• It is frequently seen in women of childbearing age (15-44 years).
• The female/male ratio is 8-10.
Risk factors
• HLA-related genes (HLA DR3)
• Lack of complement (C1q, C2, C4)
• Environmental factors (Ultraviolet rays, smoking, silica exposure)
• Female gender and estrogen (oral contraceptive use, risk increases with pregnancy)
• XXV karyotype (Klinefelter syndrome) increases the risk of developing SLE.
clinical findings
Constitutional symptoms/signs (95%). Weakness, malaise, fever, anorexia, weight loss
Musculoskeletal findings (95%)
• Arthralgia / myalgia is most common.
• Joint involvement is symmetrical and polyarticular. However, deformity development in the joint is not expected.
• Jaccoud's arthropathy (pseudo deformity), which develops due to soft tissue involvement (not joint destruction) and can be corrected manually, is seen in some patients.
• Avascular necrosis may develop (most commonly seen in the femoral head and is usually associated with steroid use).
Hematological findings (85%)
• The most common finding is normochromic normocytic anemia (anemia of chronic disease).
• Leukopenia is common and is usually related to lymphopenia.
• Autoimmune thrombocytopenia and Coombs positive hemolytic anemia may be seen.
• Lymphadenopathy, splenomegaly may be seen.
• There is an increased risk of hematological malignancy, especially nan hodgkin lymphoma, in SLE.
Skin findings (80%)
• Acute cutaneous lupus
o The most common form is photosensitive erythema.
o The most typical form is malar rash.
o Malar rash; involves the cheeks and nose, but not the nasolabial grooves.
• Subacute cutaneous lupus
o Most of the patients are positive for anti-Ro (SS-A) antibodies.
o Both acute and subacute lesions heal without scarring.
• Chronic cutaneous lupus
o The most common form is discoid lupus erythematosus (DLE).
o Causes scarring and atrophy (permanent loss of all skin appendages including hair).
Neuropsychiatric findings
• The most common finding is cognitive dysfunction (difficulty in remembering and reasoning)
• Stroke associated with antiphospholipid antibodies, Libman-Sacks endocarditis (thromboembolism) may occur.
• Other neurological findings; seizure, headache, transverse myelitis, cranial or peripheral neuropathy.
• Patients may also develop psychosis.
Pulmonary findings
• Pleura (most common): Pleuritis, pleura! effusion
• Parenchyma: Lupus pneumonia, interstitial fibrosis, diffuse alveolar hemorrhage
• Respiratory muscles: Shrinking lung syndrome
• Pulmonary artery: Pulmonary embolism, pulmonary hypertension
Cardiovascular system findings
• Pericarditis is the most common finding.
• Libman-Sacks endocarditis: It is non-bacterial endocarditis specific to SLE. It most commonly affects the mitral and aortic valves. It can lead to insufficiency and embolism of the valves.
• Pericarditis responds to medical therapy, but Libman-Sacks endocarditis does not.
• Accelerated atherosclerosis is seen in SLE.
• Presence of antiphospholipid antibodies (hypercoagulability) further increases the frequency of vascular events.
Renal Findings
• The most serious manifestation of SLE is nephritis.
• The most common finding is proteinuria (> 500 mg/day).
• Anti ds DNA is associated with a high risk of nephritis, while Anti Ro and Anti La antibodies are associated with a low risk of nephritis.
• Any compartment (glomeruli, tubule, interstitium, blood vessel) can be involved.
• Immunocomplex accumulation in the kidneys is blamed in the pathogenesis.
• Complement levels are usually low in lupus nephritis.
• Lupus nephritis is mostly asymptomatic, so urine analysis should be performed in every patient.
• Renal biopsy should be performed in all patients with clinical and laboratory suspected lupus nephritis.
WHO Lupus Nephritis Classification
• Class 1: Minimal mesangial lupus nephritis
• Class 2: Mesangial proliferative lupus nephritis
• Class 3: Focal proliferative lupus nephritis
• Class 4: Diffuse proliferative lupus nephritis
• Class 5: Membranous lupus nephritis
• Class 6: Advanced sclerosing lupus nephritis
• Mesangial lupus nephritis (class I and class 2): It is the mildest type of involvement.
• Proliferative lupus nephritis (class 3 and class 4)
o Urine examination reveals severe proteinuria, hematuria, dense cellular casts.
o Untreated cases rapidly progress to renal failure.
o The most common type of lupus nephritis is class 4.
o Class IV has the worst prognosis among active lupus nephritis.
• Membranous lupus nephritis (class 5): There is predominantly proteinuria reaching nephrotic borders.
• Advanced sclerosing lupus nephritis (class 6): > 90% of glomeruli are sclerotic.
It does not respond to immunosuppressive therapy. Therefore, it has the worst prognosis among all lupus nephritis.
