Granulomatosis with Polyangiitis (GPA)
Granulomatosis with Polyangiitis (previously termed Wegener’s granulomatosis) is an uncommon disease, characterized by inflammation of the blood vessels or “vasculitis”. The inflammation may lead to damage of internal organs by limiting blood flow to those organs leading to tissue damage.
Although the disease can involve any organ system, GPA mainly affects the respiratory tract (sinuses, nose, trachea [windpipe], and lungs) and kidneys. The disorder affects people at any age and both men and women equally. It is rare in African Americans compared to Caucasians. Researchers and clinicians have not yet identified the cause or triggers of GPA.
Initial symptoms are often vague and frequently include upper respiratory tract symptoms such as sinusitis, as well as joint pains, weakness, and fatigue. Fever and night sweats may occur.
The most common organ system involvement in GPA is as follows:
Upper respiratory tract
The most common organ system involvement, occurring in nearly all patients. Symptoms include sinus pain and congestion, discolored or bloody fluid from the nose, and, occasionally, nasal ulcers. A common initial sign is consistent rhinorrhea (“runny nose”). Rhinorrhea can result from nasal inflammation or sinus drainage and may be associated with pain.
With more advanced dissease, a hole may develop in the cartilage of the nose, leading to collapse of the nose (called saddle-nose deformity). The eustachian tubes, which are important for normal ear function, may become blocked, causing chronic ear problems and hearing loss. Bacterial infection can both complicate and cause GPA-related sinusitis (inflammation of the sinuses) with congestion and chronic sinus pain.
The lungs are affected in most people with GPA, even without the presence of symptoms . When present, the typical symptoms include cough, hemoptysis (coughing up blood), shortness of breath, and chest discomfort.
Kidney involvement, occurring in more than 75% of pateints usually does not cause overt symptoms. Confirmation of kidney inflammation is done through blood and urine testing and possibly biopsy.
Pain in the muscles and joints affects two-thirds of people with GPA. Although joint pain can be very uncomfortable, it does not lead to permanent joint damage or deformities.
GPA can affect the eyes in several ways. People may develop…
Conjunctivitis (inflammation of the conjunctiva, the inner lining of the eyelid)
Scleritis (inflammation of the scleral layer, the white part of the eyeball)
Episcleritis (inflammation of the episcleral layer, the outer surface of the sclera)
Mass lesion behind the eye globe
Symptoms include eye redness, burning, or pain. Double vision or a decrease in vision are serious symptoms requiring immediate medical attention.
Nearly half of people with GPA develop skin involvement. These often appear as small red or purple raised areas or blister-like lesions, ulcers, or nodules typically of the lower extremities that may or may not be painful.
Some may experience narrowing of the trachea, these symptoms would voice change, hoarseness, shortness of breath, or cough. The nervous system and heart occasionally may be affected.
Early diagnosis is important to treat GPA effectively to reduce to risk for organ system damage. There are several blood, urine and X-ray studies that when positive can be suggestive of GPA and lead to suspicion of specific organs being affected. Elevated levels of inflammation in the body can be determined by checking the sedimentation rate, C-reactive protein and blood counts. Kidney involvement would be suggested by red blood cells and protein found in the urine, or decreased kidney function found on blood testing.
Anti-neutrophil cytoplasmic antibodies (ANCA) are useful to support a suspected diagnosis of GPA. A positive test however is not sufficient to diagnose the condition. Furthermore the ANCA test may be negative with active GPA.
X-ray may be helpful in diagnosing GPA, particularly those people with lung problems. CT (computed tomography) scans in people with sinus problems may show thickening of theling of the sinuses.
Currently, the gold standard to diagnose GPA is biopsy of an involved organ (usually the sinuses, lung, or kidney). Biopsy is important both to confirm the presence of the disease and rule out other disorders that may have similar signs and symptoms.
With early and appropriate treatment GPA is a readily treatable disorder.
In most cases, treatment consists of a combination of a glucocorticoid (a steroid) and a cytotoxic medicine. Although these medications are effective for treating GPA, the awareness of potential serious side effects is necessary. In many instances however, these can be minimized or prevented by careful monitoring by both the doctor and patient.
Approximately half of people with GPA may experience a relapse of their disease. This can occur both during active treatment or after the discontinuation of medication. Thus, it is extremely important to routinely visit your doctor even after medications have been stopped.
Prednisone – Prednisone is the most common glucocorticoid (steroid) used by physicians and is similar to cortisol, a natural glucocorticoid hormone produced by the body. Prednisoneis used to quickly decrease inflammation in the body caused by GPA. With improvement in the condition, the dose is gradually decreased, however this is done over the course of several months. Prednisone is usually given as a single morning dose to mimic the body’s normal release of cortisol. Anytime you lower your dose or discontinue prednisone, this must be done in consultation with your prescribing physician.
Prednisone can affect the body’s ability to fight off infection, one should immediately report any infectious symptoms and fevers to their doctors. Prednisone can also cause weight gain, cataracts, brittle bones, diabetes, and changes in mood and personality.
Cyclophosphamide- Cyclophosphamide (Cytoxan) is the most commonly used cytotoxic drug used to treat GPA. It is administered either orally or intravenously. Cyclophosphamide is typical given alongside prednisone until remission is acheived and then is switched to another immunosuppressant medication such as methotrexate or azathioprine (discussed below). Frequent blood tests are required to ensure the proper dosing.
Cyclophosphamide can cause an increased risk of infection, bone marrow suppression (lowering of blood counts), sterility, hemorrhagic cystitis (bleeding from the bladder), bladder cancer, as well as other serious side effects.
Methotrexate – In people with active, non-organ system involving , GPA methotrexate can be used in combination with prednisone to bring about remission. It may also be used for maintance therapy after induction of remission with cyclophosphamide.
Methotrexate is given once a week usually by mouth, but occasionally as an injection under the skin or in the muscle. Routine blood testing is necessary to monitor for response and development of side effects. Side effects include infection, lowering of the blood counts, nausea, soreness and ulceration of the mouth lining, irritation of the lungs (pneumonitis), and inflammation and scarring of the liver. People taking methotrexate must avoid drinking alcoholic beverages. Methotrexate cannot be given to people with poor kidney function or underlying liver disease such as hepatitis.
Azathioprine – Azathioprine (brand name – Imuran) is used primarily to maintain remission for those who acheived remission after treatment with cyclophosphamide. It is taken once daily by mouth.
Side effects include infection, lowering of the blood counts, and rarely an allergic type reaction. In people who receive azathioprine to prevent rejection of a transplanted organ, there has been a suggestion of an increased risk of blood cancers (leukemia and lymphoma) but it is not clear whether this risk exists in other conditions. People with poor kidney function or liver disease can take azathioprine.
During treatment for GPA, occasionally other medications are necessary to prevent medicine-related side effects. These include:
- Trimethoprim/sulfamethoxazole (also called bactrim or septra) is an antibiotic given three times a week to prevent Pneumocystis carinii infection (a lung infection)
- A medication regimen is often given to prevent prednisone-related bone loss (osteoporosis)
- Folic acid or folinic acid (also called leucovorin) are given to reduced methotrexate related side effects.