General features and pathogenesis
According to the International Classification of Diseases (ICD-10), the group of rheumatic diseases includes over 120 different nosologies. Despite this diversity, they all share a number of fundamental common features:
- Presence of a chronic focus of infection in the body.
- Pronounced disorders of immune homeostasis. Immediate-type (Type I/immediate hypersensitivity) and delayed-type (Type IV/delayed-type hypersensitivity) hypersensitivity reactions play a key role in the pathogenesis.
- Systemic nature of connective tissue damage.
- Development of generalized vasculitis.
- Chronic course with a characteristic wave-like pattern, where periods of remission are replaced by new exacerbations.
Morphology: phases of disorganization
The essence of morphological changes in rheumatic diseases boils down to systemic and progressive disorganization of connective tissue. This process is strictly sequential and always goes through 4 phases:
- Mucoid swelling.
- Fibrinoid changes.
- Inflammatory cellular reactions. Inflammation acts as a response to tissue damage. By its nature, it can be exudative or proliferative (productive). The features of the inflammatory reaction always depend on the pathogenesis of a specific disease, the localization of the process, and its stage.
- Sclerosis. This is the final phase of disorganization, in which damaged structures are permanently replaced by dense tissue.
Immunopathology and vascular lesions
A key link in the immunopathology of rheumatic diseases is damage to the microvasculature. Arterioles, capillaries, and venules are systemically involved in the pathological process.
Due to the chronic relapsing course, these diseases are characterized by pronounced polymorphism of changes. This means that even within a single small biopsy specimen, morphological variegation is observed: all phases of the process are simultaneously detected in the tissues. Areas of fresh connective tissue disorganization, zones of active exudative or proliferative inflammation, as well as old areas of sclerosis and hyalinosis, can be located side by side.
Classification and diagnostic principles
The most common rheumatic diseases include acute rheumatic fever, rheumatoid arthritis, ankylosing spondylitis (Bekhterew's disease), and Sjögren's syndrome. It is important to remember that the term "diffuse connective tissue diseases" (DCTD) is not applied to the entire group, but specifically to five pathologies: rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis, polyarteritis nodosa, and dermatomyositis.
Diagnostic principles:
- Polyvisceral involvement: although the damage is systemic, the clinical and morphological picture always depends on which organ is primarily affected.
- Biopsy: theoretically, material sampling is possible from any part of the body, since the entire connective tissue system is affected. However, in practice, the most frequent sites for diagnostic biopsies are the skin, kidneys, mucous membranes of the upper respiratory tract, synovial membranes, and skeletal muscles.
Briefly: answers to topical questions
What morphological changes are characteristic of the mucoid swelling stage in rheumatic diseases?
The stage of mucoid swelling is characterized by the accumulation of acidic glycosaminoglycans and plasma proteins, leading to hydration and swelling of the ground substance of the extracellular matrix.
The morphological picture includes the following changes:
- Ground substance swells and increases in volume, pushing connective tissue cells apart from each other.
- Collagen fibers — retain their bundle structure, but swell, undergo fiber dissociation (loose packing of fibrils), and lose resistance to collagenase.
- Cellular reaction — lymphocytes, plasma cells, and macrophages appear.
Hematoxylin and eosin staining shows basophilia, while toluidine blue staining produces the metachromasia phenomenon (foci turn lilac or red). Macroscopically, the appearance of the organs is altered very little.
What is the difference between fibrinoid changes and mucoid swelling in connective tissue disorganization?
