Abstract

---

Wegener's granulomatosis is an uncommon autoimmue disease with multi-system involvement that manifests as vasculitis, granulomatosis and necrosis. While its standard form involves the upper and lower respiratory tracts and kidneys, it may essentially involve any organ. We present a case in a young male adult patient presenting with symptoms of chronic sinusitis having extensive sinosal and nasal disease on initial CT, with detection of lung lesions and renal involvement on further investigations and pathological confirmation by antineutrophil cytoplasmic antibody positivity and nasal biopsy findings based on radiological and clinical suspicion.

Introduction

---

This case report highlights the importance of radiological investigations and systematic clinical-radiological correlation, leading to diagnosis of an uncommon but lethal condition, Wegeners Granulomatosis in an unsuspecting young male patient.
Wegener's Granulomatosis (WG) was described in detail by Friedrich Wegener in 1936. The incidence is estimated to be 5-12 new cases/million per annum in the United States.1 WG is characterized by triad of granulomatous lesions of the upper and lower respiratory tract, focal segmental glomerulonephritis and disseminated necrotizing vasculitis.

Case history

---

A 32 years old male patient presented to our department with symptoms of nasal blockage, blood mixed nasal discharge with redness of eyes for routine CT study of paranasal sinuses. On clinical examination patient had bilateral conjucntival hyperemia, nasal mucosal hypertrophy with polypoidal projections with provisional clinical diagnosis of allergic rhino-sinusitis with polyposis. His blood examination revealed mild anemia (hemoglobin 10.2 gm/dl), leucocytosis with neutrophilia ( TLC- 13,600/ mm3 with neutrophilia) and markedly elevated ESR ( 120mm in first hour by Westergren method).
CT PNS examination revealed bilateral paranasal sinus soft tissue opacification (most marked in ethmoidal sinuses) with extension of pathology in nasal cavity with thinning of nasal turbinates and bony nasal septal perforation. No intracranial or intraorbital extension of pathology was noted [Figure 1].
On further elucidation of history patient revealed complaints of cough, occasional dyspnoea and chest discomfort. His chest X-ray revealed nodular shadow in left apical region, with subsequent CT chest revealing nodular pulmonary lesions in apical segments of both upper lobes abutting pleura [ Figures 2 ] with mild right pleural effusion [Figures 3].
Ultrasound of the abdomen of the patient revealed bilateral raised renal parenchymal echogenecity with normal renal size [Figure 4]. Subsequent pathological urine examination revealed microscopic hematuria and proteinuria. His serum creatinine was marginally raised (1.4 mg/dl).
Based on the complete radiological findings with relevant clinical and pathological data a possibility of Wegener's Granulomatosis was suggested. The diagnosis was confirmed by histopathological examination of nasal tissue excised on surgery which revealed granulomatous inflammation [Figure 5] and presence of Antineutrophil cytoplasmic antibody (C-ANCA) in serum.

