Pemphigus

Introduction to pemphigus Pemphigus is a type of severe skin disease characterized by thin-walled, easily ruptured bullae. Histopathology is an epidermal blister caused by spine release, characteristic immunological findings. Pemphigus is divided into three main types: pemphigus vulgaris, deciduous pemphigus, and paraneoplastic pemphigus. Pemphigus vulgaris and deciduous pemphigus are the classic types of pemphigus previously described. All patients with pemphigus vulgaris have mucosal erosion, and more than half of the patients also have skin blisters and erosions. The blisters of pemphigus vulgaris occur in the deep layers of the epidermis, just above the basal cell layer. Patients with deciduous pemphigus have only skin involvement and no mucosal involvement. The fissures of the epidermis occur in the superficial layer of the epidermis, mostly in the granular layer. Proliferative pemphigus is a variant of pemphigus vulgaris, and erythema pemphigus and defoliating pemphigus in Brazil represent the localized and local type of deciduous pemphigus, respectively. basic knowledge Sickness ratio: 3.5% Susceptible people: no specific population Mode of infection: non-infectious Complications: sepsis pneumonia dysphagia

Cause of pemphigus

(1) Causes of the disease

Pemphigus is an autoimmune disease. Anti-keratinocyte intercellular substance antibodies are present in the blood circulation of various pemphigus patients, and the antibody titer is parallel with the severity of the disease. Pemphigus patients are added to the epidermal organ culture. Serum, after 48 to 72 hours, spine release phenomenon can occur in the upper part of basal cells. The occurrence of acanthosis may be related to the protease produced by antigen-antibody binding. It has been confirmed that the pemphigus antibody can bind to keratinocytes to make the epidermis. The cell releases plasminogen activator, which activates the fibrin system to cause spine release. The pemphigus antigen is present in the keratinocyte-linked egg from the desmosome, which is a glycoprotein, an antigen of pemphigus vulgaris. The molecular weight is 210000 u (Dalton); the erythematous pemphigus antigen is a desmoglein protein with a molecular weight of 160,000 u.

(two) pathogenesis

Immunofluorescence found that IgG autoantibodies against the surface of keratinocytes (pemphis antibody) are important markers of pemphigus. Direct immunofluorescence revealed anti-cell surface antibodies in the epidermis of patients, and indirect immunofluorescence revealed serum anti-epidermal cell surface. IgG antibody.

Pemphigus vulgaris and deciduous pemphigus have similar direct immunofluorescence and indirect immunofluorescence. The two diseases are difficult to identify in immunofluorescence. Indirect immunofluorescent substrates have a great influence on the test results. Pemphigus is used in the guinea pig esophagus, while the monkey esophagus is more sensitive to the pemphigus vulgaris antibody. There is a correlation between the circulating pemphigus antibody titer and the severity of the disease, that is, the higher the titer, the heavier the condition. There is a statistically significant difference in this correlation. However, some patients do not fully comply with this rule. Therefore, in the treatment of such patients, the severity of the disease is more important than the pemphigus antibody titer.

The pemphigus antigen is a complex of desmosome molecules. Immunoelectron microscopy studies have shown that the pemphigus antigen is located on the surface of the keratinocytes at the junction of the desmosomes. At the molecular level, immunoprecipitation and immunoagglutination experiments show that the deciduous pemphigus antigen is The molecular weight of 100 kDa glycoprotein, the pemphigus vulgaris antigen is a molecular weight of 130 kDa glycoprotein, which are the cause of pemphigus vulgaris and deciduous pemphigus, respectively.

Passive transfer of patient serum to experimental animals can result in acantholytic release. Experiments have shown that the addition of pemphigus antibody IgG to human skin in vitro can lead to acantholytic release. This antibody-mediated acantholytic solution does not require complementation. With the involvement of inflammatory cells, the above evidence suggests that pemphigus antibodies have pathogenic effects, but the process of binding antibodies to the surface of keratinocytes to cause acantholytic release is not fully understood. One view is that the antibody interferes with the bridge after binding. The attachment of granules, another view that antibodies bind to keratinocytes, causing the release of proteases, resulting in destruction of epidermal cell junctions, acanthal release and blister formation.

