Quality of life of patients with Sjögren's disease during basic therapy

1.General information

A large group of chronic systemic (i.e. affecting the entire body as a whole) connective tissue lesions are called rheumatic diseases. Most of these diseases are not entirely clear, or not clear at all, in terms of etiopathogenesis; they have a number of common clinical and pathomorphological features, but also have their own characteristics of the course, dynamics, and outcome.

The most common diseases of this group include rheumatism itself (in the acute period - rheumatic fever), rheumatoid arthritis, as well as Sjögren's disease, the main aspects of which are discussed below.

First of all, it is necessary to clarify the differences and possible difficulties in terminology. Sjögren's disease, or primary Sjögren's syndrome (PSS), is also called in the literature "dry syndrome", "Predtechensky-Guzhero-Sjögren syndrome", "autoimmune exocrinopathy", "autoimmune epitheliitis", "Sjögren's syndrome" (the latter spelling, apparently, is most correct: Henrick SC Sjögren, who first described the disease in 1933, was a famous Swedish ophthalmologist). The difference between the disease and Sjögren's syndrome is only that the secondary syndrome is diagnosed as part of some other rheumatic disease, while pSS (primary syndrome, Sjögren's disease) manifests and develops as an independent pathological process. The symptom complex is the same in both cases.

Regarding the epidemiological, age and regional trends inherent in Sjögren's disease/syndrome, opinions in the available sources differ significantly. Thus, cases of primary detection of Sjogren's syndrome in persons of any gender, race and nationality, place of residence, age (ranging from infancy to old age) are known and described in the literature. At the same time, it has long been established that among those affected, women of mature and menopausal age predominate, but the degree of this predominance is estimated differently: from 8-10-fold to 25-fold. The absolute frequency of occurrence in the general population varies within 0.60.8%; in older age categories this proportion increases to 2.7%.

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Diagnostics

Diagnosis of Sjögren's syndrome is complicated by the variety of symptoms, as well as their similarity to symptoms of other diseases. However, a combination of certain tests can help make a diagnosis:

1. ANA profile (anti-nuclear antibody). Typical markers are SSA/Ro and SSB/La, of which SSB/La is more specific; SSA/Ro is often associated with other autoimmune conditions but is often present in patients with Sjögren's syndrome.
2. Schirmer's test. Evaluates tear production: a strip of filter paper is placed behind the lower eyelid for five minutes, then the length of the paper moistened with tears is measured. Less than 5 mm speaks in favor of Sjögren's syndrome. It must be remembered that the function of tear secretion decreases with age, as well as with some other disorders.
3. Sialometry. Normally, when stimulated with ascorbic acid, approximately 2.5-6.0 ml of saliva is released in 5 minutes.
4. Unstimulated saliva collection. The patient collects saliva into a test tube for 15 minutes. A result of less than 1.5 ml is considered positive.

2. Reasons

The etiopathogenesis of Sjogren's disease, that is, the causes and mechanisms of development, remains unknown. Only the autoimmune nature of the disease is generally accepted, while trigger factors that provoke the immune system to attack the tissues of its own exocrine glands (primarily salivary and lacrimal) are the object of intense research and scientific debate. The most discussed and reasoned include viral, genetic and hormonal hypotheses; The influence of psycho-emotional factors is also being studied. Perhaps each of these hypotheses reflects some part of a complex interrelated polyetiology (multi-causality, multi-factoriality).

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Forecast

Sjögren's syndrome can damage vital organs with a transition to a stable state, gradual progression, or, conversely, long-term remission. This behavior is also typical for other autoimmune diseases.

Some patients may have mild symptoms of dry eyes and mouth, while others develop serious complications. Some patients are completely helped by symptomatic treatment, others have to constantly struggle with deterioration of vision, constant discomfort in the eyes, often recurrent infections of the oral cavity, swelling of the parotid salivary gland, difficulty chewing and swallowing. Constant loss of strength and joint pain seriously reduce the quality of life.

In some patients, the pathological process involves the kidneys - glomerulonephritis, leading to proteinuria, impaired renal concentrating ability and distal renal tubular acidosis.

People with Sjögren's syndrome have a higher risk of developing non-Hodgkin's lymphoma compared to healthy people and people with other autoimmune diseases. About 5% of patients develop some form of lymphoma.

In addition, it has been found that children of women with Sjogren's syndrome during pregnancy have a higher risk of developing neonatal lupus erythematosus with congenital heart block.

3. Symptoms and diagnosis

It is not for nothing that Sjögren’s disease is called “dry syndrome”: the classic picture of Sjögren’s disease includes two obligate symptoms that are mandatory for diagnosis - xerophthalmia (dry eyes) and xerostomia (dry mouth); For a secondary syndrome, the presence of another, previously manifested systemic connective tissue disease is required.

