Systemic connective tissue disease. Lupus erythematosus. Polyarteritis nodosa.
Lupus is an autoimmune disease. Commonly, anti-nuclear antibodies are produced which target the body's own cells, it is fundamentally a failure in the bodies ability to maintain self-tolerance.
Etiology is a number of factors:
- Partly genetic
- HLA (Human leukocyte antigen gene complex) genotype
- Environmental factors
- UV, Smoking, Sex hormones (about 9x more common in women of reproductive age), Drugs
- Immunological abnormalities
The proposed pathogenic model is that UV irradiation and other environmental insults lead to apoptosis of cells, with inadequate clearance of the nuclei of these cells, there is a large number of nuclear antigens. Various genetic abnormalities then lead to defective ability to maintain self tolerance in B and T lymphocytes. These self reactive cells then cause systematic cellular damage.
This tissue damage is mediated in a number of ways:
- Most organ damage is due to immune complex deposition
- Antibodies of different specificities can contribute to the pathology of SLE. Autoantibodies against RBC and WBC and platelets cause cytopenias, while autoantibodies against phospholipids increased risk of thrombosis
Remember: ANA is positive in almost every patient with SLE but also in other diseases (sensitive, not specific); antibodies to double-stranded DNA and to the Smith (Sm) antigen are the specific ones. Antiphospholipid antibodies (lupus anticoagulant) cause venous and arterial thrombosis and recurrent miscarriages, despite a prolonged clotting time in vitro.
The impact of lupus is diverse:
- Blood vessels
- Causes acute necrotizing vasculitis
- Kidneys
- Causes all forms of glomerulonephritis
- Skin
- Causes photosensitivity and the butterfly rash across the face
- Joints
- Diffuse joint pain and swelling
- CNS
- Vascular lesions can cause focal or diffuse neurologic defects
- Other organs
- Onion-skin lesions on the spleen
- Pericardium and pleura may undergo inflammatory changes
- We may observe Libman-Sacks endocarditis in the heart
PAS, diffuse proliferative lupus nephritis (class IV): hypercellular glomeruli with thick, rigid "wire-loop" capillary walls and hyaline deposits from subendothelial immune complexes.
Image: “Diffuse proliferative lupus nephritis - high mag” by Nephron, CC BY-SA 3.0, via Wikimedia Commons.
Polyarteritis nodosa
- Systemic vasculitis of small or medium-sized arteries, particularly renal and visceral vessels
- ⅓ of patients have Hep B which leads to formation of immune complexes containing Hep B antigen which is deposited in the vessels. In the remaining ⅔ the cause is unknown.