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Systemic Lupus Erythematosus - Coggle Diagram
Systemic Lupus Erythematosus
DEFINITION
SYSTEMIC
AFFECTS MULTIPLE ORGANS
ERYTHEMATOSUS
REDDENING OF SKIN
LUPUS
LATIN = WOLF
diseases affecting the skin
a systemic disease that affects a wide variety of organs but notably often causes red leasions on the skin
penyakit autoimun sistemik kronik, ditandai dengan terbentuknya berbagai macam antibodi yang membentuk kompleks imun dan menimbulkan reaksi inflamasi pada berbagai organ di dalam tubuh
DIFFERENTIAL DIAGNOSIS
SARCOIDOSIS
REACTIVE ARTHRITIS
LYME DISEASE
ENDOCARDITIS
CHRONIC FATIGUE SYNDROME
HIV INFECTION
RHEUMATOID ARTHRITIS
IBD
AUTOIMMUNITY
Triggered by the development or activation of CD4 helper T cells that react with a specific autoantigen. Based on various evidence, it is now proposed that a specific antigenic stimulus is the first trigger of autoimmunity. This is called the “single initiating antigen hypothesis”.For example, molecular mimicry in which immune response occurs to both an external microbial antigen and an autoantigen because of their homology is considered one of the mechanisms of initiating autoimmunity.
HYPERSENSITIVITY
Refers to an antigenic response that results in undesirable effects
Type I (Anaphylactic) Reactions
Occurs 2 to 30 minutes after a sensitized person is reexposed to an antigen
Anaphylaxis = the opposite of protected, an inclusive term for the reactions caused when antigens combine with IgE antibodies
May be systemic reactions or localized reaction
The IgE antibodies produced in response to an antigen (such as insect venom or plant pollen) bind to the surfaces of mast cells and basophils
Mast cells and basophils can have as many as 500,000 sites per cell for IgE attachment. When an antigen encounters two adjacent antibodies of the same appropriate specificity, it can bind to one antigen-binding site on each antibody - binding the space between them. This bridge triggers the mast cell or basophil to undergo degranulation in which the granules in these cells are released which contains mediators. These mediators cause an unpleasant and damaging effect of an allergic reaction such as histamine
Released histamine -> increases blood flow and the permeability of blood capillaries -> edema (swelling) and erythema (redness)
Other effects: increased mucus secretion & smooth muscle contraction
Type II (Cytotoxic) Reactions
Activation of complement by the combination of IgG or IgM antibodies with an antigenic cell. This activation stimulates complement to lyse the affected cell which might either be a foreign or host cell
Type III (Immune Complex) Reactions
involves antibodies against soluble antigens circulating in the serum
Immune complexes form only when certain ratios of antigen and antibody occur. The antibodies involved are usually IgG. A significant excess of antibody leads to the formation of complement-fixing complexes that are rapidly removed from the body by phagocytosis. When there is excess antigens, soluble complexes that do not fix complement and do not cause inflammation. When certain antigen-antibody ratio exists, usually with a slight excess of antigen, the soluble complexes escape phagocytosis - causing inflammatory reactions and damage to basement membrane's endothelial cells
Type IV (Delayed Cell-Mediated) Reaction
involved cell-mediated immune responses and are caused mainly by T cells
References
Tjokroprawiro A. Buku Ajar Ilmu Penyakit Dalam. Edisi 2. Fakultas Kedokteran Universitas Airlangga Rumah Sakit Pendidikan Dr. Soetomo Surabaya. 2015.
Abbas, A. et al. Cellular and Molecular Immunology. 8th Ed. Elsevier Saunders. 2015.
James, JL. et al. Harrison’s Principles of Internal Medicine. 20th Ed. McGraw Hill Education. 2018.
Gordon, C. & Isenberg, D. Systemic Lupus Erythematosus. Oxford Rheumatology Library. 2016
CLASSIFICATION of LUPUS
SLE
Cutaneous lupus
Drug-induced lupus
Neonatal lupus
Classes of SLE
Class I
Minimal mesangial lupus nephritis
Class II
Mesangial proliferative lupus nephritis
Class III
Focal lupus nephritis
Class IV
Diffuse segmental or diffuse global lupus nephritis
Class V
Membranous lupus nephritis
Class VI
Advanced sclerosing lupus nephritis
ETIOLOGY
Cause of SLE is unknown, multiple genetic predispositions and gene-environment interactions have been identified
In systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody (Ab) responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity. HLA = human leukocyte antigen; UV = ultraviolet light.
RISK FACTORS
Female sex
Hormonal influence
Estrogens and prolactin promote autoimmunity and increase the B-cell activation factor production and modulate lymphocyte and pDC activation. The use of estrogen-containing contraceptives and postmenopausal hormone replacement therapy can cause flares in patients with SLE and have been associated with a higher incidence of SLE. Elevated levels of prolactin are seen in patients with SLE. Androgens, on the other hand, are considered protective.