Insufficient hydration of the eyeballs, caused by lymphoid infiltration of the lacrimal glands, leads to the development of dry keratoconjunctivitis (inflammation of the cornea and conjunctiva, sometimes ulcerative) with corresponding symptoms.

Constant drying out of the oral mucosa causes a number of serious dental disorders and leads to problems with food consumption.

Optional symptoms are very diverse: photosensitivity (pathological hypersensitivity of the skin to sunlight) with an erythematous rash in open areas, joint-muscular pain and swelling, cheilitis (inflammation and cracks on the lips and in the corners of the mouth), gastrointestinal disorders, sexual dysfunction in women (since not only salivary and lacrimal glands are affected, but also other exocrine glands, including those responsible for moisturizing the vagina), allergic reactions, dry bronchitis and other respiratory diseases, renal pathology, vasculitis (inflammation of blood vessels), damage to the central nervous system and etc. The most dangerous complications of Sjogren's disease/syndrome include oncological processes (usually lymphomas or lymphosarcoma), the likelihood of which increases by more than 40 times with this disease.

Diagnosis is based on the results of studying the anamnesis, clinical picture and dynamics, as well as on data from ophthalmological, dental, oncological, and endocrinological examinations. Additionally, imaging diagnostic methods and biopsy of affected tissues are prescribed. However, a multifaceted laboratory blood test is critical.

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Sjögren's disease

The paper fully considers the etiology and pathogenesis, pathomorphology and diagnosis, including differential diagnosis, of Sjogren's syndrome, gives recommendations on the treatment of the syndrome and symptomatic therapy of its ophthalmological, dental, gastroenterological, and other manifestations. IN AND.
Vasilyev – Institute of Rheumatology RAMS, Moscow VI Vasilyev – Institute of Rheumatology Academician of the Russian Academy of Medical Sciences, Moscow
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Sjögren's disease (N. Sjogren, Swedish ophthalmologist, 1899–1986) - Sjögren's disease is a systemic autoimmune disease related to diffuse connective tissue diseases; characterized by damage to many secreting epithelial (exocrine) glands, mainly salivary and lacrimal. There is also Sjogren's syndrome (damage to the lacrimal glands with the development of dry keratoconjunctivitis and salivary glands like parenchymal parotitis), accompanying rheumatoid arthritis, diffuse connective tissue diseases, hepatobiliary diseases and other autoimmune diseases. BS is the most common pathology among diffuse connective tissue diseases and occurs in women 10–25 times more often than in men, usually at the age of 20–60 years, and is much less common in children. Epidemiological studies conducted in recent years have made it possible to establish the presence of BS in 0.59–0.77% of the general population and in 2.7% of people over 50 years of age. Etiology unknown. Most researchers consider BS as a consequence of immunopathological reactions to a viral infection, presumably retroviral. The following facts support the possible involvement of retroviruses in the development of HD: • infection and persistence of immune system cells, such as CD 4+ lymphocytes and macrophages, in potential target organs, for example, the salivary glands; • similarities between known retroviral infections (eg HIV) and BS; • development of a disease resembling BS in transgenic mice having HTLV – 1 + tax gene; • increasing the content of cross-reacting antibodies to retrovirus antigens; • isolation of retroviral elements from cell cultures obtained from biopsy samples of the salivary glands of patients with sclerosis; • detection of antigens that react with monoclonal antibodies to some retrovirus antigens in lymphoid infiltrates in BS. Indirect evidence of the viral etiology of BS is the similarity of immunological disorders (polyclonal b-cell activation, a large number of immune complexes, decreased levels of serum b2-microglobulin, the presence of acid-labile interferon, a decrease in the amount of interleukin-2 (IL-2) and natural killer cells in the blood in BS and AIDS caused by known retroviruses, but direct evidence of the viral etiology of the disease has not yet been obtained.

Pathogenesis

The most recognized hypothesis is the autoimmune genesis of BS, which is supported by the frequent detection in patients of both organ-specific (to the epithelium of the ducts of the salivary glands and pancreas, parietal cells of the stomach, thyroglobulin, etc.) and organ-nonspecific autoantibodies (for example, rheumatoid and antinuclear factors, antibodies to some nuclear antigens - SS-A/Ro and SS-B/La). It is assumed that autoimmune disorders in HD are multifactorial in nature and consist of a combination of the following elements: • genetic control associated with the activity of specific immune response genes; • immune control, influenced by T-dependent lymphocytes; • possible viral infection; • influence of sex hormones on immune regulation; • influence of stress on the immune response. Cases of BS in identical twins, a significant prevalence of other autoimmune disorders in the families of BS patients, as well as an increased frequency of histocompatibility antigens DR 3 and B 8 in BS patients indicate the genetic determination of the disease. It has been shown that the activity of T-suppressors initially decreases, which leads to an increase in the activity of T-helpers and chronic stimulation of b-lymphocytes.

