© 2019 by Mark Street.

Vasculitis Types //

There are a number of vasculitis subtypes dependant upon the vascular vessels and location of organs affected. Some of the more common include:

Polyarteritis Nadosa (PAN)

PAN is a systemic vasculitis characterised by inflammatory lesions that affect medium-sized and small muscular arteries. PAN, like other vasculitides, affects multiple systems, although it most commonly affects skin, joints, peripheral nerves, the gut, and the kidneys.

In 1990, the American College of Rheumatology (ACR) established criteria for research purposes in order to differentiate PAN from other forms of vasculitis. A committee of ACR physicians selected 10 disease features of PAN; in order for PAN to be diagnosed, at least 3 of the 10 ACR criteria should be present when radiographic or pathological diagnosis of vasculitis is made:

  • Livedo reticularis

  • Testicular pain/tenderness

  • Myalgia or leg weakness/tenderness

  • Mononeuropathy or polyneuropathy

  • Diastolic blood pressure greater than 90 mm/Hg

  • Elevated blood urea nitrogen (BUN) or creatinine level unrelated to dehydration or obstruction

  • Presence of hepatitis B surface antigen or antibody in serum

  • Arteriogram demonstrating aneurysms or occlusions of the visceral arteries

  • Biopsy of small- or medium-sized artery containing polymorphonuclear neutrophils

The treatment includes corticosteroids and cyclophosphamide for critical organ involvement. It should be noted that cyclophosphamide is not normally used for patients with Hepatitis B. Biological agents such as Rituximab has demonstrated good results.

The prognosis for PAN is often very positive with the majority of patients living a normal life expectancy if detedcted early. Source: Polyarteritis Nadosa

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

EGPA (Formerly known as Churg-Strauss disease) is a small and medium vessel necrotising disease characterised by extravascular necrotising granulomas (usually rich in eosinophils). The disease can affect any organ, predominantly the lungs, skin, sinuses, cardiovascular system, kidneys, peripheral nervous system, CNS, joints, and GI tract, with occasional lung heamorrage.

The cause of EGPA is unknown. However, an allergic mechanism, with tissue directly injured by eosinophils and neutrophil degranulation products, may be involved. Activation of T lymphocytes seems to help maintain eosinophilic inflammation. The syndrome occurs in patients who have adult-onset asthma, allergic rhinitis, nasal polyposis, or a combination. Antineutrophil cytoplasmic autoantibodies (ANCA) are present in about 40% of cases.

Diagnosis is via clinical presentation, blood tests (ANCA and Inflammatory markers), and radiological scans (may demonstrate pulmonary infiltrates) and biopsy. Moreover, the American College of Rheumatology,classifies EGPA as consisting of:

  • Asthma

  • Eosinophilia of > 10% in peripheral blood

  • Paranasal sinusitis

  • Pulmonary infiltrates, sometimes transient

  • Histologic evidence of vasculitis with extravascular eosinophils

  • Multiple mononeuropathy or polyneuropathy

If ≥ 4 criteria are present, sensitivity is 85%, and specificity is 99.7%.

The treatment involves the use of corticosteroids, and in more severe cases involving multiple or vital organs the use of cyclophosphamide, azathioprine, methotrexate or Rituximab.

The prognosis for patients with EGPA is often very positive with early diagnosis and treatment. However, relapses may occur in up to 50% of patients and therefore require ongoing review by their specialists. For more  information on EGPA 

Giant Cell Arteritis

Giant Cell Arteritis involves inflammation of large and medium sized blood vessels such as vessels of the temple area, in the neck, and thoracic aorta. Symptoms commonly presented include headaches, scalp tenderness, jaw pain, blurred or double vision, and even blindness. It is also called temporal arteritis. Giant cell arteritis is linked to polymyalgia rheumatica, which causes pain and stiffness in muscles of the neck, shoulders, hips and thighs. A classic symptom of this condition is pain in the tongue or jaw when eating (jaw claudication). 

The diagnosis is via clinical presentation of the signs and symptoms, along with blood tests (inflammatory markers) and possibly ultrasound or biopsy of affected tissue.

Treatment involves corticosteriods, azathioprine, cyclophosphamide, methotrexate and Rituximab.

Prognosis is often good with early detection and treatment. Relapse rates are common upon reduction or withdrawal of medication, however the reintroduction of corticosteriods is often successful in remission.

Granulomatosis with Polyangiitis (GPA)

GPA (Formerly known as Wegener's Granulomatosis) is a disease that involves inflammation of the small- and medium-sized vessels, and focal inflammation of the kidneys. Typically, the upper and lower respiratory tract and the kidneys are affected, but any organ may be including the ears, skin, cardiovascular system, and nervous system. Symptoms vary depending on the organs and systems affected. Patients may present with upper and lower respiratory tract symptoms (eg, recurrent nasal discharge or epistaxis, cough), followed by hypertension and edema, or with symptoms reflecting multiorgan involvement. Other systemic illnesses are often associated with the inflammatory aspect of the disease including night sweats with or without fever, weight loss, lethargy, joint swelling and pain and malaise. It should be noted that whilst GPA is considered a systemic disease, the organs involved vary from patient to patient. Some have 'limited' disease activity where only the upper respiratory tract is implicated. In contrast, other patients develop kidney inflammation, in particular of the nephrons (termed glomerulonephritis).

The cause is unknown, although immunologic mechanisms play a role. Most patients with active generalised disease have antineutrophil cytoplasmic antibodies (ANCA).

