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![COMPLEX MEDICAL PROBLEMS 2
Develop a strategy: PROBLEM LIST
CREATE PROBLEM LIST
……… LIST EVERYTHING [split don’t lump]
PRIORITIZE PROBLEM LIST
……… WHAT’S THE BIG GORILLA(S) HERE?
“WORK” the PROBLEM LIST](https://image.slidesharecdn.com/2015systemicvasculitis-240611043634-ac662bc8/75/2015-mangement-of-Systemic-Vasculitis-ppt-16-2048.jpg)
![VASCULITIS OF SMALL >> MEDIUM-SIZED
VESSELS:
• drug-induced small vessel vasculitis
(hypersensitivity vasculitis),
• Henoch-Schönlein purpura (IgA vasculitis),
• ANCA-associated vasculitis
(granulomatosis with polyangiitis [Wegener’s],
microscopic polyangiitis, eosinophilic granulomatosis
with polyangiitis [Churg Strauss syndrome]),
• infection-related vasculitis
(bacterial endocarditis, poststreptococcal vasculitis
and glomerulonephritis) plus hepatitis C-related
cryoglobulinemia)](https://image.slidesharecdn.com/2015systemicvasculitis-240611043634-ac662bc8/75/2015-mangement-of-Systemic-Vasculitis-ppt-64-2048.jpg)
2015 mangement of Systemic Vasculitis.ppt
- 1. Systemic Vasculitis: a clinicalapproach Geordie Lawry MD Chief, Rheumatology UC IRVINE Medicine HS Noon Conference: October 2015
- 2. Objectives 1 • Listthe 4 clinical features which should prompt you to CONSIDER A DIAGNOSIS of systemic vasculitis • List the “Big 5” essential questions in patients with SUSPECTED GIANT CELL ARTERITIS • Describe what is meant by PULMONARY RENAL SYNDROME
- 3. Objectives 2 • Listat least 3 ORGANS / SITES commonly involved in: CRYOGLOBULINEMIC VASCULITIS GRANULOMATOUS POLYANGIITIS (GPA) MICROSCOPIC POLYANGIITIS (MPA) CLASSIC POLYARTERITIS NODOSA GIANT CELL ARTERITIS
- 4. Objectives 3 • Listat least 2 ANCA VASCULITIS SYNDROMES, associated ANCA pattern / target antigens • List at least 2 vasculitides which are NOT ASSOCIATED WITH ANCA • List at least 3 or more conditions that can MIMIC THE CLINICAL FEATURES OF VASCULITIS
- 5. VASCULITIS: Talk Outline •Introduction and Definitions • Approach to vasculitis • Specific Disorders: –Giant Cell Arteritis –Granulomatous polyangiitis (Wegener’s) –Microscopic Polyangiitis –Polyarteritis Nodosa –Cryoglobulinemia • Take Home
- 6. VASCULITIS: principles 1 groupof clinical syndromes characterized by inflammation of blood vessels Normal Artery Artery: WBC inflammation in wall
- 7. VASCULITIS: principles 2 systemicdiseases that can affect many different organ systems can be difficult to diagnose: challenging clinical picture even for experienced clinicians can be life-threatening
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- 9. General Approach to Vasculitis Throwup your hands….
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- 11. When should vasculitisbe suspected? 1 • MULTISYSTEM inflammatory disease • Significant CONSTITUTIONAL SYMPTOMS • RAPIDLY PROGRESSIVE organ dysfunction • HIGH ESR SEVERE anemia PLATELETS > 500K
- 12. When should vasculitisbe suspected? 2 CLINICAL FEATURES PARTICULARLY SUGGESTIVE of small vessel inflammation: • SKIN: palpable purpura * • LUNGS: pulmonary infiltrates / hemoptysis • KIDNEY: active urinary sediment • NEURO: foot drop **
- 13. What is theapproach to a patient suspected of having vasculitis? WHAT IS YOUR APPROACH TO ANY COMPLEX MEDICAL PROBLEM?
