Multisystem RadiologyFree Access

From Head to Toe: Granulomatosis with Polyangiitis

Published Online:https://doi.org/10.1148/rg.2021210132

Abstract

Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody–associated vasculitis. It is an uncommon multisystem disease involving predominantly small vessels and is characterized by granulomatous inflammation, pauci-immune necrotizing glomerulonephritis, and vasculitis. GPA can involve virtually any organ. Clinical manifestations are heterogeneous and can be classified as granulomatous (eg, ear, nose, and throat disease; lung nodules or masses; retro-orbital tumors; pachymeningitis) or vasculitic (eg, glomerulonephritis, alveolar hemorrhage, mononeuritis multiplex, scleritis). The diagnosis of GPA relies on a combination of clinical findings, imaging study results, laboratory test results, serologic markers, and histopathologic results. Radiology has a crucial role in the diagnosis and follow-up of patients with GPA. CT and MRI are the primary imaging modalities used to evaluate GPA manifestations, allowing the differentiation of GPA from other diseases that could simulate GPA. The authors review the main clinical, histopathologic, and imaging features of GPA to address the differential diagnosis in the affected organs and provide a panoramic picture of the protean manifestations of this infrequent disease. The heterogeneous manifestations of GPA pose a significant challenge in the diagnosis of this rare condition. By recognizing the common and unusual imaging findings, radiologists play an important role in the diagnosis and follow-up of patients with GPA and aid clinicians in the differentiation of disease activity versus disease-induced damage, which ultimately affects therapeutic decisions.

Online supplemental material is available for this article.

©RSNA, 2021

SA-CME LEARNING OBJECTIVES

After completing this journal-based SA-CME activity, participants will be able to:

  • ■ List specific serologic markers and histopathologic features of GPA.

  • ■ Describe the clinical presentation and differential diagnosis of GPA.

  • ■ Identify characteristic multimodality imaging features of GPA that affect multiple organ systems.

Introduction

Granulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis, is an antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. It is a rare multisystemic disease involving predominantly small vessels and characterized by granulomatous inflammation, pauci-immune necrotizing glomerulonephritis, and vasculitis, leading to endothelial injury and tissue damage (1). In 1931, Klinger provided the first description of GPA: a variant of polyarteritis nodosa. Later, in 1936 and 1939, Wegener described in detail a separate syndrome (2).

GPA is an uncommon disease, with an estimated incidence of between 0.4 and 11.9 cases per 1 million person-years. Equal numbers of males and females have GPA, with ages at onset of 45–65 years and a higher prevalence among White individuals (1,3,4). The incidence of GPA seems to have increased during the past decades, possibly owing to greater awareness of this condition following the introduction of ANCA testing (5).

The precise pathogenetic mechanisms of GPA remain unknown. Infectious, environmental, chemical, toxic, and pharmacologic triggers in genetically predisposed individuals may influence disease onset (3). A genetic association with HLA-DP, SERPINA1, and PRTN3 has been described (6). Hypotheses regarding the pathogenetic mechanisms of GPA include the participation of an infectious agent (Staphylococcus aureus) activating the immune system; the role of B cells in the production of ANCA; and imbalances in different T-cell subtypes and cytokine-chemokine networks participating in the rupture of tolerance, triggering autoimmunity and/or an oxidative burst toward endothelial cells (5,6).

ANCAs directed against proteinase 3 are present in approximately 65%–75% of individuals with GPA, and ANCAs directed against myeloperoxidase are present in 20%–30% of these individuals (4). These antibodies are involved in the activation of circulating primed neutrophils, causing them to attach to, penetrate, and damage vessel walls by undergoing respiratory burst, degranulation, NETosis (formation of neutrophil extracellular traps), apoptosis, and necrosis (5,6).

In 1990, the American College of Rheumatology developed the first formal set of criteria for the classification of GPA. The presence of at least two of the following four criteria for purposes of classification has 88.2% sensitivity and 92.0% specificity: nasal or oral inflammation, abnormal chest radiography findings, urinary sediment, and granulomatous inflammation at biopsy (7).

More recently, in 2017, the American College of Rheumatology and the European League Against Rheumatism proposed revised classification criteria for GPA that had good sensitivity (93%) and specificity (94%). With these criteria, both clinical and laboratory parameters, including ANCA testing and imaging study findings, are considered, and a different weight or score is applied to each criterion. Nodules, masses, or cavitations on chest images; and inflammation, consolidation, or effusion of the nasal or paranasal sinuses are among the imaging findings (8).

Virtually any organ can be involved by GPA. Symptoms of systemic inflammation such as fever, weight loss, malaise, arthralgia, myalgia, and fatigue are often present. Clinical manifestations are heterogeneous and can be classified as granulomatous manifestations (eg, ear, nose, and throat disease; lung nodules or masses, retro-orbital tumors, pachymeningitis), which are associated with increased risk of relapse, or vasculitic manifestations (eg, glomerulonephritis, alveolar hemorrhage, mononeuritis multiplex, scleritis), which are associated with increased mortality (9). Clinical manifestations of GPA are depicted in Figure 1.

Drawing depicts the main clinical manifestations of GPA. CNS = central                     nervous system, MPO = myeloperoxidase, PR3 = proteinase 3.

Figure 1. Drawing depicts the main clinical manifestations of GPA. CNS = central nervous system, MPO = myeloperoxidase, PR3 = proteinase 3.

