Systemic lupus erythematosus

Etiology and pathogenesis

Triggering factors include ultraviolet radiation, which induces local inflammation, and viral agents (Epstein-Barr virus, cytomegalovirus), which initiate polyclonal immune activation. The pathogenesis is based on the breakdown of immunological tolerance, accompanied by the massive production of non-organ-specific autoantibodies (against nucleosomes, native DNA, and histones).

Cellular mechanisms involve B-lymphocyte hyperactivity, which is sustained by the specific protein BlyS. In the T-cell compartment, there is a decrease in natural killers and T-suppressors alongside an increase in T-helper cells (CD4+) and the overproduction of Th2-profile cytokines.

An important role is played by apoptosis defects: the clearance of apoptotic cells is impaired, causing intracellular antigens to enter the bloodstream. Meanwhile, autoreactive T cells themselves survive abnormally long due to high levels of the Bcl-2 protein. Tissue damage is mediated through the deposition of immune complexes, activation of the complement cascade, and the direct destructive effect of cytokines on the vascular endothelium.

Clinical presentation: skin, mucous membranes, and joints

The disease follows a relapsing-remitting course. The onset is often masked by a nonspecific systemic intoxication syndrome with fatigue, fever, and hair loss (alopecia).

Specific manifestations:

• Skin: the acute cutaneous form presents as the lupus «butterfly» rash (erythematous patches on the malar prominences and the bridge of the nose). The chronic form manifests as discoid lesions with hyperkeratosis leading to cicatricial atrophy. Photosensitivity is characteristic (exacerbation of rashes after sun exposure).
• Mucous membranes: lupus enanthema, aphthous stomatitis with the formation of completely painless erosions and ulcers (more frequently on the hard palate), as well as cheilitis.
• Musculoskeletal system: non-erosive joint disease occurs in the vast majority of children. Involvement of the proximal interphalangeal joints of the hands with fusiform deformity is typical. Myalgia and aseptic necrosis of bone epiphyses due to local vasculitis and ischemia are possible.

Systemic internal organ involvement

Polysystemicity is the hallmark of SLE. Virtually all vital systems are involved in the pathological process:

1. Kidneys (lupus nephritis): develops in 70–86% of children, frequently at onset. Manifests as persistent proteinuria and cylindruria. Morphologically ranges from mesangial to diffuse proliferative glomerulonephritis.
2. Heart: a specific atypical verrucous Libman–Sacks endocarditis is diagnosed. Vegetations form on the ulcerated endocardium, posing a risk of leaflet microperforation and chordal rupture (true valve defects typically do not form).
3. Lungs: ranging from acute lupus pneumonitis and fibrosing alveolitis (restrictive impairment) to pulmonary hemorrhages with the picture of ARDS, which carry an extremely poor prognosis.
4. Nervous system: characterized by extreme polymorphism. Focal (seizures, chorea, myelopathy) and diffuse (psychoses, cognitive impairment) syndromes occur, as well as polyneuropathies.
5. Serous membranes: classical polyserositis includes bilateral dry pleuritis and pericarditis.

Immunological diagnostics and criteria (ACR, 1997)

Laboratory diagnostics are based on screening for a pool of autoantibodies. The screening test is the antinuclear factor (ANF) — it is highly sensitive, but non-specific.

Profile-specific antibodies:

• Anti-dsDNA (against native DNA): exhibit high specificity precisely for SLE.
• Anti-Sm (against Smith antigen): have the highest specificity, but are detected in only 20–30% of patients.
• Anti-histone antibodies: markers of drug-induced lupus.
• Lupus (LE) cells: neutrophils that have ingested nuclear material (found in 60–70% of children).
• Complement: a decrease in C3 and C4 fractions is characteristic, correlating with nephritis activity.

The diagnosis is established based on ACR criteria. To confirm definite SLE, the presence of 4 out of 11 criteria is required: malar rash, discoid rash, photosensitivity, painless oral ulcers, non-erosive arthritis, serositis (pleuritis/pericarditis), renal involvement, neurological disorders, hematologic abnormalities (hemolytic anemia, leukopenia, thrombocytopenia), immunological markers (anti-dsDNA, anti-Sm, APS markers), and a positive ANF.

Class and exam questions

What else to study on this topic

• Morphological classification of lupus nephritis (WHO criteria)
• Features of antiphospholipid syndrome (APS) and its cutaneous manifestations (livedo reticularis, capillaritis)
• Neuropsychiatric syndromes according to the ACR classification (1999)
• Differential diagnosis of lupus pneumonitis and pulmonary hemorrhage
• Mechanism of formation and clinical significance of LE cells

Other topics of «Chapter 9. Rheumatic Diseases»

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.