SLE Flashcards
What is Systemic lupus erythematosus (SLE)?
Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease with a relapsing and remitting course.
Its prevalence is higher in women of childbearing age, with a female predominance of 9:1 .
The exact aetiology of this disease is not understood well, however it has been demonstrated that environmental and genetic factors interact together.
This trigger immune responses resulting in the excessive production of pathogenic autoantibodies by the B cells and cytokine dysregulation leading to tissue and organ damage.
SLE is characterized by the presence of antibodies to nuclear and cytoplasmic antigens.
What autoantibodies might be present in SLE patients?
- Anti-Scl-70 antibodies (present in systemic sclerosis),
- Anti-La, and Anti-Ro antibodies (present in Sjogren disease)
- Anticardiolipin antibodies, and anti-phospholipid antibodies
- Antinuclear Antibodies (ANA): sensitive but not specific for SLE
- Anti-dsDNA (Double-Stranded DNA) Antibodies: Highly specific for SLE (~95%) but less sensitive
- Anti-Smith (Anti-Sm) Antibodies: Most specific (~99%) but found in only 20-30% of SLE cases (most sensitive for SLE)
- Anti-Ro 60, Anti-Ro 52/SSA & Anti-La/SSB Antibodies
- Anti-RNP (Ribonucleoprotein) Antibodies
- Anti-Histone Antibodies
- Anti-topoisomerase 1
Epidemiology
SLE is not rare in Nigeria.
Most patients were female in their 3rd to 4th decades of life.
8-12 F: 1 M
There is a delayed presentation to a rheumatology facility.
Arthritis and mucocutaneous manifestations were the most frequent presentation.
This study presents the first national data on SLE in Nigeria
This study showed that SLE is not rare in Nigeria in contrast to previous reports *
There appear to be ethnic disparity in the frequency of lupus among Nigerians *
Nigerians with lupus have very high titre of ANA.
In the United States, SLE is more frequent among African American, Hispanic, and Asian populations as compared to the Caucasian population.
Its occurrence is three to four times higher among African-American women
Aetiology and risk factors of SLE
- Immune system dysregulations( autoantigen and autoantibody generation).
- Failure of clearance of Apoptotic cell
- Certain genetic polymorphism are associated with SLE like HLA-DR2 and HLA-DR3
- Ultraviolet radiation like sunlight and Florescence light
- Smoking
- Exposure to silica dust
- Drugs like Hydralazine, procainamide, Isoniazid, Minocycline
- Sex hormones like oestrogen
- Epstein Barr virus infection
- Complement dysfunctions
The aetiology of SLE is unknown, but is believed to develop through the interplay of susceptibility genes, epigenetic and environmental factors.
Also the immune cells and molecules that participate in apoptosis, and innate and adaptive immune responses
In genetically predisposed individuals, environmental factors act as triggers of loss of tolerance to self-antigens.
This will lead to aberrant immune responses against endogenous nuclear and other self-antigens.
Downstream elements that drive a self-sustained loss of tolerance seem to spread and maintain autoimmunity, although the mechanisms are poorly understood.
The disease course may thus be characterised by a preclinical phase with non-specific autoimmune abnormalities that progress to a more disease-specific autoimmunity phase
It may take years for patients to develop enough clinical and immunological features that allow a diagnosis of SLE, although some patients do initially present with full-blown disease
Clinical presentation
SLE exhibits a broad spectrum of presentations ranging from mild symptoms to severe, life-threatening conditions.
Adults diagnosed before 50 years of age usually present with cutaneous symptoms (malar rash) and renal abnormalities (lupus nephritis), displayed higher 10-year survival.
And report showed they need more immunosuppressive therapy than patients got diagnosed after 50 years of age.
Various factors such as age, race, gender, genetic premise, and socioeconomic status also influence the time frame of presentation and therapy initiation .
Hence the clinical presentation can vary drastically, and a high level of suspicion is needed for early diagnosis and treatment of these patients.
Summary of the Pathophysiology of SLE
A key concept in the pathogenesis of SLE is the defective clearance of apoptotic cells leading to accumulation of apoptotic debris that may elicit an abnormal immune response
Increased apoptotic cell load may be generated by exposure to ultraviolet light, infections and other environmental risk factors for SLE.
Abnormal apoptotic pathways contribute to failure of the mechanisms that usually prevent immune activation in response to endogenous cellular debris
Pathophysiology of Systemic Lupus Erythematosus(SLE)
The basic pathophysiology of SLE involves a complex interplay between genetic, environmental, and hormonal factors, leading to a dysregulated immune response.
