《皮肤性病学》课程教学资源（教案）红斑狼疮 SLE.docx

辅助手段教学内容时间分配Connective Tissue DiseasesBasic requirementsThe subtypes oflupus erythematosus , the diagnosis of systemic lupus erythematosus.The diagnosis of dermotomyositis and the laboratory tests oflupus erythematosus.The therapy principles of lupus erythematosusanddermatomyositis.The term connective tissue disease has evolved from older designations of"collagen-vascular disease” for a group of multisystem diseases that are clinicallly similar in manyrespects.Clupus erythematosusDermatomyositisSclerodermaORheumatoid arthritisRheumatic feverPolyarteritis nodosa5分钟Chapter1Lupus erythematosusDefinition:Lupus erythematosusDefinition:LEincludesa spectrumofclinicalforms.Discoid lupus erythematosus (DLE)Subcute cutaneous lupus erythematosus (SCLE)Systemic lupus erythematosus (SLE)Etiology---Heredity:Etiology-SexHormone:Etiology-Invironment:图示Lupus erythematosusDefective immune regulatory mechanisms, such as the clearance of apoptotic cells andimmune complexes, are important contributors to thedevelopment of SLE.The loss of immune tolerance, increased antigenic load, excessT cell help,defectiveBcell suppression, and the shifting ofT helper 1(Thl) to Th2 immune responses leads to Bcell hyperactivity and the production of pathogenic autoantibodies.Thecentral immunological disturbanceinpatientswith LEis autoantibodyproductionAntinuclearantibody(ANA)andapproximately20kindsofautoantibodiescanbetested inLE.In DLE, only the skin is involved. The skin rash in discold lupus is often found on the faceand scalp. It usually isred and may have raised borders.It characterized by sharply circumscribed macules and plaques displaying erythemafollicular plugging, scales, telangiectasia, and atrophy.The incidence rate is 0.4% to 0.5%.More common in females, especially in their 40s.Patients with DLE often are divided into 2 subsets: localized and widespreadLocalized DLE occurs when the head and neck only are affected;Widespread DLEoccurswhen other areas are affected.OMalignantdegenerationofchronic lesions ofLEis possible,leadingto nonmelanomaskincancerUp to 10% ofthe patients may eventually develop varying degrees of systemic involementbut not severe.About 4% to 5% widespread DLE may develop to SLELupus erythematosusAnonscarring and non atrophy-producing photosensitive dermatosis.Serologicabnormalitiesarecommor

教学内容辅助手段时间分配 Connective Tissue Diseases ⚫Basic requirements: ⚫The subtypes of lupus erythematosus , the diagnosis of systemic lupus erythematosus. ⚫ The diagnosis of dermotomyositis and the laboratory tests of lupus erythematosus. ⚫The therapy principles of lupus erythematosus and dermatomyositis. ⚫The term connective tissue disease has evolved from older designations of “ collagenvascular disease” for a group of multisystem diseases that are clinicallly similar in many respects. ⚫lupus erythematosus ⚫Dermatomyositis ⚫Scleroderma ⚫Rheumatoid arthritis ⚫Rheumatic fever ⚫Polyarteritis nodosa Chapter 1 Lupus erythematosus ⚫Definition: Lupus erythematosus ⚫Definition: LE includes a spectrum of clinical forms. ⚫Discoid lupus erythematosus (DLE) ⚫Subcute cutaneous lupus erythematosus (SCLE) ⚫Systemic lupus erythematosus (SLE) Etiology-Heredity: Etiology-Sex Hormone: Etiology-Invironment: Lupus erythematosus ❖Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of SLE. ❖The loss of immune tolerance, increased antigenic load, excess T cell help, defective B cell suppression, and the shifting of T helper 1(Th1) to Th2 immune responses leads to B cell hyperactivity and the production of pathogenic autoantibodies. The central immunological disturbance in patients with LE is autoantibody production. Antinuclear antibody (ANA) and approximately 20 kinds of autoantibodies can be tested in LE. In DLE, only the skin is involved. The skin rash in discold lupus is often found on the face and scalp. It usually is red and may have raised borders. It characterized by