Low birthweight <2,500g
Preterm birth >1month early
Childhood exposure to agricultural pesticides
Silica dust and cigarette smoking may increase the risk of developing SLE
Photosensitivity is clearly a precipitant of skin disease
Ultraviolet light stimulates keratinocytes, which leads not only to overexpression of nuclear ribonucleoproteins (snRNPs) on their cell surfaces but also to the secretion of cytokines that simulate increased autoantibody production
Breastfeeding is associated with a decreased risk of developing SLE
CLINICAL MANIFESTATIONS
Malar Rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
Neurological disorder
Hematologic disorder
Immunologic disorder
Antinuclear antibody
CMD
ANAMNESIS
Fatigue, fever, arthralgia, and weight changes are the most common symptoms in new cases or recurrent active SLE flares. Fatigue, the most common constitutional symptom associated with SLE, can be due to active SLE, medications, lifestyle habits, or concomitant fibromyalgia or affective disorders.
Weight loss may occur in patients with active SLE. Weight gain may also be due to corticosteroid treatment or active disease, such as nephrotic syndrome (with anasarca) or myocarditis.
Arthritis , joint, or muscle pain.
Weight loss or fatigue.
Skin rashes, especially after exposure to sunlight.
Sores in the mouth, nose, or other mucous membranes.
Chest pain.
Hair loss or thinning.
Seizures , convulsions, or other nervous system symptoms.
Whether anyone in your family has lupus.
Whether you have ever had kidney disease.
PHYSICAL EXAMINATION
Constitutional symptoms (fever, malaise, fatigue, weight loss): most commonly fatigue and a low-grade fever
Achy joints (arthralgia)
Arthritis
Skin rasshes
Chest pain, difficulty breathing
cough
Anemia
Hair loss
mouth, nose or vaginal ulcers
LABORATORY DIAGNOSIS
Antinuclear antibody titer is the primary laboratory test used to diagnose systemic lupus erythematosus. Because of the low prevalence of the disease in primary care populations, the antinuclear antibody titer has a low predictive value in patients without typical clinical symptoms.
BASIC IMMUNOLOGY
The cellular components that mediate recognition and defence can be categorized by various criteria, including their developmental lineage from stem cells in the bone marrow (myeloid or lymphoid), and their morphology as mature blood leucocytes. Polymorphonuclear leucocytes (PMNs) are distinguished from mononuclear cells by their lobulated nuclei and they largely coincide with the granulocytes defined by distinctive cytoplasmic granules. The immune system’s cellular components can also be considered as mediators of either innate or adaptive immunity.
Innate Immunnity
Humoral immunity
Complement system
Cellular Immunity
Granulocytes, APCs, mast cells
Adaptive immunity
Humoral immunity
Plasma cells secreting antibodies
Cellular immunity
T lymphocytes
THERAPY
steroid adalah hormon yg berfungsi sbgai anti-inflamasi & imunoregulator yg secara normal disekresikan oleh kelenjar adrenal
glukokortikoid - steroid yang sangat kuat dgn efek mineralokortikoid yg ringan dibanding kortison
efek samping: hipertensi, hipokalemi, hiperglikemi, hiperlipidem, sklerosis, risiko infeksi, glukoma, katarak, jerawat, insomnia, cushings syndrome
obat lain dgn kombinasi steroid: chloroqion, azathioprin, siklosporin, siklophosphamide, metrotrexate
PROGNOSIS
tergantung pada organ yg terlibat, bila organ vital yg terlibat maka mortalitasnya sangat tinggi
PATHOGENESIS
Complex disease in which genetic, environmental and hormonal factors contribute to a breakdown of tolerance in self-reactive B and T lymphocytes
Genetic factors
Inheritance of particular HLA alleles
Genetic deficiencies of classical pathway complement proteins especially C1q, C2, or C4, resulting in defective clearance of immune complexes and apoptotic cells and the failure of B cell tolerance
Environmental factors
Exposure to ultraviolet (UV) light) leading to apoptotic death of cells and release of nuclear antigens
Increased amounts of apoptosis-related endogenous nucleic acids stimulate the production of IFNa and promote autoimmunity by breaking self-tolerance through the activation of antigen-presenting cells. Once initiated, immune reactants such as immune complexes amplify and sustain the inflammatory responses
EDUCATION & PREVENTION
Instruct patients with SLE to seek medical care for evaluation of new symptoms, including fever. Advise them regarding their heightened risks for infection and cardiovascular disease. Educate patients with SLE regarding aggressive lipid and blood pressure goals to minimize the risk of coronary artery disease.
Avoid sun exposure
Wear sunscreen & protective clothing when going outdoors
Get enough sleep
Take all medications as prescribed