Medium-Vessel Vasculitis

History, Epidemiology

Medium-vessel vasculitis affects medium-sized arteries. The two main types of medium-size vessel vasculitis are polyarteritis nodosa and Kawasaki disease.

Polyarteritis nodosa is a systemic necrotizing vasculitis, and Kawasaki disease is an acute febrile illness.1,2

First described in Japan by Tomisaku Kawasaki in 1967, Kawasaki disease usually occurs in children under 5 years of age.3 It often travels with a mucocutaneous lymph node syndrome.4 It typically occurs when an infectious agent enters the respiratory tract and kickstarts an inflammatory reaction. Kawasaki disease is a leading cause of acquired heart disease in the United States.3

Polyarteritis nodosa is systemic, but there is also a more limited form known as cutaneous polyarteritis nodosa. Polyarteritis nodosa can affect patients of either sex and of any ethnicity. It tends to strike people in their 50s and 60s.2

Some good news: polyarteritis nodosa is becoming more of a rarity. The reduced incidence is thought to be due to the decrease in hepatitis B virus (HBV) infection thanks to widespread vaccination efforts. Only 0 to 1.6 cases per million people are confirmed each year in European countries.2

East Asia has the highest incidence of Kawasaki disease, with 80 to 308.0 cases per 100,000 children under 5 years old. In non-Asian countries, the annual cases of Kawasaki disease are 10 to 20 per 100,000 in children younger than 5.2

Medium-Vessel Vasculitis Diagnosis

The diagnosis of polyarteritis nodosa involves clinical findings, biopsy, and sometimes arteriography.5

Symptoms of polyarteritis nodosa may include:

  • Weight loss2
  • Unexplained fever2
  • Asthenia2
  • Peripheral neuropathy. This is often the most frequent and earliest symptom of polyarteritis nodosa.2
  • Renal involvement. The kidney is the visceral organ most commonly affected by polyarteritis nodosa.2
  • Arthralgia2
  • Abdominal pain5
  • Skin ulcers5
  • Subcutaneous nodules5
  • New onset footdrop5 
  • New onset wristdrop5
  • Rapidly developing high blood pressure. This is more prevalent in patients with HBV-related polyarteritis nodosa.2
  • Heart failure, affecting the left ventricle more frequently than the right one2
  • Cardiomyopathy vasculitis2
  • Pericarditis2
  • Raynaud phenomenon. This occurs in 20% of cases, and in severe forms, digital vasculitis may lead to digital ischemia or necrosis.2
  • Stroke2
  • Seizures2
  • Headaches2
  • Encephalopathic symptoms2
  • Motor deficits2

Renal involvement in polyarteritis nodosa may be marked by the following5:

  • Hematuria
  • Moderate proteinuria
  • Slowly progressive renal failure

This occurs when there is inflammation in the renal and interlobar arteries, leading to microaneurysm formation, tissue infarction, or hematomas.2 

In cases of polyarteritis nodosa, 15% have serum creatinine levels >140 µmol/L, and 66% have kidney microaneurysms or stenoses.2

To properly diagnose polyarteritis nodosa, a biopsy will show necrotizing arteritis. Additionally, an arteriography of mid-sized arteries can reveal the typical aneurysms.5 Most biopsies are taken from skin, nerve or muscle tissue. Focus the biopsy on sites that are shown to be affected during clinical evaluation.5

An angiogram can detect narrowing of the blood vessels or aneurysms. Computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA) scans with dye may also be used to look for changes in blood vessels.11

Other lab testing should include5:

  • Antineutrophil cytoplasmic antibodies [ANCA]
  • Rheumatoid factor
  • Anticyclic citrullinated peptide [anti-CCP] antibody
  • Antinuclear antibodies [ANA]
  • C3 and C4 complement levels
  • Cryoglobulin levels
  • Nuclear antigens and antibodies

Laboratory test results with polyarteritis nodosa tend to be nonspecific.5

The following lab abnormalities are most common5:

  • Leukocytosis of up to 20,000 to 40,000/microL (20 to 40 × 109/L)
  • Thrombocytosis
  • Markedly elevated erythrocyte sedimentation rate
  • Anemia caused by blood loss or renal failure
  • Hypoalbuminemia
  • Elevated serum immunoglobulins
  • Mildly elevated Aspartate aminotransferase
  • Mildly elevated alanine aminotransferase