Pemphigus vulgaris can be triggered by the patient's potential autoimmune response to certain drugs, such as captopril, isoniazid, indomethacin (indomethacin), ethambutol, phenylbutazone, penicillin, Propranolol (propranolol), pyrithione hydrochloride, rifampicin, there are reports of burns, sunburn, ultraviolet rays and X-ray exposure. In addition, pemphigus can also be associated with other autoimmune diseases. Myasthenia gravis, lupus erythematosus, autoimmune thyroiditis, thymoma, Sjogren syndrome, bullous pemphigoid, pernicious anemia, Hodgkin's disease, etc.

Pemphigus prevention

Give high protein, high vitamin and high calcium diet, pay attention to water and electrolyte balance, those who have difficulty eating should be supplemented by intravenous supplement, anemia and malnutrition are significant for blood transfusion, long-term use of corticosteroids should be supplemented with potassium to prevent hypokalemia, such as bacteria Or a fungal infection should be given a sufficient amount of sensitive antibiotics or antifungal drugs.

1 Keep the mattress clean and flat, and the area of the skin lesion is large. All cloths are disinfected and used.

2 The hospital is UV-sterilized once a day for 30 minutes - 1 hour each time.

3 Flatten the patient's nails to avoid scratching the walls.

4 skin lesions have erosion, exudate and purulent secretions or stench, according to the doctor can be wet with 1:8000 potassium permanganate solution, thick suede with sterile vegetable oil infiltration after appropriate removal, there are bulls, first pump Apply blister fluid and apply Chinese medicine.

5 Avoid cold to prevent upper respiratory tract infection, strengthen nutrition to enhance the body's resistance, give high protein, high calorie, high vitamin, low salt diet.

6 Observe the changes in body temperature at any time.

Pemphigus complications Complications sepsis pneumonia dysphagia

Often accompanied by varying degrees of fever, anorexia, fatigue, etc., due to large area erosion of the skin, a large amount of body fluid extravasation, excessive loss of protein, electrolytes and body fluids, physical weakness, easy to combine sepsis, pneumonia and other secondary infections, buccal mucosa is the most Common affected parts, pharyngeal, larynx and esophageal mucosa may also be affected. These parts may cause the patient to eat, chew and swallow.

Pemphigus symptoms Common symptoms Sclerosing pruritus, redness, mucous membrane damage, herpes abscess, venous slow pigment loss

The basic pathological changes are the spine release of epidermal spine cells, forming intraepithelial fissures and bullae, and there are spine-slung cells in the blister fluid. This cell has large, spherical cells, large and deep nucleus, and uniform cytoplasm. Sex.

Different types of thorns are loosened, and the acne loosening of pemphigus vulgaris occurs above the basal layer. Therefore, the blister is on the basal layer, and the thorny release site of proliferative pemphigus is the same as the vulgaris, but it is obvious. Acanthosis hypertrophy and papillary-like hyperplasia, and an epidermal abscess composed of eosinophils, deciduous, erythematous pemphigus, the spine release site in the granular layer or the upper part of the spinous layer, the formation of the most superficial, tumor The thorny release of rash-like pemphigus occurs in the middle of the spinous layer, which contains eosinophils or neutrophils.

Type

Pemphigus is mainly divided into pemphigus vulgaris, proliferative pemphigus, deciduous pemphigus and erythematous pemphigus.

1. pemphigus vulgaris (remphigus vulgaris)

(1) skin damage: the symptoms of this disease are often mainly pain, rare itching, the primary damage is a relaxing blisters, which can occur on the skin surface of any part of the body, usually on the surface of normal skin, or in erythema On the sexual skin, the new blister is usually loose or becomes slack in a short time. The blister is gently pushed by the finger to make the blister wall expand, the blister is enlarged, and the blister is slightly pushed or scratched. Normal skin can also cause epidermal cells to loosen and cause epidermal detachment or epidermal blistering in the sputum shortly after sputum. This phenomenon is called acanthosis or Nikolsky's sign, and the blisters are on the head. Neck, chest, underarm, groin, etc. are more common, skin lesions can be limited to one to several months for a long time; can also spread the body within a few weeks, often leave brown pigment after the skin loss subsides Calming and millet rash, occasionally pigmentation loss.

(2) Mucosal damage: In most patients, painful mucosal erosion is a typical clinical manifestation of pemphigus vulgaris, and may be the only symptom about 5 months before the appearance of skin lesions, the most common mucosal lesions. It is the oral cavity. Buccal mucosa is the most common affected part. The pharynx, larynx and esophageal mucosa may also be affected. These parts may cause the patient to eat, chew and swallow. Other affected parts include conjunctiva, anus, ear canal, labia, vagina. , the cervix, glans, etc. at the mucosa.

