Etiology and Risk Factors
There is no single cause of the disease, but several key factors trigger the pathological process:
- Viral Theory: Considered the most likely. Paramyxovirus-like inclusions and markers of persistent infection (antibodies to measles, rubella, and parainfluenza) are found in endothelial and blood cells.
- Genetics: Susceptibility is closely linked to the carriage of histocompatibility antigens HLA-DR2 and HLA-DR3, as well as a hereditary deficiency of complement components ($C_2$ or $C_4$), which occurs in 6% of patients.
- Hormonal Background: The disease predominantly affects women of childbearing age. Estrogens have been shown to suppress suppressor T-cell activity, leading to enhanced antibody production.
- Environment: Ultraviolet radiation alters the antigenic properties of DNA and induces keratinocytes to release interleukin-1. Bacterial infections (frequent pharyngitis) and certain drugs can also act as triggers.
Pathogenesis and Immunological Abnormalities
The foundation of pathogenesis is the loss of tolerance to self-antigens and impaired clearance of cells that have died via apoptosis. Normally, apoptotic bodies are rapidly destroyed (for which the complement component C1q 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 activity of CD4+ T cells and decreased function of suppressor T lymphocytes. As a result, antibodies are formed against nuclear structures (DNA, histones, Smith antigen), cytoplasm (RNA polymerase), and cell membranes.
Tissues are damaged via two pathways:
- Direct antibody action: Attacks on blood cells cause immune cytopenias, while penetration across the blood-brain barrier leads to neuronal damage.
- Immune complexes (ICs): Circulating ICs deposit in the basement membranes of microvessels 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 dystrophy and parenchymal necrosis.
Specific microscopic features:
- Hematoxylin bodies: The result of antinuclear antibodies (ANAs) acting on cells. Nuclei lose their staining properties and disintegrate into amorphous clumps.
- Fibrinoid necrosis: Destruction of the walls of small blood vessels and connective tissue, characterized by nuclear debris.
- LE cell phenomenon (Hargraves cells): The appearance in bone marrow, lymphoid organs, and blood of phagocytes whose cytoplasm is filled with ingested nuclear debris, with their own nucleus pushed to the periphery.
- Periarterial "onion-skin" sclerosis: Characteristic concentric proliferation of connective tissue around the arteries in the spleen.
Clinical Manifestations
Symptoms are extremely diverse, as virtually all body systems are involved:
- Skin and Mucous Membranes: Classic malar erythematosus rash on the face, discoid lesions, livedo reticularis on the legs as a consequence of venulitis, alopecia, and oral erosions.
- Musculoskeletal System: Arthralgia and arthritis occur in 95% of patients. Persistent deforming arthropathy (Jaccoud syndrome) and muscle involvement (myositis) may develop.
- Internal Organs: Pleuritis and pneumonitis develop in the lungs; pericarditis, myocarditis, and Libman–Sachs endocarditis occur in the heart. Chronic glomerulonephritis and gastrointestinal involvement (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 elevated ESR. Hematological tests frequently reveal anemia, autoimmune lymphopenia, and thrombocytopenia.
The immunological profile plays a key role. Patients exhibit:
- ANAs (antinuclear antibodies) of the IgG class, known as the "lupus factor".
- Specific antibodies to DNA and RNA polymerase.
- LE cells.
- False-positive Wassermann reaction (characteristic in the presence of coexisting antiphospholipid syndrome).