressants:

　　Immunosuppressants can inhibit the formation of pemphigus autoantibodies and are often used in combination with corticosteroid hormones to improve efficacy, reduce the amount of hormones, quickly reduce the dose of hormones, thereby avoiding the side effects of long-term high-dose hormones, improving the prognosis. They can also be used alone in patients with contraindications to corticosteroid hormones.

　　Immunosuppressants generally take effect after 1 month of application. After taking effect, the dose of corticosteroids is usually reduced first, followed by the reduction of immunosuppressants to the maintenance dose. Commonly used immunosuppressants include:

　　(1) Cyclophosphamide (CTX): 1-2mg/(kg?d), taken orally in divided doses. During the medication period, plenty of water should be consumed to reduce bladder toxicity. Due to the slow onset of cyclophosphamide (CTX), long-term use can easily accumulate adverse reactions, and cyclophosphamide (CTX) pulse therapy can be used. CTX 8-12mg/(kg?d) is added to the fluid for intravenous infusion for 2 consecutive days, once every 2 weeks, with a cumulative total not exceeding 150mg/kg, or cyclophosphamide (CTX) 0.5-1g/m2 is added to the fluid for intravenous infusion, once a month, for 3-6 times in total, while using moderate amounts of glucocorticoids simultaneously.

　　(2) Azathioprine (AZA): Less toxic than cyclophosphamide (CTX), and its efficacy is also slightly poorer. The dose is 1-3mg/d, taken orally in two divided doses. The efficacy usually reaches a peak around 8 weeks after medication. After the disease is stable, the dose can be reduced by 0.5mg/(kg?d) every 2-3 weeks to maintain the lowest maintenance dose for treatment.

　　(3) Cyclosporine (CsA): Selectively inhibits CD4 T cell subsets, thus has a small bone marrow suppressive effect. When used in combination with glucocorticoids, it can achieve good results. The dose is 4-8mg/(kg?d), taken orally in two divided doses. After the disease is controlled, the dose is gradually reduced, with the minimum maintenance dose of 1mg/(kg?d), and can be continuously used for 1-2 years.

　　3. Human blood gamma globulin:

　　The mechanism of action may significantly reduce the titer of pemphigus antibodies through the following pathways:

　　(1) The anti-idiotypic antibodies in human blood gamma globulin can effectively neutralize pemphigus antibodies.

　　(2) Binding to specific B cell receptors downregulates receptor function and reduces antibody synthesis.

　　(3) Accelerates the process of the reticuloendothelial system clearing autoantibodies. The dose is 0.4g/(kg?d) intravenous infusion, administered for 3-5 days as an adjuvant treatment. When used in combination with corticosteroids and immunosuppressants, it can effectively control cases that are difficult to control or cannot be reduced quickly with conventional corticosteroids and immunosuppressants.

　　4. Plasma Exchange Therapy:

　　Can clear bullous pemphigoid antibodies from the patient's blood, alleviate acantholysis, and relieve the condition. However, due to the feedback mechanism in the immune network of the body, simply removing antibodies can activate B cells to produce more antibodies. Therefore, plasma exchange therapy as an adjuvant treatment method needs to be used in combination with corticosteroids and immunosuppressants to inhibit the production of new antibodies.

　　5. Protease Inhibitors:

　　Keratinocyte release of proteolytic enzymes leading to acantholysis is an important link in the pathogenesis of bullous pemphigoid. Therefore, protease inhibitors have certain potential in the treatment of bullous pemphigoid. Mefenamic acid 0.25-0.5g, 4 times/d, combined with moderate doses of corticosteroids, can effectively control the condition.

　　6. Others:

　　Antibiotics are used for prevention and treatment of secondary bacterial infections, and appropriate antibiotics can be selected according to the culture of the wound and the results of drug sensitivity tests. In addition, there are reports that tetracycline 1-2g/d combined with corticosteroids can be used to treat bullous pemphigoid, which can reduce the dose of corticosteroids and make it easier to reduce the dose quickly. Dapsone 100-150mg/d or tripterygium glycosides tablets 30-60mg/d can be taken orally in divided doses alone or in combination with corticosteroids for the treatment of mild patients.

　　3. Local Treatment

　　1. For those with localized skin lesions and exudate, 1:8000 potassium permanganate or 0.1% isopropylidene (iodophor) solution can be used for wet敷ment. For those with reduced or no exudate, topical applications of creams containing hormones and antibiotics can be used.

　　2. For those with large skin lesions, abundant exudate and scabs, 1:10000 potassium permanganate wet敷ment or medicated bath can be used. The blister fluid can be aspirated, and the wound can be protected with Vaseline or antibiotic ointment gauze. For those with extensive and large skin lesions, burn exposure therapy can be adopted. For those with oral ulceration, a solution containing an equal amount of 3% hydrogen peroxide (peroxide), 0.1% isopropylidene (iodophor) and 2% procaine can be used for gargling to clean the mouth and alleviate pain. If secondary candidal infection occurs, 2% baking soda or nystatin solution can be used for gargling.