systemic diseases of connective tissue m.valešová

Systemic Diseases of Systemic Diseases of Connective Tissue Connective Tissue

M.ValešováM.Valešová

Systemic Diseases of Connective Systemic Diseases of Connective TissueTissue

• The term „connective tissue diseases“ The term „connective tissue diseases“ describe a group of conditions characterised describe a group of conditions characterised by the occurrence of:by the occurrence of:

• vasculitisvasculitis

• multisystem involvementmultisystem involvement

• arthritis or artralgiaarthritis or artralgia

• abnormal immunological featuresabnormal immunological features

• (autoantibodies, immune complexes (autoantibodies, immune complexes depositiondeposition))


• Systemic lupus erythematosus (SLE)Systemic lupus erythematosus (SLE)

• Rheumatoid arthritisRheumatoid arthritis

• SjSjőőgren´s syndromagren´s syndroma

• Systemic sclerosisSystemic sclerosis

• Dermatomyositis, MyositisDermatomyositis, Myositis

• VasculitisVasculitis


The aetiology is unknownThe aetiology is unknown

• Environmetal factorsEnvironmetal factors

- exposure to sunlight- exposure to sunlight

- viral infections- viral infections

- drugs - lupus-like syndroma- drugs - lupus-like syndroma

(hydrallazine, isoniazid, (hydrallazine, isoniazid, contraceptives)contraceptives)

• Genetics-markers DR2 and DR3Genetics-markers DR2 and DR3

Systemic Diseases of Systemic Diseases of Connective TissueConnective TissueConnective tissue iscomposed essentially Connective tissue iscomposed essentially

of collagen,elastic fibres and fibroblasts of collagen,elastic fibres and fibroblasts in anamorphous ground substancein anamorphous ground substance

Common features of this diseases:Common features of this diseases:

• Vascular pathology and fibrinoid Vascular pathology and fibrinoid changes in the ground substancechanges in the ground substance

• Many clinical features in common, Many clinical features in common, difficulty to make a diagnosisdifficulty to make a diagnosis

Systemic Diseases of Systemic Diseases of Connective TissueConnective Tissue

• Deposition of immune complex in Deposition of immune complex in tissue results in:tissue results in:

- glomerulonefritisglomerulonefritis- in glomerular - in glomerular basementbasement

membranemembrane

- vasculitisvasculitis – in blood vessels – in blood vessels

- arthritisarthritis – in joint synovium – in joint synovium

Systemic Diseases of Systemic Diseases of Connective TissueConnective TissueComplement activation results in:Complement activation results in:

• Depresion of circulating complementDepresion of circulating complement

• Activation of coagulation system and Activation of coagulation system and depression of circulating plateled levelsdepression of circulating plateled levels

• Chemotaxis of PMN(polymorphonuclear Chemotaxis of PMN(polymorphonuclear leukocytese)leukocytese)

• Release of vasoactive Release of vasoactive substances(histaminesubstances(histamine))

• CytolysisCytolysis

Systemic lupus erythematosus Systemic lupus erythematosus (SLE)(SLE)

SLE SLE is a complex multi-system autoimmune diseaseis a complex multi-system autoimmune disease

Involved organs:Involved organs:

• SkinSkin

• HeartHeart

• VesselsVessels

• KidneyKidney

• CNSCNS


• The primary pathology is that of The primary pathology is that of multisystem inflammatory process, multisystem inflammatory process, probably secondary to probably secondary to

antigen-antibody reactionsantigen-antibody reactions

• Hyperactivity of B lymphocytes-Hyperactivity of B lymphocytes-production of antibodies againts nuclear production of antibodies againts nuclear antigens.: ANA, anti-ds DNA, anti-Smantigens.: ANA, anti-ds DNA, anti-Sm

SLE-AetiologySLE-Aetiology

• UnknownUnknown• Aetiological role of enviromental Aetiological role of enviromental

factors,such as -exposure to sunlightfactors,such as -exposure to sunlight• Viral infection (EBV, CMV, retroviruses)Viral infection (EBV, CMV, retroviruses)• Increased concentration of prolactin Increased concentration of prolactin andand

estrogensestrogens• Some drugs produces lupus-like Some drugs produces lupus-like

syndrome (hydrallazin,isoniazid,oral syndrome (hydrallazin,isoniazid,oral contraceptives)contraceptives)

SLE -pathogenesesSLE -pathogeneses

• The primary pathology is that of The primary pathology is that of multisystem inflammatory process multisystem inflammatory process probably secondary to antigen-antibody probably secondary to antigen-antibody reaction,autoimmunityreaction,autoimmunity

• vasculitis and vasculopathyvasculitis and vasculopathy

• Almost all patients possess an antibody Almost all patients possess an antibody against nuclear antigens(ANA)-nonspecific against nuclear antigens(ANA)-nonspecific marker,antibodies anti –dsDNA,antiSm-marker,antibodies anti –dsDNA,antiSm-more specific for SLEmore specific for SLE

Systemic lupus erythematosus Systemic lupus erythematosus (SLE) (SLE) - - clinical findingsclinical findings

