Intermittent fevers

Hepatosplenomegaly (can be evidence of portal hypertension)

Systemic hypertension

Blood pressure and other vital signs, as systemic hypertension and/or fever are common.

Skin examination for evidence of livedo reticularis/racemosa, nodules, and Raynaud phenomenon. Severe involvement can include digital infarcts/gangrene or skin ulcerations.

Assessment for lymphadenopathy and hepatosplenomegaly.

Neurologic examination for evidence of prior or recent strokes.

Ophthalmologic examination for vision loss, diplopia, retinal infarcts, optic nerve damage, uveitis, ptosis, strabismus, and nystagmus

Electrocardiogram (ECG) for manifestations of portal hypertension, including prolonged QT interval

Neurologic examination for evidence of prior or recent strokes

Ophthalmologic examination for ptosis, abnormal eye movements, retinal infarcts, optic nerve damage

ECG (if abnormal in the past). Note: Arterial hypertension, reported in 20% of patients, can lead to myocardial dysfunction.

Laboratory assessment (performed yearly or sooner if clinically indicated):

CBC and differential

ESR and CRP

Kidney and liver function

Quantitative serum immunoglobulins

Lymphocyte phenotyping for evidence of a B-cell maturation defect

Additionally, follow-up evaluation of abnormal laboratory studies identified at earlier evaluations

Imaging assessment (yearly or if clinically indicated):

Brain MRI if abnormal in the past or new symptoms or manifestations suggest brain involvement

Peripheral MRA if symptoms of peripheral arterial disease and/or neurologic dysfunction

Abdominal ultrasound examination to assess liver, spleen, and kidney size and hepatic blood flow

FibroScan® ultrasound examination (if available) to assess hepatic elasticity for evidence of early portal hypertension

Liver biopsy (if clinically indicated) is the most reliable way to diagnose diffuse hepatic disease (e.g., in the presence of portal hypertension).