Digital ulcerations:A case of cutaneous polyarteritis nodosaAlejandro Perez, MD, FSVM, RPVIProvidence Heart and Vascular Institute, Vascular MedicineRegional Medical Director for Providence Wound Care and Hyperbaric Program

Columbia Wound Care ConsortiumQuarterly Symposium - 7/26/2014

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Disclosures

None

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Objectives

• Understand workup of causes of digital ulcerations

• Diagnosis of cutaneous polyarteritis nodosa (PAN)

• Treatment of PAN

Case

• 44 y/o man c/o toe ulcerations

• Has had leg skin abnormalities for 9 months.

• First noted swelling of feet and ankles.

• Active marathon runner and kept exercising.

Case- Additional History

• After 6 months developed distal ischemia.

• Right toe ulcers 2,3 developed first and progressed to eschar by 8th month of symptoms

• Left toe ulcers 1-4 at earlier stages of progression with less involvement

Case- Additional History

• Has had bx to r/o cutaneous PAN.

• Pathology results of left arm/leg revealing for perivascular inflammatory infiltrate (plasma cells, eosinophils) without definitive vasculitis.

• Had been started on prednisone with resolution of swelling.

• Has had no systemic symptoms of fever or fatigue.

Case

Past Medical History

• Iron deficiency anemia

Past Surgical History

• Tonsillectomy

• Vasectomy

Family History

• Sister- RA, Mother- cancer

Case

Social History

• Never a smoker; no illicit drug use

• From India, but immigrated 20 yrs prior

• Works as computer programmer

Review of Systems

• (-) for fevers, weight loss; (+) for leg swelling and toe ulceration, (+) anemia

Case

Current Medications:• Acetaminophen 650 mg PRN • ASA 325 mg daily.• Cholecalciferol (Vita D-3) 1,000 U Daily • Clopidogrel 75 mg daily• Prednisone 30 mg daily• Probiotic

Allergies: NKDA

Case- On Examination

• Vital Signs: BP: 122/82 mmHg P: 70 , Weight: 128 lbs, Height: 5' 10" | BMI 18.37

• General: Well appearing thin man. No distress.

• Cardiovascular:

• Regular rhythm. Normal S1 and S2. No murmurs.

• Normal carotid pulses. No carotid bruits.

• Abdominal aorta: Normal aortic impulse. No abdominal bruit.

• Peripheral pulses: 2+ Radial, Femoral, DP, PT

• No edema

Case- Toe ulcerations

Skin examination:

• Right toe ulcers 2,3. Left toe ulcers 1-4. Toe ulcers with eschar and no purulence. Livedo pattern to feet

• Hyperpigmentation of distal legs.

Right foot ulcer

Left foot ulcer

Laboratory Testing

• Negative: Factor V Leiden mutation, Prothrombin gene mutation, Protein C/S deficiency, AntiThrombin III deficiency, Lupus anticoagulant.

• Mild elevation of cardiolipin Ig M antibody, beta2 glycoprotein Ig M antibody

• ESR has been elevated on 2 checks

Laboratory Testing

• RA negative:RF and anti-CCP ab

• Normal: ANA, cryoglobulin, Hepatitis B/C, platelet function, ANCA panel( including myeloperoxidase and serine PR3 testing)

Imaging studies

• Arterial leg study, CTA chest/abdomen/pelvis and TTE without pathology

Digital testing:

• Right 2nd, 3rd, 4th digit: ischemia noted.

• Left 2nd,3rd,4th, 5th digit: ischemia noted.

