This document discusses Wegener's granulomatosis (now called granulomatosis with polyangiitis or GPA), a rare multisystem autoimmune disease characterized by necrotizing vasculitis and granulomatous inflammation that commonly involves the respiratory tract and kidneys. Key points include: - GPA is associated with circulating ANCA antibodies and causes necrotizing inflammation of small to medium vessels. - Common clinical manifestations involve the upper respiratory tract, lungs, and kidneys. Chest imaging often shows nodules/masses, cavities, ground glass opacities and consolidations. - Diagnosis is based on clinical features, labs including positive ANCA, and biopsy

1. DR. AMEEN RAGEH
FORMERLY KNOWN AS WEGENER GRANULOMATOSIS

2. • Classification of vasculitis
• Wegener’s granulomatosis
• Epidemiology
• Clinical features
• Pathogenesis
• Diagnosis
• Differential diagnosis
• Treatment

3. Vasculitis
Primary Secondary
Connective tissue disorder
Infection
Drug
Cancer

4. Primary vasculitis
Small vessels
ANCA vasculitis
Immune complex
vasculitis
Medium vessels
Polyarthritis
nodosa
Kawasaki disease
Large vessels
Giant cell arteritis
Takayasu aortitis
Other
Bachet’s

6. Multisystem autoimmune disease of unknown
etiology characterized by:
•Granulomatous necrotizing small vessel vasculitis of
the upper & lower respiratory tract
•Glomerulonephritis.
GRANULOMATOUSIS: Necrosis of lung parenchyma not related to blood vessel occlusion

7. • In 1931, two patients died from
prolonged sepsis with inflammation of
blood vessels scattered throughout the
body.
• In 1936, Dr. Frederich Wegener first
described a distinct syndrome in three
patients found to have necrotizing
granulomas involving the upper and
lower respiratory tract.
• In 1954, Goodman and Churg provided
the definitive description with seven
more patients described, resulting in
definite criteria

8. • The cause of Wegener granulomatosis is unknown.
• An autoimmune element has been proposed
because of the presence of circulating anti-
neutrophil cytoplasmic antibodies (ANCAs) directed
against proteinase 3 and, less commonly,
myeloperoxidase.
Other ANCA-associated vasculitides::
Churg-Strauss syndrome and microscopic polyangiitis

9. Wegener granulomatosis is
characterized pathologically by three
features:
1. Systemic necrotizing angiitis,
2. Necrotizing granulomatous
inflammation of the respiratory tract,
3. Necrotizing glomerulonephritis.
Gross Pathology
Necrotic nodules
➢ With and without cavitation
Parenchymal consolidation
Massive hemorrhage
Airway narrowing

10. Wegner’s granulomatosis involves the
• upper respiratory tract 100%
• lower respiratory tract 90%
• kidneys 80%
• Tracheo-bronchial tree 60%
Wegener’s Granulomatosis: Limited
• Involvement of lungs alone
• Clinical sparing
➢ Kidneys
➢ Upper respiratory tract
• Biopsy positive
➢ When clinically normal
• Better prognosis

11. • Chronic sinusitis (67%)
• Rhinitis 22%
• Epistaxis 11%
• Serous otitis media
(ear pain) and
hearing loss
• Stridor
URT
• Cough (34%)
• Hemoptysis (18%)
• Chest discomfort (8%)
• Dyspnea (7%)
LRT
• Glomerulonephritis
• (hematuria, blood
pressure, Oligoruia)
• Renal failure 11%
RENAL
Any age, although the mean age at diagnosis is 50 years.
Males and females are affected equally.
has a broad clinical spectrum( localized disease  severe life-threatening)
Classic clinical triad

12. •Conjunctivitis
•Episcleritis
•Uveitis
•Optic nerve vasculitis
•Retinal artery occlusion
•Nasolacrimal duct
occlusion
•Proptosis
Eye 52%
•papules, vesicles, palpable
purpura, ulcers, or
subcutaneous nodules.
Skin lesions
46%
•cranial nerve palsies
•mononeuritis multiplex
•sensorimotor
polyneuropathy
NS 23%
Non
specific
Fevers, night sweats
Fatigue, lethargy
Loss of appetite
Weight loss

13. Destruction of cartilaginous nasal septum

14. • Classified on the basis of organ involvement

15. American College of Rheumatology –not intended to be used in routine clinical practice and
established before ANCA.
Presence of 2 or more yield 88% sensitivity and 92% specificity

16. Routine
Labs
Radiological
evaluation
ANCA ASSAY
Tissue
Biopsy

17. •Nonspecific- Leukocytosis, thrombocytosis
(>400,000), marked ESR, and normocytic,
normochromic anemia, mildly elevated
Rheumatoid Factor.

18. • Production of ANCA (anti-neutrophil cytoplasmic antibodies)
is one of the hallmarks of WG and related forms of vasculitis
(Churg-strauss, MPA, pauciimmune glomerulonephritis, drug –
induced).
• ANCA are directed against antigens present within the
primary granules of neutrophils and monocytes, and thus
produce tissue damage via interactions with primed
neutrophils and endothelial calls.
• ~90% of pts with active generalized WG are ANCA positive,
but some do not have ANCA, and those with limited forms of
the disease , up to 40% may be ANCA negative, thus the
absence of ANCA does not exclude the diagnosis of
Wegener’s Granulomatosis.

19. • Whether tissue diagnosis is always required for GPA
remains controversial. As the therapy for severe GPA
is not benign, tissue diagnosis is recommended if a
biopsy site is available, provided that the patient
understands the risks of the procedure.

