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Systemic autoimmune diseases
Reaction against universaly expressed antigen
Infliction of several organs or organ systems Laboratory: FW, CRP, proteins of acute
phase
Systemic autoimmune diseases
Often infliction of joints, skin and kidney Sytemic symptoms including fever (Felty‘s syndrome, Still‘s disease) Pacients with systemic autoimmunity are
often examined with the diagnosis Fever of unknown origin Lymphadenopaty of unknown origin
Systemic autoimmune diseases
Often secondary diseases Polyarteritis nodosa – hepatitis B Polymyositis, dermatomyositis - tumors
Systemic lupus erytematosus - etiology Genetic predispozition: HLA A1-A8-DR3,
genes for complement Environmental factors – viruses (herpes, EB,
CMV) Drugs – hydralazin, prokainamid, INH Sex hormones 1:4000 Young women, 20-30 years
Systemic lupus erytematosus - pathogenesis Polyclonal activation of B cells Defect of apoptosis (experimetal model
lpr/lpr, gld/gld = Fas/FasL) Production of antibodies against DNA (ds
DNA), antinuclear antibodies and antibodies against nuclear antigens
Formation of immunocomplexes Defect of complement Immunopatologic rection of 2. a 3. type Vaskulitis
Systemic lupus erytematosus - lyboratory Production of antibodies against DNA (ds
DNA), antinuclear antibodies and antibodies against nuclear antigens (SS-A, SS-B), antibodies against fosfolipides and blood elements
Formation of immunocomplexes Decreased C3, C4 and total complement
(CH50) Hyperglobulinémia FW, CRP and proteins of acute phase
SLE - symptoms
Perikarditis, myokarditis, endokarditisPleuritis, intersticial alveolitisVaskulitis of CNS – thrombosis, microembolisations, epilepsieLupus anticoagulans – APTT, antikardiolipin antibodies – thrombosis, leukopenie, trombopenie, anemiePolyarteritis, deformations, revmatoid artritislike
Intersticial nefiritis, mezangial glomerulonefritis (GN), fokal progrssing GN, difuse proliferative GN, membranoz GNAmyloidosis
SLE - therapy
Immunosuppression – glukokortikoids, azathioprin, cyklofosfamid, cyklosporin A
Antimalariks Plazmapheresis Symptomatic therapy Anti CD20
Revmatoid arthritis - etiology
Chronic, relapsing systemic inflamatory disease of joints
Destruction of joints, infliction of other organs Genetic risk – HLA DR1, HLA DR4 Environmental factors – viruses, bacteria??? 1-3% population females (2-3x)
Revmatoid arthritis - pathogenesis
Reaction of CD4 T lymfocytes and macrophages against antigens of synovial membrane
Secretion of antibodies IgM against Fc part of IgG (revamtoid factor, Latex), diagnostic importance, not pathogenetic
Vasculitis, synovitis
Revmatoid arthritis – laboratory findings Latex fixation test – detection of RF (IgM anti
IgG) FW, CRP, proteins of acute phase CIK, complement
Revmatoid arthritis – clinical findings MCP, PIP, RC joints Polyarticular symetric
affection Intumescens, synovial
thiskening, exudate, erosion of cartilage and bone by inflammatory tissue
Generation of contractures a deformations
Revmatoid arthritis – extraarthral findings Revmatoid noduses Tendosynovitis Keratokojunktivitis Intersticial lung processes Perikarditis, myokarditis, endokarditis Amyloidosis
Revmatoid arthritis – clonical course In a minority of patients long-lasting or
complete remissin spontaneous or drug-induced
Remisions – relapses Progressive course Kontractures, ankylosis, invalidization
Revmatoid arthritis – therapy Regime – prevention of contractures, rehabilitation NSA DMD – antimalarika, Au, sulfasalazin, metotrexát,
penicilamin, azathioprin, cyklofosfamid, prednison Infliximab Surgical – sinovectomy, joint replacement
Ankylosing spondilytis
HLA B27 Young men, 9x more than
females Sacroileitis Spondylartritis Clinical course – progressive
invalidisation Therapy: rehabilitation!, NSA,
metotrexát Extraarticular complications:
uveitis, entezitis, lung fibrosis, perikarditis
Sclerodermy – systemic sclerosis
Etiology unknown Detection of autoantibodies ANA,
anticentromeric antibodies Stimulation of fibroblasts Clinic – CREST: calcifications, Raynaud‘s
phenomenon, defect of motility of ezophagus, sklerodaktylie, teleangiektazie
