Grand Round Grand Round

主講者主講者 : : 李振威李振威

96-10-0996-10-09

Mixed Connective Tissue Mixed Connective Tissue DiseaseDisease

1.The central premise of MCTD is that of an1.The central premise of MCTD is that of an overlap syndrome embracing features ofoverlap syndrome embracing features of SLE. Scl and PM/DM.SLE. Scl and PM/DM.2.Firstly described by Sharp and his collea-2.Firstly described by Sharp and his collea- -gues in a 1972 papper report.-gues in a 1972 papper report.3.This was the first overlap syndrome defin3.This was the first overlap syndrome defin ed in terms of a specific Ab.ed in terms of a specific Ab.

Serological FeaturesSerological Features

1.The basic premise of MCTD is that the pre1.The basic premise of MCTD is that the pre sence of high titer anti-U1 RNP.sence of high titer anti-U1 RNP.2.The first clue to diagnosing MCTD is usua2.The first clue to diagnosing MCTD is usua lly a positive ANA with a high titer specklelly a positive ANA with a high titer speckle pattern.pattern.3.The titer is often greater than 1:1000 and 3.The titer is often greater than 1:1000 and sometimes greater than 1:10000sometimes greater than 1:10000

• 4.The finding should prompt the measure4.The finding should prompt the measure• ment of Ab to U1 RNP,Sm,Ro and La.ment of Ab to U1 RNP,Sm,Ro and La.• 5.Ab.to ds-DNA,Sm and Ro. Are occasion-5.Ab.to ds-DNA,Sm and Ro. Are occasion-• -ally seen as a transient phenomenon in-ally seen as a transient phenomenon in• patient with MCTD.patient with MCTD.• 6.68 Kd U1 RNP specific polypeptide was6.68 Kd U1 RNP specific polypeptide was• identified as the disease-defining targetidentified as the disease-defining target• Ab. Of MCTDAb. Of MCTD

Clinical FeaturesClinical Features

• 1.The central premise of MCTD IS THAT1.The central premise of MCTD IS THAT• of an overlap syndrome embracing feaof an overlap syndrome embracing fea• -tures of SLE,Scl and PM/DM.-tures of SLE,Scl and PM/DM.• 2.These overlap features seldom occur 2.These overlap features seldom occur • concurrently.concurrently.• 3.The symptom of early phase are hand3.The symptom of early phase are hand• edema,arthritis,Raynaud’s phenomenonedema,arthritis,Raynaud’s phenomenon• and inflammatory muscle disease.and inflammatory muscle disease.

Diagnostic CriteriaDiagnostic Criteria

• 1.Alarco’n-Segovia’s Criteria:1.Alarco’n-Segovia’s Criteria:• -A: serological criteria:-A: serological criteria:• -Anti-RNP at hemagglutination-Anti-RNP at hemagglutination• -B: clinical criteria-B: clinical criteria• -swollen hand,synovitis,myositis-swollen hand,synovitis,myositis• raynaud’s phenomenon.acrosclerosraynaud’s phenomenon.acroscleros

isis

Kahn’s CriteriaKahn’s Criteria

• A :serological criteriaA :serological criteria• -high titer anti-RNP-high titer anti-RNP• B: clinical criteriaB: clinical criteria• swollen fingersswollen fingers• synovitissynovitis• myositismyositis• Raynaud’s phenomenonRaynaud’s phenomenon

General Features and General Features and EpidemiologyEpidemiology

• 1.Prevalence: 2.7%1.Prevalence: 2.7%

• 2.female-to-male ratio:16:12.female-to-male ratio:16:1

• 3.age at onset:20-30 years old3.age at onset:20-30 years old

Early SymptomsEarly Symptoms

• 1.In the early stage, most pt to develop1.In the early stage, most pt to develop• MCTD cant be differentiated from theMCTD cant be differentiated from the• other classic DCTD.other classic DCTD.• 2.Early in the course of the disease most2.Early in the course of the disease most• pt. complain of easy fatigability,poorlypt. complain of easy fatigability,poorly• defined myalgia,arthralgia and Raynauddefined myalgia,arthralgia and Raynaud• phenomenon.phenomenon.

• 3.If such a pt. is found to have swollen3.If such a pt. is found to have swollen• hands,puffy fingers,or both in associationhands,puffy fingers,or both in association• with a high titer,speckle ANA, they shou-with a high titer,speckle ANA, they shou-• -ld be carefully followed for the evolution-ld be carefully followed for the evolution• of overlap features.of overlap features.• 4.A high-titer of anti-RNP Ab. In a pt with4.A high-titer of anti-RNP Ab. In a pt with• UCTD is a powerful predictor for MCTD.UCTD is a powerful predictor for MCTD.

