Predominately small vessel

Microscopic polyangiitis (MPA)

  • What is it?
    • Microscopic polyangiitis is a form of vasculitis that mainly affects small blood vessels in the body, commonly those in the kidneys. It is a part of a group of pediatric conditions known as ANCA-associated vasculitides (AAV). This group of conditions involves patients who are found to display the presence of ANCA (anti-neutrophil cytoplasmic antibodies). For example, 90% of patients with either MPA or GPA were found to be positive for ANCAs. Overall, the two most common symptoms in patients with MPA include the involvement of the kidneys and the lungs.
    • It is tough to separate MPA from GPA; however, there are a couple features that can help doctors make a diagnosis. For example, MPA does not lead to the formation of granulomas, which are organized collections of immune cells that form in the body. Not only does GPA involve the formation of these granulomas, but also more commonly involves the lungs and airways of the nose and sinuses. Additionally, MPA is less common, and less well-known than GPA, and therefore there is less information available about this disease.
  • How does it happen?
    • Since MPA does not involve granulomas, it can often be separated from GPA and EGPA. So in the case of MPA, like in other forms of vasculitis, there can be swelling that occurs in the walls of the blood vessels. This leads to the walls thickening, and therefore the narrowing of the blood vessels. This narrowing then can lead to damaging the cells around the blood vessel.
  • The causes of MPA are currently unknown, but various factors have been discussed in different studies. Also, the presence of ANCAs play a role in causing blood vessel inflammation by activating immune cells, but the origin of ANCAs is still unknown.
  • MPA is rarer than GPA as a disease, with rates that are much smaller than 1 out of every 1 million children each year. Patients with MPA are most commonly white, while both genders are equally affected.
  • Children with MPA are usually found to be positive for ANCA, and the most common organs that become involved include the lungs and the kidneys.
  • Click here for more detailed information on classifying and diagnosing GPA.
  • Induction therapy is comprised of a combination of corticosteroids and cyclophosphamide (common chemotherapy drug) and is used in treating patients with GPA. After the disease settles, a combination of different drugs is used as a form of maintenance therapy.
    • Click here for more detailed information on suggested treatment protocols.
  • There are specific criteria that are set by the EULAR/PRINTO/PRES, however there are some criteria that can help doctors distinguish MPA from similar diseases like GPA and EGPA.
    • For example, if there is a necrotizing vasculitis (resulting in cells dying), and an absence of granuloma formation, then doctors can be more sure that the patient has MPA, and probably not GPA or EGPA.

Diagnosis:

In order to reach a diagnosis, it is important to consider a combination of clinical features, laboratory tests, along with biopsy results. For more details view the diagnostic algorithm for MPA.

    • Below is a table of symptoms of MPA patients in various studies. The most common symptoms that are seen in patients with MPA include pulmonary/respiratory symptoms (lung-related) and renal symptoms (kidney-related).
      • It is important to note that not all of the symptoms mentioned below are displayed by every patient.

    Type of Symptom

    Symptoms

    Constitutional/General

    Malaise, fatigue

    Fever

    Weight loss

    Cutaneous (skin-related)

    Palpable purpura/petechiae (lower limbs)

    Eye

    Nonspecific red eye

    Conjunctivitis

    Scleritis

    Retinal vasculitis

    Optic nerve damage

    Corneal ulceration

    Renal

    Abnormal urianalysis results

    Biopsy-proven glomerulonephritis

    Elevated serum creatinine

    Ears, Nose, Throat

    Nasal involvement

    Sinusitis

    Otitis/mastoiditis

    Hearing loss

    Oral ulcers

    Pulmonary/Respiratory

    Shortness of breath

    Chronic cough

    Hemoptysis/alveolar hemorrhage

    Nodules

    Abnormal pulmonary function test results

     

    Venous thrombotic event

    Deep vein thrombosis

     

    Other

    In MPA, any of the body’s organs can be affected. Some other organs that can be involved include the heart, breast, liver, thyroid, or the gastrointestinal tract.
    • Patients with MPA can experience some or all of the following:

     