Therapy – cyclophosphamid, D-penicilamin = minimal effect, progression
Polymyozitis, dermatomyozitis
Inflammatory diseases of sceletal muscles of unknown origin
Antibodies against nuclear and cytoplazmic components of cells (antisynthetase antibodies (anti Jo-1), ENA, ANA)
CK, LDH, ALT, AST Diagnosis – muscle biopsy
Polymyozitis, dermatomyozitis
In 20% association with cancer
Fatigue of proximal muscle groups
Intersticiál lung fibrosis etc. Therapy: Prednison,
Metotrexát, Cyklofosfamid, Cyklosporin A
Sjogren syndrome
Inflammation and destruction of exocrine glands
Pankreas, mucous, vaginal and bronchial glands
Secondary (RA, SLE, hepatitis) syndrome, primary = disease
9x more often females, HLA DR3 + RF, ENA SS-A, SS-B Therapy – substitution, corticosteroids
Case report
Pain of lower limbs the last 2 weeks Erythema of lower limbs Symetric oedema of LL Fever 2 days before admission
Laboratory
FW 84/88, BC: ok, CRP 240. Biochemistry: ok Urine analysis: ok EKG ok Blood cultures and bacteriological survey wo
identification of microbial agent RF, autoantibodies and other immunologic
investigations ok
Clinical course
Muscle biopsy – inflammatory disease similar to polymyositis
Resection and biopsy of suspected lung focus
BALT lymphoma Complete remission
Vasculitis
Descriptive therm for the description of heterogenous inflammatory diseases of vessels (art, cap, ven)
Vasculitis - etiology
Primary vasculitis Secondary vasculitis
environmental antigens (infection, allergy, drugs, postiradition)
Self antigens (autoimmune disorders, Tu, GVHD)
Vasculitis - patophysiology
Inflammation of vascullar wall leading to the development of stenosis and aneurysma
Ischemia Immunology
type 3 IPR type 2 IPR Activation of endothel Coagulopathy
Vasculitis - autoantigens
ANCA (antineutrophil cytoplasmic antibodies) proteinase 3 (PR3) myeloperoxidase (MPO) C (cytoplasmic) P (perinuclear) A (atypical) …….
AECA (antiendothelial cell antibodies) Colagen IV Infection Ag
Vasculitis - autoantigens
Wegener gr. C-ANCA, PR3-ANCA Microscopic polyangiitis MPO Goodpasture sy anti-GBM Ab (colagen IV)
3-15% ANCA Polyarteriitis nodosa P-ANCA
Symptomatology
General symptoms: fever, weight loss, fatigue, myalgia, arthralgia
„Organ specific symptoms“: Lung: hemoptysa, cough, dyspnoe, asthma, infiltration
of lungs (X-ray) ORL: sinusitis, otitis, deafness Skin: purpura, pyodermie, necrosis Eye: uveitis, iridocyclitis,episcleritis CNS a PNS: polyneuropatie, paresis, epileptic
paroxysms, psychotic features Renal: hypertension, proteinuria, erytrocyturia, renal
failure
Therapy of vasculitis
Induction Corticosteroids Cyclophosphamid Plasmapheresis ivig MoAb
Maintenance Corticosteroids Immunosupression
(azathioprin, MTX)
Wegener granulomatosis
Fever, weight loss, fatigue, sinusitis, pneumonia, cough, hemoptysis
Pulmonary infiltrates + glomerulonefritis
Wegenero granulomatosis - diagnosis
+ c-ANCA + anti-PR3
2/4 criteria Nasal/oral
inflammation Abnormal chest X-ray
findings Microhematuria Granulomatous
inflammation of small artheries (biopsy)
88% sensitivity, 92% specifity
Wegenerova granulomatosa – therapy + prognosis w/o therapy 100% deaths median survival 5
months Therapy 87% achieve remission after
corticosteroids + immunosuppression (53% relapses)
Vasculitis - syndoms
Kawasaki disease children Fever, conjunctivitis,
lymph node enlargement, scarlet exantema
15% vasculitis of coronary vessels
AEAb, ANCA, Vbeta 2,8 - superantigens
Goodpasture sy
pulmorenal sy anti-GBM nefritis anti-GBM Ab (colagen
IV) 3-15% ANCA
Vasculitis - syndoms
Churg-Strauss sy (Allergic granulomatous angiitis, AGA)
astma Lung infiltration capilaritis of lung vessels eosinofilia >1500 P-ANCA, MPO cca 50%
Polyarteriitis nodosa
Muscular arteries medium size
kidney, nerves, muscules, skin
(P-ANCA)
Vasculitis - syndoms
Henoch-Schonlein purpura purpura hemorhagic enteritis artritis nefritis Immune complex with IgA (similar to IgA
nephropathy – limited form of H-S) ANCA < 10%
Vasculitis - syndomy
Takayasu arteritis
Younger patients females:males 7:1
Aortal arch, renal arteries
Malignant hypertention ANCA negative
Horton temporal arteritis Older patients 3:2 polymyalgia rheumatica Carotis and its
branches amaurosis ANCA negativ