FEVERFEVER

• 1.Fever may be a prominent feature of 1.Fever may be a prominent feature of • MCTD in the absence of an obvious cau-MCTD in the absence of an obvious cau-• -se.-se.• 2.F.U.O has been the initial presentation2.F.U.O has been the initial presentation• of MCTD.of MCTD.• 3.Fever in MCTD can usually be traced to3.Fever in MCTD can usually be traced to• a coexistent myositis,aseptic meningitisa coexistent myositis,aseptic meningitis• serositis,lymphadenopathy,or intercurrent inf.serositis,lymphadenopathy,or intercurrent inf.

JOINTSJOINTS

• 1.Joint pain and stiffness is an early symp1.Joint pain and stiffness is an early symp• tom in nearly all patients who developtom in nearly all patients who develop• MCTD syndrome.MCTD syndrome.• 2.Joint involvement in MCTD is more com-2.Joint involvement in MCTD is more com-• -mon and more severe than in classic SLE-mon and more severe than in classic SLE• 3.About 60% pt eventually develop an3.About 60% pt eventually develop an• obvious arthritis.obvious arthritis.

• 4.Radiograph usually show a 4.Radiograph usually show a characteristiccharacteristic

• absence of severe erosive changeabsence of severe erosive change

• 5.Small marginal erosion,often with a 5.Small marginal erosion,often with a

• well-demarcated edge,are the most well-demarcated edge,are the most

• characteristic radiological feature in ptcharacteristic radiological feature in pt

• with severe joint disease.with severe joint disease.

• 6.A positive RF is found in 50-70% of pt6.A positive RF is found in 50-70% of pt• with MCTD,indeed,pt may be diagnosedwith MCTD,indeed,pt may be diagnosed• as having RA and fulfill ACR criteria foras having RA and fulfill ACR criteria for• RA.RA.• 7.Joint histology in MCTD reveal a hyperp7.Joint histology in MCTD reveal a hyperp• lastic synovium with surface fibrinoid nelastic synovium with surface fibrinoid ne• -crosis,increased vascularity,interstitial-crosis,increased vascularity,interstitial• edema and infiltration of macrophage,lymphedema and infiltration of macrophage,lymph

oo• cyte,neutrophil and multinuclear giant cell.cyte,neutrophil and multinuclear giant cell.

Skin and Mucous MembraneSkin and Mucous Membraness• 1.Raynaud phenomenon is the most com-1.Raynaud phenomenon is the most com-• -mon problem and one of the earliest-mon problem and one of the earliest• manifestation of MCTD.manifestation of MCTD.• 2.In some pts ,skin change commonly ass2.In some pts ,skin change commonly ass• -ociated with SLE are prominent finding-ociated with SLE are prominent finding• particularly malar rash and discoid rash.particularly malar rash and discoid rash.

• 3.Mucous membrane lesions have includ3.Mucous membrane lesions have includeded

• buccal ulceration,livedo vasculitis,siccabuccal ulceration,livedo vasculitis,sicca• syndrome,oralgenital ulceration and syndrome,oralgenital ulceration and • nasal septal perforation.nasal septal perforation.

MUSCLEMUSCLE

• 1.Sometimes an inflammatory myositis1.Sometimes an inflammatory myositis• is seen in patient with anti-U1RNP whois seen in patient with anti-U1RNP who• do not have the feature of MCTD.do not have the feature of MCTD.• 2.The inflammatory myopathy associate2.The inflammatory myopathy associate

dd• with MCTD is identical clinically and his-with MCTD is identical clinically and his-• -tologically to classical PM.-tologically to classical PM.

HEARTHEART

• 1.All three layers of the heart may be1.All three layers of the heart may be• involved in MCTD.involved in MCTD.• 2.20% of MCTD pt EKG abnormal.2.20% of MCTD pt EKG abnormal.• 3.The most common EKG findings are RV3.The most common EKG findings are RV

HH• ,RAE and interventricular conduction,RAE and interventricular conduction• defect.defect.

• 4.Pericarditis is the most common clinic4.Pericarditis is the most common clinicalal

• finding of cardiac involvement.finding of cardiac involvement.• 5.Early detection of pul. Hypertension is5.Early detection of pul. Hypertension is• important for initiating early therapy.important for initiating early therapy.

LUNGLUNG

• 1.Pleuropulmonary involvement in 25%1.Pleuropulmonary involvement in 25%• of patient.of patient.• 2.Symptoms were dyspnea,chest pain and2.Symptoms were dyspnea,chest pain and• cough.cough.• 3.CXR showed interstial change,pleural3.CXR showed interstial change,pleural• effusion,pneumonic infiltration and pleu-effusion,pneumonic infiltration and pleu-• -ral thickening-ral thickening

• 4.The most discriminatory lung function4.The most discriminatory lung function• test is DLCO.test is DLCO.• 5.High-resolution CT is the most sensitive5.High-resolution CT is the most sensitive• test to determine the presence of inter-test to determine the presence of inter-• -stitial lung disease in MCTD.-stitial lung disease in MCTD.• 6.The major cause of death in MCTD is6.The major cause of death in MCTD is• pul. H/Tpul. H/T

• 7.Intimal hyperplasia and smooth muscl7.Intimal hyperplasia and smooth musclee

• hypertrophy without accompanyinghypertrophy without accompanying• inflammation are the characteristic fea-inflammation are the characteristic fea-• -ture of vasculopathy in MCTD.-ture of vasculopathy in MCTD.