- 14. General Approach to Vasculitis Gatheryour equipment…. Find the target…. Take aim….. NAIL IT !
- 15. COMPLEX MEDICAL PROBLEMS1 HISTORY: PATIENT’S STORY get careful CHRONOLOGY …….PROBLEMS PHYSICAL EXAM: BODY’S STORY thoughtful, thorough ……..MORE PROBLEMS LABORATORY: BEHIND-THE-SCENES STORY Basic CBC, CHEMS, LFTs, UA/micro, CXR ……..MORE PROBLEMS
- 16. COMPLEX MEDICAL PROBLEMS2 Develop a strategy: PROBLEM LIST CREATE PROBLEM LIST ……… LIST EVERYTHING [split don’t lump] PRIORITIZE PROBLEM LIST ……… WHAT’S THE BIG GORILLA(S) HERE? “WORK” the PROBLEM LIST
- 17. COMPLEX MEDICAL PROBLEMS3 “WORK” the PROBLEM LIST • Think of 3 explanations for each problem Create a differential diagnosis • What are the major organs involved? • Do they inter-relate? Do the patient’s, body’s and the behind-the- scenes stories fit together in some way?
- 18. COMPLEX MEDICAL PROBLEMS4 SYSTEMIC VASCULITIS ? • Are there additional tests which could help confirm this suspicion? • Serologic tests • Imaging studies • Tissue biopsy
- 19. VASCULITIS: additional testing1 Serologic tests • ANCA • Hepatitis B surface antigen • Hepatitis C, C3 & C4 • HIV • ANA • ACA, “lupus” anticoag panel
- 20. VASCULITIS: additional testing2 Imaging studies • Sinus CT scan • Chest CT scan • Mesenteric angiogram
- 21. VASCULITIS: additional testing3 Tissue biopsy • Temporal artery • Sural nerve • Muscle • Lung • Renal
- 22. Common Clinical Manifestations • Systemic –Fever, sweats, weight loss • Skin – Palpable Purpura • Neurologic – Mononeuritis Multiplex • Musculoskeletal – Arthralgia / arthritis – Muscle pain / claudication • Respiratory – Sinusitis / Epistaxis – Pulmonary infiltrates • Gastrointestinal – Abdominal Pain – Bloody stools • Renal – Glomerulonephritis – Hypertension
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- 26. NEUROLOGIC • Mononeuritis multiplex: checkfor FOOT DROP Sural nerve biopsy showing vasculitis
- 27. RESPIRATORY: upper • Sinusitis •Or…… www.conseils-orl.com/.../sommaire_epistaxis.htm
- 28. RESPIRATORY: lower • Pulmonaryinfiltrates • Nodules • Cavities
- 29. GENITOURINARY • Glomerulonephritis • Hypertension •Hematuria • RBC casts • Testicular pain (especially PAN) www.bio.davidson.edu/.../Cresgn.jpg
- 30. MUSCULOSKELETAL • Polyarthralgias -common • Polyarthritis - less common • Myalgias - common • Myositis - biopsy may demonstrate vasculitis in muscle
- 31. GASTROINTESTINAL • Mesenteric ischemia –pain 30 minutes after eating – bloody diarrhea – bowel perforation • hepatitis • pancreatitis • cholecystitis library.med.utah.edu/WebPath/COW/COW125.html
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- 33. Common Laboratory Findings INFLAMMATION: ElevatedESR (can be > 100) Elevated CRP Leukocytosis Thrombocytosis Anemia Low Albumin
- 34. VASCULITIS MIMICS • INFECTIOUSDISEASES – Endocarditis – HIV • DRUGS – Cocaine – Methamphetamine • CHOLESTEROL EMBOLI • ANTIPHOSPHOLIPID ANTIBODY SYNDROME
- 35. Questions? • In theACR diagnostic criteria for Giant Cell Arteritis (Temporal Arteritis), a patient needs to be greater than what age? A. > 40 years B. > 50 years C. > 60 years D. > 70 years E. > 80 years
- 36. Questions? • In theACR diagnostic criteria for Giant Cell Arteritis (Temporal Arteritis), a patient needs to be greater than what age? A. > 40 years B. > 50 years C. > 60 years D. > 70 years E. > 80 years -Almost all are > 60 -Average age is 70