Pathomorphology

The main and pathognomonic morphological sign of BS is lymphoplasmatic infiltration of the parenchyma of the secreting glands. The majority of cells infiltrating the glands are T-lymphocytes, while b-lymphocytes account for 20%, monocytes, macrophages and NK cells - no more than 5%, 60-70% of T-lymphocytes are CD 4+ cells. Lymphoid infiltrates synthesize large amounts of IgG, IgM, rheumatoid factors, and produce large amounts of IL (IL-2, IL-6, IL-10), and their amount directly depends on the degree of lymphoid infiltration. In a third of patients, lymphoplasma cell infiltration is not limited to the tissue of the secreting epithelial glands and takes on a generalized character with the involvement of muscles (myositis), lungs (lymphocytic infiltrates with the development of interstitial pneumonia or foci of infiltration like pseudolymphoma), kidneys (interstitial nephritis), blood vessels (productive, productive-destructive vasculitis), causing functional changes in the affected organs with the development of various clinical manifestations. Involvement of the phagocytic macrophage system in the process in 5–10% of BS leads to the development of malignant lymphoproliferative diseases, mainly b-cell lymphomas and Waldenström macroglobulinemia.

Clinical picture

Clinical manifestations of BS can be divided into glandular and extraglandular. Glandular symptoms are caused by damage to the secreting epithelial glands, characterized mainly by their hypofunction. A constant clinical sign of damage to the lacrimal glands

