Vasculitis

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

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.

History

BP= 190/100, P= 100, T=101o F, RR= 18 Normal lung, heart and rectal/prostate exam

without masses Other abnormalities: 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.

Physical exam

Diabetes Endocarditis Malignancy with/without cryoglobulins SLE with APL Syphilis Vasculitis with mononeuritis multiplex Viral infection with/without cryoglobulins

(Hep B, Hep C, HIV)

Differential Diagnosis

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

Evaluation based on the differential diagnoses list

Blood and urine culture- negative Chest radiograph- normal CBC: Hct= 32% ( 39-44 %)

WBC= 7.7 (3.2-9.8 x 109/L) Plts= 500 ( 160-350x109/L)

CMP normal except Creat= 2.4 (0.6-1.2 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

Labs results

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).

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

Vasculitis Mimics

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.

Diagnosis

Classification of Vasculitis

Medium Vessel vasculitis

Polyarteritis Nodosa Kawasaki’s disease

Small Vessel vasculitis

ANCA + Churg Strauss syndrome Granulomatosis with polyangiitis Microscopic polyangiitis

ANCA – Henoch Schonlein Purpura Cryoglobulinemic vasculitis Leukocytoclastic vasculitis

Large Vessel vasculitis

Takayasu’s arteritis Temporal arteritis

Age: 40-60 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.

Polyarteritis Nodosa (PAN)

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.

Clinical Features

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

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.

Diagnosis

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%

Treatment and Prognosis

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.

Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss syndrome)

(Allergic Granulomatosis/Angiitis)

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

Clinical Features

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.

Large Vessel Arteritis (Giant cell arteritis)

Patients > 50 years of age. Mean age is 70. Women >> men. 15-25/100,000. High prevalence in Scandinavian countries. Less common in blacks and hispanics.

Temporal Arteritis (TA)

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).

Clinical Features

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.

Treatment and Prognosis

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

Takayasu’s Arteritis

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.

Diagnosis/Treatment/Prognosis

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.

Granulomatosis with Polyangiitis (Wegener’s Granulomatosis)

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.

Clinical Features

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.

Diagnostic Studies

Diagnosis: Open lung biopsy Biopsy of other tissues Angiogram

Treatment:

Steroids plus

Rituximab Cyclophosphamide Methotrexate (in absence of life threatening lung or kidney disease).

Diagnosis/Treatment

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

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), high-

intensity T2-weighted fluid attenuation inversion recovery (FLAIR) lesions on MRI in the subcortical white and deep gray matter.

Diagnosis: granulomatous angiitis on biopsy.

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).

PACNS- Atypical PACNS subtype

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).

PACNS

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.

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)

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).