Lever’s disease (benign universal pemphigoid) is a chronic autoimmune non-cytolytic vesicular dermatosis. Clinically characterized by a rash of tense blisters, both on the background of cutaneous erythema and on the unchanged mucosa. Inside the bull is a serous, serous-hemorrhagic content. Bubbles are opened almost without the formation of crusts, which do not have time to form due to the rapid epithelization of erosive surfaces in place of former vesicles. Subjectively, itching, slight malaise is noted. The diagnosis is made on the basis of the clinic, microscopy, immune testing. Treatment is complex, according to individual schemes.
General information
Lever’s disease is the most common bullous subepidermal dermatosis from the group of pemphigoids (mucosal pemphigoid, monomorphic and polymorphic skin pemphigoid, universal pemphigoid with skin and mucosal lesions). Clinically resembles true pemphigus, but has a benign course and never forms acantholytic cells. In dermatology, all vesicular dermatoses up to the middle of the twentieth century were designated by the name “pemphigus”. In 1951-1953, V. Lever distinguished from this large group of skin ailments diseases with a benign course, calling them “pemphigoids”. He confirmed his clinical observations histologically, indicating the absence of acantholytic cells in the studied areas of the skin.
Decades later, Jordan and his students discovered antibodies in the blood of patients suffering from Lever’s disease that exfoliate the epithelium of the epidermis, which became the basis of the autoimmune theory of the development of dermatosis. Lever’s disease has no gender component, seasonality, racial characteristics. There is a geometric progression in the incidence of pathology with age: by the age of 90, the risk of contracting Lever’s pemphigoid increases 300 times compared to 60 years. Bullous pemphigoid can coexist with other autoimmune and tumor processes.
Causes
The exact cause of the disease has not yet been named. It is believed that Lever’s disease is autoimmune in nature, occurs against the background of a hereditary predisposition to autoimmune failures. However, scientists have identified a number of reasons that provoke the onset of dermatosis: severe skin irritation (hyperinsolation, burn, radiation therapy), vaccination, tissue transplantation, lifelong medication, tumors. As a result of the indirect effect of these factors on immunity, both local (skin) and general (natural defenses of the body), a humoral-cellular response occurs in the form of the production of antibodies to individual skin cells that have become spontaneously “alien”. An autoimmune process is triggered, the connections between the cells of the lower layer of the epidermis are broken, vesicles filled with fluid appear in it.
The bubbles merge with each other. In order to somehow limit their growth, some of the cells of the epidermis that are not involved in the process turn into their dense tires. Over time, the cells of the walls of the formed bubble age, begin to die. In parallel, the physiological regeneration process is launched along the perimeter of the bull: the bottom of the vesicle is lined with new cells. Thus, the bubble itself appears between the layers of the epidermis: the old tire is on top, the new epithelium is on the bottom. An objective confirmation of the autoimmune theory is the detection of antibodies to the basement membrane of the epidermis in the blood of patients and in the fluid of vesicular elements.
Symptoms
The formation of bubbles occurs with the phenomena of prodroma, rather large bulls appear on the skin, filled with a transparent liquid, sometimes with an admixture of blood due to the destruction of the capillaries of the papillary layer of the epidermis. Rashes do not have a typical localization, they are more often located on the extremities, in the folds of the skin. Mucous membranes are rarely affected. However, the possibility of damage to both the skin and mucous membranes is a distinctive feature of pathology.
At the base of the skin blisters of exotic outlines lies an elevated (slightly convex) erythematous spot. The size of the bubbles ranges from 3 mm to 3 cm, the bulls are elastic, tend to merge with each other, forming erosions that give painful sensations when localized on the mucous membranes. In the folds of the skin on intertriginous areas (hyperemic, cracked, with detachment of the epidermis), the sensations are identical. Lever’s disease is a recurrent dermatosis that haunts the patient until the end of his days, in the case of intercurrent diseases due to the age of the patient, despite the good quality, it can end in death.
Diagnostics
Diagnosis of Lever’s disease is carried out on the basis of a clinic confirmed histologically (intraepidermal bladders), laboratory data (blood test, biochemistry). Cytological studies are used: smears from the base of the bladder, reliably confirming the absence of acantholytic cells (the Tsanka test is negative). Microscopy is no less important: light, electronic (acantholysis is excluded), immunofluorescence (direct and indirect – fixes the place of the autoimmune reaction – glow in the area of the basement membrane of the epidermis), immunoelectronic (establishes the presence of immunoglobulins interested in the autoimmune process).
Immunochemical research methods aimed at identifying autoantibodies are carried out (immunoprecipitation is an antigen–antibody binding reaction, immunoblotting is the use of specific antiserums). Lever’s disease is differentiated with vulgar pemphigus, During dermatitis, epidermolysis bullosa, multiform exudative erythema, multiform drug exanthema, other pemphigoids, paraneoplastic processes.
Treatment
Therapy is carried out according to individual schemes developed by a dermatologist after consultation, examination (especially thorough in order to exclude oncology). When developing a treatment program, the patient’s age, concomitant pathology, and the severity of the course of the disease are taken into account. The basis of therapy is systemic glucocorticoid drugs (prednisone) in combination with antibacterial agents (diaphenylsulfone), cytostatics (azathioprine).
Mild forms of the disease are well stopped by the appointment of antibiotics (erythromycin), sulfonic drugs. Symptomatic therapy is carried out taking into account somatic diseases (diabetes mellitus, osteoporosis), possible infections. To increase the effectiveness of treatment, vitamin therapy (C, P, PP), enzymes (pancreatin, trypsin, chymotrypsin, amylase, lipase), drugs that strengthen the vascular wall (nicotinamide) are used. Plasmapheresis with double filtration (removes cytokines) is shown. Externally, aniline paints are used (after opening the bubbles), aerosols with antibiotics and hormones. A good effect is noted when taking baths with a succession of celandine. If the area of erosive surfaces is significant, surgical dressings are used.
During the course of therapy, it is necessary to observe a protective regime, avoid physical exertion, stressful situations. After the end of the course of treatment, dermatologists advise not to travel for several months, as a change in the climate zone can cause a new exacerbation. If a paraneoplastic syndrome is detected, an oncologist’s consultation is indicated, followed by chemotherapy, radiation, and surgical intervention. The prognosis of Lever’s disease, provided timely diagnosis and treatment, is favorable for life.