with BS there is dry keratoconjunctivitis, associated with a decrease in the secretion of tear fluid.
Patients complain of burning sensations, “scratching” and “sand” in the eyes. Often there is itching of the eyelids, redness, and accumulation of viscous white discharge in the corners. Later, photophobia, narrowing of the palpebral fissures appear, and visual acuity decreases. A sharp decrease or complete absence of tear production leads to the development of pinpoint infiltrates, as well as the formation of deep xerosis of the cornea and its clouding. Secondary bacterial conjunctivitis is often associated. Enlargement of the lacrimal glands in BS is rarely observed. A serious complication of dry keratoconjunctivitis is the appearance of infiltrates, which can lead to the formation of purulent ulcers and perforation of the cornea. The second mandatory and constant sign of BS is damage to the salivary glands
with the development of chronic parenchymal mumps.
It is characterized by xerostomia and enlargement of the salivary glands. Often, even before the appearance of these signs, dryness of the red border of the lips, seizures, stomatitis, enlargement of regional lymph nodes, and multiple (usually cervical) dental caries are noted. Approximately half of the patients experience a recurrent course of mumps; in some patients, after the next exacerbation, the parotid glands remain constantly enlarged. In a third of patients, a gradual enlargement of the parotid glands is observed, leading to a characteristic change in the oval of the face, described in the literature as a “hamster face” or “chipmunk face.” The parotid glands are painless or slightly painful on palpation. Enlargement of the submandibular, sublingual and palatine salivary glands is rare. In the initial stage of the disease, dry mouth appears only during physical activity and anxiety. In the severe stage, dry mouth becomes constant, accompanied by the need to drink dry food and the desire to moisten the mouth during a conversation. The oral mucosa becomes bright pink and is easily injured. There is little free saliva, it is foamy or viscous. The tongue is dry. The lips are covered with crusts, symptoms of angular stomatitis and glossitis are observed, and a secondary infection, including fungal and viral, may occur. Multiple cervical dental caries is characteristic. The late stage is manifested by severe dryness of the mouth, the inability to speak, or swallow food without washing it down with liquid. The lips of such patients are dry, cracked, the oral mucosa shows signs of keratinization, the tongue is folded, its papillae are atrophic, free saliva is not detectable in the oral cavity. Partial or complete adentia is observed due to the progression of dental caries. Dryness of the nasopharynx
with the formation of dry crusts in the nose and in the lumen of the auditory tubes can lead to temporary deafness and the development of otitis media.
Dryness of the pharynx and vocal cords causes hoarseness. Subatrophic (or atrophic) rhinopharyngolaryngitis develops. Frequent complications are secondary infections: sinusitis, recurrent tracheobronchitis and pneumonia. Damage to the apocrine glands of the external genitalia
is observed in approximately 1/3 of patients with BS.
The vaginal mucosa is hyperemic, dry, atrophic, and patients are often bothered by burning pain and itching. A common symptom of sclerosis is dry skin. Sweating may be reduced. Changes in the digestive system
during BS are observed frequently and are diverse in nature.
Dysphagia is caused by the presence of xerostomia, as well as, in some cases, hypokinesia of the esophagus. Many patients develop chronic atrophic gastritis with severe secretory insufficiency, clinically manifested by gastric dyspepsia syndrome (severity and discomfort in the epigastrium after eating, belching of air, nausea, loss of appetite). Pain in the epigastric region is less common. There is a direct relationship between the degree of xerostomia and inhibition of the secretory function of the stomach. Pathology of the biliary tract (chronic cholecystitis) and liver (persistent hepatitis) is observed in most patients. There are complaints of heaviness and pain in the right hypochondrium, bitterness in the mouth, nausea, and poor tolerance to fatty foods. Involvement of the pancreas in the process (pancreatitis) is manifested by pain and dyspeptic syndromes. Clinical signs of intestinal damage (colitis) are usually mild, but most patients with BS are present. Extraglandular manifestations of BS
are very diverse and systemic in nature.
Arthralgia, slight stiffness in the morning, recurrent non-erosive (i.e. without bone destruction on radiographs) arthritis of small, less often large joints and painful flexion contractures occur in approximately 2/3 of patients. Signs of molymyositis (myalgia, moderate muscle weakness, a slight increase in the level of creatine phosphokinase in the blood) are observed in 5–10% of patients. It is extremely rare that severe myositis may develop. Most patients with BS have regional lymphadenopathy
(enlargement of the submandibular, cervical, occipital, supraclavicular lymph nodes), and in 1/3 of patients the lymphadenopathy is generalized.
In the latter case, hepato- and splenomegaly are often detected. The incidence of these symptoms increases with the presence of vasculitis and the development of malignant lymphoproliferation (pseudolymphomas, b-cell lymphomas and Waldenström's macroglobulinemia). Various respiratory tract lesions
are observed in 50% of patients.
A targeted X-ray and functional examination reveals signs of lung damage in 2/3 of patients. Dry throat, soreness and scratching, dry cough and shortness of breath are the most common complaints. Dyspnea most often indicates damage to the pulmonary parenchyma (interstitial pneumonia and interstitial fibrosis). Recurrent dry and effusion pleurisy is observed relatively rarely with BS. In 20–30% of patients, various lesions of the kidneys
, more often of the tubular apparatus: tubular acidosis, generalized aminoaciduria and phosphaturia with the development in some cases of nephrogenic diabetes.
The consequences of tubular acidosis can be osteomalacia, nephrocalcinosis and hypokalemia, leading to muscle weakness. The development of chronic renal failure is the result of a long course of tubular acidosis. Diffuse glomerulonephritis of a membranous-proliferative or membranous type of an immunocomplex nature is observed much less frequently. Severe forms of glomerulonephritis with nephrotic syndrome and the development of renal failure are observed in patients with BS with cryoglobulinemia. Acute renal failure due to renal artery thrombosis can cause death in patients with BS with productive-destructive vasculitis. In 1/3 of patients with BS, Raynaud's syndrome
, more often its erased forms.
In BS, there are two types of vasculitis: productive and productive-destructive. Changes in the type of obliterating endarteritis are also observed, which are not independent in nature and often accompany productive-destructive (70%), less often productive (30%) vasculitis. Cutaneous vasculitis in BS is caused by damage to small and medium-sized vessels. With BS, capillaritis, livedo reticularis, and various types of purpura are observed. Recurrent hypergammaglobulinemic and cryoglobulinemic purpura are observed in approximately 1/4 of patients. Pinpoint hemorrhagic rashes most often appear on the skin of the legs, but over time they spread higher and can be found on the skin of the thighs, buttocks and abdomen. The rash is accompanied by itching, painful burning and increased skin temperature in the affected area. Patients with long-term recurrent hypergammaglobulinemic purpura usually develop skin hyperpigmentation due to hemosiderin deposition. Skin biopsies of such patients reveal a picture of productive vasculitis. Severe forms of vasculitis with the development of multiple ulcerative-necrotic changes in the skin of the extremities, trunk and face, the formation of long-term non-healing ulcers and the occurrence of gangrene are observed in patients with recurrent cryoglobulinemic purpura. It is characterized by the appearance of rashes like vesicles and pustules with hemorrhagic contents. Skin biopsies reveal signs of productive-destructive vasculitis, often its necrotizing form. Patients with BS with productive vasculitis are characterized by the presence in the blood of high levels of g-globulin, circulating immune complexes, and rheumatoid factor, while the immunological marker of productive-destructive vasculitis is cryoglobulinemia, found in 95% of patients with this form of vasculitis. Clinical signs of peripheral polyneuropathy
with sensory disturbances of the “socks” and “gloves” type, paresthesia, less commonly, polyneuritis and mononeuritis, neuritis of the facial and trigeminal nerves are observed in a third of patients.
Myelopolyradiculoneuritis and cerebrovasculitis can develop much less frequently in patients with productive-destructive vasculitis. Clinically obvious signs of hypothyroidism
are found in 10–15% of patients (extremely rare - thyrotoxicosis).
Antibodies to thyroglobulin, the microsomal fraction of the thyroid gland and thyroid-stimulating hormone are detected in half of patients with BS; It is assumed that subclinical thyroid lesions are more common. Thus, endocrine glands, as well as exocrine glands, can be targets for immune attacks in HD. The known similarities in genetic susceptibility of HLA-DR 3 and the histological similarities between Hashimoto's thyroiditis and HS support speculation that similar mechanisms may be involved in these diseases. Insulin-dependent diabetes and pernicious anemia are rare in patients with BS. A third of patients experience allergic reactions
, more often to antibiotics, sulfonamides, novocaine, group B drugs, as well as to chemicals (washing powders, etc.) and food products.