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- 38. Arthritis Rheum. 1990;33:1122. GiantCell Arteritis ACR Criteria (3 of 5) • Age > 50 • New onset headache • ESR (Westergren) 50 • Abnormal artery biopsy (mononuclear cell infiltrate, granulomatous inflammation, usually multinucleated giant cells) • Temporal artery abnormality (tender or decreased pulse)
- 39. Giant Cell Arteritis (Otherclinical manifestations) • Visual loss, jaw/tongue claudication, scalp tenderness • Fever, weight loss • PMR symptoms (proximal muscle pain) • 10% with large vessel involvement (e.g. subclavian artery) • Blindness (ischemic optic neuropathy) is major complication to avoid
- 40. GCA:Biopsy • Temporal arterybiopsy – large specimen (4-6 cm) – multiple sections evaluated • Infiltration of vessel wall with WBC • Granulomata, Giant Cells • Necrotic material
- 41. GCA: Therapy • Corticosteroidsmainstay of therapy (~1 mg/kg) – Calcium and vitamin D – Consider bisphosphonates • Try to prevent visual loss with therapy: – Treat, then biopsy!
- 42. Questions? • The confirmatoryantibody for a positive C- ANCA in a patient suspected of having Wegener’s Granulomatosus is: A. Topoisomerase B. Histidine tRNA synthetase C. Smith D. Proteinase-3 E. Myeloperoxidase
- 43. Questions? • The confirmatoryantibody for a positive C- ANCA in a patient suspected of having Wegener’s Granulomatosus is: A. Topoisomerase B. Histidine tRNA synthetase C. Smith (Sm) D. Proteinase-3 E. Myeloperoxidase C is the 3rd letter of the alphabet: Pr-3 C-ANCA
- 44. Granulomatous Polyangiitis (GPA) …formerly Wegener’s • Necrotizing vasculitis that affects the small vessels of the respiratory tract and renal system: PULMONARY-RENAL SYNDROME • Age ~ 40s: M > F 2:1
- 45. Arthritis Rheum 1990;33:1101. GranulomatousPolyangiitis (GPA) ACR Criteria (3 of 5) • Nasal or oral inflammation (oral ulcers or bloody nasal drainage) • Abnormal chest radiograph (nodules, fixed infiltrates, cavities) • Urinary sediment (> 5 RBC/ hpf or casts) • Abnormal Biopsy: showing vasculitis • Proteinase-3 antibodies
- 46. Granulomatous Polyangiitis (GPA) :Respiratory Involvement • Sinusitis – Nasal septal ulceration • Pneumonitis – few symptoms until late – usually no mediastinal lymphadenopathy – nodules that can cavitate
- 47. Granulomatous Polyangiitis (GPA) :Renal Involvement • 85% of patients • Focal/segmental necrotizing glomerulonephritis • Usually progressive www.bio.davidson.edu/.../Cresgn.jpg
- 48. Granulomatous Polyangiitis (GPA) :ANCA • AntiNeutrophil Cytoplasmic Antibody – C (cytoplasmic staining) ANCA – Proteinase 3 (C is the 3rd letter) • Pulmonary-renal disease – sensitivity of 95% – specificity of 95% • Limited disease… – lower sensitivity and specificity
- 49. Granulomatous Polyangiitis (GPA): TissueBiopsy • Yield of biopsy – Lung • Open – highest yield • Bronchoscopy - lower yield – Sinus - 40% yield – Renal • Vasculitis rarely seen • Focal proliferative GN is the typical finding
- 50. Granulomatous Polyangiitis (GPA) :Rx • Prior to cyclophosphamide, 80-90% mortality • With cyclophosphamide, 5-10% mortality • Concern about long-term toxicity of PO cyclophosphamide (bladder especially) • IV CYTOXAN no significant bladder risk • Rituximab: very effective for induction & maintenance • Azathioprine for maintenance