Digital ulcers – Multiple Causes

• Trauma/Thermal Injury/Radiation fibrosis• Spider bite• Drug induced, Ergotism• Atheroembolic• Cardioembolic• Raynaud’s, Chilblains(pernio)• Rheumatologic/Autoimmune• Buerger’s(TAO)

Polyarteritis Nodosa

• Systemic necrotizing vasculitis that affects medium-sized muscular arteries; occasional involvement of small muscular arteries

• Kidneys, skin, joints, muscles, nerves, and gastrointestinal tract are commonly involved

• Spares the lungs

Polyarteritis Nodosa

• Diagnosis usually in middle-aged or older adults

• Incidence rises with age, with a peak in the sixth decade

• 1.5:1 male predominance• Can affect children• Hepatitis B/C virus,and hairy cell

leukemia lead to secondary PAN

Diagnosis of PAN –ACR criteriaAt least three of the following criteria are present:•Otherwise unexplained weight loss >4 kg•Livedo reticularis•Testicular pain or tenderness•Myalgias/weakness•Mononeuropathy or polyneuropathy•New-onset diastolic BP > 90 mmHg•Elevated BUN(>40 mg/dL) or creatinine (>1.5 mg/dL)•Evidence of HBV infection •arteriographic abnormalities not from noninflammatory disease processes •A biopsy of small/ medium-sized artery with PMNs

Biopsy

• Nodules and ulcers: small 2 to 4 mm “punch” biopsies of the skin sample only the epidermis and superficial dermis and unlikely to include muscular arteries.

• Elliptical surgical skin biopsies that include deeper dermis and subcutaneous fat more helpful

PAN- histology

• PAN does not involve veins. • cellular infiltrate contains PMLs and

mononuclear cells. • Fragments of WBCs (leukocytoclasis).• Fibrinoid necrosis: Necrosis of the arterial wall

results in a homogeneous, eosinophilic appearance.

• Disruption of the internal and external elastic lamina -> aneurysms

Cutaneous PAN

Skin manifestations:

•Tender erythematous nodules

•Purpura

•Livedo reticularis

•Ulcers

•Bullous/vesicular eruption

Cutaneous PAN

• Lesions may be focal or diffuse

• Typically on lower extremities.

• Limb edema is common.

• Infarction and gangrene of the fingers, toes, extending into the subcutaneous tissue.

Other possible vasculitis

• Granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

• Henoch-Schönlein purpura (IgA vasculitis)• Cryoglobulinemic vasculitis• Drug-induced vasculitis• Vasculitis secondary to connective tissue disease

(eg, systemic lupus erythematosus, rheumatoid arthritis)

Laboratory studies

• creatinine, muscle enzymes, LFTs, HBV and HCV, and urinalysis.

• ESR and CRP• Antineutrophil cytoplasmic Ab (ANCA)• Antinuclear antibodies (ANA)• Complement components (C3 and C4)• Cryoglobulins• Serum and urine electrophoresis for monoclonal

gammopathy• Testing for HIV

Treatment of cutaneous PAN

• Initially glucocorticoids alone

• Prednisone 1 mg/kg daily (max 60- 80 mg daily) x four weeks

• Taper to 20 mg daily by month 3 or 4

• Taper slowed: -2.5 mg daily every 14 days

• If not improving can consider azathioprine, methotrexate, mycophenolate

PAN

• Untreated, 13 percent five-year survival

• If treated, five-year survival is approximately 80 percent

Followup

deeper sections are obtained … at the dermal subcutaneous fatty tissue junction, there is a single medium-sized blood vessel which wall is infiltrated byneutrophils. There is a surrounding inflammatory infiltrate, containing neutrophils, eosinophils, plasma cells, and lymphocytes…most consistent with subtle vasculitis. Similar changes can be seen in POLYARTERITIS NODOSA as well as other vasculitides, affecting medium sized vessels."

Followup – Toe ulcerations

• Maintained on prednisone and continues to improve.

• Started on CCB to help with peripheral flow.

• Left toe ulcers nearly healed• Right toe ulcers demarcated• Foot pain greatly improved

Summary

• Suspect vasculitis in setting of digital ulcerations.

• Biopsy is often necessary for diagnosis of PAN.

• Steroid therapy helps most for treatment of cutaneous PAN.