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Granulomatosis with Polyangiitis (Wegener Granulomatosis) Clinical Presentation

  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Nov 02, 2015
 

History

Clinician awareness is important to prevent delayed or missed diagnosis. Recurrent respiratory infection in an adult may be an indicator of granulomatosis with polyangiitis (GPA). However, the clinician must remain mindful that GPA has a spectrum of clinical presentations.

Patients may report the following chronic, nonspecific constitutional complaints:

  • Fevers, night sweats
  • Fatigue, lethargy
  • Loss of appetite
  • Weight loss

Ophthalmic signs

Ocular involvement occurs in many patients, including the following:

  • Conjunctivitis
  • Episcleritis
  • Uveitis
  • Optic nerve vasculitis
  • Retinal artery occlusion
  • Nasolacrimal duct occlusion
  • Proptosis

Ear, nose, and throat manifestations

The symptoms causing pediatric patients to seek medical care are usually attributable to the upper and lower respiratory tract.

Chronic sinusitis is the most common initial complaint (67%); failure to respond to conventional treatment is suggestive. Rhinitis and epistaxis occur in 22% and 11% of patients with GPA, respectively.[1]

The development of a saddle nose deformity caused by collapse of nasal support is common. Serous otitis media and hearing loss are the presenting manifestations of GPA in some patients. Tracheal or subglottic granulomatous masses can cause stridor and lead to respiratory compromise.

Granulomatosis with polyangiitis (formerly known a Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis). Large ulceration of the pharynx covered with a dense necrotic membrane.

Pulmonary manifestations

Pulmonary involvement can be asymptomatic, insidious in onset, or severe and fulminant. Pulmonary disease may cause any of the following[1] :

  • Pulmonary infiltrates (71% of patients)
  • Cough (34%)
  • Hemoptysis (18%)
  • Chest discomfort (8%)
  • Dyspnea (7%)
  • Diffuse alveolar hemorrhage (DAH) due to alveolar capillaritis (5%-45% [2] )

Musculoskeletal symptoms

Musculoskeletal symptoms are common. Arthralgias are usually polyarticular and symmetric, affecting small and large joints. Arthritis can also occur, and typically affects large joints, but is rarely deforming.

Renal involvement

Renal disease is present in 17% of patients at initial diagnosis and is usually asymptomatic.[3] Renal failure occurs in 11% at presentation.[1] Renal disease manifests as crescentic necrotizing glomerulonephritis characterized by urinary sediment with more than 5 red blood cells per high-power field or erythrocyte casts.

Nervous system involvement

The nervous system is affected in numerous patients. Peripheral nervous system (PNS) involvement may occur in as many as 67% of patients, typically later in the disease course. PNS manifestations include mononeuritis multiplex, sensorimotor polyneuropathy, and cranial nerve palsies. Central nervous system (CNS) manifestations include vasculitis of small to medium–sized vessels of the brain or spinal cord and granulomatous masses that involve the orbit, optic nerve, meninges or brain.[4]

Cutaneous signs

The skin is involved in 45% of patients with GPA due to vasculitis. Cutaneous involvement can lead to palpable purpura or skin ulcers.[1]

Necrotic, purpuric, and blistering plaque on the w Necrotic, purpuric, and blistering plaque on the wrist in a patient with granulomatosis with polyangiitis.

Cardiac involvement

Cardiac involvement most often consists of pericarditis or coronary vasculitis, but myocarditis, endocarditis, conduction system granulomata, and valvular involvement may also occur.[45] Necrotizing vasculitis of the coronary vessels can result in myocardial infarction or sudden death.

Estimates of the frequency of cardiac involvement vary widely, with a North American study reporting a rate of 33.3% and no association with a higher rate of relapse or premature death,[46] while a European study reported cardiac involvement in 46% of GPA patients assessed with electrocardiography and echocardiography, along with increased all-cause and cardiovascular mortality.[47]

 

Next

Physical Examination

Signs related to the head, ears, eyes, nose, and throat

Sinusitis and disease in the nasal mucosa are the most common findings. Ocular findings include scleritis, episcleritis, keratitis, uveitis, and conjunctivitis. Proptosis may signal a retrobulbar granulomatous mass. Xanthelasma has also been reported.

