systemic lupus erythematosus (SLE)

see also:

• rheumatology
• autoimmune disease
• anti-nuclear antibodies (ANA)
• Sjögren's syndrome (SS)
• wikipedia

• a chronic autoimmune connective tissue disease that can affect any part of the body, but most often the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system, and is thus one of the great imitators of diseases.
• occurs nine times more often in women than in men, especially between the ages of 15 and 50, and is more common in those of non-European descent.
• drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness. Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped.
• discoid lupus is limited to skin symptoms and is diagnosed by biopsy of skin rash on the face, neck, or scalp.

• tends to run in families
  • a single point mutation in the Toll-like receptor 7 (TLR7) gene on the X chromosome that senses viral RNA appears to be the cause of severe lupus ¹⁾
    • this mutation causes the TLR7 protein to bind more easily to a nucleic acid component called guanosine and become more active. This increases the sensitivity of the immune cell, making it more likely to incorrectly identify healthy tissue as foreign or damaged and mount an attack against it.
    • females with a mutation in this gene can have two functioning copies with incomplete silencing of one gene and this may explain why luus is 10x more frequent in women than in men
    • conversely, other mutations that cause TLR7 to become less active are associated with some cases of severe COVID-19 infection, highlighting the delicate balance of a healthy immune system.
  • rare cases are associated with one gene (complement components C1q and C4)
  • most are associated with a large number of genes but as of 2011, identified loci account for only 15% of hereditability ²⁾
  • epigenetic changes ? associated with smoking, UV exposure, medications, viral load, EBV
  • XX chromosome seems to cause more severe SLE than accounted for by female sex hormones
• triggers include:
  • certain medications
  • extreme stress
  • exposure to sunlight
  • hormones - oestrogen in particular
  • infections
  • possibly lipstick usage??
• potential pathophysiologic mechanisms:
  • a single genetic mutation in the UNC93B1 gene may be the trigger for a form of the autoimmune disease lupus in children³⁾
  • EBV / glandular fever / infectious mononucleosis infections in susceptible people perhaps by certain strains of EBV produce a protein called EBNA2 which results in activation of pro-inflammatory genes (ZEB2 and TBX21) in B memory cells which appear to mediate SLE⁴⁾⁵⁾
  • ETV5 (a specific transcription factor expressed in T cells) enhances the expression of its target protein, osteopontin (OPN) which in turn activates the AKT protein, leading to the differentiation into T follicular helper (TFH) cells potentially leading to SLE. An overabundance of TFHs can cause B cells to become overly active, resulting in autoimmune diseases. In such cases, B cells mistakenly recognize the body's own tissues and cells as pathogens and produce autoantibodies even when no external pathogens are present. ⁶⁾

• common initial and chronic complaints include fever, malaise, joint pains, myalgias, fatigue, and temporary loss of cognitive abilities.
• as they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE.

• 30% to 50% suffering from the classic malar rash (or butterfly rash)
• some have discoid lupus, alopecia, mouth, nasal, and vaginal ulcers.

• generally, a non-destructive arthritis - most commonly of small joints of hand and wrist
• increased risk of osteoarticular tuberculosis (TB)

• ~50% devlop anaemia and iron deficiency
• may have an association with antiphospholipid antibody syndrome (lupus anticoagulant-positive) which is associated with thrombosis, deep venous thrombosis (DVT), increased risk of miscarriages, etc.
• may have anticardiolipin antibody which may cause a false positive syphilis serology

• pericarditis, myocarditis, and endocarditis.
• atherosclerosis and primary prevention also tends to occur more often and advances more rapidly than normal persons

• pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, and shrinking lung syndrome

• painless hematuria or proteinuria may often be the only presenting renal symptom of lupus nephritis which may lead to acute or end-stage renal failure (now uncommon if nephritis treated early).
• histological hallmark of SLE is membranous glomerulonephritis with “wire loop” abnormalities.
• type I renal tubular acidosis (RTA)

• neuropsychiatric syndromes
• headache, cognitive dysfunction, mood disorder, cerebrovascular disease,[19] seizures, polyneuropathy,[19] anxiety disorder, and psychosis.
• other rare manifestations

• anti-nuclear antibodies (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE.
  • speckled pattern may be normal, especially in those aged over 60yrs, if anti-ENA is negative
  • a low titre 1:40, 1:80, 1:160 often suggests there is no auto-immune disease
  • a medium titre 1:320 is less clear and needs further context to interpret
  • a high titre 1:640, 1:1280 or 1:2560 generally indicates more severe auto-immune disease
• Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus).
• Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE.

• see wikipedia

• anti-dsDNA (double-stranded DNA) antibodies, complement (C3 and C4), ESR, PLT, 24 hours urinary protein
• these markers are not specific and can be affected by the primary disease, glucocorticoids, immunosuppressants
• a logistic model combining disease course, procalcitonin, and platelet count may be used to predict SLE activity, and its diagnostic efficacy seems better than any of the single variables⁷⁾
• older patients (≥50 years old) with longer disease course generally have lower primary disease activity

• Up to 50% of SLE patients experience major infections during the disease course, and 20% to 55% of them die
• CRP is normally low to moderate levels in patients with SLE alone unless there is active serositis in which case levels commonly exceed 60 mg/L
• a high CRP > 24 mg/L is suggestive of either infection⁸⁾ or SLE with active serositis (median CRP levels of 76mg/L)

• SLE patients are significantly higher risk for developing herpes zoster (shingles)