| What is SLE? | Chronic autoimmune inflammatory multisystem disorder, with waxing and waning course, significant morbidity, diverse clinical manifestations and variable course and outcome.
Prototype of autoimmune disease, loss of tolerance to self leads to immune system mediated damage, unknown etiology, expresses itself differently in each individual |
| How is natural history of SLE? | A combination fo genes and environment play a role, gets to preclinical setting where we get autoantibodies general/specific, then we get to clinical phase with inflammation and involvement of first organs, then get flares, additional organs, damage and comorbidities increase the course of action (infections, atherosclerosis and malignancies) |
| How is epidemiology of SLE? | WW, radial variation (black, chinese and asian more common), prevalence 12-50/10000, female predominance 9 to 1 (increases during child bearing age 30 to 1.
Genetics (familial aggregation [5-12%, concordance increase risk in monozygotic twins to 24-70% and dizygotic to 2-5%] HLA II DR2 and DR3 involved, inheritied complement deficiencies involved (C1q, C2, C4), some may influence clinical manifestations)
Environmental (Physical [UV, thermal burns], chemical [drug], infectious [EBV], hormonal [estrogens], and autoantiboides) |
| How is pathogenesis of SLE? | Apoptosis (abnormal, source of autoantigen, UV induced in skin and impaired clearance)
Nucleic acids (target in SLE linked to apoptosis, loss of T cell tolerance and self-recognition)
Innate immunity (TLRs and inflammasomes on cell membranes activate Dc, Dc autophagy occurs and regulates IFNa prodcution and makes APCs to CD4+ T cells, IFNa activates autoantibodies specific, complement clearance of apoptotic material, Neutrophils promote inflammation, and endothelia impaired repair due to DNA degradation)
Adaptive immunity (T and B cells activated polyclonal B cells form autoantibodies, B lymphocyte stimulator soluble TNF for B cell survival and differentiation, Immune complexes impaired clearance cause tissue injury at sites like skin and kidney) |
| How is SLE disease mechanism and tissue damage? | Mediate by inflammatory cells, ROS, cytokine production, and modulation of coagulation cascades.
Deposition in tissues and vessels, cell mediated cytotoxicity, autoantiboides, and proinflammatory cytokines. |
| How is SLE clinical manifestation of skin? | Acute rashes, malar rash (butterfly rash, transient or permanent rash non scarring, erythematous raised lesion pruritic or painful, malar distribution photosensitive), subacute rashes, subacute cutaneous LE (10% of SLE pt, photosensitive, begin as small erythematous lesion in back), chronic rashes, discoid lupus erythematous (DLE, up to 25% of pt, discrete erythematous slightly infiltrated plaques, active inflammation at periphery and heal leave a scar or dyspigmentation, on face neck and scalp
Others (lupus profundus, lupus tumidus, livedo reticularis, vasculitis, periungeal erythema, alopecia [scarring or lupus hair])
Photosensitivity (inflammatory rash after UV exposure, from sunlight or fluorescent light, lasts days to weeks, 60-100% of pt with SLE) |
| How is SLE clinical manifestation in mucus membranes and musculoskeletal system? | Mucus membranes (25-45% of pt, ulcers, painless, mouth>nasal)
Musculoskeletal (53-95% of pt, arthritis (non-erosive, non-deforming arthritis, transient migratory or reversible, rhupis, Jaccoud arthropathy [hand deformity MCP joints/swan neck])
Myositis (generalized, inflammatory 4-16%) avascular bone necrosis (major cause of morbidity and disability, shoulders hips and knees, induced ischemia by raynauds vasculitis, fat emboli, cortisol, Antiphospholipid syndrome (APS), osteonecrosis shortly after shot of high dose corticosteroids) |
| How is SLE renal clinical manifestations? | 40-50% of pt, major cause of morbidity and hospitalization, immune complexes formation in kidney, proteinuria, dysmorphic erythrocytes, to be detected important to have urine analysis sees kidney function)
Classification of Lupus nephritis by WHO:
Class I minimal mesangial involvement, Class II mesangial, Class III focal glomerulonephritis, Class IV diffuse glomerulonephritis, Class V membraneous nephritis, Class VI advanced sclerosing |
| How is SLE neuropsychiatric clinical manifestations? | common 25-50% of pt, CNS see any neuro disorder, PNS any neuropathy |
| How is SLE cardiovascular clinical manifestation? | Pericarditis 12-25% of pt, pericardial effusion may be asymptomatic mild to moderate, increased M&M from CVD by accelerated premature atherosclerosis and valvular heart disease (linked to APS), Libman-Sacks endocarditis. |
| How is SLE pleuropulmonary clinical manifestation? | Pleuritic chest pain common, pleural effusion exudate uni or bilateral, acute pneumonia uncommon with high MR, ILD, bronchiolitis obliterans with organising pneumonia required biopsy to dx and respnds to corticosteroids, capillaritis or diffuse alveolar hemorrhage rare due to APS, poor prognosis.
Shrinking-lung syndrome, possible cause is diaphragmatic weakness in longstanding SLE, PE or infarct, Pulmonary HTN, infection, malignancy. |
| How is SLE lymphadenopathy and splenomegaly clinical manifestation? | •Lymphadenopathy occurs in about 40% of patients
• usually at the onset of disease or during disease flares (Shapira et al, 1996).
• more likely to have constitutional symptoms
•A lymph node biopsy may be warranted when the degree of lymphadenopathy is out of
proportion to the activity of the lupus
•Splenomegaly occurs in 10–45% of patients, particularly during active disease |
| How is SLE hematologic clinical manifestations? | Anemia (common, chronic disease, hemolysis, blood loss, renal insufficiency drugs, infections, hypersplenism, myelodysplasia, aplastic anemia)
Leukopenia (WBC <4500 reported 30-40% of pt, lymphocytopenia in 20% of pt <1500)
Thrombocytopenia (mild in 25-50% of pt, immune mediated platelet destruction, microangio hemolytic anemia or hypersplenism, drug induced) |
| How is SLE GI clinical manifestations? | GI manifestations are reported in 25–40% of patients with SLE, and represent either lupus GI involvement or effects of drug treatment (Ebert and Hagspiel, 2011).
Dyspepsia
peptic ulcer
Acute abdomen
Pancreatitis
Autoimmune hepatitis |
| How are criteria of dx for SLE? | We have clinical and immunologic criteria, required >4 or biopsy
ANAs (seen by immunofluorescence, low specificity, in healthy/low titer individuals)
Ab to extractable nuclear Ag (anti-dsDNA [LN end stage renal disease increased severity and poor survival], APS [venous, CNS, death], anti-Ro/La [neonatal lupus, congentical heart block, seropositive mothers and children) |
| How is prognosis, M&M of SLE? | Prognosis dramatic improvement when managed but long term.
M&M (infections [after immune regulation], atherosclerosis, osteoporosis, malignancies) |