20. Pulmonary finding
Extra Pulmonary
finding

21. Pulmonary nodules and masses 70%
Central cavitation 50%
ground-glass opacity and consolidation 50%
Tracheal involvement 16-23%
Pleural Involvement 12-20%
Mediastinal lymphadenopathy 10-20%
COMMON
Les
common

22. RADIOLOGICAL EVALUATION
Pulmonary findings of Wegner’s granulomatosis
Nodules/
Masses
Cavitating
Non
cavitating
Alveolar
opacities
Ground
glass
opacities
Consolidation
Airways
Subglottic
tracheal
stenosis
Bronchial
stenosis

23. RADIOLOGICAL EVALUATION
Un common findings of Wegner’s granulomatosis
PLUERAL
INVOLVMENT
Pleural
effusions
RENAL FAILURE
PRIMARY INVOLVMTN OF WG
pleural
thickening
Mediastinal
lymphadenopathy

24. • Single or multiple.
• Small or large (few mm to 10 cm).
• Waxing and waning of the pulmonary nodules and masses are
features of WG.
• Cavitating or non cavitating.
• Usually have a random distribution
• Thin smooth walled (1-3 mm) or thick irregular walled (> 3 mm)
cavities.
• Halo sign (due to surrounding alveolar hemorrhage).
• Reversed halo sign.
• Feeding vessel sign

25. NODULES
Nodule: is a rounded opacity, well or poorly defied,
measuring up to 3 cm in diameter.

26. NODULES/MASSES  CAVITIES

27. CAVITITING NODULE
Cavity: is a gas filed space, seen as a lucency or low-
attenuation area, within pulmonary consolidation, a
mass, or a nodule.

28. Suspicious looking nodules that do not correlate with
clinical or immunologic activity should be biopsied
because of the two fold increased risk of malignancy
in patients with Wegener granulomatosis

29. Due to alveolar hemorrhage or intraalveolar cellular debris
Alveolar WG
Ground glass
opacities
Bilateral
perihilar
peribronchovascular
Consolidation
Wegener granulomatosis is
considered when ground-glass
opacity and consolidation occur
in isolation suggesting infection,
which fail to resolve with
adequate antibiotic therapy

30. • Consolidation is a homogeneous increase in pulmonary parenchymal attenuation that obscures the margins of vessels
and airway walls, while GGO is hazy increased opacity of lung, with preservation of bronchial and vascular margins

31. • Feeding vessels sign: a vessel leading to the apex of a peripheral area of consolidation

32. Halo sign is a CT finding of ground –glass opacity surrounding a nodule or mass

33. • Reversed halo sign is a focal rounded area of ground – glass opacity surrounded by a more of
less complete ring of consolidation

34. Airways
Subglottic
tracheal
Stenosis
Bronchial
Stenosis
(wall thickening)
The subglottic portion of the trachea is most
often affected
Wall thickening is usually circumferential
and can be smooth or nodular.
Involvement of the posterior membrane
of the trachea is the rule

37. Pulmonary finding
Extra Pulmonary
finding

38. • The most common findings on CT
scans of the paranasal sinuses and
fossae are the presence of
mucosal oedema with bone
destruction foci in the paranasal
sinuses, as well as foci of sclerosing
osteitis and bone thickening in the
same location

39. PARANASAL SINUSES + OPHTHALMIC INVOLVMENT

40. DIFFRENTIAL DIAGNOSIS
• Due to broad spectrum of presentation, differentiation
include paranasal sinuses diseases, causes of
glomuroniphrits, and pulmonary diseases, and other ANCA
vasculitis
• The differential diagnosis including those diseases causing:
1. Nodules and masses
2. Air space opacities
3. Airway Thickening

44. • The mainstay of treatment for granulomatosis with
polyangiitis (GPA) is a combination of corticosteroids
and cytotoxic agents.
• Approximately 90% of patients with GPA respond to
cyclophosphamide, with approximately 75%
experiencing complete remission.

46. 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 is seen
A 32 YEARS OLD MALE PATIENT PRESENTED WITH SYMPTOMS
OF NASAL BLOCKAGE, BLOOD MIXED NASAL DISCHARGE
WITH REDNESS OF EYES
CT chest at the level of clavicur heads revealing
nodular pulmonary lesions having lobulated
margin showing no calcification, located in
apical segments of both upper lobes abutting
pleura
Biopsy result: WG

47. ADULT FEMALE WITH HISTORY OF
FEVER, COUGH AND HEMOPTYSIS
• Computed tomographic
scan image at the level of
the inferior pulmonary
veins shows bilateral areas
of consolidation in a
peribronchovascular
distribution with
surrounded GGO (halo
sign) and left pulmonary
nodules the (one at
posterior segment show
feeding vessels sign)

48. KNOWN CASE OF WG
• . a, Chest
radiograph shows
tracheostomy, with
tracheal narrowing
above and below
the level of the
tracheostomy.
• B, C, CT images
confirm the
marked subglottic
mucosal
thickening with
airway narrowing,
and narrowing of
both main bronchi.

49. • PA chest radiograph demonstrates a right upper lobe
mass-like consolidation.
• Enhanced chest CT at level of aortic arch (lung
window) shows a peripheral wedge-shaped right
upper lobe consolidation lower sections show
peripheral subpleural and angiocentric pulmonary
masses and nodules. (feeding vessel sign)
72-year-old womanH/O: cough, sinusitis, and renal insuffiency
• Multicentric Primary or Secondary Neoplasia
• Multifocal Pneumonia
• Bland or Septic Emboli, Pulmonary Infarcts
• Pulmonary Vasculitis
• Cryptogenic Organizing Pneumonia
Top DDX: WEGNER GRANULOMATOSIS