Wegener's Granulomatosis

Stuffy
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Diagnosis and reasoning

This middle aged gentleman has presented with a mix of upper and lower respiratory tract symptoms. His examination is significant only for multiple nasal polyps, a non-specific finding which might just be due to chronic inflammation. In the majority of such patients, these clinical findings are usually due to benign causes - most often asthma combined with rhinosinusitis. However, this patient's basic investigations show several anomalies: mild anemia, neutrophilia, and, very importantly, a significantly elevated ESR. These findings suggest that a more sinister cause may be at play. The differential diagnosis for an elevated ESR in conjunction with mixed upper and lower respiratory symptoms is quite broad. However, in practice, the causative etiologies can be classified into three main categories: - Small vessel vasculitides (such as Wegener’s granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis); - Connective tissue disorders such as Sjogren’s syndrome; - Immunodeficiencies such as HIV/AIDS. A careful history and examination and targeted investigations are crucial in differentiating between the above. Wegener's Granulomatosis (WG) is well known to present in this manner and is a key diagnosis to keep in mind. Churg-Strauss syndrome typically presents with asthma and peripheral blood eosinophilia, making this diagnosis less likely. Microscopic polyangiitis rarely manifests as otorhinolaryngologic disease. The lack of musculoskeletal and skin manifestations (which are common presenting features of connective tissue diseases), makes this group of conditions less likely. Immunodeficiencies are almost impossible to exclude on clinical grounds alone. A chest x-ray is a good first step in his workup; this shows nodular pulmonary lesions in both lung fields. Considering the clinical context, these could very likely be granulomata (i.e. WG). Simultaneous pulmonary and renal disease is common in WG - thus, urinalysis is a good next investigation. This reveals an active sediment suggestive of glomerulonephritis. Given the strong suspicion of Wegener’s Granulomatosis, the step after this should probably be an autoimmune assay; the presence of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) is almost confirmatory. However, a tissue sample is required for definitive diagnosis, necessitating a lung biopsy. This reveals characteristic histological features of Wegener’s Granulomatosis, confirming the diagnosis. Corticosteroids and immunosuppressive therapy form the mainstay of treatment in these patients. Note that resection of pulmonary nodules, antituberculous therapy, and radiotherapy are of no use these individuals.


Discussion

Wegener’s granulomatosis (WG) is a rare ANCA (antineutrophil cytoplasmic antibodies) associated systemic vasculitis characterized by involvement of the upper and lower respiratory tract and glomerulonephritis. The peak incidence of WG is in the fourth decade of life, although it can also present at any age; The condition is slightly more common in males. Upper respiratory tract disease is the most common presenting feature in these patients. This includes sinusitis, epistaxis, rhinorrhea, otitis, hearing impairment and destructive lesions that might lead to saddle-nose deformity. Pulmonary symptoms include cough, hemoptysis, chest pain and dyspnea. Diffuse alveolar hemorrhage and subglottic stenosis are other well known manifestations of WG. Many patients ultimately develop renal disease, but this is less common than respiratory tract involvement at the initial presentation. Constitutional symptoms such as fever, malaise and weight loss are often seen at the initial presentation. Vasculitis may also involve the musculoskeletal system, skin, nervous system and the coronary vessels. The chest x-ray is frequently abnormal in these patients; this may demonstrate alveolar or interstitial infiltrates and nodular or cavitary disease. Serum c-ANCA (anti-proteinase-3 ANCA) is found in most patients, and is highly sensitive (90% to 95%) and specific (90%) in detection of active systemic WG. Note however that c-ANCA alone is not sufficient to confirm or exclude the diagnosis. Tissue biopsy from an affected site provides a definitive diagnosis; when the lung is affected thoracoscopic or open lung biopsy almost always confirms the diagnosis. A renal biopsy may be considered if the kidney is involved; note that while biopsies of the upper respiratory tract (i.e. sinuses) may also be obtained, their diagnostic yield is often very poor. The treatment of WG has 3 phases; remission induction, maintenance of remission and treatment of relapse. The intensity of the initial treatment depends on the severity of the disease. Induction of remission is usually with corticosteroids and cyclophosphamide. Other agents that are used in the management include azathioprine, methotrexate, plasma exchange and intravenous immunoglobulin. Patients should be monitored during treatment for the development of drug toxicity, infection or disease relapse. Poor prognostic factors include advanced age, more severe renal impairment and alveolar hemorrhage.


Take home messages

  1. Upper respiratory tract disease is the most common presenting feature in Wegener’s granulomatosis.
  2. Many patients ultimately develop renal disease, but this is less common than respiratory tract involvement at the initial presentation.
  3. Tissue biopsy from an affected site provides a definitive diagnosis.

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  1. Am Fam Physician. 2002 Apr 15;65(8):1615-20.,ANCA-associated small-vessel vasculitis.,Mansi IA, Opran A, Rosner F.
  2. Curr Rheumatol Rep. 2000 Oct;2(5):417-22.,Laboratory testing in the evaluation and diagnosis of vasculitis.,Cuellar ML, Espinoza LR.
  3. Proc Am Thorac Soc. 2006 March; 3(1): 48–57,Pulmonary Vasculitis,Kevin K. Brown
  4. Semin Ultrasound CT MR. 2012 Dec;33(6):567-79,Imaging findings in pulmonary vasculitis,Castañer E, Alguersuari A, Andreu M, Gallardo X, Spinu C, Mata JM.
  5. Surv Ophthalmol. 2010 Sep-Oct;55(5):429-44,j.survophthal.2009.12.003. Epub 2010 Jul 17. Wegener's granulomatosis: clinical manifestations, differential diagnosis, and management of ocular and systemic disease.,Tarabishy AB, Schulte M, Papaliodis GN, Hoffman GS.