Vasculitis. Seth Mark Berney, MD Professor of Medicine Chief, Division of Rheumatology University of Arkansas for Medical Sciences

Transcription

1 Vasculitis Seth Mark Berney, MD Professor of Medicine Chief, Division of Rheumatology University of Arkansas for Medical Sciences

2 History A 50 year old white male with a history of intravenous drug use (but none for 5 years), hepatitis B & hepatitis C presents with two months of subjective fever, two days of left upper quadrant abdominal pain, several weeks of numbness of his right thigh and dragging of his left foot and 10 pound unintentional weight loss.

3 BP= 190/100, P= 100, T=101 o F, RR= 18 Normal lung, heart and rectal/prostate exam without masses Other abnormalities: Physical exam Livedo reticularis of hands and thighs; RUQ slightly tender to palpation without rebound; Decreased sensation of his right thigh; Mild weakness on dorsiflexion of his left foot.

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5 Differential Diagnosis Diabetes Endocarditis Malignancy with/without cryoglobulins SLE with APL Syphilis Vasculitis with mononeuritis multiplex Viral infection with/without cryoglobulins (Hep B, Hep C, HIV)

6 Evaluation based on the differential diagnoses list APL ab Blood cultures CBC with diff Chest radiograph Complete Metabolic Panel (CMP) (including creatinine, blood sugar, liver enzymes) Cryoglobulins Echocardiogram ESR Hepatitis B and C viral load HIV RPR (Rapid Plasma Reagin) Stool hemoccult Urinalysis

7 Labs results Blood and urine culture- negative Chest radiograph- normal CBC: Hct= 32% ( %) WBC= 7.7 ( x 10 9 /L) Plts= 500 ( x10 9 /L) CMP normal except Creat= 2.4 ( mg/dl) Cryoglobulins= negative Echocardiogram- normal ESR= 90 (<20mm/hr) Hepatitis viral load- hepatitis B virus is present hep C is absent HIV= negative RPR= negative Stool hemoccult- negative for occult blood UA= 1+protein, 5-10 rbc, 0 wbc,1-2 granular casts

8 We suspect Vasculitis! The patient s: new hypertension, livido reticularis, abdominal pain, numbness, anemia, elevated creatinine and hematuria indicate the presence of a multisystem disease involving the kidney, skin, GI tract, peripheral nervous system. Vasculitis is a heterogeneous group of conditions characterized by inflammation and necrosis of blood vessel walls (arteries and/or veins).

9 Vasculitis Mimics Atrial myxoma Cholesterol emboli Diabetes Endocarditis Fibromuscular dysplasia Fungal infection Hepatitis C HIV Lymphatoid granulomatosis Malignancy Mycobacterial infection Sarcoidosis Syphilis

10 Diagnosis To distinguish it from a mimic, vasculitis is diagnosed either histopathologically or radiographically (catheter angiogram). MRA and frequently CTA do not have the spatial resolution for a definitive diagnosis of small vessel vasculitis.

11 Classification of Vasculitis Large Vessel vasculitis Medium Vessel vasculitis Small Vessel vasculitis Takayasu s arteritis Temporal arteritis Polyarteritis Nodosa Kawasaki s disease ANCA + Churg Strauss syndrome Granulomatosis with polyangiitis Microscopic polyangiitis ANCA Henoch Schonlein Purpura Cryoglobulinemic vasculitis Leukocytoclastic vasculitis

12 Polyarteritis Nodosa (PAN) Age: years. Males and females equally involved. 25% of patients with PAN are (Hep BsAg+). Pathology: small - medium sized arteries with neutrophilic infiltration/inflammation and fibrinoid necrosis of vessel wall.

13 Clinical Features Involves all organs and tissues (except the lungs). Skin- nodules, palpable purpura, ulcerations,etc. Heart- coronary arteritis can cause manifestations including tachycardia, MI and CHF (with SOB). GI tract- (up to 50% pts)- pain, bleeding, perforation. Renal- vasculitis may cause renal dysfunction and/or HTN. Nervous System- CNS and PNS (mononeuritis multiplex). Testicles, liver, breast, eye, ovary, gallbladder can also be involved.

