Polyarteritis Nodosa

The NEJM released a recent study about Polyarteritis Nodosa, which is a vasculitis of the medium size vessels, and identified a mutant ADA2 (Adenosine Deanimase 2) as a possible cause. Normal ADA 2 will degrade adenosine into inosine. Adenosine will suppress inflammation in acute events such as ischemia or infection but if it is chronically elevated, adenosine can actually promote inflammation. If the enzyme ADA2 is mutated, there will be chronically elevated levels of adenosine around and this supports the possible connection of ADA2 to vasculitits. It was an interesting article to read as Rheumatology is a strong interest of mine and I felt the need to brush up on Polyarteritis Nodosa.

Etiology

Most cases are idiopathic however Hepatitis B and C as well as Hairy Cell Leukemia are among the infections that can cause Polyarteritis Nodosa.

Pathology

Polyarteritis nodosa is a systemic segmental transmural necrotizing vasculitis that typically affects medium-sized muscular arteries (spares the veins), with occasional involvement of small muscular arteries. Unfortunately, the pathogenesis of the disease is poorly understood and thought to be autoimmune related although the NEJM article mentioned above postulates a mutation in ADA2 as a possible cause. Polyarteritis nodosa is not associated with antineutrophil cytoplasmic antibodies (ANCA) which sets it apart from granulomatous with polyangitis (Wegner's) and microscopic polyangitis.

Symptoms

Patients typically present with systemic symptoms and commonly affects the kidneys, skin, muscles, nerves, coronary arteries and gastrointestinal tract tendency to spare the lungs.

• Renal - renal insufficiency, hypertension, perirenal anerurysms, infarction, glomerulonephritis is typically not present and more consistent with the ANCA vasculitis
• Skin - tender erythematous nodules, purpura, raynauds, livedo reticularis, ulcers, and bullous or vesicular eruption. Skin lesions may be focal or diffuse and often more marked over the lower extremities. If the skin involvement progresses there can be infarction and gangrene of the fingers, toes, or other areas and ulceration extending into the subcutaneous tissue. 
• Muscles - The muscles are commonly involved and symptoms include myalgia and muscle weakness. Serum creatinine kinase levels may be elevated but not as elevated as a inflammatory myopathy.
• Nerves - A mononeuropathy multiplex, also known as asymmetric polyneuropathy, is one of the most common symptoms in polyarteritis nodosa affecting about 70% of patients. It typically affects the radial, ulnar and peroneal nerves and can present with both motor and sensory deficits. The neuropathy is typically asymmetric at the onset of the disease but can progress and involve multiple nerve branches causing a symmetric polyneuropathy.
• Gastrointestinal - May present as nausea, vomiting, melena, bloody or nonbloody diarrhea or life-threatening gastrointestinal bleeding. Mesenteric arteritis may present as post prandial abdominal pain and may lead to weight loss from fear of pain after eating. 
• Coronary arteries - Myocardial ischemia or heart failure from either vasculitis of the coronary arteries or from uncontrolled hypertension from renal insufficiency. 

Diagnosis 

Vasculitis should be considered in patients who present with systemic symptoms (fatigue, weakness, fever and arthralgias) in addition to single and/or multiorgan dysfunction (abdominal pain, renal insufficiency/failure). As with all of the other vasculitidies, you ultimately need a biopsy for an accurate diagnosis. The biopsy can be done anywhere where there is disease such as the sural nerve or an ulcer. If a biopsy cannot be done, you can do an arteriogram to look for aneuryms. The American College of Rheumatology has a list of criteria for the classification of PAN with a sensitivity of 82% and specificity of 87%.  To fit the classification of PAN, patient must have 3/10 of the following criteria 

• Otherwise unexplained weight loss >4 kg (about 9lbs or more)
• Livedo reticularis
• Testicular pain or tenderness
• Myalgias (excluding the shoulder and hip girdle), weakness, or polyneuropathy
• Mononeuropathy or polyneuropathy
• New onset diastolic blood pressure >90 mmHg
• Elevated levels of serum blood urea nitrogen (>40 mg/dL or 14.3 mmol/L) or creatinine (>1.5 mg/dL or 132 mcmol/L)
• Evidence of hepatitis B virus infection via serum antibody or antigen serology
• Characteristic arteriographic abnormalities (microaneurysms) not resulting from noninflammatory disease processes or occlusions of visceral arteries
• A biopsy of medium- or small-sized artery containing polymorphonuclear cells

Treatment

Without treatment, the prognosis of PAN is quite poor. Remission may be induced in about 50% of cases treated with glucocorticoids. The other cases need cyclophosphamide in addition to glucocorticoids. If the patient's PAN is secondary to Hep B or C infection, you may not treat the patient with cyclophosphamide. Once the patient is in remission, cyclophosphamide may be replaced with Methotrexate or azathioprine.