Laboratory research

The most informative laboratory indicators for BS are high ESR, leukopenia, hypergammaglobulinemia (80–70%), the presence of antinuclear and rheumatoid factors (90–100%), as well as antibodies to soluble nuclear antigens SS-A/Ro and SS-B/La (60–100%). In a third of patients, cryoglobulins are detected, which can be polyclonal or monoclonal depending on the immunoglobulins included in their composition. Monoclonal immunoglobulins (IgM and IgA) with light chains are detected in cryoprecipitates and biopsies of the salivary glands in the early stages of the disease, which makes it difficult to differentiate between BS with transformation into malignant lymphoma and benign lymphoproliferation in this disease.

Diagnosis

In outpatient settings, it is advisable to take into account various combinations of the following symptoms: • arthralgia or (less often) non-erosive arthritis of the small joints of the hands; • recurrent parotitis and gradual enlargement of the parotid glands; • dryness of the oral mucosa (nasopharynx) and the rapid development of multiple, mainly cervical, dental caries; • recurrent chronic conjunctivitis; • Raynaud's syndrome; • persistent increase in ESR (over 30 mm/h); • hypergammaglobulinemia (over 20%); • presence of rheumatoid factor in the blood (titer more than 1:80). Although none of these signs, taken individually, is specific for BS, the presence of four or more signs allows in 80–70% of cases to suspect and subsequently confirm the diagnosis of BS using special research methods.

Criteria for diagnosis of BS

• Keratoconjunctivitis sicca: a) decreased tear production after stimulation with ammonia, Schirmer test (less than 10 mm/5 min); b) staining of the epithelium of the conjunctiva and cornea with rose bengal or fluorescein, followed by biomicroscopy. • Parenchymal parotitis: a) detection of cavities more than 1 mm during sialography; b) the level of stimulated salivary secretion is less than 2.5 ml/5 min; c) focal-diffuse, diffuse lymphoplasma cell infiltration in biopsy samples of the salivary glands of the lower lip. • Laboratory signs of systemic autoimmune disease: a) positive rheumatoid (antinuclear) factor; b) detection of Ro/La antinuclear antibodies. The diagnosis of definite BS can be made if three criteria are met and other diffuse connective tissue diseases, rheumatoid arthritis and autoimmune hepatobiliary diseases are excluded. Differential diagnosis for BS includes rheumatoid arthritis, systemic lupus erythematosus, autoimmune diseases of the liver and biliary tract in combination with Sjögren's syndrome. Despite the long-term existence of arthralgia for BS, in contrast to rheumatoid arthritis, the presence of persistent arthritis and joint deformities is uncharacteristic; X-rays do not show signs of erosive joint damage; arthritis with BS usually completely disappears on the 2-3rd day after the administration of small doses of corticosteroids. Systemic lupus erythematosus is characterized by erythematous rashes on the face in the form of a “butterfly”, endocarditis, exudative serositis, nephrotic syndrome, the presence of LE cells in the blood, etc. In chronic active hepatitis, biliary cirrhosis of the liver, in contrast to BS, disturbances in liver function tests are constant a sign that markers of the hepatitis B virus are detected in the blood; the material obtained from liver biopsy reveals the morphological changes inherent in these diseases. Some symptoms that occur with BS can be observed in various other diseases. Thus, an increase in the salivary glands is observed in gland tumors, Mikulicz's disease, malignant lymphomas, sarcoidosis, tuberculosis, actinomycosis, acute bacterial and viral sialadenitis, chronic parenchymal mumps, sialodochitis, hyperlipidemia and diabetes mellitus, as well as in neuroendocrine diseases (dysfunction of the reproductive and thyroid glands ). The use of criteria for diagnosing BS, the absence of signs of an autoimmune disease in these conditions, as well as a biopsy of the minor salivary glands of the lower lip make it possible to exclude BS in the majority of patients with these conditions.

