Cicatricial pemphigoid is an autoimmune exfoliation of the epidermis with preservation of intercellular connections in the elderly. Mainly the mucous membranes suffer, less often there is a simultaneous lesion of the skin and mucous membranes, even less often – an isolated skin lesion. The primary element is a strained transparent vesicle with an outcome in erosion and scarring. A dermatologist diagnoses cicatricial pemphigoid based on the clinical picture, biopsy of the affected area with conventional, immunofluorescence, immunoelectronic microscopy. Immunoblotting and immunoprecipitation are used. Glucocorticoids, cytostatics, systemic enzymes, vitamin therapy are used in the treatment. Externally, antiseptics and anti-inflammatory drugs are prescribed.
General information
Cicatricial pemphigoid is a chronic benign gerontological bullous dermatosis of the mucous membranes and skin without acantholysis. The Cicatricial process has many synonyms, but most often the cicatricial pemphigoid is called bullous synechial dermatosis due to the fact that the clinical picture is dominated by sclerosing changes on the skin and mucous membranes. A feature of cicatricial pemphigoid is the occurrence of bullae in the same place for a long time, which determines the development of scars. If the pathological process is localized on the conjunctiva, blindness may result. Cicatricial pemphigoid is a rare dermatosis. The disease has a gender coloring, women get sick 2 times more often than men. The age range is from 46 to 90 years, however, individual cases of the occurrence of a pathological process in children are described. Cicatricial pemphigoid occurs on all continents and geographical latitudes, has no seasonality, has no racial characteristics.
In dermatological practice, the concept of “cicatricial pemphigoid” came together with the term “bullous pemphigoid” in 1953. Priority belongs to the American dermatologist V. Lever, who identified a group of pemphigoids from all vesicular dermatoses, based on the absence of acantholysis and the benign course. A decade later, experts established the autoimmune nature of the pathological process by determining the immune characteristics of target proteins. Currently, an “animal model” of this disease has been created, gene cloning has been carried out, which is of great importance for the transplantation of affected tissues. The relevance in dermatology is associated with the need for its accurate and timely diagnosis in order to prevent serious complications (blindness, ectropion, strictures of the esophagus and genitals).
Causes
The exact cause of the disease is still unknown. The pathogenesis is considered as an autoimmune process in which immune complexes are located under the basement membrane of the epidermis and cause the scarring process. When endogenous or exogenous pathological antigens are exposed to the skin and mucous membranes, the production of antibodies to proteins of the basement membrane of the epidermis begins. Endogenous factors include the use of medications, including eye drops and dental pastes. The most likely exogenous factors that provoke the appearance of cicatricial pemphigoid include eyelash epilation, unsuccessful bite correction with braces and prolonged excessive hyperinsolation.
Foreign antigens that have got on the skin and mucous membranes or have penetrated into the blood form autoimmune complexes that are fixed in a certain area of the basement membrane, namely in the place where bulls are subsequently formed. In 70% of cases with cicatricial pemphigoid, the mucous membranes are affected by immune complexes, much less often the skin and mucous membranes, only about 1-3% are isolated skin lesions.
The mucous membrane consists of 4 layers: a membrane with basal semidesmosomes, a transparent zone, a dense zone and a subbasal membrane. IgG and IgA affect the least durable transparent zone that reacts to pathogenic effects with the formation of bullae. It is in the transparent zone that an autoimmune process occurs, mediated by T-lymphocytes, which activate B-lymphocytes and trigger the process of inflammation in the epidermis and dermis. The production of proinflammatory cytokines, including TNF, begins, activating the antigenic reactivity of B-lymphocytes and destroying the membrane.
In the basal layer of the epidermis, the connection between the processes of epidermal cells is disrupted due to the occurrence of many inflammatory vacuoles between them. Merging, vacuoles form a bubble between a layer with half-chromosomes and a dense layer of membrane. This bubble is filled with inflammatory exudate and is covered with an unchanged epidermis. Over time, the bladder necrotizes, due to regenerative processes in the epidermis, its bottom is lined with new cells. Thus, the bubble turns into an intraepidermal vesicle without the process of acantholysis, but only due to the destruction of intercellular connections with their subsequent regeneration.
The autoimmune reaction in cicatricial pemphigoid is constantly stimulated by new immune complexes that are produced in response to autoantibodies circulating in the blood. However, the number of immune complexes decreases over time, and the occurrence of new bulls becomes less intense. At the same time, T-lymphocytes and cytokines stimulate the proliferation of epidermal cells that form the basis of pemphigoid scar tissue. The ongoing autoimmune processes are confirmed by histological studies and RIF data, which, with the development of cicatricial pemphigoid, state the presence of IgG in 70% of biopsies of the oral mucosa. In 1% of the studied material, a combination of IgG and IgA is detected in the area of the basement membrane. After the occurrence of bull and their scarring, IgG and IgA are detected in the blood only in isolated patients with cicatricial pemphigoid.
