Systemic Diseases of Connective Tissue M.Valešová

The term „connective tissue diseases“ describe a group of conditions characterised by the occurrence of: The term „connective tissue diseases“ describe a group of conditions characterised by the occurrence of: vasculitis vasculitis multisystem involvement multisystem involvement arthritis or artralgia arthritis or artralgia abnormal immunological features abnormal immunological features (autoantibodies, immune complexes deposition ) (autoantibodies, immune complexes deposition )

Systemic Diseases of Connective Tissue Systemic lupus erythematosus (SLE) Systemic lupus erythematosus (SLE) Rheumatoid arthritis Rheumatoid arthritis Sj ő gren´s syndroma Sj ő gren´s syndroma Systemic sclerosis Systemic sclerosis Dermatomyositis, Myositis Dermatomyositis, Myositis Vasculitis Vasculitis

Systemic Diseases of Connective Tissue The aetiology is unknown Environmetal factors Environmetal factors - exposure to sunlight - exposure to sunlight - viral infections - viral infections - drugs - lupus-like syndroma - drugs - lupus-like syndroma (hydrallazine, isoniazid, contraceptives) (hydrallazine, isoniazid, contraceptives) Genetics-markers DR2 and DR3 Genetics-markers DR2 and DR3

Systemic Diseases of Connective Tissue Connective tissue iscomposed essentially of collagen,elastic fibres and fibroblasts in anamorphous ground substance Common features of this diseases: Vascular pathology and fibrinoid changes in the ground substance Vascular pathology and fibrinoid changes in the ground substance Many clinical features in common, difficulty to make a diagnosis Many clinical features in common, difficulty to make a diagnosis

Systemic Diseases of Connective Tissue Deposition of immune complex in tissue results in: Deposition of immune complex in tissue results in: - glomerulonefritis- in glomerular basement membrane membrane - vasculitis – in blood vessels - arthritis – in joint synovium

Systemic Diseases of Connective Tissue Complement activation results in: Depresion of circulating complement Depresion of circulating complement Activation of coagulation system and depression of circulating plateled levels Activation of coagulation system and depression of circulating plateled levels Chemotaxis of PMN(polymorphonuclear leukocytese) Chemotaxis of PMN(polymorphonuclear leukocytese) Release of vasoactive substances(histamine ) Release of vasoactive substances(histamine ) Cytolysis Cytolysis

Systemic lupus erythematosus (SLE) SLE is a complex multi-system autoimmune disease is a complex multi-system autoimmune disease Involved organs: Skin Skin Heart Heart Vessels Vessels Kidney Kidney CNS CNS

Systemic lupus erythematosus (SLE) The primary pathology is that of multisystem inflammatory process, probably secondary to The primary pathology is that of multisystem inflammatory process, probably secondary to antigen-antibody reactions antigen-antibody reactions Hyperactivity of B lymphocytes- production of antibodies againts nuclear antigens.: ANA, anti-ds DNA, anti-Sm Hyperactivity of B lymphocytes- production of antibodies againts nuclear antigens.: ANA, anti-ds DNA, anti-Sm

SLE-Aetiology Unknown Unknown Aetiological role of enviromental factors,such as -exposure to sunlight Aetiological role of enviromental factors,such as -exposure to sunlight Viral infection (EBV, CMV, retroviruses) Viral infection (EBV, CMV, retroviruses) Increased concentration of prolactin and estrogens Increased concentration of prolactin and estrogens Some drugs produces lupus-like syndrome (hydrallazin,isoniazid,oral contraceptives) Some drugs produces lupus-like syndrome (hydrallazin,isoniazid,oral contraceptives)

SLE -pathogeneses The primary pathology is that of multisystem inflammatory process probably secondary to antigen-antibody reaction,autoimmunity The primary pathology is that of multisystem inflammatory process probably secondary to antigen-antibody reaction,autoimmunity vasculitis and vasculopathy vasculitis and vasculopathy Almost all patients possess an antibody against nuclear antigens(ANA)-nonspecific marker,antibodies anti –dsDNA,antiSm-more specific for SLE Almost all patients possess an antibody against nuclear antigens(ANA)-nonspecific marker,antibodies anti –dsDNA,antiSm-more specific for SLE