Treatment

The main place in the treatment of BS belongs to corticosteroids and cytostatic immunosuppressants (chlorbutin, cyclophosphamide). In the initial stage of the disease, in the absence of signs of systemic manifestations and moderate abnormalities in laboratory parameters, long-term treatment with prednisolone in small doses (5–10 mg/day) is advisable. In severe and late stages of the disease, in the absence of signs of systemic manifestations, it is necessary to prescribe prednisolone (5–10 mg/day) and chlorobutine (2–4 mg/day), followed by long-term, for several years, maintenance doses of prednisolone (5 mg/day ) and chlorobutine (6–14 mg/week). This regimen can be used to treat patients in the initial stages of the disease in the presence of severe disturbances in laboratory indicators of process activity, as well as cryoglobulinemia without clear signs of systemic manifestations. In the presence of systemic manifestations, regardless of the stage of the disease, hormonal and cytotoxic drugs are used in significantly higher doses, taking into account the severity of systemic manifestations. Pulse therapy with high doses of prednisolone and cyclophosphamide (1000 mg of 6-methylprednisolone intravenously daily for three days in a row and a single intravenous injection of 1000 mg of cyclophosphamide), followed by transfer to moderate doses of prednisolone (30–40 mg/day) and cytostatics (chlorobutin 4- 6 mg/day or cyclophosphamide 200 mg intramuscularly 1–2 times a week) in the absence of hepatotoxic effects is the most effective method of treating patients with severe systemic manifestations of BS, as a rule, it is well tolerated by patients and avoids many complications associated with long-term use of high doses prednisolone and cytostatics. Extracorporeal treatment methods (hemosorption, cryoadsorption, plasmapheresis, double plasma filtration) in combination with pulse therapy are most effective in the treatment of patients with BS with ulcerative-necrotizing vasculitis, glomerulonephritis, polyneuritis, myelopolyradiculoneuritis, cerebrovasculitis, caused by cryoglobulinemia. The experience of previous studies indicates the need to use software, i.e. carried out over a long period of time, extracorporeal therapy

, especially in patients with BS with monoclonal cryoglobulinemia.
Upon achieving a pronounced clinical effect (improvement in general condition, regression of polyserositis, nephritis, polyneuritis, vasculitis, etc.) and a decrease in laboratory indicators of the activity of the process, patients are gradually transferred to maintenance doses of glucocorticosteroids and cytostatics. In parallel, symptomatic therapy is carried out for ophthalmological, dental, gastroenterological and other manifestations of the disease. Local therapy for keratoconjunctivitis sicca
is aimed at overcoming hypolacrimia, preventing secondary infection, accelerating the regeneration processes of the conjunctival and corneal epithelium.
Hypolacrimia is an indication for the use of artificial tears. They replenish the deficiency of the aqueous layer of the precorneal tear film and keep it in a stable position. The frequency of use of drugs depends on the severity of damage to the organ of vision and ranges from 3 to 10 times a day. In many artificial tear compositions, cellulose ethers are used as a polymer ingredient: hydroxylpropylcellulose - lacrisert, lacril, tiarisol, hydroxylcellulose - clerz, lyteers, hydroxymethylcellulose - lacrisin, lacrisify. Other hydrophilic polymers are widely used: polyvinyl alcohol - ligufilm, polyvinylpyrrolidone. In order to preserve residual tear secretion, various methods of blocking the lacrimal ducts are used: cauterization, the introduction of gelatin or adhesive tissue (N-butylcyanocryl) directly into the lacrimal canaliculi, as well as silicone plugs (punctum plug) for permanent tamponade of the lacrimal punctum and creating a physiological block. To protect the cornea, therapeutic soft contact lenses are used. To prevent secondary infection, use solutions of furatsilin (at a dilution of 1:5000), 0.25% solution of chloramphenicol, ciprofloxacin, etc. The use of trypsin, chemotrypsin (2 mg per 10 ml of isotonic sodium chloride solution), fibrinolysin and lecozyme helps to reduce the viscosity of the precorneal layer . In order to influence the regeneration of the epithelium of the cornea and conjunctiva, citral with riboflavin is instilled, and 0.5% thiamine, 10% methyluracil, and solcoseryl ointments are applied overnight. Therapy for chronic sialadenitis
is aimed at overcoming hyposalivation, strengthening the walls of the salivary gland ducts, preventing exacerbations of sialadenitis, improving the regeneration of the epithelium of the oral mucosa and fighting secondary infections.
In order to normalize the trophism and secretion of the salivary glands, novocaine blockades are used. In cases of exacerbation of chronic parotitis (and to prevent its relapses), applications of a 10–30% dimexide solution are used. In cases of the development of purulent parotitis, antibiotics are injected into the ducts of the salivary glands and antifungal drugs (nystatin, levorin, nystatin ointment) are prescribed locally. To reduce the permeability of the ducts, calcium preparations are administered intravenously or intramuscularly. It is possible to accelerate the epithelization of the mucous membrane of the oral cavity and the red border of the lips when erosions and cracks occur with the help of rosehip and sea buckthorn oils, solcoseryl and methyluracil ointments, as well as by treating the oral mucosa with the drug ENKAD (active nucleic acid derivatives). Decamine caramel also has antibacterial properties. For dry nasal mucosa, frequent applications of isotonic sodium chloride solution are used (using turundas). Vaginal dryness is reduced by using potassium iodide jelly. For dry trachea and bronchi, long-term use of bromhexine is recommended (8–16 mg 3 times a day for 2–3 months). If there are symptoms of chronic gastritis with secretory insufficiency, replacement therapy is carried out for a long time (hydrochloric acid, natural gastric juice, pepsidil). Insufficiency of pancreatic secretion requires taking enzymes: Panzinorm, Creon, Festal in courses of 2-3 months or continuously, treatment is also carried out with solcoseryl (2 ml intramuscularly 2 times a day for 15-30 days). The prognosis for life
is favorable.
With timely treatment, it is possible to slow down the progression of the disease and restore the ability of patients to work. With a late start of treatment, severe ophthalmological, dental, and systemic manifestations of the disease usually quickly develop, and the patient becomes disabled. A patient with BS with monoclonal cryoglobulinemia and in cases of the development of malignant lymphoproliferative diseases has a less favorable prognosis. Prevention
is aimed at preventing exacerbations and progression of the disease. It provides for early diagnosis and timely initiation of adequate therapy. Some patients need to limit physical activity and stress on the visual organs, and eliminate allergenic effects. Vaccination is contraindicated for patients; thermal procedures should be used with great caution. Sanitation of the mouth and timely dental prosthetics are necessary.

