Collagenosis are a group of diseases united by the same type of functional and morphological changes on the part of connective tissue (mainly collagen–containing fibers). A characteristic manifestation of collagenosis is a progressive course, involvement in the pathological process of various internal organs, blood vessels, skin, musculoskeletal systems. Diagnosis is based on multiple organ lesions, identification of positive laboratory markers, and biopsy data of connective tissue (skin or synovial membranes of joints). Most often, corticosteroids, immunosuppressants, NSAIDs, aminoquinoline derivatives, etc. are used for the treatment.
Meaning
Collagenosis (collagen diseases) are immunopathological processes characterized by systemic disorganization of connective tissue, polysystemic lesion, progressive course and polymorphic clinical manifestations. In rheumatology, the number of collagenosis usually includes rheumatoid arthritis, rheumatism, systemic lupus erythematosus, systemic scleroderma, nodular periarteritis, dermatomyositis, Wegener’s granulomatosis, etc. These diseases are grouped into a single group based on a common pathomorphological feature (fibrinoid changes in collagen) and a pathogenetic mechanism (violations of immune homeostasis).
Connective tissue forms the skeleton, skin, stroma of internal organs, blood vessels, fills the gaps between organs and makes up more than half of the mass of the human body. The main functions of connective tissue in the body include protective, trophic, supporting, plastic, structural. Connective tissue is represented by cellular elements (fibroblasts, macrophages, lymphocytes) and intercellular matrix (the main substance, collagen, elastic, reticular fibers). Thus, the term “collagenosis” does not fully reflect the pathological changes occurring in the body, so at present this group is commonly referred to as “diffuse connective tissue diseases”.
Classification
There are congenital (hereditary) and acquired collagenosis. Congenital connective tissue dysplasia is represented, in particular, by mucopolysaccharidoses, Marfan syndrome, osteogenesis imperfecta, Ehlers-Danlos syndrome, elastic pseudoxanthoma, Stickler syndrome, etc.
Acquired collagenosis, in turn, include SLE, scleroderma, nodular periarteritis, dermatomyositis, rheumatoid polyarthritis, Sjogren’s syndrome, rheumatism, systemic vasculitis, diffuse eosinophilic fasciitis, etc. Of these, the first four nosological units are classified as large collagenosis, characterized by a truly systemic nature of the lesion and the severity of the prognosis; the rest are small collagen diseases. It is also customary to distinguish transitional and mixed forms of diffuse connective tissue diseases (Sharpe syndrome).
Causes
Congenital collagenosis are caused by hereditary (genetic) disorders of the collagen structure or metabolism. The etiology of acquired systemic connective tissue diseases is less studied and understood. It is considered from the point of view of multifactorial immunopathology due to the interaction of genetic, infectious, endocrine factors and environmental influences. Numerous studies confirm the relationship between specific systemic connective tissue diseases and the carriage of certain HLA antigens, mainly class II histocompatibility antigens (HLA-D). Thus, systemic lupus erythematosus is associated with the carrier of the DR3 antigen, scleroderma – A1, B8, DR3 and DR5 antigens, Sjogren’s syndrome – with HLA-B8 and DR3. In families of patients with collagenosis, more often than in the general population, systemic diseases are registered among relatives of the first degree of kinship.
Scientific research is still being conducted on infectious agents involved in the development of collagenosis. The infectious and allergic genesis of diffuse connective tissue diseases is not excluded; the possible role of intrauterine infections, staphylococci, streptococci, parainfluenza viruses, measles, rubella, mumps, herpes simplex, cytomegalovirus, Epstein-Barr, Coxsackie A, etc. is considered.
It should be noted that collagenosis are associated with changes in endocrine and hormonal regulation: with the onset of the menstrual cycle, abortions, pregnancy or childbirth, menopause. External environmental factors, as a rule, provoke an exacerbation of latent pathology or act as triggers for the occurrence of collagenosis in the presence of an appropriate genetic predisposition. Such triggers can be stress, trauma, hypothermia, insolation, vaccination, medication, etc.
Pathogenesis and pathomorphology
The pathogenesis of collagenosis can be presented in the form of the following general scheme. Against the background of bacterial-viral sensitization of the body, pathogenic immune complexes are formed, which settle on the basement membrane of blood vessels, synovial and serous membranes and provoke the development of nonspecific allergic inflammation. These processes cause autoallergia and autosensitization to their own tissues, violation of cellular and humoral factors of immunogenesis, hyperproduction of autoantibodies to cell nuclei, collagen, vascular endothelium, muscles.
Perverted immune, vascular and inflammatory reactions in collagenosis are accompanied by pathological disorganization of connective tissue. Pathomorphological changes go through 4 stages: mucoid swelling, fibrinoid necrosis, cell proliferation and sclerosis.
