Etiology and risk factors
There is no single cause of the disease; however, several key factors triggering the pathological process are distinguished:
- Viral theory: considered the most likely. Inclusions resembling paramyxoviruses, as well as markers of persistent infection (antibodies to measles, rubella, and parainfluenza), are found in endothelial and blood cells.
- Genetics: predisposition is closely associated with the carriage of histocompatibility antigens HLA-DR2 and HLA-DR3, as well as with a hereditary deficiency of complement components ($C_2$ or $C_4$), which occurs in 6% of patients.
- Hormonal background: the disease more frequently affects women of childbearing age. Estrogens have been proven to suppress the activity of suppressor T cells, leading to increased antibody production.
- Environment: ultraviolet radiation alters the antigenic properties of DNA and causes keratinocytes to release interleukin-1. Bacterial infections (frequent tonsillitis) and certain medications can also act as triggers.
Pathogenesis and immunological disorders
The foundation of pathogenesis is the loss of tolerance to self-antigens and impaired clearance of cells that died via apoptosis. Normally, apoptotic bodies are rapidly cleared (for which the C1q complement component is essential). In lupus, they accumulate, and autoantigens on their membranes provoke secondary immune stimulation.
Hyperactivation of B lymphocytes occurs, leading to massive synthesis of autoantibodies. This is promoted by enhanced CD4+ T cell function and reduced suppressor T lymphocyte function. As a result, antibodies are formed against nuclear structures (DNA, histones, Smith antigen), cytoplasm (RNA polymerase), and cell membranes.
Tissues are damaged through two pathways:
- Direct antibody action: attacks on blood cells cause immune cytopenias, and penetration through the blood-brain barrier leads to neuronal damage.
- Immune complexes (ICs): circulating ICs deposit in the basement membranes of microcirculatory vessels and renal glomeruli, causing severe inflammation (lupus nephritis).
Pathological anatomy and microscopy
Morphological changes are generalized. Disorganization of connective tissue, interstitial inflammation, polyserositis, and vasculitis are observed in all organs, leading to parenchymal dystrophy and necrosis.
Specific microscopic features:
- Hematoxylin bodies: the result of antinuclear antibody (ANA) action on cells. Nuclei lose color and disintegrate into amorphous clumps.
- Fibrinoid necrosis: destruction of small blood vessel walls and connective tissue, characterized by the presence of nuclear debris.
- Lupus erythematosus cell phenomenon (Hargraves cells): the appearance in the bone marrow, lymphoid organs, and blood of phagocytes whose cytoplasm is filled with engulfed nuclear debris, with their own nucleus flattened against the periphery.
- Perivascular «onion-skin» sclerosis: characteristic concentric proliferation of connective tissue around arteries in the spleen.
Clinical manifestations
Symptoms are extremely diverse, as virtually all body systems are involved:
- Skin and mucous membranes: classic erythematous «butterfly» dermatitis on the face, discoid lesions, livedo reticularis (Livedo reticularis) on the legs as a consequence of venulitis, alopecia, and oral erosions.
- Musculoskeletal system: arthralgia and arthritis occur in 95% of patients. Permanent deforming arthropathy (Jaccoud's syndrome) and muscle involvement (myositis) are possible.
- Internal organs: pleuritis and pneumonitis develop in the lungs; pericarditis, myocarditis, and Libman–Sachs endocarditis occur in the heart. Chronic glomerulonephritis and gastrointestinal tract lesions (intestinal vasculitis, ulcers) are diagnosed in half of the patients.
- Nervous system: manifestations range from depression and seizures to hemiparesis and chorea.
Laboratory diagnostics
The activity of the inflammatory process correlates well with an increased ESR. Hematological tests frequently reveal anemia, autoimmune lymphopenia, and thrombocytopenia.
The immunological profile plays a key role. Patients are found to have:
- ANA (antinuclear antibodies) of the IgG class, known as the «lupus factor».
- Specific antibodies to DNA and RNA polymerase.
- LE cells.
- A false-positive Wassermann reaction (characteristic in the presence of concomitant antiphospholipid syndrome).
Briefly: answers to topical questions
What hematological disorders are detected in blood tests for systemic lupus erythematosus?
In systemic lupus erythematosus, blood tests reveal characteristic cytopenias. The main hematological disorders include:
- Leukopenia — a decrease in the leukocyte count below 4×10^9/L, including autoimmune lymphopenia.
- Thrombocytopenia — a decrease in the platelet count below 100×10^9/L.
- Autoimmune hemolytic anemia — accompanied by reticulocytosis, decreased haptoglobin, elevated indirect bilirubin and lactate dehydrogenase, as well as a positive Coombs test.
Isolated neutropenia is not a typical manifestation or classification criterion for the disease.
What stages of connective tissue disorganization develop sequentially in systemic lupus erythematosus?
In systemic lupus erythematosus, connective tissue disorganization with interstitial organ inflammation is observed. Rheumatic diseases are characterized by a polymorphism of changes: different phases of the process can be simultaneously detected in organs.
Stages of connective tissue disorganization include:
- Mucoid swelling — initial changes localize in the ground substance of connective tissue and are associated with the accumulation of glycosaminoglycans.
- Fibrinoid swelling / fibrinoid changes.
- Hyalinosis.
The sequence of the process is described as: mucoid swelling → fibrinoid swelling → hyalinosis. Sclerosis is considered the final phase of connective tissue disorganization. Due to the chronic relapsing course, connective tissue disorganization, exudative and proliferative inflammation, and areas of sclerosis and hyalinosis may be simultaneously detected in organs.
What pathomorphological changes occur in the spleen in systemic lupus erythematosus?
In systemic lupus erythematosus, macroscopic and microscopic pathomorphological changes develop in the spleen.
Macroscopically, the spleen is enlarged.
Microscopically, the following are revealed:
- Follicular hyperplasia.
- Plasmacytic infiltration of the pulp.
- Perivascular «onion-skin» sclerosis — a characteristic sign of splenic involvement in SLE.
Class and exam questions
What are LE cells and where are they found?
These are neutrophils or macrophages that have phagocytosed degraded nuclear material. They can be found in peripheral blood, bone marrow, and lymphoid organs.
What role does ultraviolet light play in the development of the disease?
UV radiation acts as a potent triggering factor: it alters the antigenic properties of DNA and stimulates the production of interleukin-1 by keratinocytes, enhancing the autoimmune response.
How exactly are the kidneys damaged in lupus?
The primary mechanism is the deposition of circulating immune complexes (especially those containing DNA) in the basement membranes of renal glomerular capillaries, leading to the development of lupus nephritis.
What are hematoxylin bodies?
These are pale clumps of disintegrated nuclei formed when antinuclear antibodies bind to affected cells. They serve as a specific microscopic sign of the disease.
What else to study on this topic
- Mechanisms of Libman–Sachs endocarditis development and its complications
- Types of autoantibodies: Smith antigen, Ro, La and their clinical significance
- Gastrointestinal tract involvement: risks of intestinal vasculitis
- Jaccoud's syndrome: pathogenesis and features of joint deformities
- The role of impaired negative selection of T cells in the thymus
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