Otitis media and/or hearing loss may be present. Purulent or serosanguinous nasal discharge may be seen. Saddle nose deformity may be present. (See image below.)

Saddle nose deformity in a 26-year-old man with gr Saddle nose deformity in a 26-year-old man with granulomatosis with polyangiitis. Image courtesy of P. Papadopoulos, MD.

Oral involvement is rare; however, a classic presentation includes "strawberry gingival hyperplasia."

Pulmonary/respiratory signs/symptoms

Pulmonary/respiratory symptoms can include the following:

  • Atelectasis - May be present, with examination findings of dullness on percussion, decreased breath sounds, and crackles on auscultation
  • Lower respiratory tract involvement - May also produce signs of pulmonary consolidation and/or pleural effusion
  • Tracheobronchial disease - May manifest as hoarseness, cough, dyspnea, stridor, and wheezing
  • Subglottic or tracheal stenosis – May also manifest as stridor; stenosis may prove fatal if untreated
  • Hemoptysis - may result from cavitated pulmonary parenchymal lesions, DAH, or bronchiectasis

Cutaneous findings

Cutaneous findings are variable and nonspecific and usually affect the lower extremities. Palpable purpura, papules, subcutaneous nodules, and ulcerations are the most common findings. Ulcerations may resemble pyoderma gangrenosum.

Petechiae, vesicles, pustules, hemorrhagic bullae, livedo reticularis, digital necrosis, subungual splinter hemorrhages, and genital ulcers resembling squamous cell carcinoma have been reported.

Several necrotic, purpuric, and blistering papules Several necrotic, purpuric, and blistering papules and plaques on the hands in a patient with granulomatosis with polyangiitis.

Additional findings

Other symptoms may include the following:

  • General - Patients may be febrile and appear ill
  • Cardiac - Pericardial rub may occur with pericarditis
  • Gastrointestinal - Abdominal pain may be present with splanchnic vasculitis
  • Musculoskeletal - Large- and medium-joint arthritis; polyarticular, symmetrical small- and medium-joint arthralgias; and myalgias may be appreciated
  • Neurologic - Examination of the nervous system may confirm a pattern of mononeuritis multiplex, polyneuropathy, or cranial nerve paralysis
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Contributor Information and Disclosures
Author

Christopher L Tracy, MD Associate Program Director, Rheumatology Fellowship Program, Walter Reed National Military Medical Center

Christopher L Tracy, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Patricia J Papadopoulos, MD Staff Rheumatologist, MultiCare Rheumatology Specialists

Patricia J Papadopoulos, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Michael R Bye, MD Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Heidi Connolly, MD Associate Professor of Pediatrics and Psychiatry, University of Rochester; Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center

Heidi Connolly, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Robert John O'Brian, MD Staff Rheumatologist, National Naval Medical Center

Robert John O'Brian, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Girish D Sharma, MD Associate Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush University Medical Center

Girish D Sharma, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Royal College of Physicians of Ireland

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Debbie S Toder, MD Director of Cystic Fibrosis Center, Department of Pediatrics, Division of Pulmonary Medicine, Assistant Professor, Wayne State University and Children's Hospital of Michigan

Debbie S Toder, MD is a member of the following medical societies: American Academy of Pediatrics and American Thoracic Society

Disclosure: Nothing to disclose.

Rudolph P Valentini, MD Director of Dialysis Services, Associate Professor, Department of Pediatrics, Division of Pediatric Nephrology, Wayne State University; Vice Chief of Staff, Children's Hospital of Michigan

Rudolph P Valentini, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert E Wolf, MD, PhD Professor Emeritus, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Administration Medical Center of Shreveport

Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, and Society for Leukocyte Biology

Disclosure: Nothing to disclose.

Acknowledgments

The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense, or the US Government. Additionally, this publication does not imply the Federal or Department of Defense endorsement of any product.