Fibrinoid changes represent a profound and irreversible stage of connective tissue disorganization, in contrast to superficial and reversible mucoid swelling.
| Sign | Mucoid swelling | Fibrinoid changes |
|---|---|---|
| Reversibility | Reversible phase | Irreversible destruction |
| Glycosaminoglycans | Accumulation and/or redistribution of acidic glycosaminoglycans | Depolymerization and virtually complete destruction of glycosaminoglycans |
| Ground substance and fibers | Hydration and swelling of the ground substance and fibrous structures | Destruction of the ground substance and fibers |
| Collagen fibers | Retain bundle structure, swell, and dissociate into fibers | Homogeneous, eosinophilic; signs of fiber rupture appear |
| Metachromasia | Present when stained with toluidine blue | Absent |
| Fibrinoid | Not described as a characteristic sign | Fibrinoid is formed; an obligatory component of fibrinoid is fibrin |
During fibrinoid swelling, vascular permeability increases sharply, blood plasma proteins infiltrate the connective tissue, and fibrinoid is formed. The outcome of fibrinoid swelling can be fibrinoid necrosis.
What specific granulomas are formed in rheumatism (Sokolsky-Bouillaud disease)?
In rheumatism, specific Aschoff-Talalaev granulomas (rheumatic granulomas) are formed, developing predominantly in the perivascular stroma of the heart in response to fibrinoid necrosis.
The cellular composition of the granuloma includes:
- Anitschkow cells — large epithelioid cells with basophilic cytoplasm. The nuclei have a characteristic appearance: "owl-eye" in transverse section or "caterpillar" in longitudinal section. They are pathognomonic for rheumatic carditis.
- Aschoff cells — multinucleated giant histiocytes.
In its development, the granuloma goes through three successive stages: "flower-like" (maximal cellular activity and macrophage accumulation), "worsening" (reduction of cellular composition with a shift from type I to type IV hypersensitivity), and "cicatricial" (outcome into focal sclerosis).
What changes occur in the organs of the immune system (lymph nodes, spleen) in rheumatic diseases?
Changes associated with the immunopathological process have been described in the immune system organs during rheumatic diseases.
Confirmed morphological changes:
- Lymphoid tissue — hyperplasia with plasma cell transformation.
- In rheumatoid arthritis — hyperplasia of the lymph nodes and spleen with plasma cell transformation, as well as bone marrow plasmacytosis.
- In systemic lupus erythematosus, onion-skin periarterial fibrosis, follicular hyperplasia, and pulp plasmacytic infiltration have been described in the spleen.
These changes are considered in the context of the chronic immune-inflammatory process in rheumatic diseases.
To memorize the 4 stages of connective tissue disorganization, use the mnemonic: Muscles Fix Inflammatory Traces (Mucoid swelling, Fibrinoid changes, Inflammatory reactions, Sclerosis).
Class and exam questions
Why can different stages of tissue damage be found in a single biopsy specimen?
This occurs due to a chronic relapsing (fluctuating) course. New exacerbations overlap with old ones, so fresh disorganization, active inflammation, and areas of sclerosis with hyalinosis are simultaneously present in the tissue.
What is the difference between rheumatic diseases and DCTD?
Rheumatic diseases are a vast group of over 120 nosological entities. The term «diffuse connective tissue diseases» (DCTD) is applied specifically to five of them: rheumatoid arthritis, SLE, systemic sclerosis, polyarteritis nodosa, and dermatomyositis.
Where is the biopsy taken from to confirm the diagnosis?
Since the lesion is systemic, theoretically any part of the body can be affected. In practice, the skin, kidneys, upper respiratory tract mucosa, synovial membranes, and skeletal muscles are most frequently involved.
What is the unifying principle for all diseases in this group?
The main unifying principle is the involvement of connective tissue, which forms the stroma of internal organs and the musculoskeletal system.
What else to study on this topic
- Pathogenesis and morphology of rheumatism
- Pathological anatomy of rheumatoid arthritis and Bekhterev's disease
- Specifics of renal involvement in systemic lupus erythematosus (SLE)
- Skin and internal organ changes in systemic sclerosis
- Morphology of vasculitis in polyarteritis nodosa
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on «Rheumatic diseases» and 4,414 more pages on the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 153 video lessons on the subject
Other topics in the "Rheumatic Diseases" section
Free video lessons: pathological anatomyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.