Loss of Tolerance
1. Genetic predisposition: Individuals with a family history of SLE or other autoimmune diseases are more susceptible.
2. Environmental triggers: Exposure to UV light, infections, or certain medications like hydralazine can initiate the disease process.
Immune System Dysregulation A - Activation of immune cells: Antigens (e.g., nuclear components) trigger the activation of immune cells, such as dendritic cells, T cells, and B cells. B--Production of autoantibodies: Activated B cells produce autoantibodies, which target self-antigens (e.g., dsDNA, histones) C-- Formation of immune complexes: Autoantibodies bind to self-antigens, forming immune complexes that can deposit in tissues and organs.
Tissue Damage and Inflammation A- Complement activation: Immune complexes activate the complement system, leading to the production of pro-inflammatory molecules leading to hypocomplementaemia. B- Inflammation and tissue damage: Activated immune cells, complement, and autoantibodies contribute to inflammation and tissue damage in various organs.
Type I interferons (IFN) -Play a crucial role in the activation of immune cells and the production of autoantibodies.
T cells and B cells: Dysregulated T cell and B cell responses contribute to the development of autoantibodies and tissue damage.
Dendritic cells: Activated dendritic cells present self-antigens to T cells, perpetuating the autoimmune response.
This complex interplay of genetic, environmental, and immune system factors leads to the characteristic features of SLE, including autoantibody production, immune complex formation, and tissue damage.
clinical presentation on each system
Musculoskeletal: Jaccoud’s arthropathy, arthralgia, arthritis, synovitis, tenosynovitis, myositis
Central and peripheral nervous system: Central Nervous system: Neuropsychiatric lupus, lupus cerebritis (seizure, headache), aseptic meningitis. Peripheral Nervous system: Transverse myelitis, mononeuritis multiplex, peripheral neuropathy, small fiber neuropathy, autonomic neuropathy.
Additionally, delirium, and psychosis are also present
Gastrointestinal: Ascites, peritonitis, oral ulcers, esophageal dysmotility, protein-losing enteropathy
Hematological: Anemia, microangiopathic hemolytic anemia, thrombocytopenia
Pulmonary: Pleuritis, pulmonary arterial HTN, interstitial lung disease, pleural effusion
Cardiovascular: Libman-sacks-endocarditis, pericarditis, myocarditis
Renal: Proteinuria, hematuria, and glomerulonephritis
Types of SLE and their clinical presentation
- Acute cutaneous Lupus Erythemtosus: hallmark: malar or butterfly rash, erythematous raised pruitic rash, nasolabial folds are spared
- Subcutaneous Lupus Erythemtosus: photosensitive widespread, non-indurated rash
- Chronic cutaneous Lupus Erythemtosus: discoid lupus erythematosus (DLE) is the most common type
Investigations
FBC
ESR
CRP
E/U/Cr
Urinalysis and Urine Protein/Creatinine ratio
CXR
HBsAG, Anti-HCV
HIV Screening
RBS and HBA1c
ENA panel
C3,C4
Antiphospholipid antibodies
Lipid profiles
ECG
Abdominal USS
Ophthalmology Eye Examination
LFT
Stages of Lupus Nephritis (POSSIBLE QUESTION) and their prognosis
Class I: Minimal mesangial lupus nephritis
- Excellent prognosis
Class II: Mesangial proliferative lupus nephritis - Excellent prognosis
Class III: Focal lupus nephritis- Poor outcome
Class IV: Diffuse segmental nephritis
- Poor outcome
Class V: Membranous lupus nephritis
- Prognosis is favorable but with certain complications: Thromboembolism
Class VI: Advanced sclerosing lupus nephritis - Poor outcome as most symptoms are of irreversible injury
Diagnosis
The major limitation of the 1997 ACR as diagnostic criteria was a low sensitivity of 83%.
According to this classification, one in six patients of SLE would not be correctly classified, with sensitivity dropping to 66% early in the disease.
Because the criteria items may need time to accumulate during disease, which was a further limitation to using 1997 ACR as a diagnostic criterion.
To rectify this, the 2012 SLICC was introduced with improved sensitivity of 97% and an increase in sensitivity to 84% early in the disease.
However, the specificity decreased to 84%, whereas ACR criteria specificity was 93%
The 2019 ACR/ EULAR classification criteria were devised to maintain the high specificity of the ACR criteria and the high sensitivity of the SLICC criteria.