2. Proliferative pemphigus (pemphigus vegetans)

Rare, a variant of pemphigus vulgaris.

(1) It is characterized by the appearance of sputum-like and papillary-like proliferation on the erosion surface, surrounded by inflammatory redness, thick sputum on the surface, odor, and fresh blisters around.

(2) occurs in the armpit, groin, anus, vulva, breast, umbilical fossa and other wrinkles.

(3) The disease is divided into two types, heavy (neumann type) and benign process (Hallopeau). Although the latter has many similarities with proliferative dermatitis, immunofluorescence shows that both types of proliferative pemphigus There is cell surface IgG deposition.

(4) The course of the disease is chronic, the symptoms are mild, and the disease can be relieved for a long time.

3. deciduous pemphigus (pemphigus foliaceas)

(1) The characteristic clinical damage is the scaly and scarred erosion surface on the erythematous base.

(2) The primary lesion is the erythematous basal plane, which may appear as blisters, the blister wall is thin, and it is easy to rupture, forming a shallow erosion surface, and the blister is less likely to occur later.

(3) In the early or limited lesions, the skin lesions are mostly distributed in the face, the scalp and the upper back and other seborrhea, the damage is gradually enlarged, consciously burning, pain and itching.

(4) Oral mucosa is rarely affected, and the Nissl sign is positive.

4. erythematous pemphigus (pemphigus erythematosus)

Also known as Senear-Assel Syndrome (Senear-ushel syndrome), can be converted into deciduous pemphigus, some people think that defolitic pemphigus is limited and benign, the lesion is mainly located in the scalp, face, chest and back Such as skin seboration, generally no mucosal damage, erythematous pemphigus lesions are limited, lasting for several years, its characteristics are in its immunopathology, erythematous pemphigus patients with anti-nuclear antibodies, basement membrane IgG and C3 deposition can also be seen.

Pemphigus examination

Laboratory inspection

(1) Scrape fresh blister base tissue smear and stain with Giemsa. It can be seen that single or groups of loosened free spine cells have large nuclei and uniform staining. There is a transparent band around the nucleus, and the surrounding cells are densely stained. The spinous process disappears, and this is the spine process that loosens the cells and has a diagnostic significance for pemphigus.

(2) Direct immunofluorescence: Take the blister or its surrounding skin for frozen section, and there are immunoglobulin and complement deposition between the spine cells.

(3) Indirect immunofluorescence: The patient's serum was taken to detect pemphigus antibody, and the titer was positively correlated with the condition.

(4) There is a decrease in total plasma protein and different degrees of anemia. The initial blood tests can have a total number of white blood cells, neutrophils and eosinophils increase, and erythrocyte sedimentation rate often accelerates to varying degrees.

Lack of specificity, patients with mild anemia, the degree of anemia is directly proportional to the severity of the disease, the total number of white blood cells increased, half of the patients with eosinophils increased, erythrocyte sedimentation increased, liver and kidney function tests were basically normal.

Cytological examination (Tzanck smear): use a blunt knife to scrape the erosion surface and apply it thinly on the slide, or use a slide to gently press on the erosion surface, then fix it, and stain it with Reiter or Giemsa. The cells are round and oval. The intercellular bridge disappears, and the nucleus is rounded and stained lightly. The nucleolus and cytoplasmic alkaloids, so-called pemphigus cells or Tzanck cells, are visible.

Indirect immunofluorescence: more than 90% of the patients have antibodies against the surface of epidermal cells. The antibody titer of the fetus is parallel with the severity and activity of the disease. The titer may decrease or turn negative after the clinical symptoms are improved. However, it is not the only indication for judging the severity of the disease. Pemphigus antibodies can be found in burns, Lyell toxic epidermal necrolysis, penicillin drug eruption, etc., but this antibody titer is weak and cannot be combined with epidermal cells in vivo. Does not cause tissue damage.

Histopathology:

The histopathological changes of various types of pemphigus are as follows:

1. Pemphigus vulgaris in the lower layer of the spine, the spinous process is released on the basal cell layer, causing fissures and blisters. There is only one layer of basal cells on the basal cell. It is located on the dermal papilla, similar to the villi of the intestine, and has vesicular fluid. The spinous process releases cells, which are larger than normal cells, round, with concentrated nuclear center, uniform cytoplasm, and a clear area of light staining around the nucleus. This cell is also called Tzanck cell, mild edema in the upper part of the dermis, a few Eosinophils and neutrophil infiltration.

