1. Tiggers

2. Immunopathic Abnormalities

• primary B-cell abnormality: antilymphocyte & antineuronal antibodies
• primary T-cell abnormality
• stem cell defect

1. Hard Palate Lesions

• a shallow, erythematous, painless ulcer with an irregular border
• can also get erythematous lesions without ulceration
• mucous membrane involvement almost always indicates active SLE

2. Nasal Septum Lesions

• perforation of Little's area
• asymptomatic and uncommon

3. Aphthous Ulcers

• involve the mouth and pharynx
• develop early in SLE and with exacerbations

1. Maculopapular Rashs

• develop anywhere on the body but particularly on sun-exposed areas (face, upper chest)
• can be tender
• heal without scarring or pigmentation changes
• due to a subcutaneous vasculitis

1. Organic Brain Syndrome

• characterized by disorientation, memory loss, and progressive intellectual deterioration
• a poor prognostic indicator

2. Others

• depression, delirium, hallucinations, severe anxiety
• emotional lability with inappropriate affect
• abnormal cognitive impairment
• lower IQ with long disease duration
• specific deficit in complex problem-solving ability
• schizophrenic states (rare) with paranoia and suicidal ideation

1. Pericarditis

• occurs in up to 30% of children with acute SLE
• may be asymptomatic
• when symptomatic may be associated with precordial chest pain which worsens with lying down or deep breathing and relieved by sitting up and leaning forward
• complications include constrictive pericarditis and cardiac tamponade but are rare

2. Myocarditis

• occurs in up to 25% of children with SLE
• associated with congestive heart failure, arrhythmias, cardiomegaly, and/or narrow pulse pressure
• aortic insufficiency may be a complication

3. Endocarditis

• Libman-Sacks verrucous endocarditis
• may develop in acutely ill patients
• may be associated with a clinically significant murmur or changing murmur
• associated with 1-4mm nodes of fibrinoid necrosis of the supporting connective tissue of the valves
• mitral > aortic > pulmonic > tricuspid valve (in descending order of involvement)
• lesions are demonstrable on 2D echo

4. Others

1. Raynaud's Phenomenon

• a frequent finding in children with SLE
• represents digital ischemia due to vasospasm and/or structural vascular disease
• characterized by sequential colour changes in the finger tips usually in response to exposure to cold or emotional stress: blanching -> cyanosis (bluish discolouration) -> reddness and pain due to hyperemia
• later associated with sclerodactyly (atrophic and shiny skin of the fingers)

2. Lupus Crisis

• the sudden development of overwhelming systemic disease due to widespread acute vasculitis
• often fatal

1. Background

• a screening test to determine if autoantibodies to cell nuclei are present in the patient's blood
• this test does not indicate which autoantibodies are present (there are at least 6)
• is a more sensitive test for SLE than the LE cell preparation test
• is the best screening test currently available for identifying SLE
• is positive in almost all patients with SLE
• a positive test is not sufficient in itself to diagnose SLE or to moniter the disease course

2. ANA Test

• is called the immunofluorescent anti-nuclear antibody test (ANA or FANA)
• the patient's blood is mixed with rat or mouse liver cells or HEp-2 cells, exposed to fluorescein-tagged anti-IgG antibodies, and then examined under a microscope
• the preparations are assessed in two ways:

  1. ANA Titre

  • this tells how many times the patient's plasma had to be diluted to get a sample free of the fluorescein-tagged anti-IgG antibodies

  2. ANA Pattern

  • this looks at the distribution of fluorescein-tagged anti-IgG antibodies on the cells
  • there are 4 patterns

3. Interpretation

1. Background

• the first laboratory test devised to screen for SLE
• less sensitive than the ANA test (i.e, positive in diseases other than SLE)
• the lupus erythematosus (LE) cell factor is an antibody which is directed towards deoxyribonucleoprotein (DNP)
• in cells where this antibody has reacted with the nuclei, the damaged cell nuclei forms into a hematoxylin body which is seen as a homogeneous mass of nuclear material which has a characteristic histological appearance
• a WBC which has ingested a cell containing a hematoxylin body is called a lupus erythromatosus cell (LE cell)

2. LE Cell Test

• the patient's blood is examined under the microscope for the presence of LE cells
• the patient's tissues are examined under the microscope for the presence of hematoxylin bodies

3. Interpretation

• is positive in between 40-50% of patients with SLE
• the presence of hematoxylin bodies in tissue sections not showing profound necrosis is pathognomonic of SLE

Note: If the screening tests return as positive and the patient has symptoms, further testing needs to be done. A positive ANA screening test suggests that antinuclear antibodies are present but it does not identify which of these antibodies are present. A positive ANA test in a healthy individual does not need to be further investigated.

1. Natural DNA (nDNA)

• also called double-stranded (dsDNA)
• auto-antibodies to nDNA are virtually pathognomonic of SLE
• specific for SLE (i.e., rarely associated with other rheumatic diseases)
• present in high titres in children with active nephritis - for diagnostic purposes, the fluorescence microscopy assay using Crithidia luciliae is often preferred over the radioimmunoassay

2. Single-Stranded DNA (ssDNA)

• also called denatured DNA
• is present in 50% of children with SLE
• non-specific for SLE (i.e., found in a variety of rheumatic diseases and infections)
• of little diagnostic significance

1. Anti-Sm Antibodies

• Sm (Smith)
• these auto-antibodies are specific for SLE
• presence is related to CNS disease
• the Sm antigen is comprised of 5 small uridine-rich nuclear RNA's and a number of polypeptides (B/B',D,E,F, and G)

2. Anti-U1RNP Antibodies

• the RNP antigen represents a portion of a polypeptide associated with U1 RNA
• these auto-antibodies are less specific for SLE:
  • found in low titres in children with SLE
  • found in high titres in patients with mixed connective tissue disease
  • these auto-antibodies are responsible for the speckled ANA pattern outlined above

3. Anti-Ro Antibodies

• also called SS-A (Sjogren's Syndrome A antigen)
• these auto-antibodies are less specific for SLE:
  • found in about 25% of cases of SLE and associated with renal and pulmonary manifestations of SLE
  • most often found in Sjogren's Syndrome
  • found in neonatal lupus syndrome and associated with complete congenital heart block
  • found in subacute cutaneous lupus
  • found in 5-15% of normal individuals

4. Anti-La Antibodies

• also called SS-B (Sjogren's Syndrome B antigen)
• these auto-antibodies are less specific for SLE:
  • most often found in Sjogren's Syndrome
  • found in neonatal lupus syndrome
  • found at low levels in 5% of normal individuals
• anti-La antibodies are almost always found in association with anti-Ro antibodies

1. Anemia

• seen in 50% of children with SLE
• in SLE, there are several causes of anemia:
  • anemia of chronic disease (normocytic, hypochromic)
  • hemolytic anemia associated with auto-antibodies directed against erythrocytes (seen in 5% of cases)
  • hypersplenism, microangiopathy

2. Thrombocytopenia

• PLT <150,000 in 30% of children with SLE
• PLT <100,000 in 5% of children with SLE
• may have normal platelet number despite increased production and destruction of platelets
• may result in menorrhagia or gastrointestinal bleeding
• may be severe enough to produce ITP or TTP

3. Leukopenia

• WBC <4.5 in 40% of children with SLE
• WBC <2.0 in 10% of children with SLE
• leukopenia (particularly lymphocytopenia) is a hallmark of acute SLE
• children with leukopenia (WBC <2.0) may not response to septicemia with leukocytosis