SLE
General information
Systemic lupus erythematosus is a multisystemic disease with widespread inflammation in connective tissues and immunocomplex vasculitis with spontaneous attacks and spontaneous remissions.
It is characterized by immunocomplex deposition in blood vessels, kidneys, connective tissue, and skin.
Cellular immunity is impaired and there is suppressor T-cell dysfunction and is an autoimmune disease of unknown cause.
It affects many organs due to inflammation of many tissues and organs such as skin, joints, kidneys, pericardium, pleura. Kidney involvement is one of the most common involvements in children.
Most patients with SLE in childhood are adolescent girls. It is rare under 5 years old. They are usually diagnosed at the age of 11 -12 years. One-fifth of lupus patients get it under the age of 16.
Clinical Findings:
• The most common presentation findings of the patients; fever, fatigue, haematological disorders, arthralgia or arthritis and rash (Malar rash often occurs. Discoid rash is extremely rare in children).
• Symptoms may develop intermittently or persistently, and may show spontaneous remission.
Skin findings
- Malar rash (characteristic)
- Discoid rash
- Photosensitive rash
- Cutaneous vasculitis (petechiae, purpura, urticaria, gangrene, finger ulcers)
- Raynaud's phenomenon
- Alopecia, oral-nasal ulcers
gastrointestinal
- Hepatosplenomegaly
- Pancreatitis, peritonitis, protein-losing enteropathy
Cardiovascular (Pancarditis)
- Most common pericarditis
- Libman-Sacks endocarditis
- Myocarditis, cardiomegaly
- Coronary artery vasculitis and thrombosis
- Antiphospholipid syndrome and diffuse ischemic artery and vein thrombosis
Pulmonary
- Pleuritis
- Pulmonary hemorrhage, pulmonary embolism, pulmonary hypertension
- Pulmonary fibrosis (interstitial lung disease)
Neurological
- Convulsions, cognitive disorders, headache, chorea
- Cerebrovascular disease
- Psychosis, mood disorder
Renal involvement and lupus nephritis
• Stage I: Minimal mesangial LN; there is no renal finding.
• Stage II: Mesangial proliferative LN; mild renal disease, non-nephrotic proteinuria
• Stage III: Focal proliferative LN; proteinuria (25% nephrotic) and hypertension.
• Stage IV: Diffuse proliferative lupus nephritis; It is the most common and most serious form of lupus nephritis. All glomeruli are thickened due to mesenchial and subendothelial deposition of immunoglobulins. The "copper wire" scene is seen in this phase. There is necrosis, crescent formation and scarring. He has decreased kidney functions, nephrotic proteinuria, hypertension, active serology, and active urinary sediment.
• Stage V: Membranous lupus nephritis; Nephrotic syndrome is common. It is the rarest form.
• Stage VI: Advanced sclerosing LN; >90% glomerulosclerosis, renal failure is inevitable.
Other findings:
• General: Lymphadenopathy, fever, fatigue, loss of appetite, weight loss
• Ocular: Retinal vasculitis, scleritis, papilledema, dry eye, optic neuritis
• Musculoskeletal: Arthritis, myositis, tendinitis, aseptic necrosis, osteoporosis
Laboratory Findings:
• The screening test for SLE is the fluorescent antinuclear antibody (ANA) test.
• Anti-dsDNA antibodies and anti-Smith antibody are specific for SLE.
• CH(50) ↓, C3 and C4 ↓ in active disease
• Gammaglobulin high (hypergammaglobulinemia)
• There may be thrombocytopenia, leukopenia (ITP can sometimes be the first manifestation of SLE). The most specific is lymphopenia.
• There may be PTT prolongation due to antiphospholipid antibodies.
• Sedimentation increases especially in active disease. CRP is less associated with disease activation. Acute CRP elevation is an indicator of infection, and chronic CRP elevation is an indicator of cardiovascular risk.
Diagnosis
11 criteria for SLE (a diagnosis of SLE is made if 4 or more)
1. Butterfly-shaped malar rash
2. Discoid rash
3. Photosensitivity
4. Oral or nasal ulcers
5. Nonerosive arthritis (≥2 joints)
6. Serositis (pleuritis, pericarditis, peritonitis)
7. Renal disorders (persistent proteinuria or casts, compatible renal biopsy)
8. Neurological disorder (convulsion or psychosis)
9. Hematological disorder (hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia)
10. Immunological disorder (anti-DNAAb+, anti-Sm Ab+, False+ VDRL, anticardiolipin Ab+, positive lupus anticoagulant test)
11. Antinuclear antibody positivity ANA
Presence of at least 4 criteria (at least 1 clinical and 1 laboratory) makes the diagnosis.