- 51. Microscopic Polyangiitis (MPA) • Systemicvasculitis with predominant small vessel involvement • Separate disease from PAN (Initially thought to be a variant of PAN) • Usually RPGN and sometimes with pulmonary hemorrhage • More common than PAN (both are rare)
- 52. MPA: Clinical Manifestations •Renal manifestations 79% • Weight loss 73% • Skin involvement 62% • Mononeuritis multiplex 58% • Fever 55% • Arthralgias/Myalgias 50% • Pulmonary involvement 25%
- 53. MPA: ANCA • P(perinuclear) ANCA • Myeloperoxidase antibodies • Sensitivity/Specificity unclear
- 54. MPA: Epidemiology &Rx • Ave. age 57 • Males > Females (slightly) • Cyclophosphamide decreases mortality • IV CYTOXAN no significant bladder risk • Rituximab: very effective for induction & maintenance • Azathioprine for maintenance
- 55. Polyarteritis Nodosa • Necrotizingvasculitis of medium & small arteries • Age ~ 40s; M > F • Constitutional symptoms are common – fever 50% – weight loss 50% • Vasculitis can be variable in distribution making diagnosis difficult
- 56. Arthritis Rheum. 1990;33:1088 PolyarteritisNodosa ACR Criteria (3 of 10) • Wt loss > 4 kg • Livedo reticularis • Testicular pain • Myalgias, weakness or leg tenderness • Mononeuropathy or polyneuropathy • Diastolic BP > 90 • BUN or Creatinine • Hepatitis B virus • Arteriographic abnormality • Biopsy of small or medium artery containing PAN
- 57. Classic PAN: Manifestations •Mononeuritis multiplex 50% • Renal involvement: 60% (renal arteries, interlobular arteries) – Hypertension (more common) – Glomerulonephritis (uncommon) • Abdominal involvement 45% • Arthralgias/Myalgias/Myositis 64% • Testicular pain 25% • Pulmonary involvement rare
- 58. Polyarteritis Nodosa • Associationwith Hepatitis B (surface antigen) • Classic PAN is NOT associated with ANCA ANCA
- 59. Cryoglobulinemia 1 • Paradigmof small vessel vasculitis • Association with hepatitis C infection • Damage is immune complex-mediated • Cryoprecipitate Hepatitis C Ag – Ab • Complement fixing: C4 consumption C4 levels VERY low
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- 61. Cryoglobulinemia 3 PATTERN OFORGAN INVOLVEMENT: • constitutional • Cutaneous • articular • vascular • neurologic
- 62. Cryoglobulinemia 4 PATTERN OFLABORATORY FINDINGS: • rheumatoid factor • complement C4 ↓ ↓ ↓ • cryoglobulin (cryocrit) TREATMENT: • Antiviral therapy …. clearance of hep C virus!
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- 64. VASCULITIS OF SMALL>> MEDIUM-SIZED VESSELS: • drug-induced small vessel vasculitis (hypersensitivity vasculitis), • Henoch-Schönlein purpura (IgA vasculitis), • ANCA-associated vasculitis (granulomatosis with polyangiitis [Wegener’s], microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis [Churg Strauss syndrome]), • infection-related vasculitis (bacterial endocarditis, poststreptococcal vasculitis and glomerulonephritis) plus hepatitis C-related cryoglobulinemia)
- 65. • vasculitis associatedwith CTD (SLE, RA, Sjögren's) VASCULITIS OF MEDIUM-SIZED VESSELS: • classic polyarteritis nodosa (PAN) VASCULITIS OF LARGE VESSELS: • Giant cell arteritis • Takayasu arteritis MIMICS OF VASCULITIS: • infectious, thrombotic, and embolic disorders