sharply circumscribed macules and plaques displaying erythema, follicular plugging, scales, telangiectasia, and atrophy. ❖The incidence rate is 0.4% to 0.5%. ❖More common in females, especially in their 40s. ❖Patients with DLE often are divided into 2 subsets: localized and widespread Localized DLE occurs when the head and neck only are affected; Widespread DLE occurs when other areas are affected. ⚫Malignant degeneration of chronic lesions of LE is possible, leading to nonmelanoma skin cancer. ⚫Up to 10% of the patients may eventually develop varying degrees of systemic involement, but not severe. ⚫About 4% to 5% widespread DLE may develop to SLE. Lupus erythematosus ⚫A nonscarring and non atrophy-producing photosensitive dermatosis. ⚫Serologic abnormalities are common. 5 分钟图示

Male-to-femaleratio:1:4OPatients aged 15-70 years. The mean age is 43 years.oSLE is a chronic inflammatory autoimmune disorder which may affect many organsystems图示The disease may be mild or severe and life-threatening.About 90% patients have eruptions: a butterfly-shaped erythema that spreads across theface. The "wings" of the butterfly appear across the cheekbones, and the "body" appearsacross the bridge of the noseSLE patients tend tobe very easily sunburned (40%)(photosensitive).Occur in approximately 90% of patients and exist for years before other manifestationsappearRanging from intermittent arthralgias to acute polyarthritis.In long-standing disease, capsular insertional erosions at the metacarpophalangeal jointswith marked secondary joint deformity may occur without X-ray evidence of obviousmarginal erosions.May be benign and asymptomatic or relentlessly progressive and fatalOMost common manifestation is proteinuria, which occur in approximately 75% patientsSomemay developto uraemiaThe histopathology ofthe renal lesion varies from afocal, usually benign glomerulitis toadiffusemembranoproliferativeglomerulonephritis.Lupus erythematosus70% patients have cardiovascular involvement.Pericarditis isoftenpresent.More serious rare complications are coronary artery vasculitis orfibrosing myocarditis.Lupus erythematosusRecurrent pleurisy is commonLupus pneumonitis,pulmonaryhemorrhage may rarely occur.Lupus erythematosuscNs involvement can causeheadaches,personalitychanges,stroke,epilepsy,psychoses,and organic brain syndrome.The patients may also have nausea, vomit, bellyache, diarrhea, hemolysis anemiadiminishofleucocyte and/orplatelet.Lupus erythematosusextremefatiguejoint/musclepaineye problemsdepression20分钟mouth ulcersfacial or other rashes+miscarriagehair lossanaemiafeverpossible involvement ofthe kidneys, heart, lungs & brain+Kidneys: Painless hematuria or proteinuriaHeart:myocarditis and endocarditis+Lungs: pleuritisNeurologic symptoms: headaches, dizziness, memory disturbances, vision problemsseizures, stroke, or changes in behaviorBlood vessels: Blood vessels may become inflamed (vasculitis).Currently there is no single test that can definitely say whether a person has lupus or notOnlyby comprehensiveexamination and consideration of symptoms and their history can adiagnosis be achieved.Full Blood Count-Detects anaemia, low platelets, low white blood cells

⚫Male-to-female ratio: 1:4 ⚫Patients aged 15-70 years. The mean age is 43 years. ⚫SLE is a chronic inflammatory autoimmune disorder which may affect many organ systems. ⚫The disease may be mild or severe and life-threatening. ⚫About 90% patients have eruptions: a butterfly-shaped erythema that spreads across the face. The "wings" of the butterfly appear across the cheekbones, and the "body" appears across the bridge of the nose. ⚫SLE patients tend to be very easily sunburned (40%)(photosensitive). ⚫Occur in approximately 90% of patients and exist for years before other manifestations appear. ⚫Ranging from intermittent arthralgias to acute polyarthritis . ⚫In long-standing disease, capsular insertional erosions at the metacarpophalangeal