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Saddle nose deformity in a 26-year-old man with granulomatosis with polyangiitis. Image courtesy of P. Papadopoulos, MD.
Necrotic, purpuric, and blistering plaque on the wrist in a patient with granulomatosis with polyangiitis.
Several necrotic, purpuric, and blistering papules and plaques on the hands in a patient with granulomatosis with polyangiitis.
Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis). Large ulceration of the pharynx covered with a dense necrotic membrane.
Extensive thickening of the maxillary sinuses in a patient with granulomatosis with polyangiitis. The patient also had intermittent epistaxis.
Granulomatosis with polyangiitis. Bilateral nodules observed on a plain chest radiograph in a patient with hemoptysis and hematuria. Image courtesy of G. Eschun, MD.
This 42-year-old man presented with hemoptysis, weight loss, and night sweats. He was diagnosed with the limited form of granulomatosis with polyangiitis.
Bilateral cavitating nodules in a patient with granulomatosis with polyangiitis.
Granulomatosis with polyangiitis. This patient presented with massive hemoptysis. No nodules are identified on the chest radiograph, although a subsequent CT scan showed several noncavitating nodules.
Diffuse alveolar hemorrhage in a 21-year-old man with granulomatosis with polyangiitis. Image courtesy of the US Government.
Diffuse alveolar hemorrhage in a 21-year-old man with granulomatosis with polyangiitis. Image courtesy of the US Government.
Shown is a chest radiograph of an 11-year-old girl who presented with an upper respiratory tract infection, myalgias, and arthralgias for 1 month, followed by an abrupt presentation with pallor, hemoptysis, and hypertension. Her bilateral fluffy infiltrates are suggestive of a pulmonary hemorrhage. She had an antineutrophil cytoplasmic autoantibody (ANCA)–positive pauci-immune necrotizing and crescentic glomerulonephritis associated with her pulmonary hemorrhage. Supportive therapy consisted of mechanical ventilation and hemodialysis along with immunosuppressive therapy. Her anti–glomerular basement membrane antibody test result was negative. Nearly 2 years later, she had a serum creatinine of 0.7mg/dL and no residual pulmonary disease.
An 11-year-old girl presented with an upper respiratory tract infection, myalgias, and arthralgias for 1 month followed by an abrupt presentation with pallor, hemoptysis, and hypertension. She had an antineutrophil cytoplasmic autoantibody (ANCA)–positive pauci-immune necrotizing and crescentic glomerulonephritis associated with her pulmonary hemorrhage. A follow-up chest radiograph obtained several days later shows a complete resolution of her pulmonary infiltrates. This rapid resolution is more consistent with hemorrhage than with pneumonia.
A renal biopsy specimen from a 13-year-old girl with antineutrophil cytoplasmic antibody (C-ANCA)–positive pulmonary renal syndrome. Seven weeks after presenting with sinusitis, she presented with an acute abdomen, pulmonary hemorrhage, and acute renal failure (creatinine 4.9mg/dL). This biopsy specimen shows a necrotizing and crescentic glomerulonephritis (Silver stain).
Lung biopsy specimen from a patient with granulomatosis with polyangiitis showing evidence of vasculitis and inflammation (high-power view). Image courtesy of Z. Xu, MD.
Lung biopsy specimen from a patient with granulomatosis with polyangiitis showing evidence of vasculitis and inflammation (high-power view). Image courtesy of Z. Xu, MD.
Focal glomerulonephritis with crescent formation on renal biopsy specimen, characteristic of granulomatosis with polyangiitis.
C-ANCA immunofluorescence pattern. Staining for antineutrophil cytoplasmic antibody by indirect immunofluorescence shows heavy cytoplasmic staining, whereas nuclei are nonreactive. Image courtesy of K. Orr, MD.
P-ANCA immunofluorescence pattern. Perinuclear antineutrophil cytoplasmic antibody staining pattern by indirect immunofluorescence shows perinuclear staining, whereas cytoplasm is nonreactive. Image courtesy of K. Orr, MD.
Goodpasture syndrome: Linear deposition of immunoglobulin G and C3 are observed on a renal biopsy specimen from a patient with Goodpasture syndrome. Immunofluorescence staining. Image courtesy of K. Orr, MD.
 
 
 
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