Collagenosis are accompanied by various pathoanatomic changes, however, all diseases are united by diffuse involvement in the pathological process of the connective tissue of the body, which can occur in various combinations. Thus, with nodular periarteritis, muscle-type vessels are mainly affected, which leads to scarring and desolation of the latter, therefore, vascular aneurysms, hemorrhages, bleeding, and heart attacks are often noted in the clinical course. For scleroderma, the development of widespread sclerosis (lesions of the skin and subcutaneous tissue, pneumosclerosis, cardiosclerosis, nephrosclerosis) is typical. Dermatomyositis is dominated by lesions of the skin and muscles, as well as arterioles located in them. Systemic lupus erythematosus is characterized by a polysyndromic course with the development of dermatosis, polyarthritis, Raynaud’s syndrome, pleurisy, nephritis, endocarditis, meningoencephalitis, pneumonitis, neuritis, plexitis, etc.
Symptoms
Despite the variety of clinical and morphological forms of collagenosis, there are common features in their development. All diseases have a long undulating course with alternating exacerbations and remissions, a steady progression of pathological changes. Characterized by persistent fever of the wrong type with chills and profuse sweats, signs of allergies, unexplained increasing weakness. Common to all collagenosis are systemic vasculitis, musculoskeletal syndrome, including myalgia, arthralgia, polyarthritis, myositis, synovitis. Often there is a lesion of the skin and mucous membranes – erythematous rash, petechiae, subcutaneous nodules, aphthous stomatitis, etc.
Heart damage in collagenosis may be accompanied by the development of myocarditis, pericarditis, myocardiodystrophy, cardiosclerosis, hypertension, ischemia, angina pectoris. From the respiratory organs, pneumonitis, pleurisy, lung infarction, pneumosclerosis are noted. Renal syndrome includes hematuria, proteinuria, kidney amyloidosis, chronic renal failure. Disorders of the gastrointestinal tract can be represented by dyspepsia, gastrointestinal bleeding, attacks of abdominal pain, simulating cholecystitis, appendicitis, etc.
The polymorphism of the clinical picture is explained by the organ-specificity of the lesion in various forms of collagenosis. Exacerbations of diffuse connective tissue diseases are usually associated with infections, hypothermia, hyperinsolation, and injuries.
Diagnostics
The basis for the assumption of one or another form of collagenosis is the presence of classical clinical and laboratory signs. Typically, the appearance of nonspecific markers of inflammation in the blood: C-reactive protein, increased α2-globulins, fibrinogen, seromucoid, ESR, etc. Of great diagnostic importance is the determination of immunological markers characteristic of each disease: CEC, antinuclear and rheumatoid factors, antibodies to single- and double-spiral DNA, antistreptolysin-0, antibodies to nuclear antigens, complement level, etc. Often, in order to make a pathomorphological diagnosis, it is necessary to resort to a biopsy of the skin, muscles, synovial membrane of joints, kidneys.
Some help in the diagnosis of collagenosis can be provided by X-ray examination of bones and joints, which reveals general (osteoporosis, narrowing of articular gaps), as well as specific radiological signs (usuration of articular surfaces in rheumatoid arthritis, aseptic necrosis of articular surfaces in SLE, osteolysis of distal phalanges in scleroderma, etc.). To identify the nature and degree of lesions of internal organs are used ultrasound diagnostic methods (EchoCG, ultrasound of the pleural cavity, ultrasound of the kidneys, abdominal ultrasound), MRI, CT. Differential diagnosis of various forms of collagenosis is carried out by a rheumatologist; if necessary, the patient is consulted by other specialists: cardiologist, pulmonologist, immunologist, dermatologist, etc.
Treatment and prognosis
The course of most collagen diseases is progressive and recurrent, which requires gradual, long-term, often lifelong treatment. Most often, the following groups of drugs are used for the treatment of various forms of collagenosis: steroid (glucocorticoids) and nonsteroidal anti-inflammatory drugs, cytostatics, aminoquinoline derivatives, gold preparations. The dosage and duration of the courses are determined strictly individually, taking into account the type of disease, severity and severity of the course, age and individual characteristics of the patient.
During periods of exacerbations, the use of extracorporeal methods of hemocorrection (plasmapheresis, cascade plasma filtration, hemosorption) is effective. During the remission of collagenosis, physical rehabilitation can be recommended: physical therapy, medicinal electrophoresis, ultrasound, ultraphonophoresis, magnetotherapy, DMV therapy, radon, carbon dioxide, hydrogen sulfide therapeutic baths, spa treatment.
All types of collagenosis are characterized by a chronic progressive course with a multi-system lesion. The appointment of corticosteroid or immunosuppressive therapy helps to reduce the severity of clinical symptoms, lead to more or less prolonged remission. The most transient development and severe course are the so-called large collagenosis. The death of patients may occur as a result of renal, cardiovascular, respiratory failure, intercurrent infection. To prevent exacerbations of collagenosis, it is important to eliminate foci of chronic infection, undergo a medical examination, avoid excessive insolation, hypothermia and other provoking factors.