joints with marked secondary joint deformity may occur without X-ray evidence of obvious marginal erosions. ⚫May be benign and asymptomatic or relentlessly progressive and fatal. ⚫Most common manifestation is proteinuria, which occur in approximately 75% patients. Some may develop to uraemia. ⚫The histopathology of the renal lesion varies from a focal, usually benign glomerulitis to a diffuse membranoproliferative glomerulonephritis. Lupus erythematosus ⚫70% patients have cardiovascular involvement. ⚫Pericarditis is often present. ⚫More serious rare complications are coronary artery vasculitis or fibrosing myocarditis. Lupus erythematosus ⚫Recurrent pleurisy is common. ⚫Lupus pneumonitis , pulmonary hemorrhage may rarely occur. Lupus erythematosus ⚫CNS involvement can cause headaches, personality changes, stroke, epilepsy, psychoses, and organic brain syndrome. ⚫The patients may also have nausea, vomit, bellyache, diarrhea, hemolysis anemia, diminish of leucocyte and/or platelet. Lupus erythematosus ❖extreme fatigue joint/muscle pain ❖eye problems depression ❖mouth ulcers facial or other rashes ❖miscarriage hair loss ❖anaemia fever ❖possible involvement of the kidneys, heart, lungs & brain ❖Kidneys: Painless hematuria or proteinuria ❖Heart: myocarditis and endocarditis ❖Lungs: pleuritis ❖Neurologic symptoms: headaches, dizziness, memory disturbances, vision problems, seizures, stroke, or changes in behavior . ❖Blood vessels: Blood vessels may become inflamed (vasculitis). Currently there is no single test that can definitely say whether a person has lupus or not. Only by comprehensive examination and consideration of symptoms and their history can a diagnosis be achieved. Full Blood Count - Detects anaemia, low platelets, low white blood cells 图示 20 分钟

oCreatinine and electrolytes -Measures the salts in the blood and gives an idea of kidneyfunctionoLiver function tests - Includes measurement of liver enzymes (indicator of liver celldamage). Measures albumin (marker of kidney problem with leakage of the proteins)oESR(ErythrocyteSedimentationRate)-Amarkerofnon-specific inflammation,tendstobe raised in lupusoUrine-Measureprotein and blood cells in urine(shouldbe none).Identifycasts(blobsofproteinescapedfromthebloodstreambecausethekidneysareleaky)eComplement-C3,C4ANA test -It is the mainstay in diagnosis of SLE. This test has high sensitivity but poorspecificity. High titers are seen in 95% of active flares and in drug-induced lupus.dsDNA-antibodies todouble-stranded DNA(anti-dsDNA).Specific,not very sensitiveIndicateshighriskofrenal diseaseAnti-SMantibody-Sensitivity only 20%to30%but has highest specificity of any test forSLEfixed red rash over the cheeksMalar erythemaoDiscoldLEred patches of skin associated with scalingoPhotosensitivityrash after exposure to sunlightoOralulcerulcers in the nose or mouth, usually painlessoNonerosive arthritisinvolvingtwoormoreperipheral jointsoSerositisPleuritis or pericarditisNephropathyusually detected by routine blood and urine analysis , may observedalbuinuria or cellar casts.oCNS disorderunexplained serzures or psychosis·Haematological disorderhaemolytic anaemia,leukopenia,thrombocytopeniaImmunologicdisorderanti-DNAand anti-SMantibodiesAnti-NuclearAntibodyPositivetestfor antinuclear antibodies(ANA)in theabsenceof drugs known to induce it.Atpuberty+during the menopauseafter childbirthafter viral infection+through sunlightas a result of traumaafter a prolonged course of medication30分钟Earlytreatment isadvisable,beforeatrophybecomespermanent.Exposure to sunlight or ultraviolet light should be minimized. Sunscreen should be appliedwhenever the patient goes outsideRegular medical evaluation is important to monitor SLE.Drug treatment must beindividualized for each patient, depending on the particular problems and their severity.Treat constitutional symptoms of fatigue, musculo-skeletal pain, and serositis.Response is variable,and