Makindo Medical Notes.com

Related Subjects: Granulomatosis with Polyangiitis GPA (Wegener's) | Goodpasture's syndrome (Anti GBM disease) | Respiratory Failure | Acute Kidney Injury |

Early diagnosis and immunosuppression is key to reducing damage so if suspicious get an urgent cANCA (proteinase 3). Otherwise, can destroy kidneys in a matter of weeks

About

• Described by Dr Friedrich Wegener, a German pathologist in 1936
• Friedrich Wegener was a member of the Nazi party during WWII
• Now called Granulomatosis with polyangiitis (GPA)

Aetiology

• Systemic vasculitis commoner in exams than in life
• Affects upper respiratory tract, lungs, and kidneys
• However early diagnosis is key to preventing damage

Epidemiology

• Affects 3 in 100,000 in USA
• Mean age is 50 Males = females
• 90% of cases are seen in Whites

Granuloma formation

Aetiology

• Medium sized vasculitis possibly a hypersensitivity reaction to an external antigen
• Eradicating Staph aureus carriage reduces the risk of recurrence
• Renal disease in 40% at presentation but eventually 90%

Clinical

• Fever, night sweats, lethargy, malaise
• Ear Nose and throat - rhinorrhoea, epistaxis and sinusitis otitis media nasal perforation and saddle nose
• Lungs - Cough, Haemoptysis, Pulmonary haemorrhage - causing a false high transfer factor or Kco, Alveolar shadowing and cavitatory lesions
• Kidneys - Hypertension, haematuria, Focal necrotizing glomerulonephritis is the characteristic renal lesion. Pauci-immune necrotizing glomerulonephritis
• Others - Eyes - uveitis , Vasculitis - a red-eye, proptosis

Investigations

• FBC: anaemia, elevated WCC
• Renal failure: Elevated Urea and creatinine
• Raised CRP and ESR and inflammatory markers
• Low Complement levels
• CXR - nodular masses, infiltrates or cavitation or pulmonary haemorrhage.
• Urinalysis should be performed to look for proteinuria or haematuria. If these are present, consider a renal biopsy. Significant dysmorphic RBCs or RBC casts is indicative of glomerular disease.
• HRCT chest: diffuse alveolar haemorrhage, cavitary nodules, consolidations, airspace opacities, and airway stenosis
• Antiproteinase-3 (PR3) antibodies cANCA is usually positive in 80-90% Granulomatosis with polyangiitis. There is a close association between ANCA titers and disease activity, particularly c-ANCA (proteinase 3) in Wegener granulomatosis. Negative c-ANCA test results are not enough to exclude the diagnosis, and biopsy remains the standard means of diagnosis
• Anti Myeloperoxidase (MPO) antibodies pANCA positive in 10-20%
• The diagnostic test will be a nasal biopsy looking for granulomata and his cANCA
• DLCO will be high with alveolar haemorrhage as Hb binds the CO
• Bronchoalveolar lavage (BAL): suspected pulmonary disease
• Tissue biopsy is useful in most situations for the diagnosis from involved organs and never blindly (from unaffected sites). ENT and lung. Renal biopsies are generally not specific for GPA. There is no pattern on histopathology that is pathognomonic of GPA. Skin biopsies may show a pattern of leukocytoclastic vasculitis and, in themselves, are not useful for the specific diagnosis of GPA.
• Associated necrotising glomerulonephritis - check U&E and CRP and Urinalysis

CT scan: Multiple cavitary (arrows) and noncavitary (arrowheads) pulmonary nodules of GPA

Management

• Wegener granulomatosis is associated with considerable morbidity and mortality from irreversible organ damage caused by inflammatory injury or chronic or overzealous immunosuppressive therapy.
• Without treatment, approximately 90% of patients with Wegener granulomatosis die within 2 years of diagnosis
• High dose Prednisone 1 mg/kg/day or methylprednisolone 1g for 3 doses are started and Azathioprine and methotrexate are usually used as maintenance
• Methotrexate (MTX) or Rituximab (RTX) for non-severe disease and cyclophosphamide (CYC) or Rituximab for severe disease
• Maintenance preemptive Rituximab infusions should be prolonged for a total of 42 months for patients at high risk for relapses, such as those with PR3 ANCAs and those who have already had a relapse.
• There is a close association between ANCA titers and disease activity, particularly c-ANCA in Wegener granulomatosis so can be used to guide treatment
• Nasal carriage of Staphylococcus aureus is associated with an increased risk of relapse and so long-term use of mupirocin cream may be a useful adjunct in affected patients.
• Co-trimoxazole should be given as prophylaxis against Pneumocystis jirovecii and staphylococcal colonization.
• PLEX: Indications for plasma exchange include patients presenting with severe renal disease (eg creatinine >500umol/L)

References

• Common and Uncommon Manifestations of Wegener Granulomatosis at Chest CT: Radiologic-Pathologic Correlation