Diagnosis usually requires blood tests (Inflammation markers and white blood cell counts), clinical presentation, radiological scans (particularly of the lung/s to reveal granuloma infiltrates), urinalysis, and biopsy of the primary inflammation site. The latter considered the 'gold standard' or confirmatory diagnostic test for GPA.  

Treatment involves two (2) aspects, namely induction and maintenance. The induction drug regime is dependant upon the disease severity. For non-critical organ involvement, a combination of corticosteroids plus an immunosuppressant such as methotrexate or azathioprine. For more severe disease cyclophosphamide or, Rituximab along with high doses of corticosteriod which is tapered down over time. Refer to Treatment to watch a video on the mechanism of action of Rituximab, which is proving to be a much safer and just as efficacious as traditional immunosuppresants.

Prognosis is dependant upon disease progression, however early diagnosis and treatment often results in a good prognosis. Remission is usually possible, although relapses are common.

For more information on GPA.

Henoch-Schönlein Purpura (HSP)

HSP is the most common form of vasculitis in children. It affects predominantly small blood vessels and capillararies. It can affect the skin, joints, bowel and kidneys. If it affects the kidneys it is usually called Henoch-Schönlein Nephritis or Vasculitic IgA Nephropathy. Skin involvement is often indicated by the display of a widespread palpable (small bumps) purpuric (red/purple) rash.

Diagnosis is via blood tests (Inflammatory markers) and possibly IgA levels. With kidney involvement, a biopsy may be ordered as a differential diagnosis.

Treatment seldomly requires the use of corticosteroids or immunosuppressants, unless kidney involvement. Patients with the disease often are in permanent remission as they age.

Whilst relapses are common, the disease is often mild and self-limiting. Prognosis is therefore very good.

Microscopic Polyarteriitis (MPA)

MPA is is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels. It may begin as a pulmonary-renal syndrome with rapidly progressing glomerulonephritis and alveolar hemorrhage, but the pattern of disease depends on the organs affected. The symptoms include general systemic symptoms of fever, weight loss, myalgia, and arthralgia occurs. Other symptoms depend on which organs and systems are affected:

  • Renal: The kidneys are affected in up to 90% of patients. Hematuria, proteinuria (sometimes > 3 g/24 h), and RBC casts are present. Without prompt diagnosis and treatment, renal failure may follow rapidly.

  • Cutaneous: About one third of patients have a purpuric rash at the time of the diagnosis. Nail bed infarcts and splinter hemorrhages may occur; digital ischemia occurs rarely.

  • Respiratory: If the lungs are affected, alveolar hemorrhage may occur and may be followed by pulmonary fibrosis. Rapid-onset dyspnea and anemia, with or without hemoptysis and bilateral patchy infiltrates (seen on chest x-ray) may be due to alveolar hemorrhage, a medical emergency that requires immediate treatment. Mild symptoms of rhinitis, epistaxis, and sinusitis may occur; however, if the upper respiratory tract is severely affected, the cause is more likely to be GPA.

  • GI: GI symptoms include abdominal pain, nausea, vomiting, diarrhea, and bloody stools.

  • Neurologic: If the nervous system is affected, multiple mononeuropathy (mononeuritis multiplex) that affects peripheral or cranial nerves usually occurs. Rarely, cerebral hemorrhage, infarction, seizures, or headache results from cerebral vasculitis.

  • Cardiac: Rarely, the heart is affected.

  • Ocular: If the eyes are affected, episcleritis usually results.

Diagnosis is through blood tests, radiological scans, clinical presentation, and biopsy.

Treatment involves the use of corticosteriods along with azathiprine or methotrexate for less severe disease or cyclophoshamide or Rituximab for critical organ involvement. Kidney involvement may require plasma exchange.

Prognosis is deemed good with early detection and treatment. Relapses can occur, however suitable retreatment often results in remission.

 

For more information on MPA.

Kawasaki Disease

Kawasaki disease is a systemic disease that affects predominately children <5 years of age. Like many autoimmune diseases, cause of the disease is not known, however it has been suggested that prior infection of some sort may be a contributing factor. Patients with the disease normally present with prolonged fever (5+ days), as well as:

  • polymorphous rash

  • bilateral (non purulent) conjunctival infection of the eye.

  • mucous membrane changes, e.g. reddened or dry cracked lips, strawberry tongue, diffuse redness of oral or pharyngeal mucosa

  • peripheral changes, e.g. erythema of the palms or soles, oedema of the hands or feet.

  • cervical lymphadenopathy (> 15 mm diameter, usually unilateral, single, non purulent and painful)

Additionally, blood tests may indicate elevated neutrophils and white blood cell counts, elevated liver enzymes, mild anemia, and raised CRP and ESR.

Patients require admission to hospital if Kawasaki Disease is diagnosed or strongly suspected, particularly as the disease may affect the coronary arteries of the heart.

  • Intravenous immunoglobulin (2 g/kg over 10 hours; preferably within the first 10 days of the illness but should also be given to patients diagnosed after 10 days of illness if there is evidence of ongoing inflammation - eg fever, raised ESR/CRP) 
    Administration of Intragam Guideline

  • Aspirin 3 - 5 mg/kg once a day for at least 6 to 8 weeks.  
    Some give a higher dose (10mg/kg 8 hourly for the first few days) but this probably adds nothing over immunoglobulin. (Source: The Royal Children's Hospital Melbourne)

For more information on any of these vasculitis diseases refer to the Resources section.