Granulomatosis with Polyangiitis

Definition/Description

"Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis(WG)'' 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[1].

Prevalence

Granulomatosis with polyangiitis is most common in middle aged adults, but has been seen in children as young as 3 months of age[1]. There is also increased incidence in caucasians versus African-American populations [2]

Characteristics/Clinical Presentation[3]

The signs and symptoms of Granulomatosis with polyangiitis 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 these are the most prevalent signs Granulomatosis with polyangiitis is rarely the cause.


Lungs:  Commonly affected in patients with Granulomatosis with polyangiitis 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.


Patient presentation chart.gif[3]

Associated Co-morbidities

Ischemic heart disease [4]

Glucocorticoid-induced osteoporosis[5]

Medications

In an article published in the Annals of Internal Medicine an analysis of 158 patients with Granulomatosis with polyangiitis was prospectively studied 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.[6]


91% percent of the patients experienced marked improvement, and 75% achieved complete remission.[6]  

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 maintenance that have been reported with cyclophophamide treatment.[6]  

A major concern with the long term follow up of these patients is the toxicity resulting from prolonged cyclophosphamide therapy.[6]


According pubmedhealth, treatment may include medicines that slow down the immune system response.  Some of these medications include:[7]

  • 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.[7]
  • Folic acid
  • Trimethoprim-to prevent lung infections.

Diagnostic Tests/Lab Tests/Lab Values[1]

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

The cause of this disease is unknown.  It appears to develop as a result from an inflammation causing event that triggers an abnormal reaction from the immune system.  Researchers think that the triggering event may be an infection although no infection has been identified.[8]

Systemic Involvement [1][2]

  • 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[9]
  • Musculoskeletal issues such as myalgia and arthralgia are also common due to vascular dysfunction[10]

Medical Management (current best evidence)[11]

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**

In an article published in the Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology BSACI suggest that treatment is primarily medical and should include douching of the nasal cavity, corticosteroids, antibiotics, anti-leukotrines, and anti-histamines.[12]


Physical Therapy Management (current best evidence)

There is no current evidence-based standard of care for patients with Granulomatosis with polyangiitis 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.

Differential Diagnosis [10][13]

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

Case Reports/ Case Studies

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

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 [14]

References

  1. 1.0 1.1 1.2 1.3 Wegener's Granulomatosis. Reviewed Feb 8, 2011; accessed March 29, 2012. Available from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001192/
  2. 2.0 2.1 Mayo Clinic Staff.Wegener's Granulomatosis. Updated Sept 25,2010. Accessed March 29, 2012. Available from mayoclinic.com/health/wegeners-granulomatosis
  3. 3.0 3.1 Schilder AM. Wegener's Granulomatosis. [homepage on the Internet]. 2010 [cited 2012 Apr 3]. Available from: http://http://my.clevelandclinic.org/disorders/wegener_granulomatosis/hic_wegeners_granulomatosis.aspx
  4. Faurschou M, Mellemkjaer L, Sorensen IJ, Thomsen BS, Dreyer L, Baslund B. Increased morbidity from ischemic heart disease in patients with wegener's granulomatosis. Arthritis & Rheumatism. 2009 April;60(4):1187-1192
  5. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001;44:1496-1503
  6. 6.0 6.1 6.2 6.3 Hoffman GS, Kerr GS, Leavitt RY. Wegener granulomatosis: an analysis of 158 pa..[Ann Intern Med. 1992] - PubMed -NCBI. Annals of Internal Medicine [serial on the Internet]. No date [cited 2012 Apr 1].;6(116) Available from: US National Library of Medicine, National Institutes of Health Web site: http://http://www.ncbi.nlm.nih.gov/pubmed/1739240
  7. 7.0 7.1 Pubmed Health AM. Wegener's granulomatosis-PubMed Health. [database on the Internet]. 2011 [cited 2012 Apr 1]. Available from: U.S National Library of Medicine, Web site: http://http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001192/
  8. Mayo Clinic GK. Wegener's granulomatosis-MayoClinic.com. [homepage on the Internet]. 2010 [cited 2012 Mar 22]. Available from: American College of Rheumatology, Web site: http://http://www.mayoclinic.com/health/wegeners-granulomatosis/DS00833/DSECTION=causes
  9. Storesund B, Gran JT, Koldingsnes W.Sever intestinal involvement in Wegener's Granulomatosis: report of two cases and review of the literature. Rheumatology. 1998 April: 37(4):387-390
  10. 10.0 10.1 Hoffman GS, Kerr GS, Leavitt RY, Hallahan C,Lebovics RS, Travis WD et al. Wegener granulomatosis: an analysis of 158 patients. Annals of Internal Medicine. 1992 March 15; 116(6):488-498
  11. Langford CA. Wegener's granulomatosis. [homepage on the Internet]. 2006 [cited 2012 Mar 31]. Available from: American College of Rheumatology, Web site: http://http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/wegeners.pdf#search="wegener's granulomatosis"
  12. Scadding GK, Durham SR, Mirakian R. BSACI guidelines for the management of rhin..[Clin Exp Allergy. 2008]-Pubmed-NCBI. Clinical and Experimental allergy: Journal of the British Society for Allergy and Clinical Immunology [serial on the Internet]. 2008 [cited 2012 Apr 2].;2(38) Available from: American College of Rheumatology, Web site: http://http://www.ncbi.nlm.nih.gov/pubmed/18167126
  13. Devaney KO, Travis WD, Hoffman G, Leavitt R, Lebovics R, Fauci AS. Interpretation of head and neck biopsies in wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients. The American Journal of Surgical Pathology. 1990, 14(6):555-64
  14. Wegener's Granulomatosis.Available from http://www.youtube.com/watch?v=1pDBY8mfgVY. Accessed April 2,2012.