  • Inflammatory markers
    • Certain abnormalities in the blood such as an increased erythrocyte sedimentation rate (ESR) or an increase in C-reactive protein (CRP) levels can help doctors understand a patient’s condition. However, a patient may have normal results but still have an ANCA-associated vasculitis such as MPA.
  • Autoantibodies
    • A large proportion of pediatric patients with MPA are found to be positive for ANCA (antineutrophil cytoplasmic antibodies). A majority of these ANCA-positive patients are found to have myeloperoxidase (MPO) ANCA. This is different compared to patients with GPA, who often are found to have PR3-ANCA (also known as cANCA). However, there are 20% of patients who have a different form of ANCA, and another 10% of patients are found not to have the presence of ANCAs.
  • Additional tests
    • Blood tests
      • Some patients have been found to have a lower number of red blood cells (anemic)
    • Urine tests and Kidney Function tests
      • Patients that are suspected to have MPA should have tests done to test for kidney involvement, which often indicates damage to the kidney.
  • These tests can be done to help check whether there is lung involvement, and understand what course of treatment to take.
  • In terms of lung involvement, interstitial lung disease (ILD) was found in a study to be more commonly seen in patients with MPA. ILD can actually be found to be present in patients before systemic vasculitis even becomes present.
  • Compared to the role of imaging in diagnosing large-vessel systemic vasculitis diseases, imaging plays a far more limited role with small-vessel diseases. The vessels in GPA are too small to be captured by techniques that visualize blood vessels. However, imaging techniques can still assist in assessing tissue damage caused by GPA.
  • Possible imaging tools used in assessing GPA:
    • Ultrasound
    • Chest Radiographs
      • 1 – Chest radiography and thin-section CT can be used to check for lung involvement in patients with MPA.
    • Computed Tomography (CT)
      • See Ex. 1 above.
  • A biopsy of an affected organ is a very important technique in diagnosing MPA. Though it may not be ideal in many cases because of how invasive it can be, it is still the most accurate method available. Skin or kidney biopsies are the ones most commonly done, however in certain cases, lung biopsies can also be done.

Corticosteroids

  • Glucocorticoids (ex. prednisone) are usually used in the treatment of MPA in order to suppress the systemic symptoms and arrest the progression of MPA. More specifically, these medications suppress the immune system and help reduce the amount of inflammation of the blood vessels.

Traditional immunosuppressants

  • Cyclophosphamide (CYC)
  • Methotrexate (MTX)
  • Azathioprine (AZA)
  • Mycophenolate mofetil (MMF)

Immunosupressants are often used in combination with steroids. It is important to note that different combinations of medications are used at different phases in the treatment of GPA. For example, initially, corticosteroids and cyclophosphamide are used together to begin treatment (induction therapy). Later on, maintenance therapy (see below) consists of drugs such as mycophenolate mofetil (MMF) or azathioprine (AZA). Also note that in milder cases of MPA, methotrexate (MTX) is used in conjunction with corticosteroids instead of cyclophosphamide.

Biological therapy

  • Rituximab

Refractory diseases, which do not respond to medications such as steroids and immunosupressants, can be treated using biological therapies.

 

Plasmapheresis

  • A technique that removes the liquid portion of the patient’s blood (called plasma) which may contain disease-related substances. After this, the body is given an infusion of fresh protein or plasma which allows the body to produce new plasma. This technique can be used for adult patients with serious MPA in order to help the kidneys recover.
  • During maintenance therapy, it has been found that relapses are common in children with MPA. Across a few studies, it was found that patients with MPA were found to show relapses in approximately 8% of patients after 1.5 years, and in 30-35% of patients after 4-7 years.
  • Birmingham Vasculitis Activity Score (BVAS)
    • 9 groups organized by organ system, and each system has various items to select
    • Each section has a maximum score, which can be used to find the total value for the BVAS
      • You can calculate the total value for BVAS for either a new/worse disease or a persistent disease.
      • The maximum score for persistent disease is 33, while the maximum new/worse disease score is 63.
    • Specific to the paediatric population
    • Paediatric Vasculitis Activity Score (PVAS)
      • A paediatric vasculitis assessment tool that is based off of BVAS
      • 64 active items with 9 organ sub-systems
      • This tool reports an overall score which reflects disease activity
    • Paediatric Vasculitis Damage Index (PVDI)
      • This is a modified version of the original Vasculitis Damage Index (VDI)
      • Contains 72 items across 10 systems in the body
      • Contains a separate page which reports school absence.
      • Each item receives one point, and reports an overall score.

Below you can find downloadable PDF files of suggested treatment protocols for patients with MPA.

Suggested Treatment Protocols:

  1. (These numbers depend on the types of treatment protocols provided for MPA)
  2. (These numbers depend on the types of treatment protocols provided for MPA)
  3. (These numbers depend on the types of treatment protocols provided for MPA)