KIDNEYKIDNEY

• 1.Renal involvement occurred in 25% 1.Renal involvement occurred in 25% • MCTD pt.MCTD pt.• 2.High titer of anti-U1RNP Ab are relative2.High titer of anti-U1RNP Ab are relative• -ly protective against the development-ly protective against the development• diffuse proliferative GN.diffuse proliferative GN.• 3.When pt do develop renal change,they3.When pt do develop renal change,they• usually develop membranous GNusually develop membranous GN

GASTROINTESTINALGASTROINTESTINAL

• 1.A major feature of MCTD, occurring in1.A major feature of MCTD, occurring in• 60-80 % of pt.60-80 % of pt.• 2.The most common abdominal problem2.The most common abdominal problem• in MCTD is disordered mortility in thein MCTD is disordered mortility in the• upper GI tract.upper GI tract.• 3.Abdominal pain in MCTD may result fro3.Abdominal pain in MCTD may result fro

m bowel hypomotility,serositis,m bowel hypomotility,serositis,

• Mesenteric vasculitis,colonic perforationMesenteric vasculitis,colonic perforation• and pancreatitis.and pancreatitis.• 4.Malabsorption syndrome can occur se4.Malabsorption syndrome can occur se

cc• ondary to small bowel dilatation and baondary to small bowel dilatation and ba

cc• teric overgrowth.teric overgrowth.

Central Nervous SystemCentral Nervous System

• 1.There is general agreement that the1.There is general agreement that the• most common problem is a trigeminalmost common problem is a trigeminal• neuropathy.neuropathy.• 2.Headache is a relative common symp2.Headache is a relative common symp• -tom in MCTD, in the majority of pt they-tom in MCTD, in the majority of pt they• are probably vascular in origin with cla-are probably vascular in origin with cla-• -ssical migrain.-ssical migrain.

Blood VesselBlood Vessel

• 1.A bland ,intimal proliferation and medial1.A bland ,intimal proliferation and medial• hypertrophy affecting medium and smallhypertrophy affecting medium and small• vessels is the characteristic vascular les-vessels is the characteristic vascular les-• -ion of MCTD.-ion of MCTD.• 2.When the condition is widespread in the2.When the condition is widespread in the• lung and kidney,there is association withlung and kidney,there is association with• pul. H/T and renal crisis.pul. H/T and renal crisis.

• 3.An angiographic study reported a high3.An angiographic study reported a high• prevelence of medium-size vessel occl-prevelence of medium-size vessel occl-• -usion.-usion.• 4.Fingernail capillaroscopy showed bus4.Fingernail capillaroscopy showed bus

hyhy• like lesion(capillary dilatation and drop like lesion(capillary dilatation and drop

out)out)

• 5.Anti-endothelial cell Ab. Have been rep-5.Anti-endothelial cell Ab. Have been rep-• -orted in 45% pt,the condition correlate-orted in 45% pt,the condition correlate• with pul. Change and spontaneous abor-with pul. Change and spontaneous abor-• -tion.-tion.• 6.Anti-U1 RNP AB. May have a pathologic6.Anti-U1 RNP AB. May have a pathologic• role in the small-vessel pathologyrole in the small-vessel pathology

BLOODBLOOD

1.Anemia of chronic disease is found in 751.Anemia of chronic disease is found in 75%%

• of pt.of pt.• 2.RF. Positive in 50% of patient,the con-2.RF. Positive in 50% of patient,the con-• -dition is associated with severe arthriti-dition is associated with severe arthriti

s.s.

PrognosisPrognosis

• 1.Pt with high-titer U1RNP Ab. Have a lo1.Pt with high-titer U1RNP Ab. Have a loww

• prevalence of serious renal disease and prevalence of serious renal disease and • life-threatening neurological problem.life-threatening neurological problem.• 2.Pul. H/T sometime follow a rapid acce-2.Pul. H/T sometime follow a rapid acce-• -lerated course, which lead death in a -lerated course, which lead death in a • few weeks.few weeks.

• 3. 5 years survival rate was 90.5%3. 5 years survival rate was 90.5%• 10 years survival rate was 82.1%10 years survival rate was 82.1%• 4.Pt with predominent Scl-PM overlap w4.Pt with predominent Scl-PM overlap w

ithith• a worse prognosis. With a 33% 10 yearsa worse prognosis. With a 33% 10 years• survival rate.survival rate.

ManagementManagement

1.There is no cure for MCTD.1.There is no cure for MCTD.2.Pul. H/T is the main cause of death.2.Pul. H/T is the main cause of death.3.Recommendation for management are3.Recommendation for management are base on conventional treatment for SLEbase on conventional treatment for SLE PM,DM,RA and Scl.PM,DM,RA and Scl.