Literature:

1. V.I. Vasiliev, M.V. Simonova, T.N. Safonova. Sjögren’s disease // Guide to internal medicine “Rheumatic diseases”, under the guidance of. V.A. Nasonova, N.V. Bunchuk. M., “Medicine”, 1997;196–210. 2. International Seminar on SjЪurgren's Syndrome. Editors R. Manthorpe, J. U. Prause. Scand Jorn of Rheum 1986;61:1–291. 3. Sjogren's Syndrome. Clinical and Immunologic Aspects. Editors N. Talal, Moutsopoulos HM, Kassan SS. Springer-Verlag, Berlin-Heidelberg, 1987;1–299. 4. Siogren's Syndrome. State of the art. Kugler Publications. Amsterdam/New York. Editors Homma M., Sugaj S., Tojo T., Miysaka N., Akizuki M. 1994;1–615. 5. Fifth International Symposium on Sjbgren's Syndrome. Fox RI. Arthritis Rheum 1996;39(2):195–6.

4.Treatment

There is currently no etiopathogenetic treatment. Palliative therapy is prescribed - salivary stimulants, artificial tears, as well as, as necessary, non-steroidal and hormonal anti-inflammatory drugs, antibiotics and other drugs for symptomatic treatment.

With timely initiation of treatment, the prognosis is favorable; if it is delayed, it is questionable, since the autoimmune process that progresses over a long time leads to the development of severe complications from a number of key body systems. In such cases, disability often occurs, and certain life-threatening conditions may develop.

Treatment

At the moment, there is no specific treatment aimed at restoring the function of the glands. Instead, symptomatic and supportive care is provided.

For the treatment of xerophthalmia, artificial tears and preparations containing the active substance hypromellose, a protector of the corneal epithelium, are used. Some patients are forced to use glasses to increase local humidity. Additionally, cyclosporine is used, which inhibits inflammation of the lacrimal glands.

Drugs that stimulate saliva flow, such as pilocarpine, are available to combat xerostomia. It is recommended to wash down your food with water. For severe dryness of the oropharynx, use a plastic spray bottle with a 1% aqueous solution of glycerin.

Sjögren's syndrome has an increased risk of tooth decay, so careful dental care is necessary.

Nonsteroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms.

For patients with severe complications, corticosteroids, immunosuppressive drugs, and sometimes intravenous immunoglobulins may be prescribed. Methotrexate and hydroxychloroquine (Plaquenil) also help.

Treatment of Sjögren's syndrome

In the presence of Sjögren's syndrome, treatment is carried out depending on the stage of the disease and the presence of systemic manifestations.

In order to stimulate the function of the glands, the following is carried out:

• drip administration of contrical.
• subcutaneous administration of galantamine.
• Vitamin therapy courses are conducted for general strengthening purposes.
• As a symptomatic treatment, “artificial tears” (drops in the eyes) are prescribed - with low viscosity - Lakrisifi (200-250 rubles), Natural Tear (250 rubles), medium viscosity Lakrisin, high viscosity Oftagel 180 rubles, Vidisik 200 rubles, Lacropos 150 rubles .

At the initial stages, in the absence of damage to other systems and unexpressed laboratory changes, long courses of glucocorticosteroids (prednisolone, dexamethasone) in small doses are prescribed.

If symptoms and laboratory parameters are significantly pronounced, but there are no systemic manifestations, cytostatic immunosuppressive drugs - cyclophosphamide, chlorbutin, azathioprine - are added to corticosteroids. Maintenance therapy is carried out with the same drugs for several years.

