Granulomatosis with Polyangiitis

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Original Editors - Dalie Camic & Daryl Williams from Bellarmine University's Pathophysiology of Complex Patient Problems project.

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Definition/Description

Wegener's granulomatosis is a rare disorder characterized by inflammation in the blood vessels, which in turn decreases blood flow to organs and systems.  Most affected areas include the kidneys, lungs, and upper respiratory tracts.

Prevalence

Wegener's granulomatosis is most common in middle aged adults, but has been seen in children as young as 3 months of age. There is also increased incidence in caucasians versus African-American populations

Characteristics/Clinical Presentation

The signs and symptoms of Wegener's Granulomatosis are not only common signs and symptoms of other diseases or illnesses but are often vague in the beginning presentations of this disease.  The first signs and symptoms include upper respiratory tract symptoms, joint pains, weakness, and tiredness.

Respiratory System

Common involvement occurs in the upper respiratory tract in nearly all patients.  

Symptoms include:  sinus pain, discolored or bloody fluid from nose, and nasal ulcers.  

Common signs include:  rhinorrhea ("runny nose"), common cold symptoms that do NOT respond to usual treatment and become increasingly worse.  Although this these are the most prevelant signs Wegener's Granulomatosis is rarely the cause.

Lungs:  Commonly affected in patients with Wegener's Granulomatosis there are rarely signs and symptoms that present.  Possible S&S can include cough, hemoptysis, shortness of breath, and chest discomfort.

Musculoskeletal system

Although it does not lead to permanent joint damage or deformities, pain in the muscle and joints, along with joint swelling affects two-thirds of individuals with this disease.

-Other signs and symptoms can include develop skin lesions resmembling red or purple raised lesions.  The eyes can be affected causing conjunctivitis, scleritis, episcleritis causing double vision, redness, burrning, and pain.  Symptoms involving the eyes require immediate medical attention.

Associated Co-morbidities

Ischemic heart disease

Glucocorticoid-induced osteoporosis

Medications

In an article published in the Annals of Internal Medicine an analysis of 158 patients with Wegener Granulomatosis was prospectively studied to to analyze the clinical features, pathophysiology, treatment, and prognosis of the disease.

-138 Patients recieved "standard therapy" with daily low cyclophosphamide and glucocorticoids; 8 patients recieved only low-dose cyclophophamide; 6 patients were treated with other cytotoxic agents and glucocorticoids, and 10 patients were treated with only glucocorticoids.

- 91% percent of the patients experienced marked improvement, and 75% achieved complete remission.  

-The use of these medications shown a dramatic improvement by daily treatment with cyclophosphamide and glucocorticoids.  Alternative forms have not yet achieved the high rates of remission induction and maintaenece that have been reported with cyclophophamide treatment.  

-A major concern with the long term follow up of these patients is the toxicity resulting from prolonged cyclophosphamide therapy.

According pubmedhealth, treatment may include medicines that slow down the immune system response.  Some of these medications include:

-Gucocorticoids (Prednisone)

-Azathioprine

-Cyclophosphamide

-Methotrexate

These medications may be used in combination with other medications to help reduce side effects:

-Biphosphonate-to prevenent bone loss caused by prednisone.

-Folic acid

-Trimethoprim-to prevent lung infections.

Diagnostic Tests/Lab Tests/Lab Values

Blood panel

• Antineutrophil cytoplasmic antibodies (ANCA) is a common protein found in patients with WG.

Urinalysis

• Assess kidney function and check for output, blood or proteins in the urine

Biopsy is common and will vary depending on organ involvement. Can include:

• lung
• kidney
• nasal mucosa
• upper airway
• skin

Other tests may be order to further evaluate the patient and confirm diagnosis:

• chest x-ray
• chest CT
• bone marrow aspiration

Etiology/Causes

Wegener's granulomatosis is a rare disorder that can effect the blood vessels.  Although its causes are unknown it is thought to be an autoimmune disorder that mainly effects the blood vessels of the nose, sinuses, ears, lungs, and kidneys.

Systemic Involvement

• Nose and sinus involvement often leads to sinusitus, nose bleeds, ear infections, and can progress to lesions, sores, and nasal septum perforation if untreated
• Lung tissue involvement can produce wheezing, shortness of breath, hemoptysis, and can also progress to lesions that lead to lung failure if untreated
• Kidney involvement can include protein and blood in the urine, or in more severe cases includes lesions which lead to glomerulonephritis and eventual kidney failure if untreated. 
• Integumentary changes are common and highly variable among patients
• Vision changes can include swelling, redness of the eyes or cases of conjunctivitis
• Intestinal involvement is rare, but can include vasculitis, ischemia, inflammation and ulceration of the large and/or small bowel
• Musculoskeletal issues such as myalgia and arthralgia are also common due to vascular dysfunction

Medical Management (current best evidence)

Treatment options depend on the organs and disease severity.

Treatment options include:

-Active severe disease:  Patients will recieve a glucocorticoid medication i.e. Prednisone along with a cyclophosphamide which is a chemotherapy type of medication.  Prednisone is given at high doses in the beginning of the treatment and is gradually reduced.  Cyclophosphamide is given for 3-6 months.

-If improvements are noted than the patient is switched to another medication such a methotrexate for 2 or more years.

-Treatment options for severe granulomatosis include rituximab combined with glucocorticoids.  A medication such as rituximab is type of biologic agent given by vein that targets B lymphocyte cells. 

• • Each medication has significant side effects that should seriously be considered**

Physical Therapy Management (current best evidence)

There is no current evidence-based standard of care for patients with Wegener's Granulomatosis and no research was found using CINAHL, PEDro, Proquest, Ebscohost, or Academic Search Premier.

Upon discussion with the cardiopulmonary section and having seen two patients on a clinical rotation, it seems that the current practice is focused primarily on cardiovascular endurance, treatment of pulmonary disfunction, and pain management from arthralgia and myalgia.

Alternative/Holistic Management (current best evidence)

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Differential Diagnosis

• Allergies
• Sinus infection
• Glomerulonephritis
• Rheumatoid arthritis
• Occult malingnancy
• Granulomatous infectious processes

Case Reports/ Case Studies

• 42 y.o. male with pansinusitis: http://www.jabfm.org/content/16/6/555.full
• 58 y.o. male with alveolar infiltrates and hepatic involvement: http://www.jmedicalcasereports.com/content/4/1/9
• Renal cancer and WG: http://www.wjso.com/content/9/1/165

Resources

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001192/

http://www.mayoclinic.com/health/wegeners-granulomatosis/DS00833

http://www.nlm.nih.gov/medlineplus/wegenersgranulomatosis.html

http://my.clevelandclinic.org/disorders/wegener_granulomatosis/hic_wegeners_granulomatosis.aspx

Recent Related Research (from Pubmed)

see tutorial on Adding PubMed Feed

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References

see adding references tutorial.