Gastrointestinal findings
• Non-specific findings (nausea, vomiting and diarrhea) are most common.
• The most serious involvement is mesenteric vasculitis; related perforation, infarction and bleeding may develop.
• Elevated liver enzymes, pancreatitis may be seen.
eye findings
• Sicca syndrome (keratoconjunctivitis sicca) is the most common involvement.
• In addition, posterior subcapsular cataract due to steroid use and retinal toxicity due to antimalarial drug use may occur.
Antiphospholipid antibody syndrome (AFAS)
• The most common cause of secondary AFAS is SLE.
• AFAS-associated antibodies; anticardiolipin antibody, lupus anticoagulant and anti B2 glycoprotein1.
• clinical picture; arterial-venous thrombosis and/or pregnancy-related complications.
Pregnancy and Neonatal lupus in SLE
• Pregnancy problems are more common in patients with active lupus. Therefore, patients must become pregnant while in remission. It should also be kept in mind that SLE may exacerbate during pregnancy.
• SLE causes morbidity/mortality of both mother and fetus. The presence of antiphospholipid antibodies further increases these risks.
• Transient rash (resolves within 6 months after birth) and permanent congenital heart block are seen in neonatal lupus.
• Anti-Ro (SS-A) and/or anti-La (SS-B) antibodies in the mother are responsible for congenital heart block.
Clinical conditions associated with Anti Ro (SS-A)
Sjogren's syndrome
neonatal lupus
subacute cutaneous lupus
laboratory findings
• There is no increased cell count in SLE (all series are decreased).
• APTT is prolonged due to antiphospholipid antibodies (thrombosis is expected, not bleeding).
• The syphilis test (VDRL) may be false positive due to antiphospholipid antibodies.
• In the evaluation of disease activity, erythrocyte sedimentation rate (ESR) is preferred rather than CRP.
o CRP may be normal in most patients despite intense inflammation.
o CRP is usually increased in the presence of serositis, synovitis and infection.
• In relation to kidney involvement;
o Increase in serum BUN and creatinine values may be observed. Proteinuria, hematuria and active urinary sediment (telescopic urine) can be detected in the urine analysis.
o Complement level is usually low.
Diagnosis
• According to SLICC (SLE International Collaborating Clinics) 2012 criteria, at least 4 findings, including at least 1 clinical and at least 1 immunological finding, make the diagnosis of SLE.
(Note: While there is lupus nephritis in kidney biopsy, SLE-associated autoantibody positivity is sufficient for the diagnosis of SLE)
SLICC 2012 SLE Classification Criteria
Clinical Findings
* Acute, subacute cutaneous lupus
*Chronic cutaneous lupus
* Non-scarring alopecia
* Oral / Nasal ulcer
* Synovitis
* Serositis
* Renal involvement
* Neurological involvement
* Hemolytic anemia
* Leukopenia / Lymphopenia
* Thrombocytopenia
Immunologic Findings
* ANA
* Anti ds DNA
* Anti-Smith
* Low complement level
* Antiphospholipid antibodies
- Anticardiolipin
- AntiB2 glycoprotein 1
- Lupus anticoagulant
* Coombs test positivity in the absence of hemolytic anemia
Treatment
General approaches
• Patients should be advised to avoid the sun and oral contraceptives.
• Due to the increased risk of cardiovascular disease, other risk factors such as HT, dyslipidemia, obesity, high blood sugar should be managed appropriately.
• Live vaccines (except Zostavax-VZV) should be avoided and appropriate vaccines such as influenza and pneumococcus should be administered.
• Every patient without contraindications should be given hydroxychloroquine.
Non-life-threatening (mild) involvement
• Among these involvements; skin involvement, arthritis/arthralgia, and serositis.
• Treatment options; hydroxychloroquine, low-dose steroids, NSAIDs, and methotrexate
Life-threatening (severe) involvements
• Among these involvements; lupus nephritis (especially class III and IV), CNS lupus, lung parenchymal involvement, vasculitis, hematological involvement etc.
• Joint treatment approach;
o Induction: In addition to high-dose steroid, cyclophosphamide or mycophenolate mofetil is given.
o Maintenance: Azathioprine or mycophenolate mofetil is given in addition to low-dose steroids.
• In resistant cases; Rituximab, IVIG, Plasmafarez, calcineurin inh, belimumab, a monoclonal antibody developed against B lymphocyte stimulator (BLyS), etc. available.
Immunosuppressive drugs
• Cyclophosphamide
It is originally an alkylating chemotherapy agent.
o Pregnancy category is D. It is not recommended for use during pregnancy and lactation.
• Mycophenolate mofetil
It inhibits purine synthesis by inhibiting inosine monophosphate dehydrogenase.
o Side effects; GIS findings (nausea, diarrhea) and bone marrow suppression.
o Pregnancy category is D. It is not recommended for use during pregnancy and lactation.