no one particular NSAID has proved to be better than another.Adverse effects include reversible gastrointestinal and renal impairment, confusion, anddizziness.Hydroxychloroquine was originally used totreat malaria and later found to be useful inrheumatoid arthritis.It alleviates cutaneous,musculoskeletal,and constitutional symptomsImprovementoccursovera matter of days toweeks.Side effects include gastrointestinal symptoms, pigment changes, and retinal damage. Ifacuteneurologic symptomsdevelop,themedication should bewithdrawn.Topical preparations are used for rashes, intralesional injectionsfor discoid rash,low oraldosesformildsymptoms,andhighoral or intravenousdosesforseveresymptoms.The type of steroid used is less important than the dose. High doses should not be givenformorethanamonthLocal:potent or superpotent topical corticosteroids is beneficial.Systemic:The safest and most beneficial systemic therapy antimalarialsAntimalarias: Hydroxychloroquine (particularly when joint and skin manifestations areprominent)+Corticosteroids: severe diseaseStarting oral prednisone dosages are lmg/kg daily.Thedosage is usually determined by decreasing it 10% at intervals.In CNs lupus or other ctitical

⚫Creatinine and electrolytes - Measures the salts in the blood and gives an idea of kidney function ⚫Liver function tests - Includes measurement of liver enzymes (indicator of liver cell damage). Measures albumin (marker of kidney problem with leakage of the proteins) ⚫ESR (Erythrocyte Sedimentation Rate) - A marker of non-specific inflammation, tends to be raised in lupus ⚫Urine - Measure protein and blood cells in urine (should be none). Identify ‘casts’ (blobs of protein escaped from the bloodstream because the kidneys are leaky) ⚫Complement-C3,C4↓ ANA test –It is the mainstay in diagnosis of SLE. This test has high sensitivity but poor specificity. High titers are seen in 95% of active flares and in drug-induced lupus. ❖ dsDNA - antibodies to double-stranded DNA (anti-dsDNA). Specific, not very sensitive. Indicates high risk of renal disease. ❖Anti-SM antibody-Sensitivity only 20% to 30% but has highest specificity of any test for SLE. Malar erythema fixed red rash over the cheeks ⚫Discold LE red patches of skin associated with scaling ⚫Photosensitivity rash after exposure to sunlight ⚫Oral ulcer ulcers in the nose or mouth, usually painless ⚫Nonerosive arthritis involving two or more peripheral joints ⚫Serositis Pleuritis or pericarditis ⚫Nephropathy usually detected by routine blood and urine analysis , may observed albuinuria or cellar casts. ⚫CNS disorder unexplained serzures or psychosis ⚫ Haematological disorder haemolytic anaemia, leukopenia, thrombocytopenia ⚫Immunologic disorder anti-DNA and anti-SM antibodies ⚫Anti-Nuclear Antibody Positive test for antinuclear antibodies (ANA) in the absence of drugs known to induce it. At puberty ❖during the menopause ❖after childbirth ❖after viral infection ❖through sunlight ❖as a result of trauma ❖after a prolonged course of medication Early treatment is advisable, before atrophy becomes permanent. ⚫Exposure to sunlight or ultraviolet light should be minimized. Sunscreen should be applied whenever the patient goes outside. ⚫Regular medical evaluation is important to monitor SLE. Drug treatment must be individualized for each patient, depending on the particular problems and their severity. ❖Treat constitutional symptoms of fatigue, musculo-skeletal pain, and serositis. ❖Response is variable, and no one particular NSAID has proved to be better than another. ❖Adverse effects include reversible gastrointestinal and renal impairment, confusion, and dizziness. Hydroxychloroquine was originally used to treat malaria and later found to be useful in rheumatoid arthritis. It alleviates cutaneous, musculoskeletal, and constitutional symptoms. Improvement occurs over a matter of days to weeks. ❖Side effects include gastrointestinal