14 Inflammatory labs: Normocytic normochromic anemia Elevated ESR Elevated platelet count + elevated globulin Abnormal urinalysis 25% patients are hepatitis B sag positive (thus viremic). +ANCA Laboratories

15 Diagnosis Biopsy or angiogram (of any involved tissue) Biopsy should be guided by how accessible the tissue is and easy the biopsy would be. Angiogram is the diagnostic procedure of choice, if it is easier and safer.

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20 Treatment and Prognosis Depends on whether it is hepatitis B related: If Hep B negative - steroids and cytoxan or If Hep B positive - steroids for? 2 weeks followed by plasmapheresis (qod for several weeks) then tapered and antiviral agents (lamivudine). Prognosis: 5 year survival when treated= 60%

21 Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss syndrome) (Allergic Granulomatosis/Angiitis) Annual incidence is 3 per million people. Patients of any age can be affected. Pathology: eosinophilic vasculitis. Presentation: Initially: 1. Increased allergic manifestations (esp asthma) 2. Eosinophilia (>10% WBC) Eventually: Vasculitis typically develops as asthma/allergies improve- especially in sinopulmonary tree.

22 Clinical Features Manifestations: SinoPulmonary- allergic rhinitis, sinusitis, chest pain, shortness of breath, asthma. Skin, PNS, and GI tract similar to PAN. Renal and Cardiac involvement less severe than PAN. Labs: eosinophilia >10% WBC Sinus x-ray opacification Chest x-ray- fleeting patchy or nodular infiltrates Treatment: high dose steroids

23 Large Vessel Arteritis (Giant cell arteritis) Temporal arteritis (Cranial arteritis) is a chronic vasculitis of aorta and large branches (especially in cranium). Takayasu s arteritis (pulseless disease) is a chronic vasculitis of aorta and large branches (especially outside cranium). Histologically identical granulomatous vasculitis of large/muscular arteries. Inflammation with fragmentation and disruption of the internal elastic lamina and multinucleated giant cells.

24 Temporal Arteritis (TA) Patients > 50 years of age. Mean age is 70. Women >> men /100,000. High prevalence in Scandinavian countries. Less common in blacks and hispanics.

25 Clinical Features Signs of vascular insufficiency: jaw claudication, CNS ischemia (CVA), ischemic optic neuropathy scalp tenderness, etc. Inflammatory labs with very high ESR Up to 50% of patients with TA have already been diagnosed with PMR Giant cell arteritis may manifest as fever of unknown origin or failure to thrive (weight loss and the dwindles).

26 Treatment and Prognosis Diagnosis: Temporal artery biopsy (bilateral biopsies increase diagnostic sensitivity) Treatment: Prolonged high dose glucocorticoids (> 2 years) or tocilizumab. Prognosis: The most significant morbidity is associated with blindness and?? CVA resulting from hypoperfusion of these tissues. Many patients relapse.

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28 Takayasu s Arteritis Rare vasculitis of aorta and large branches that affects adolescent girls and young (< 40 year old) women (especially japanese). Symptoms depend on what arteries are involved. For example: Aortic arch causes aortic insufficiency or affects branches Abdominal aorta causes claudication, HTN Common carotid artery causes strokes Renal artery causes HTN Subclavian artery causes arm claudication, pulseless arm Vertebral artery causes dizziness

29 Diagnosis/Treatment/Prognosis Diagnosis: Conventional angiogram or MRI/MRA. Treatment: If inflamed: Glucocorticoids. If not inflamed: Revascularization (either surgically or percutaneously). Prognosis: >90% 5 year survival with treatment.

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31 Granulomatosis with Polyangiitis (Wegener s Granulomatosis) Incidence= 8.5 cases per million people. Mean age at onset is 55 years and Whites comprise 90 % of cases. Necrotizing granulomatous vasculitis involving small arteries/arterioles/venules with classic triad: Upper respiratory airway involvement Lower respiratory airway involvement Kidney involvement Pathology: fibrinoid necrosis, granulomatous vasculitis and pauci-immune glomerulonephritis.