In addition, testing for hepatitis B and C should be done in patients with suspected polyarteritis nodosa.5

There is no specific test that can confirm Kawasaki disease. Early diagnosis of Kawasaki disease is essential as coronary abnormalities, including aneurysms, may develop within the first week of disease onset.6

Kawasaki disease may be characterized by the following6:

  • Elevated erythrocyte sedimentation rate
  • C-reactive protein level
  • Hyponatremia
  • Hypoalbuminemia
  • Coronary aneurysms

Time of year may also tip the scale in favor of a diagnosis. Kawasaki disease appears to be  seasonal, most often occuring from January to March in the U.S.6

Mnemonics for Kawasaki disease criteria4,12:

Warm CREAM and FEBRILE

Warm = Fever for > 5 days

C = Conjunctivitis without exudate
R = Rash
E = Edema or erythema of hands or feet, followed by desquamation and nail changes
A = Adenopathy, often unilateral, cervical node > 1.5 cm
M = Mucosal erythema, fissures or crusting of lips or strawberry tongue
 
F = Fever for > 5 days
E = Enanthem of mucosal membranes
B = Bulbar conjunctivitis
R = Rash, erythematous, polymorphous
I = Internal organ involvement: coronary abdominal, pneumonitis, hepatitis, orchitis
L = Lymphadenopathy: >1.5 cm, non-suppurative
E = Extremity changes, initial edema, and erythema, desquamation, nail changes

Kawasaki disease symptoms may include:

  • Fever3
  • Rash3
  • Swelling of the hands and feet3
  • Irritation and redness of the sclera6
  • Cervical lymphadenopathy6
  • Irritation and inflammation of the oral cavity6
  • Hydrops of the gallbladder, causing abdominal pain6
  • Hearing loss caused by nerve damage8
  • Sterile meningitis8

Although a diagnosis of Kawasaki disease usually requires a majority of these symptoms, patients may still be diagnosed with the condition if coronary artery abnormalities are found on echocardiography.6

Diagnostic Workup

Diagnosing Kawasaki disease involves a thorough physical exam.

Blood testing can help detect8:

  • Mild anemia
  • Elevated white-blood-cell count
  • Elevated erythrocyte sedimentation rate
  • Platelet elevation

Other tests include8:

  • Urinalysis for unusual white blood cells
  • Electrocardiogram (EKG) to test for arrhythmia and evidence of heart muscle strain
  • Echocardiography to identify possible damage to the heart or large blood vessels

Differential Diagnosis

Differential diagnoses of polyarteritis nodosa may include the following conditions9:

  • Infective endocarditis
  • Mycotic aneurysm with emboli
  • Human immunodeficiency virus  
  • Granulomatosis with polyangiitis
  • Microscopic polyangiitis
  • Churg-Strauss syndrome
  • Henoch-Schonlein purpura
  • Cryoglobulinemic vasculitis
  • Drug-induced vasculitis

Differential diagnoses with Kawasaki disease can include the following10:

  • Streptococcal and staphylococcal infections (including scarlet fever and toxic shock syndrome)
  • Measles
  • Glandular fever
  • Drug reactions such as Stevens-Johnson syndrome

Medium-Vessel Vasculitis Management
(Nonpharmacotherapy and Pharmacotherapy)

When hepatitis is not present, polyarteritis nodosa treatment includes corticosteroids like prednisone and immunosuppressants such as methotrexate and azathioprine.11 In the presence of hepatitis infection, antiviral agents are used in combination with plasma exchanges and corticosteroids during the first weeks of overt vasculitis.11

For Kawasaki disease, treatment entails high doses of intravenous gamma globulin (IVIG) 2 g/kg given as a single intravenous infusion) to cool inflammation and stave off coronary artery damage immediately after diagnosis. High doses of aspirin are also given with gamma globulin during the acute phase of the illness until the fever subsides.10

Not all patients respond to initial IVIG. In such cases, a second IVIG infusion of 2 g/kg with or without corticosteroids is most frequently used.4 Infliximab (anti–TNF-α, single 5 mg/kg infusion) is an alternative to a second IVIG infusion.6

Other alternative treatments in highly refractory Kawasaki disease include the following7:

  • Cyclosporine or cyclophosphamide
  • Glucocorticoids
  • Monoclonal antibody therapy
  • Plasmapheresis

