Granulomatosis With Polyangiitis: A Rare Autoimmune Disorder

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare autoimmune disorder that causes the inflammation of blood vessels in different parts of the body.

Causes

As with all autoimmune disorders, GPA is characterized by an immune system gone awry. For reasons unknown, the body will mistakenly identify normal tissue in blood vessels as foreign. In order to contain the perceived threat, immune cells will surround the cells and form a hardened nodule known as a granuloma.

The formation of granulomas can lead to the development of chronic inflammation in the affected blood vessels (a condition known as vasculitis). Over time, this can structurally weaken the vessels and cause them to burst, usually at the site of the granulomatous growths. It can also cause the blood vessels to harden and narrow, cutting the blood supply to key parts of the body.

GPA mainly affects small- to medium-sized blood vessels. While the respiratory tract, lungs, and kidneys are the main targets of attacks, GPA can also cause damage to the skin, joints, and nervous system. The heart, brain, and gastrointestinal tract are rarely affected.

GPA affects men and women equally, primarily between the ages of 40 and 60. It is considered an uncommon illness with an annual incidence of only around 10 to 20 cases per one million people.

Early Signs and Symptoms

The symptoms of GPA vary by the location of the vascular inflammation. In early-stage disease, the symptoms can often be vague and non-specific such as a runny nose, nasal pain, sneezing, and post-nasal drip.

However, as the disease progresses, other, more serious symptoms may develop, including:

• Weight loss
• Fatigue
• Loss of appetite
• Fever
• Nose bleeds
• Chest pains (with or without shortness of breath)
• Middle ear pain

The generalized nature of these symptoms can often make the diagnosis difficult. It is not uncommon, for example, for GPA to be misdiagnosed and treated as a respiratory infection. It only when healthcare providers can find no evidence of a viral or bacterial cause that further investigations may be ordered, particularly when there is evidence of vasculitis.

Systemic Symptoms

As a systemic disease, GPA can cause injury one or several organ systems at once. While the location of symptoms can vary, the underlying cause (vasculitis) can usually point the healthcare provider in the direction of an autoimmune diagnosis if multiple organs are involved.

Systemic symptoms of GPA may include:

• The collapse of the nasal bridge due to a perforated septum (also known as the "saddle nose" deformity similar to that seen with long-term cocaine use)
• Tooth loss due to underlying bone destruction
• Sensorineural hearing loss caused by damage to the inner ear
• The development of granulomatous growths in parts of the eye
• Voice changes due to the narrowing of the trachea
• Blood in urine (hematuria)
• The rapid loss of kidney function leading to kidney failure
• A cough with bloody phlegm due to the formation of granulomatous lesions and cavities in the lungs
• Arthritis (often initially diagnosed as rheumatoid arthritis)
• The development of red or purple patches on the skin (purpura)
• Numbness, tingling, or burning sensations caused by nerve damage (neuropathy)

Methods of Diagnosis

The diagnosis of GPA is typically only made after several, unrelated symptoms go unexplained for a long period of time. While there are blood tests available to identify the specific autoantibodies associated with the disease, the presence (or lack) of antibodies is not enough to confirm (or reject) a diagnosis.

Instead, diagnoses are made based on the combination of symptoms, lab tests, X-rays, and the results of a physical examination.

Other tools may be needed to support a diagnosis, including a biopsy of the affected tissue. A lung biopsy is usually the best place to start even if there are no respiratory symptoms. Biopsies of the upper respiratory tract, by contrast, tend to be the least helpful since 50 percent will show no signs of granulomas or tissue damage.

Similarly, a chest X-ray or CT scan can often reveal lung abnormalities in persons with otherwise normal lung function.

Together, the combination of tests and symptoms may be enough to support a GPA diagnosis.

Current Treatment

Before the 1970s, granulomatosis with polyangiitis was considered almost universally fatal, most often due to respiratory failure or uremia (a condition involving abnormally high levels of waste products in the blood).

In recent years, the combination of high-dose corticosteroid and immune suppressive drugs has proven effective in achieving remission in 75 percent of cases.

By actively reducing inflammation with corticosteroids and tempering the autoimmune response with immune suppressive drugs like cyclophosphamide, many persons with GPA can live long, healthy lives and remain in remission for 20 years or more.

After initial treatment, corticosteroid dosages are usually reduced as the disease is brought under control. In some cases, the drugs may be stopped altogether.

Cyclophosphamide, by contrast, is usually prescribed for three to six months and then switched to another, a less toxic immunosuppressant. The duration of maintenance therapy can vary but typically lasts for a year or two before any dose changes are considered.

In persons with severe disease, other, more aggressive interventions may be needed, including:

• Higher-dose intravenous therapy
• Plasma exchange (where blood is separated to remove the autoantibodies)
• Kidney transplant

Prognosis

Despite high remission rates, up to 50 percent of treated individuals will experience a relapse. Moreover, persons with GPA are at risk of long-term complications, including chronic kidney failure, hearing loss, and deafness. The best way to avoid these is to schedule regular checkups with your healthcare provider as well as routine blood and imaging tests.

With the proper management of the disease, 80 percent of successfully treated patients will live for at least eight years. Newer antibody-based therapies and a penicillin-like derivative called CellCept (mycophenolate mofetil) may further improve those results in the coming years.