Validation cohorts suggested this goal was reached with a specificity of 93% and a sensitivity of 96%.
The 2019 ACR/ EULAR classification criteria for SLE include a positive ANA test followed by additive weighted criteria that are grouped into seven clinical.
Constitutional, haematological, musculoskeletal, mucocutaneous, serosal, renal, neuropsychiatric.
And three immunological (SLE-specific antibodies, anti-phospholipid antibodies, complement proteins,) domains; weighted from 2 to10.
Patients accumulating ≥10 points are classified as having SLE.
ACR 1997 criteria
Antinuclear antibodies
Arthritis
Discoid rash
Hematologic disorder
Immunologic disorder
Malar rash
Neurologic disorder
Oral ulcers
Photosensitivity
Renal disorder
Serositis
EULAR
Treatment
Systemic lupus erythematosus is a disease of heterogenic manifestation involving multiple organs.
Therefore, the disease severity and organ involvement vary from patient to patient.
Thus this pose a significant challenge in disease management and requiring a multidisciplinary approach.
The treatment aims is to prevent the flare-ups of the disease, promote remission and maintenance but @ worse low disease activity, and prevent relapse at a minimum cost of side effects of the medications used.
The goal of the treatment is to get optimum control of symptoms and remission of the disease, improve long-term outcomes for the patient, prevent end organ damage, and better quality of life for the patient.
Management
History take is very important in the management of SLE this will also help us to arrive at a diagnosis.
The above history are important
Arthralgia/arthritis
Body rashes either acute or Chronic
Photosensitive rash
Fever
Fatigue
Weight loss
Chest pain
Dyspnoea
Oral & Nasal ulcer
Genital ulcer
Facial swelling
Leg swelling
Passage of frothy urine
Exposure to radiation
Childhood viral infection
Recurrent pregnancy loss
Leg ulcer
Psychosis
Convulsion
Transient memory loss
Bleeding gum
Family history of autoimmune diseases
Smoking
Medications
Immunosuppressive drugs (HCQ, MMF,CYC,RTX,MTX,AZA,Tacrolimus,Dapsone,Belimumab)
Glucocorticoid , this can be low dose, medium and high doses and pulse therapy, we can also use topical steroid cream.
Oral steroid is usually used as a bridging therapy before the immunosuppressive medications take their maximal effect between 3- 6months, however some patient may be steroid dependent.
Low dose steroid 7.5mg daily
Moderate dose 10 -30mg daily
High dose 30-60mg daily
Very dose 60-100mg
>125mg to 1000mg are pulse therapy doses
Hydroxychloroquine( HCQ)
Methotrexate (MTX)
Azathioprine (AZA)
Mycophenolate mofetil (MMF)
Tacrolimus
Dapsone
Cyclophoshamide (CYC)
Belimumab
Rituximab (RTX)
SPF 50 cream
Calcium
Vitamin D
In term of treatment of Systemic lupus erythematosus we usually divide lupus into.
Mild lupus –Patient with SLE presenting majorly with acute skin manifestation without bullous formation and discoid lupus but with joint involvement ( Arthralgia/ Arthritis)
Moderate lupus-Patient presenting with thrombocytopenia of <50,000/ul and lupus serositis ( pleural effusion, pericardial effusion and ascites)
Severe lupus-Patient with SLE presenting with neuropsychiatry lupus and lupus nephritis and thrombocytopenia of < 50,000/ul
Treatment based on type
The mainstay of treatment of SLE regardless of their mode of presentation is Hydroxychloroquine (HCQ) and is usually given at a dose of not >5mg/kg/day and one must not exceed 400mg daily.
Eye examination must done before prescribing the medication, then after one year and later every 5 years because it can cause maculopathy, worsening of glaucoma.
Mild lupus give low dose steroid , HCQ @ 200mg daily, if there are very severe arthritis with synovitis considered MTX @ a dose of 0.3mg/kg/weekly ,remember to add folic acid @ 10mg /weekly.
Moderate lupus give steroid @ 0.5mg/kg/day, in case of pleural effusion and pericardial effusion pulse patient for at least 3 days with 500mg of IV methylprednisolone and commence on MMF or AZA and HCQ.
For severe lupus pulse with 500mg of methylprednisolone daily for 5daily, then commence oral steroid @ a dose of 0.5-1mg/kg/day.
Commence on MMF or CYC
For refractory lupus nephritis treat with RTX or belimumab
Which is more sensitive in SLE C3 or C4?
C3