If an aneurysm or any other heart or blood vessel abnormality is present, medical or surgical intervention may be required.8

Monitoring Side Effects, Adverse Events, Drug-Drug Interactions

Potential complications of treating polyarteritis nodosa may include the following11:

  • Aneurysms in kidneys, liver or GI tract
  • Abdominal pain, nausea, vomiting, or bleeding
  • Blood clots in affected arteries
  • Tissue damage or loss in affected areas 

Some of the medications that treat polyarteritis nodosa cause side effects. They may increase risk for infection and the brittle-bone disease, osteoporosis.11 Medications may be prescribed to offset these side effects. Recommend the flu shot, pneumonia vaccination, and/or shingles vaccination to reduce patients’ risk of infection.5

Complications from Kawasaki disease treatment are rare. IVIG infusions may cause chills, fever, and a drop in blood pressure. Halting the infusion and giving the patient an antihistamine before restarting can reverse these side effects.8

High doses of aspirin may sometimes cause the following8:

  • Abdominal pain
  • Gastrointestinal bleeds
  • Tinnitus
  • Reye Syndrome

Consider referral to a cardiologist to monitor a heart or blood vessel problems following recovery from Kawasaki disease.8 

There may be scarring of the blood vessels and heart muscle that can cause new problems in some young adults who have recovered from Kawasaki disease.8

Order a hearing test for kids with Kawasaki disease if there is any question about their hearing.8

Monitor for eczema and psoriasis in the weeks following the onset of fever.8 

In addition, temporary arthritis of the hips, knees, or ankles may occur after resolution of the fever.8

References

  1. Merkel PA. Overview of and approach to the vasculitides in adults. UptoDate. Accessed October 1, 2022
  2. Saadoun S, Vautier M, Cacoub P. Medium- and Large-Vessel Vasculitis. Circulation. 2021;143:267–282. Accessed October 1, 2022
  3. Centers for Disease Control and Prevention. About Kawasaki Disease. Updated May 29, 2020. Accessed October 1, 2022
  4. Owens AM. Kawasaki Disease. In: Statpearls. NCBI Bookshelf Version. StatPearls Publishing; 2022. Accessed October 1, 2022.
  5. Villa-Forte A. Polyarteritis Nodosa (PAN). Merck Manual Professional Version. Updated Sept. 2022. Accessed October 1, 2022.
  6. Saguil A, Fargo M, Grogan, S. Diagnosis and Management of Kawasaki Disease. Am Fam Physician. 2015;91:365-371. Accessed October 1, 2022.
  7. Sundel R.Refractory Kawasaki disease. UptoDate. Updated August 6, 2021. Accessed October 1, 2022.
  8. Kawasaki Disease Foundation. Kawasaki Disease Frequently Asked Questions. Accessed October 1, 2022.
  9. Stanton M, Tiwari V. Polyarteritis Nodosa. In: Statpearls. NCBI Bookshelf version. StatPearls Publishing; 2022. Accessed October 1, 2022.
  10. Harnden A, Takahashi M, Burgner D. Kawasaki disease. BMJ 2009;338:b1514. Accessed October 1, 2022.
  11. Polyarteritis Nodosa. Vasculitis Foundation. Accessed October 1, 2022.
  12. Kawasaki Disease – Diagnostic Criteria Mnemonic. Epomedicine. Updated October 7, 2016. Accessed October 18, 2022.

Author Bio

Denise Mann, MS, is a veteran freelance health writer in New York. Her work has appeared on HealthDay, among other outlets. She was awarded the 2004 and 2011 Journalistic Achievement Awards from the American Society for Aesthetic Plastic Surgery. She was also named the 2011 National Newsmaker of the Year by the Community Anti-Drug Coalitions of America. She has also been awarded the Arthritis Foundation’s Northeast Region Prize for Online Journalism, the Excellence in Women’s Health Research Journalism Award, the Gold Award for Best Service Journalism from the Magazine Association of the Southeast, a Bronze Award from The American Society of Healthcare Publication Editors, and an honorable mention in the International Osteoporosis Foundation Journalism Awards. She was part of the writing team awarded a 2008 Sigma Delta Chi award for her part in a WebMD series on autism. Mann has a graduate degree from the Medill School of Journalism at Northwestern University in Evanston, Ill.