Symptoms
A distinctive feature of the clinical picture of the pathological process is the appearance of primary elements on the mucous membranes of the oral cavity and conjunctiva. In addition, with cicatricial pemphigoid, the mucous membranes of the nasal cavity, pharynx, esophagus and genitals are affected. In 30-50% of patients with cicatricial pemphigoid, the skin is affected. The most serious is the localization of bull on the conjunctiva. The pathological process begins with hyperemia, swelling and pain of the conjunctiva in combination with photophobia. Then subconjunctival bubbles the size of a pinhead are poured out.
Bulls with tight lids, tense, filled with serous or hemorrhagic contents. They exist on the mucous membranes for 2-3 days, and then they erode. In their place, new bubbles appear, which are opened again. As a result, first tender and then rough scars are formed, leading to wrinkling of the conjunctiva, adhesions of the conjunctival sac, loss of mobility of the eyeball. In some cases, there is an eversion of the eyelid (ectropion), cicatricial deformation of the tear ducts occurs. Rarely, the conjunctiva ulcerates with the formation of a cataract.
Bullae on the oral mucosa with cicatricial pemphigoid do not have such serious consequences, causing only unpleasant sensations during the formation of scars. Typical localization – tonsils, tongue, soft palate, cheeks. If the red border of the lips is affected, the mouth opening may narrow (microstomy). Vesicular elements on the esophageal mucosa are fraught with the development of strictures that make it difficult to eat, leading to exhaustion. Bullae on the mucous membrane of the genitals provoke the formation of adhesions that interfere with normal sexual life, lead to urethritis. In addition, there is a special form of cicatricial pemphigoid – local, atypical, in the form of limited bullae on the skin of the extremities or scalp, causing soreness, hyperemia and local swelling of the skin. The course of the cicatricial pemphigoid is undulating, long-term, without a significant violation of the general condition.
Diagnostics
The clinical diagnosis is made by a dermatologist on the basis of typical symptoms, a negative Nikolsky symptom (lack of desquamation when rubbing the skin), the absence of acantholytic cells (Tzanka cells) in the smear imprint from the bottom of erosion. If necessary, additional research methods are used. First of all, a biopsy of the skin and mucous membranes affected by cicatricial pemphigoid is taken and conventional microscopy is used, which excludes acantholysis. Histologically, lymphocytic inflammatory infiltrate in the submucosal layer of the dermis, angioplasia are noted. Immunofluorescence microscopy confirms the specific glow of the epidermis in the area of the basement membrane. Immunoelectronic microscopy uses gold-labeled immunoglobulins, fixing their location. Immunoblotting and immunoprecipitation (IgG and IgA) are also used.
Differentiate cicatricial pemphigoid with lichen planus, vulgar and seborrheic pemphigoid, bullous pemphigoid, Stevenson-Johnson syndrome, Behcet’s disease, chronic lupus erythematosus, herpetiform dermatitis.
Treatment
The pathological process does not respond well to therapy. It should be noted that cicatricial pemphigoid with localization on the conjunctiva is treated by an ophthalmologist according to individual schemes with the use of anti-inflammatory and resorbing agents. The main drugs in the treatment of cicatricial pemphigoid in modern dermatological practice are glucocorticosteroids, which are used internally according to special schemes calculated taking into account the severity of the disease and the age of the patient, as well as externally as part of anti-inflammatory ointments, sprays, creams, gels.
In addition, cytostatics or a combination of hormones and cytostatics are used. Antimalarial drugs and retinoids are prescribed. In severe cases, the use of immunosuppressants and sulfones in large doses is justified. Vitamin therapy, antihistamines, biostimulants, absorbants are indicated. Patients with reduced immunity are given blood and plasma transfusions, and a high-calorie diet is recommended. The formed scars are surgically excised with subsequent plastic surgery of the defect. If necessary, antibiotic therapy is used. Taking into account the age of patients, it is mandatory to consult an oncologist, endocrinologist, cardiologist with correction of concomitant pathology and foci of chronic infection.
The prognosis of cicatricial pemphigoid is uncertain. In some patients, the disease resolves spontaneously or against the background of ongoing therapy, in others there is a progression of pathology, despite timely therapeutic measures.