32 Clinical Features Upper respiratory (sinus/nasal manifestations): Any sinus/nasal signs/sx including: saddle nose deformity, erosive sinusitis and tracheal/laryngeal narrowing. Lower respiratory (pulmonary manifestations): Any chest signs/sx including: hemoptysis, cough, chest pain, shortness of breath abnormal CXR. Renal symptoms (secondary to renal inflammation and ischemia). Also affects Skin, PNS and CNS, and GI tract.

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35 Diagnostic Studies Inflammatory labs Abnormal urinalysis with: hematuria/ proteinuria/ RBC casts (nephritic). Anti-neutrophil cytoplasmic antibody (ANCA): 80% of patients have a canca. They may also have an anti-proteinase 3 ab. Chest x-ray: nodules and cavitary lesions.

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37 Diagnosis/Treatment Diagnosis: Open lung biopsy Biopsy of other tissues Angiogram Treatment: Steroids plus Rituximab Cyclophosphamide Methotrexate (in absence of life threatening lung or kidney disease).

38 Primary CNS Angiitis = Primary Angiitis of the CNS (PACNS) Dfn: vasculitis that is confined only to the brain, meninges, or spinal cord. PACNS subtypes: 1. Granulomatous angiitis 2. Atypical: Nongranulomatous angiitis Masslike angiitis Cerebral amyloid angiopathy Epidemiology: Estimated incidence = 2.4/1 million/yr Median age at onset- 50 years Male:Female = 2 : 1

39 PACNS- granulomatous angiitis subtype Clinical: chronic headaches with both diffuse and focal neurologic deficits but fever, fatigue and weight loss are usually not prominent. Systemic inflammatory labs (elevated ESR or CRP, anemia of chronic disease, thrombocytosis) are usually absent. CSF indicates asceptic meningitis. Imaging: Most common: infarcts (bi>unilateral), highintensity T2-weighted fluid attenuation inversion recovery (FLAIR) lesions on MRI in the subcortical white and deep gray matter. Diagnosis: granulomatous angiitis on biopsy.

40 PACNS- Atypical PACNS subtype Most frequent and heterogeneous subset of PACNS Masslike presentation is a rare manifestation of PACNS occurring in less than 5% of the cases. Cerebral amyloid angiopathy (CAA) perivascular inflammation referred to as amyloid-β related angiitis (ABRA).

41 PACNS The diagnosis of PACNS is based on compatible clinical features together with evidence from spinal fluid, brain and vascular imaging, and often brain biopsy to confirm diagnosis and exclude mimics (especially if lymphocytic inflammation on biopsy). When the diagnosis of PACNS is based on angiographic findings, a thorough evaluation should be performed to rule out mimics, especially Reversible Cerebral Vasoconstriction Syndrome (RCVS).

42 PACNS Abnormalities on cerebral catheter angiogram are not specific for PACNS and can be seen in many other conditions. RCVS syndrome is the most common mimic, characterized by: thunderclap headaches, normal CSF, abnormal cerebral angiogram which resolves within 12 weeks.

43 Differential Diagnosis for PACNS Hypercoagulable States Strokelike Syndromes Leukoencephalopathies Cerebral Hemorrhage Embolic Disease Sarcoid Infections (Bacterial, mycobacterial, fungal, viral, protozoal) Malignancy (lymphoma, glioma, metastasis) Vasospastic disorders (RCVS, drugs) Other vascular diseases (atherosclerosis, fibromuscular dysplasia, moyamoya, dissection, postpartum CNS angiopathy)

44 Treatment and Outcome PACNS Treatment: Glucocorticoids Cyclophosphamide induction Azathioprine or mycophenolate maintenance Outcome: Estimated mortality rate of 10% to 17% at 1 year. Up to 20% of patients are moderately severe to severely disabled (needs assistance to walk or care for own bodily needs or requires constant nursing care).