1. If there are symptoms of systemic damage, regardless of the stage of the disease, high doses of corticosteroids and immunosuppressants are immediately prescribed for several days with a gradual transfer to maintenance doses.
2. For generalized polyneuritis, vasculitis, kidney damage and other severe manifestations of the disease, the following methods are added to the above treatment, extracorporeal treatment - plasmapheresis, hemosorption, plasma ultrafiltration.
3. The remaining drugs are prescribed depending on complications and concomitant diseases - cholecystitis, gastritis, pneumonia, endocervicitis, etc.

In certain cases, it is necessary to follow a dietary diet and limit physical activity.

Complications

Common consequences of Sjögren's syndrome:

• lymphomas (neoplasms affecting the blood and lymph nodes);
• vasculitis (an inflammatory process in blood vessels that can occur everywhere);
• addition of a secondary infection;
• development of cancer;
• inhibition of blood formation, reduction in the blood of leukocytes, erythrocytes and/or platelets.

If the patient does not take any measures to treat Sjögren’s disease for a long time or he was prescribed the wrong therapy, the pathology progresses, leading to serious disruptions in the functioning of organs and systems.

Symptoms of Sjögren's syndrome

Symptoms of the disease are divided into two groups:

1. Glandular manifestations in which epithelial glands are affected and their functions are disrupted.
2. Extraglandular manifestations. The symptoms of this group vary greatly, due to damage to various human organs.

Glandular symptoms include the following:

1. Pathology of the lacrimal glands. In this case, unpleasant and painful sensations occur in the eyes (burning, as if the eyes are starting to sting, a sensation of sand in them), and characteristic itching and redness appear near the eyes. As a result, vision decreases, pinpoint hemorrhages, swelling, sensitivity to light, and eye pain occur.
2. Pathology of the salivary glands. The manifestation of inflammation is mainly of the parotid glands, which are increased in size, sometimes with painful sensations. Dryness of the oral mucosa also occurs, swallowing food is difficult, often patients have to wash down food with water due to the problem of swallowing. In this case, the mucous membrane of the mouth takes on a bright pinkish tint.
3. Dryness of the respiratory tract, which leads to inflammation of the bronchi, trachea, and lungs.
4. Skin disorders resulting in dry skin.
5. Damage to the nasal mucosa. The occurrence of dryness in the nose, covering with an intranasal crust, as a result of which inflammation develops.

Extraglandular manifestations are characterized by the following signs:

1. The occurrence of tracheobronchitis, accompanied by cough and shortness of breath. It is not uncommon for a patient to be examined for pneumonia or pulmonary fibrosis.
2. Enlarged lymph nodes.
3. Damage to the peripheral nervous system. At the same time, painful sensations (tingling, burning) begin to appear.
4. Fever;
5. Pain in joints and muscles.
6. Damage to the thyroid gland. It is a rare disorder in which allergic reactions to various foods, medications and other drugs begin to appear.
7. Enlarged lymph nodes (submandibular, cervical, occipital). Enlargement of the liver and spleen is often observed.
8. Inflammation of blood vessels, which occurs as a result of atherosclerosis of the lower extremities, due to circulatory disorders. When the functioning of blood vessels is disrupted, skin diseases (rashes) appear, which are accompanied by itching, burning and fever.

Often, against the background of the pathology we describe, patients develop increased individual sensitivity to certain drugs, in particular to non-steroidal anti-inflammatory drugs, some antibiotics (penicillin), so-called basic therapy drugs, and cytostatics.

Reasons for development

The causes of Sjögren's syndrome have not yet been fully established. Among the most likely is the theory of a pathological reaction of the body's immune system. This reaction develops in response to damage to the cells of the external glands by a retrovirus, in particular the Epstein-Barr virus, herpes virus VI, cytomegalovirus, and human immunodeficiency virus. Despite the significant similarity of immunological disorders with changes in the body affected by the virus, direct evidence of the role of the virus as the cause of the development of pathology has not been obtained.

The viruses themselves and the epithelial cells of the glands changed by their influence are perceived by the immune system as antigens (foreign agents). The immune system produces antibodies against such cells and gradually causes the destruction of gland tissue. The disease often occurs as a hereditary or familial disorder, particularly among twins, suggesting that there is a genetic predisposition.

Thus, it is assumed that in the mechanism of development and occurrence of pathology, a combination of many factors is important:

• stress reaction of the body, which occurs as a result of the immune response;
• immune regulation with the participation of sex hormones, as evidenced by the rare incidence among people under 20 years of age, while girls are most often affected among children;
• immune control using T lymphocytes;
• viral;
• genetic.

There are two types of Sjögren's syndrome: primary, where symptoms of the disease are the first manifestations of it, and secondary, when symptoms appear in patients suffering from other rheumatic diseases, such as scleroderma, rheumatoid arthritis or systemic lupus erythematosus. Primary and secondary variants of the syndrome occur with approximately the same frequency. This sometimes makes it difficult to make an accurate diagnosis. Sjögren's syndrome is quite common: in the UK, for example, there are about half a million sufferers. Women aged 40 to 60 years are most often affected, while only one patient in 13 is male.