symptoms, pigment changes, and retinal damage. If acute neurologic symptoms develop, the medication should be withdrawn. ❖Topical preparations are used for rashes, intralesional injections for discoid rash, low oral doses for mild symptoms, and high oral or intravenous doses for severe symptoms. ❖ The type of steroid used is less important than the dose. High doses should not be given for more than a month. ❖Local: potent or superpotent topical corticosteroids is beneficial. ❖Systemic: The safest and most beneficial systemic therapy antimalarials ❖Antimalarias: Hydroxychloroquine (particularly when joint and skin manifestations are prominent) ❖Corticosteroids: severe disease . Starting oral prednisone dosages are 1mg/kg daily. The dosage is usually determined by decreasing it 10% at intervals. In CNS lupus or other ctitical 30 分钟

crises,methylprednisolone1.Ogby slow(1hour)intraveneouslyinfusion on3successivedays often is the initial form,together with IV cyclophosphamideImmunosuppressive therapy: recommended in active, serious CNS lupus or activereversiblelupusnephritisCyclophosphamide or Methotrexate in doses up to2.5mg/kg daily is often used forrenalSLE+OthertreatmentsTraditional Chinese Medicine,high-doseVgammaglobulinForty years ago, most people withSLE survived less than 5 years. Changes in diagnosisandtreatmenthaveimproved survival tothepointwheremorethan90%ofpatientsnowsurviveformorethan10 years.Most livearelatively asymptomatic lifeThe most common cause of death is infection resulting from the immunosuppressive sideeffects of medications used totreat the diseaseRenal and neurologic manifestations causethegreatest morbidityand areassociated witha worse prognosis than other manifestations.Life-threatening complications aremost common in the first 5 yearsofmanifestations.+Symptomsthatbeginafterage60tend torunamorebenigncourse.DMis an autoimmunesystemic connective tissue diseases,characterized by noninfectiousacute, subacute or chronic inflammatory and degeneration changes in the muscles(polymyositis) and frequently in the skin (dermatomyositis)40分钟Occur most commonly from age 40 to 60 or, in children, from age 5 to 16.Omale-female ratio:1:2DermatomyositisMyositis includes 6 subsets:dematomyositis(DM)polymyositis (PM)PM/DM associated with malignacy@childhoodPM/DMOPM/DM overlapping with another connective tissue disorderAmyopathicdematomyositis(ADM)图示Thecauseof DM is unknown.Factorsthathavebeen implicated arelisted below:Heredity:a genetic predisposition may exist. PM/DM was considered to be a geneticallydetermined aberrantimmuneresponseto an infectious agentbecause a greater than expectedfrequency of HLA-DR3 has been observed.The true diseases-susceptibility gene might beassociated with the HLA-DR3 region by linkage disequilirium.Infectious agents, including viruses, particularly coxsackievirus, echovirus, human T-lymphotropicvirus 1(HTLV-1),and Toxoplasma species,have been suggested aspossibletriggers of the disease.Picornavirus-like structures have been found in muscle cells, and tubular inclusions similarto those seen in some viral infections have been identified by electron microscopy inmyocytes and endothelial cells of vessels in the skin and muscle.An associated malignacy occurs in about 20% of DM/PM.A tumor may incite myositis as the result of an autoimmue reaction directed against acommonantigeninmuscleandtumor.ODeposits of IgM, IgG, and the third component of complement have been found in theblood vessel walls of skeletal muscle, particularly in childhood DM.Patients have circulating autoantibodies: PM-1, Jo-1.Abnormal T-cell activity may be involved in the pathogenesis of both the skin disease andthe muscle disease.Cutaneous eruptionGottron papules are found over bony prominences, particularly the metacarpophalangeal5分钟Nailjoints,theproximal interphalangeal joints, and /or the distal interphalangeal joints.fold changes consist of periungual telangiectases and/or a characteristic cuticular changewithhypertrophyof the cuticleand small, hemorrhagic infarcts in thishypertrophic area.Several other cutaneousfeaturesare characteristic ofthedisease:Malar erythemapoikiloderma inaphotosensive distributionviolaceous erythema on the extensor surfacesperiungual and cuticular changes

