목차 Vasculitis syndrome – 개념 – 언제 의심하는가 ? P-ANCA associated vasculitis –MPA Renal involvement ANCA associated GN with IgA deposit Hypothyroid myopathy

Vasculitis syndrome

Vasculitis 란 ? 혈관의 염증과 손상을 특징으로 하는 clinic opathologic process → Vessel lumen 이 막혀서 침범된 혈관이 supply 하 는 장기에 ischemia 초래

언제 vasculitis 를 의심하는가 ?  FUO with constitutional symptoms  Unexplained multi-system organ disease  Unexplained inflammatory arthritis  Unexplained myositis  Suspicious rash  Unexplained peripheral neuropathy  Unexplained end organ ischemia  Glomerulonephritis

purpuric rash nodules Skin signs digital infarction/ulceration Raynaud syndrome

Oro-genital ulcers mouth ulcers nasal ulcers genital ulcers Red eyes uveitis Mucous membranes

Renal signs renal insufficiency hypertension proteinuria active urine sediment (red cell and other cellular/granular casts)

Abdominal signs abdominal pain gastrointestinal bleeding nausea/vomiting, diarrhea Neurologic Signs mononeuritis multiplex asymmetric polyneuropathy

Respiratory / Cardiovascular hemoptysis crackles wheeze pericarditis

Vasculitis 가 의심될때 시행해볼 검사 serum creatinine muscle enzyme concentrations liver function studies erythrocyte sedimentation rate hepatitis serologies urinalysis chest x-ray electrocardiogram ANCA, ANA EMG tissue biopsy arteriogram

P-ANCA associated vasculitis

Microscopic Polyangiitis Presence of glomerulonephritis in patients with P AN Chapel Hill Consensus Conference on the Nome nclature of Systemic Vasculitis –necrotizing vasculitis with few or no immune complex es affecting small vessels –necrotizing glomerulonephritis is common –DDx. Wegener’s granulomatosis : granulomatous infla mmation

MPA with Renal involvement Glomerulonephritis (79%) –can be rapidly progressive, leading to renal failure Renal pathology : –necrotizing glomerulonephritis without immune deposi ts

ANCA associated GN with IgA deposit

RPGN type Type I (anti-GBM) Anti-GBM disease Goodpasture’ s sydrome Type II (immune complex) IgA nephropathy PSGN, SLE Mixed cryoglobulinemia Type III (Pauci-immune, ANCA) Wegener’s granulomatosis Microscopic polyangiitis

IgAN 과의 관련성 ? Case report of 6 patients Am J Kidney Dis 2000; 36: All crescentic GN ANCA associated crescentic GN > IgAN –Crescent more than 50% –Only focal, mild or segmental mesangial deposit

IgAN vs IgA deposit IgANcase

IgAN case

ANCA (+) IgAN Clin Exp Nephrol (2007) 11:326–331

IF IgA × 100 EM × 9,000 PAS × 100 Clinical Nephrology 2007(68)

Hypothyroid myopathy

Causes of myopathies Idiopathic myopathy – immune mediated Acute alcoholic myopathy Infectious causes Endocrine causes Drug-induced or toxic Acute periodic paralysis –Trichinosis –Cysticercosis –Toxoplasmosis –HIV –Coxsackie A and B viruses –Influenza –Lyme disease –Staphylococcus aureus –Addison disease –Cushing disease –Hypothyroidism (CK may be mildly elevated) –Hyperthyroidism (CK may be normal) –Hyperparathyroidism –steroids –clofibrate, –statins –colchicine –amiodarone –penicillamine –drugs causing hypokalemia - hypokalemic, hyperkalemic, or normokalemic

Clinical manifestations Elevation in serum creatine kinase (57~90%) Muscle stiffness, myalgias, mild weakness (80%) Muscle hypertrophy Proximal myopathy Rhabdomyolysis Myoedema (1/3, but not specific) infrequent

Diagnosis TSH – if high, thyroxine level Electromyography (EMG) –normal in 50% –myopathic changes with increased low-amplitude, polyphasic potentials –delayed relaxation phase of the deep tendon refle xes –lack of fibrillation potentials on electromyogram wi th relatively normal appearing motor units Muscle biopsy –not usually required Useful in ddx. inflammatory myositis

Diagnosis –presence of typical myopathic symptoms –hypothyroidism → sufficient to make the diagnosis Treatment –thyroid hormone replacement Response –CK levels →TSH levels → clinical symptoms recover over weeks recover over months

Autoimmune thyroiditis 와 ANCA(+) vasculitis?

새로 진단된 58 명의 Graves’ pateints → PTU 치료 후 9 명이 ANCA(+) Int J Clin Pract, 2009, 63, 2, 299–302 –PTU therapy → asymptomatic production of ANCA in a time-dependent manner → 대개 치료 중단 후 사라짐 –Hyperthyroidism / autoimmunity 자체는 ANCA positivity 와 관련 없다 Autoimmune thyroiditis 와 ANCA(+) vasculitis?