A biopsy-proven lupus nephritis+ANA or anti-ds DNA positivity makes the diagnosis.
These criteria were developed for classification of studies, not for clinical diagnosis.
Antibodies in SLE
• ANA: Sensitivity of ANA positivity in SLE is 95-99%; its specificity is 50%.
Conditions that make ANA positive
• drug-induced lupus
• JIA
• Juvenile dermatomyositis
• Scleroderma
• Infectious mononucleosis
• Chronic active hepatitis
• Hyperextensibility
• Anti-ds DNA and anti-Smith:
Anti-ds DNA correlated with disease activity (especially nephritis), while anti-Smith antibody was not associated with disease. While the specificity of anti-ds DNA and anti-Smith antibodies is 98%, the sensitivity is 40-65%. These two tests are the most specific for the diagnosis of SLE.
• Anti-Ro/SS-A and anti-La/SS-B
It is seen in skin and lung involvement of SLE. Neonatal lupus is associated with Sjögren's syndrome and isolated discoid lupus.
• Anti-RNP (ribonucleoprotein) antibody
It poses a risk for Raynaud's phenomenon and pulmonary hypertension. It is also elevated in mixed connective tissue disease.
• Antiphospholipid antibodies
Associated with venous and arterial thrombosis.
• Anti-histone antibody
It is seen in drug-induced lupus.
• Anti-ribosomal P antibody
Associated with lupus cerebritis.
Treatment and Prognosis:
• Hydroxychloroquine is the first choice for the treatment of skin manifestations and mild arthritis. It prevents lupus exacerbations and has a positive effect on mortality and renal involvement.
• NSAIDs are used for arthralgia and arthritis.
• High dose (pulse) IV methylprednisolone is used for patients with severe symptoms.
• Medicines used to reduce the steroid dose (steroid sparing)
cyclophosphamide
Mycophenolate mofetil
methotrexate
Leflunomide
Azothiopurine
Belimumab (monoclonal antibody against B cell activation factor BLyS)
• The most common causes of death in the early period are infection, complications of glomerulonephritis and neurological involvement.
• The most common causes of death in the long term are atherosclerosis and malignancies.
Drug-Induced Lupus
• Some drugs such as procainamide, hydralazine, diphenylhydantoin, isoniazid, minocycline, penicillamine, diltiazem, infliximab, etanercept may cause a clinical picture similar to lupus.
• Differences of drug-induced lupus from SLE:
o Equal incidence of boys and girls
o Antihistone antibodies, which are seen in 20% of SLE, are detected much more frequently
o Rare hepatitis seen in SLE
o Very rare renal involvement
o Most cases resolve with discontinuation of the drug
Neonatal Lupus Syndrome (NLS)
General Information
• Intrauterine anti-Ro (SSA), anti-La (SSB) and anti RNP (ribonucleoprotein) antibodies, 12-16 weeks of pregnancy. It occurs when it crosses into the fetus at 12-16 weeks of gestation.
• Anti Ro antibodies are more specific.
• This picture develops in 2% of babies whose mothers are positive for these antibodies.
• It can be seen in infants of mothers with SLE or Sjögren's syndrome.
• Mothers of infants with neonatal lupus syndrome may be asymptomatic or may have only mild P-R prolongation.
• The antibody-positive fetus is followed up by echocardiography since the 16th week of pregnancy.
Clinic
• Cutaneous lesions (erythema annulare): It is the most common and first finding. It usually occurs in the first 6 weeks after exposure to sunlight and ultraviolet light. It is often found on the face and scalp. No treatment is required.
• Congenital heart blocks: It can be permanent after birth and sometimes a pacemaker is inserted.
• Thrombocytopenia
• Neutropenia
• Hepatitis
• Pulmonary and neurological disease
There is no renal involvement in neonatal lupus syndrome.
Treatment
It is tried to prevent the development of heart blocks, endocardial fibroelastosis and hydrops with corticosteroid or intravenous immunoglobulin, plasmapheresis, hydroxychloroquine and terbutaline+steroid treatment given to anti-Ro and anti-La positive mothers.
The most effective drug preventing the formation of heart blocks is hydroxychloroquine.