2. Proliferative pemphigus early damage under the spinous layer has spinous process to resolve fissures or cavity formation, visible villi, epidermal eosinophilic small abscess, advanced keratosis, acanthosis hypertrophy papilloma-like hyperplasia, pathology The change is similar to pemphigus vulgaris, but the formation of villi and the extension of the epidermis are particularly obvious, and the old skin lesions have no diagnostic value.

3. The deciduous pemphigus spines are loosened, cracks or blisters occur in the granule layer and below, and the granule layer cells are loosened to form keratinocytes similar to keratinization (nuclear shrinkage, cytoplasmic comparison) Red), has diagnostic value, inflammatory cell infiltration in the dermis, more eosinophils.

4. The pathological changes of erythematous pemphigus are similar to deciduous pemphigus, but the old lesions damage the hyperkeratosis of the hair follicles, the granule layer spines are loosened, and the keratinized cells are often significant.

Direct immunofluorescence: valuable for the diagnosis and differential diagnosis of pemphigus. Take skin lesions and normal skin examination. Almost all patients have IgG and C3 on the surface of epidermal cells, pemphigus vulgaris and proliferative days. In acne, the fluorescence reaction is mainly in the lower layer of the epidermis. The fluorescein of deciduous pemphigus and erythematous pemphigus is mainly in the upper layer of the epidermis. The DIF of erythematous pemphigus skin lesions is characterized by IgC and C3 deposition in the basement membrane zone.

Observation by electron microscopy: Early studies suggested that the interstitial cells were partially or completely dissolved, and the intercellular space became wider. Subsequently, the disappearance of desmosomes caused the formation of spinous processes. In recent years, studies have shown that the destruction or formation of desmosomes is the cause of blister formation. The main reason is that the damage of the bridge particles and the number of the non-lesional lesions can be seen by electron microscopy.

Diagnosis of pemphigus

The diagnosis of pemphigus is mainly based on histopathology and immunofluorescence of clinically manifested lesions.

diagnosis

1. Diagnosis from clinical manifestations:

(1) The basic damage of various types of pemphigus is loosening of the skin, with scarring, or refractory erosion surface.

(2) Mucosa, especially the oral mucosa, is often an early symptom of pemphigus.

(3) Nikolsky's sign is positive.

Differential diagnosis

1. Bullous pemphigoid is more common in elderly patients, the basic damage is thick-walled tension blister or blood blister, not easy to rupture, easy to heal after rupture, Nissl's sign negative, mucosal damage is rare, histopathological examination of blister is located Under the epidermis, direct immunofluorescence revealed linear deposition of C3 and IgG in the basement membrane.

2. Severe polymorphous erythema skin and mucous membranes can have bullous damage, often with pleomorphic rash, papules, or purpura, Nissl's sign negative, fever, acute onset, early treatment healed faster.

3. Toxic epidermal necrolysis is sudden, rapid progress, severe systemic symptoms, bullous plaque occurs on the basis of erythema, large area, blister wall wrinkles, similar to large area burns, Nissl positive, adult mostly Caused by drug allergy, often useful drug history, histopathology and immunofluorescence can be identified.

4. Exfoliative dermatitis drug eruption should be differentiated from deciduous pemphigus. The drug eruption has a history of useful drugs before the onset of the disease. It usually occurs within 3 weeks after taking the drug. The rash damage is mostly measles-like, or scarlet fever-like erythema, which gradually develops into the whole body. Skin exfoliation, onset is more urgent, often accompanied by high fever and other systemic symptoms, the rash gradually relieved after stopping the drug, the incidence of deciduous pemphigus is slow, rarely self-healing, histopathology and immunofluorescence can be identified.

5. Herpes-like dermatitis damage is pleomorphic, clusters of tension mung bean to cherry-sized thick-walled blisters, which occur in the scapula, the humerus and the extremities and other parts of the extremities, Nissl's sign is negative, itchy, can be relieved, However, recurrent episodes, histopathological examination of vesicles under the epidermis, direct immunofluorescence examination of granular IgA deposition with dermal papilla.

In addition to the above diseases, mucosal pemphigus damage must be differentiated from aphthous stomatitis, lichen planus, erosive lupus erythematosus and benign mucosal pemphigus. Other diseases that should be differentiated from pemphigus are acquired bullae. Sexual epidermolysis, delayed skin porphyria, etc.

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