Discussion

---

Limited form of WG with involvement of the upper respiratory tract and the lungs with renal sparing is frequently seen in women, while the kidneys are involved in the common form frequently seen in men.2 Sinus and nasal involvement is seen in 70-90% of patients, lung lesions are noted in 80-90% of patients with pleural involvement seen in 25-30% of patients and renal involvement is seen in 70-80% of patients throughout the course of disease.3
Although WG may occur at any age, the mean age of occurrence is 40 to 55 years old. The M/F ratio is equal.
The four criteria of diagnosis defined by the American College of Rheumatology (ACR) for WG are as follows: 1) Oral or nasal ulcers, or purulent bloody flux 2) An abnormal lung X-ray revealing nodules and cavities 3) An abnormal urinary sediment 4) Granulomatous inflammation in the extra vascular region at biopsy.4 The presence of two or more of these criteria has a sensitivity of 88% and a specificity of 99%.4,5
Pathologically, WG is characterized by necrotizing granulomatous inflammation of small vessel walls, resulting in areas of necrosis surrounded by hemorrhage, small micro abscesses and granulomata within the lungs. A normocytic anaemia, leucocytosis, elevated erythrocyte sedimentation rate (ESR), positive rheumatoid factor and antineutrophil cytoplasmic antibody (specifically PR3-ANCA) are often shown on serology. PR3- ANCA is positive in 85% of patients with active multiorgan WG, but this reduces to 30-40% in remission.5,6
Imaging findings
Chest
The most common imaging findings are discrete focal opacities that vary in size and appearance from diffuse consolidation to nodular masses. The latter may measure up to ten centimeter in diameter, but are usually two to four centimeter. They show no zonal predilection, are usually multiple, are rounded or oval in shape, and when two centimeter, cavitate in at least 25%.7 Cavity walls vary in thickness considerably, but tend to become thinner with time. They may contain air fluid levels if secondarily infected.8 Nodules often occur concurrently with consolidation, and commonly resolve spontaneously, with or without scarring. On high resolution CT, ground glass shadowing may surround the nodules, which may be due to hemorrhage. Relapse is frequently seen in areas of previous disease. Patchy or diffuse consolidation occurs usually secondary to pulmonary hemorrhage, and may also cavitate(5%). Subpleural and wedge-shaped, focal parenchymal or peri broncho-arterial consolidation may reflect granulomatous changes and pneumonia.8 Subglottic tracheal and bronchial wall thickening and subsequent narrowing may cause secondary lobar collapse, and is often refractory to systemic treatment.9 Pleural thickening and small effusions may occur variably depending on the series quoted.7, 9
Nasal cavity and paranasal sinuses
Non-specific mucosal thickening or antral opacification are typical early features, followed by nasal septal thinning and granulomatous ulcerated change. Bony destruction is also frequently demonstrated on CT including a necrosed nasal septum (saddle nose deformity), though the sinuses may atrophy and the maxillary bone progressively ossify.10 On MRI, granulomatous tissue varies in signal with the stage of inflammation. In the early phase of inflammation nonspecific T2 weighted signal hyperintensity is present, but as granulomatous transformation progresses, granulomata appear hypointense.11
Kidneys
Limited forms of WG sparing the kidney are rare. Usually severe progressive necrotizing glomerulonephritis occurs resulting in rapid deterioration of renal function. Large echogenic kidneys on ultrasound without specific Doppler abnormalities are typical early findings. However, this may rapidly progress to scarred shrunken kidneys with chronic renal failure.12 More rarely, a pseudotumour may also be present as a non-specific infiltrative lesion indistinguishable from many other renal masses, isointense on T1 weighted and mixed signal on T2 weighted MRI.13
Our patient clinically meets the criteria of diagnosis (ACR) based on the clinical, radiology and pathological findings. Glucocorticoids and cyclophosphamide are recommended for treatment. The monitoring of ESR may determine the efficacy of the treatment. While formerly WG was universally fatal within a few months of onset of clinically apparent renal disease, using the above therapy, the prognosis of disease is excellent with marked improvement seen in > 90% of patients and complete remissions are achieved in 75% of the patients.14 Our patient was also put on prednisone and cyclophosphamide therapy with significant remission of symptoms on subsequent follow up. As a conclusion, WG should be considered in cases presenting with extensive sino-nasal disease and associated chest signs and symptoms and early diagnosis and prompt treatment should be performed.

References

---

1. Seaton A. Pulmonary lymphocytic angitis and granulomatosis. In, Seaton A (ed). Crofton and Douglas's Respiratory Diseases. 5th edition, London, Blackwell Science Inc, 2000;1063
2. Cotch MF, Hoffman GS, Yerg DE, Kaufman GI, Targonski P, Kaslow RA. The epidemiology of Wegener's granulomatosis. Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources. Arthritis Rheum 1996;39:87-92.
3. Sneller MC, Langford CA, Fauci AS. The vasculitis syndromes. In, Kasper DL (ed). Harrison's principles of internal medicine, 16th edition. New York, McGraw-Hill Companies, 2005; 2005
4. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum 1990;33:1101-7.
5. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD et al. Wegener's Granulomatosis: An Analysis of 158 Patients. Ann Intern Med 1992;116:488-98.
6. Rao JK, Weinberger M, Oddone EZ, Allen NB, Landsman P, Feussner JR. The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener
Granulomatosis : A literature review and meta-analysis. Ann Intern Med 1995;123:925-32.
7. Maskell GF, Lockwood CM, Flower CD. Computed tomography of the lung in Wegener's granulomatosis. Clin Radiol 1993;48:377-80.
8. Lohrmann C, Uhl M, Kotter E, Burger D, Ghanem N, Langer M. Pulmonary manifestations of Wegener granulomatosis: CT findings in 57 patients and a review of the literature. Eur J Radiol 2005;53:471-7.
9. Kuhlman JE, Hruban RH, Fishman EK. Wegener's Granulomatosis: CT Features of Parenchymal Lung Disease. J Comput Assist Tomogr 1991;15:948-52.
10. Rasmussen N. Management of ear, nose and throat manifestations of Wegener's granulomatosis: an otorhinolaryngologist's perspective. Curr Opin Rheumatol
2001;13:3-11.
11. Muhle C, Reinhold-Keller E, Richter C, Duncker G, Beigel A, Brinkmann G et al. MRI of the nasal cavity, the paranasal sinuses and orbits in Wegener's granulomatosis. Eur Radiol 1997;7:566-70.
12. Allen SD, Harvey CJ. Imaging of Wegener's granulomatosis. Br J Radiol 2007; 80: 757-65.
13. Verswijvel G, Eerens I, Messiaen T, Oyen R. Granulomatous renal pseudotumor in Wegener's granulomatosis: imaging findings in one case. Eur Radiol 2000;10:1265-7.
14. Sneller MC, Langford CA, Fauci AS. The vasculitis syndromes. In: Kasper DL (ed). Harrison's principles of internal medicine, 16th edition. New York, McGraw-Hill Companies, 2005;2006.

Source(s) of Funding

---

None

Competing Interests

---

None

Disclaimer

---

This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.