Systemic lupus erythematosus (SLE) - clinical findings The most constant features: Fever, Fever, Arthritis or arthralgia Arthritis or arthralgia Skin rashes Skin rashes Polyserositis Polyserositis

Systemic lupus erythematosus (SLE)- clinical findings Constitutional syptoms- anorexia,tiredness,fever,weight loss Constitutional syptoms- anorexia,tiredness,fever,weight loss Many organ systems may be involved Many organ systems may be involved

Systemic lupus erythematosus (SLE) Skin involvement rash – erythematosus lessions rash – erythematosus lessions - discoid lessions - discoid lessions photosensitivity photosensitivity urtica urtica various exanthemas various exanthemas

Systemic lupus erythematosus Skin involvement

Systemic lupus erythematosus Skin involvement Systemic lupus erythematosus Skin involvement

Systemic lupus erythematosus Skin involvement ( 80% patients) Rash may occur in sun exposed areas

Systemic lupus erythematosus (SLE) Heart involvement Endo,myo,peri carditis Endo,myo,peri carditis Pericarditis with efusion- ECHO Pericarditis with efusion- ECHO Vasculopathy of coronary arterias ( atherosclerosis) Vasculopathy of coronary arterias ( atherosclerosis)

Systemic lupus erythematosus (SLE) Pleuri sy ( effusion ) Pleuri sy ( effusion ) Acute pneumonitid is – vas c uliti s of lung Acute pneumonitid is – vas c uliti s of lung vessels vessels Pulmonary infarcts Pulmonary infarcts

Systemic lupus erythematosus (SLE) Central nervous system involvement. Increasingly important manifestation develops later than renal disease Seizures Seizures Focal neurologic signs Focal neurologic signs Organic brain syndrome Organic brain syndrome Non organic mental disorders Non organic mental disorders

Systemic lupus erythematosus (SLE) Renal involvement : glomerulonefritis glomerulonefritis Mesangial type-mesangial deposition of immune complexes Mesangial type-mesangial deposition of immune complexes Focal proliferative type –local thickening Focal proliferative type –local thickening Diffuse proliferative type Diffuse proliferative type thickening of glomerular basement membrane, thickening of glomerular basement membrane, masive deposition of immunocomplexes subepithelialy masive deposition of immunocomplexes subepithelialy Membranous type Membranous type

Systemic lupus erythematosus (SLE) Renal involvement Proteinurie, mi c rohematurie Proteinurie, mi c rohematurie Nefrotic syndrom a Nefrotic syndrom a Renal hypertension Renal hypertension Renal insuficiency Renal insuficiency

Systemic lupus erythematosus (SLE) Joint involvement Arthralgias Arthralgias Arthritis- may resemble RA Arthritis- may resemble RA

Systemic lupus erythematosus(SLE) Blood involvement Hemolytic anemia Leukopenia or lymphopenia Trombocytopenia Lymfadenopthy Trombotic tendency

Systemic lupus erythematosus(SLE) Blood involvement Trombotic tendency are more marked in patients with positive Anticardiolipin antibodies ACLA Anti-phospholipid antibodies „Lupus anticoagulans“

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

Systemic lupus erythematosus(SLE) Theraphy: Mild disease – skin, joints ´ – hydroxychloroqine (Plaquenil) Active disease – systemic steroids - immunosupressive agents (Methotrexate, cyclophosphamide azathioprim,

Systemic Sclerosis (S Sc ) 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

Systemic Sclerosis (S Sc ) The skin is thickned and tight and this results in contractures The skin is thickned and tight and this results in contractures Raynaud´s phenomenon in 95% pts Raynaud´s phenomenon in 95% pts Organs involvement- GIT, lung,kidney Organs involvement- GIT, lung,kidney

Systemic Sclerosis (S Sc )

D ermatomyo sitis and Polymyoi sits

Sj ő gren´s syndrom e

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