The most constant features:The most constant features:

• Fever,Fever,

• Arthritis or arthralgiaArthritis or arthralgia

• Skin rashesSkin rashes

• PolyserositisPolyserositis

Systemic lupus erythematosus Systemic lupus erythematosus (SLE)- clinical findings(SLE)- clinical findings

• Constitutional syptoms-Constitutional syptoms-anorexia,tiredness,fever,weight lossanorexia,tiredness,fever,weight loss

• ManyMany organ systems may be organ systems may be involvedinvolved


Skin involvementSkin involvement

• rash rash – erythematosus lessions– erythematosus lessions

- discoid lessions- discoid lessions

• photosensitivityphotosensitivity

• urticaurtica

• various exanthemasvarious exanthemas

Systemic lupus erythematosus Systemic lupus erythematosus Skin involvementSkin involvement

Systemic lupus erythematosus Systemic lupus erythematosus Skin involvementSkin involvement ( (80%80% patients)patients)

Rash may occur in Rash may occur in sun exposed areassun exposed areas


Heart involvement Heart involvement • Endo,myo,peri carditisEndo,myo,peri carditis

• Pericarditis with efusion- ECHOPericarditis with efusion- ECHO

• Vasculopathy of coronary arterias ( atherosclerosis)Vasculopathy of coronary arterias ( atherosclerosis)


• PleuriPleurisysy ( (effusioneffusion))

• AcuteAcute pneumonitid pneumonitidis is –– vasvascculitiulitis of s of lung lung

vesselsvessels

• Pulmonary infarctsPulmonary infarcts


Central nervous system involvement.Central nervous system involvement.Increasingly important manifestation develops later Increasingly important manifestation develops later

than renal diseasethan renal disease

• SeizuresSeizures

• Focal neurologic signsFocal neurologic signs

• Organic brain syndromeOrganic brain syndrome

• Non organic mental disordersNon organic mental disorders


Renal involvement :Renal involvement :

glomerulonefritisglomerulonefritis• Mesangial typeMesangial type-mesangial deposition of immune -mesangial deposition of immune

complexescomplexes

• Focal proliferativeFocal proliferative type –local thickeningtype –local thickening

• Diffuse proliferative type Diffuse proliferative type

thickening of glomerular basement membrane,thickening of glomerular basement membrane,

masive deposition of immunocomplexes masive deposition of immunocomplexes subepithelialysubepithelialy

• Membranous typeMembranous type


Renal involvementRenal involvement• Proteinurie, miProteinurie, miccrohematurierohematurie

• NefroticNefrotic syndromsyndromaa

• Renal hypertensionRenal hypertension

• Renal insuficiencyRenal insuficiency


Joint involvementJoint involvement

•ArthralgiasArthralgias

•Arthritis- may resemble RAArthritis- may resemble RA

Systemic lupus Systemic lupus erythematosus(SLE)erythematosus(SLE)

Blood involvement

•Hemolytic anemia

•Leukopenia or lymphopenia

•Trombocytopenia

•Lymfadenopthy

•Trombotic tendency


Blood involvement

Trombotic tendency are more marked in patients with positive

•Anticardiolipin antibodies ACLA

•Anti-phospholipid antibodies

•„Lupus anticoagulans“

Systemic lupus Systemic lupus erythematosus(SLE)erythematosus(SLE)Investigations: increased : ESR,CRP immunoglobulinspositivity : ANA ( 90% pts) anti ds- DNA sublclasses of ANA- anti - Ro anti - Sm


Theraphy:

• Mild disease – skin, joints

´ – hydroxychloroqine (Plaquenil)

• Active disease

– systemic steroids

- immunosupressive agents

(Methotrexate, cyclophosphamide

azathioprim,

Systemic Systemic Sclerosis Sclerosis (S(SScSc))

Uncommon idiophatic multisystem disease

Predominantly affects the skin and blood vessels

Female preponderance 3:1

Main pathological feature-progressive fibrosis and atrophy

2 types – diffuse

localised

Typhical autoantibody


• The skin is thickned The skin is thickned and tight and this and tight and this results in contracturesresults in contractures

• Raynaud´s Raynaud´s phenomenon in 95% phenomenon in 95% ptspts

• Organs involvement- Organs involvement- GIT, lung,kidneyGIT, lung,kidney

DDermatomyoermatomyositis andsitis and PolymyoiPolymyoisitssits

SjSjőőgren´s syndromgren´s syndromee

• Dryness of the eyes(sicca syndrome)Dryness of the eyes(sicca syndrome)

• Dryness of the mouth (xerostomia)Dryness of the mouth (xerostomia)

Caused by chronic dysfunction of the Caused by chronic dysfunction of the exocrine glandsexocrine glands

It may occur alone or in assotiation with RA It may occur alone or in assotiation with RA or other connective tissue disordersor other connective tissue disorders

systemic diseases of connective tissue m.valešová

Documents

dr3 slide

valeov slide

antism slide

joint synovium slide

artralgia arthritis

clinical features

blood vessels arthritis

syndroma sj