crises, methylprednisolone 1.0g by slow (1 hour) intraveneously infusion on 3 successive days often is the initial form ,together with Ⅳ cyclophosphamide. ❖Immunosuppressive therapy: recommended in active, serious CNS lupus or active reversible lupus nephritis. Cyclophosphamide or Methotrexate in doses up to 2.5mg/kg daily is often used for renal SLE. ❖Other treatments Traditional Chinese Medicine, high-dose IV gamma globulin ❖Forty years ago, most people with SLE survived less than 5 years. Changes in diagnosis and treatment have improved survival to the point where more than 90% of patients now survive for more than 10 years. Most live a relatively asymptomatic life. The most common cause of death is infection resulting from the immunosuppressive side effects of medications used to treat the disease. ❖ Renal and neurologic manifestations cause the greatest morbidity and are associated with a worse prognosis than other manifestations. ❖Life-threatening complications are most common in the first 5 years of manifestations. ❖Symptoms that begin after age 60 tend to run a more benign course. DM is an autoimmune systemic connective tissue diseases, characterized by noninfectious acute, subacute or chronic inflammatory and degeneration changes in the muscles (polymyositis) and frequently in the skin (dermatomyositis). ⚫Occur most commonly from age 40 to 60 or, in children, from age 5 to 16. ⚫male-female ratio: 1:2 Dermatomyositis Myositis includes 6 subsets: ●dematomyositis (DM) ●polymyositis (PM) ● PM/DM associated with malignacy ● childhood PM/DM ●PM/DM overlapping with another connective tissue disorder ●Amyopathic dematomyositis (ADM) The cause of DM is unknown. Factors that have been implicated are listed below: ⚫Heredity: a genetic predisposition may exist. PM/DM was considered to be a genetically determined aberrant immune response to an infectious agent because a greater than expected frequency of HLA-DR3 has been observed. The true diseases-susceptibility gene might be associated with the HLA-DR3 region by linkage disequilirium. ⚫Infectious agents, including viruses, particularly coxsackievirus, echovirus, human Tlymphotropic virus 1(HTLV-1), and Toxoplasma species, have been suggested as possible triggers of the disease. ⚫Picornavirus-like structures have been found in muscle cells, and tubular inclusions similar to those seen in some viral infections have been identified by electron microscopy in myocytes and endothelial cells of vessels in the skin and muscle. ⚫An associated malignacy occurs in about 20% of DM/PM. ⚫A tumor may incite myositis as the result of an autoimmue reaction directed against a common antigen in muscle and tumor. ⚫Deposits of IgM, IgG, and the third component of complement have been found in the blood vessel walls of skeletal muscle, particularly in childhood DM. ⚫Patients have circulating autoantibodies: PM-1, Jo-1. ⚫Abnormal T-cell activity may be involved in the pathogenesis of both the skin disease and the muscle disease. ⚫Cutaneous eruption: Gottron papules are found over bony prominences, particularly the metacarpophalangeal joints, the proximal interphalangeal joints, and /or the distal interphalangeal joints. Nail fold changes consist of periungual telangiectases and/or a characteristic cuticular change with hypertrophy of the cuticle and small, hemorrhagic infarcts in this hypertrophic area. ⚫Several other cutaneous features are characteristic of the disease: ⚫Malar erythema ⚫poikiloderma in a photosensive distribution ⚫violaceous erythema on the extensor surfaces ⚫periungual and cuticular changes. 40 分钟图示 5 分钟