Teaching Point The diagnosis of GPA relies on the combination of clinical findings, imaging study results, laboratory test measurements (eg, of inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein, complete blood count, and renal and urinary parameters), serologic markers (ANCA testing), and histopathologic results when biopsy is feasible
(5). The distinction between active disease and disease-induced damage is relevant and has therapeutic and prognostic implications (10,11). Radiology plays a crucial role in the diagnosis and follow-up of patients with GPA. CT and MRI are the primary imaging modalities used to evaluate GPA manifestations, allowing differentiation of GPA from other diseases that could simulate GPA. Differential diagnoses of GPA are summarized in the Table.

Differential Diagnosis of GPA

Following the introduction of immunosuppressant therapies, the 5-year survival rate among individuals with GPA has been approximately 70%–80% during the past 40–50 years (4). The management of GPA involves two phases: remission induction (first 3–6 months), based on therapy with a combination of glucocorticoids and either cyclophosphamide or rituximab, and maintenance (next 24–48 months) aimed at preventing disease relapse, based on therapy with low-dose glucocorticoids and either rituximab, azathioprine, methotrexate, or mycophenolate mofetil (5,12).

In this article, we review the main clinical, histopathologic, and imaging features of GPA; address the differential diagnoses in the affected organs; and provide a panoramic picture of the protean manifestations of this infrequent disease.

Head and Neck

The head and neck are involved in 90% of patients with GPA, being the areas of presenting symptoms in 73% of them, and the sites most commonly affected are the nose, eyes, ears, and mouth (13,14). Neurologic involvement in GPA occurs in 22%–54% of these patients. Peripheral neuropathy and granulomatous orbital masses are the most common neurologic manifestations, occurring in 10%–45% of patients with GPA (15). When cranial nerve palsies are excluded from central nervous system (CNS) manifestations, CNS involvement is rare, seen in 7%–11% of patients with GPA at the time of diagnosis or during exacerbations (16,17). Direct extension of the granulomatous process, vasculitis of the cerebral vessels, and direct formation of granulomas within the brain parenchyma are the pathogenic mechanisms proposed in the CNS involvement (18).

Meninges

Pachymeningitis, a disorder caused by localized or diffuse thickening of intracranial or spinal dura mater, has been reported in 0.6%–8.0% of patients with GPA (19). It is considered a granulomatous manifestation of GPA, being that chronic hypertrophic pachymeningitis is more frequent than leptomeningitis (15). Chronic hypertrophic pachymeningitis may occur as an initial manifestation of GPA or as the only site of active disease (20). Although this manifestation is considered rare, it may be responsible for other more common neurologic manifestations such as cranial neuropathies with permanent damage, headache, diabetes insipidus, hydrocephalus, and opthalmoplegia (21).

Symptoms include severe chronic headache that is refractory to common analgesics but responsive to corticosteroids, multiple cranial nerve palsy (most commonly of cranial nerves III, VI, VII, and X), meningism, seizures, encephalopathy, proptosis, ataxia, blurred vision, limb palsy, and paraplegia (due to spinal cord involvement) (15,20,22).

Teaching Point MRI with gadolinium-based contrast material is the imaging technique of choice for detection of meningeal involvement in GPA. It is useful for determining whether the meningitis developed in situ or from extracranial sites, and it depicts diffuse or focal thickening of the dura in 75% of GPA cases (Fig 2) and involvement of the leptomeninges in the remaining cases
(Fig 3) (21,23). Two patterns of distribution have been described: diffusely abnormal meninges unrelated to sinus or orbital disease, and focal dural thickening and enhancement adjacent to sinus or orbital disease (24). Tentorial involvement is very common (22). Additional patterns and sites of enhancement include linear or nodular, peripheral or uniform, and symmetric or asymmetric (25). The “Eiffel-by-night” sign at MRI represents thickened dura in the posterior falx and the tentorium due to fibrosis, seen as central hypointensity on contrast-enhanced T1-weighted fat-saturated images, with an enhancing periphery representing areas of active inflammation (Fig 4) (25). In contrast, the sensitivity of CT for these lesions is low (20).

GPA in a 32-year-old man. Axial contrast-enhanced T1-weighted MR images                     show diffuse pachymeningeal enhancement (black arrows), as well as left                     ethmoidal sinus disease (white arrow in B).

Figure 2. GPA in a 32-year-old man. Axial contrast-enhanced T1-weighted MR images show diffuse pachymeningeal enhancement (black arrows), as well as left ethmoidal sinus disease (white arrow in B).

GPA-related leptomeningeal enhancement (arrow) and vasogenic edema                     (*) on an axial contrast-enhanced CT image in a 34-year-old                     woman.

Figure 3. GPA-related leptomeningeal enhancement (arrow) and vasogenic edema (*) on an axial contrast-enhanced CT image in a 34-year-old woman.

Eiffel-by-night sign (thickened dura in posterior falx and tentorium)                     (arrows) on a coronal contrast-enhanced T1-weighted MR image in a 34-year-old                     woman (same patient as in Fig 3).

Figure 4. Eiffel-by-night sign (thickened dura in posterior falx and tentorium) (arrows) on a coronal contrast-enhanced T1-weighted MR image in a 34-year-old woman (same patient as in Fig 3).

Cerebrospinal fluid analysis is useful for ruling out infections and may yield normal results or show nonspecific abnormalities such as lymphocytic pleocytosis, hyperproteinorrachia, or elevated opening pressure (15,23). Meningeal biopsy should be reserved for cases in which there is suspicion for neoplastic meningitis or the treatment response is inadequate. Biopsy can reveal granulomatous inflammation, small-vessel vasculitis, or a combination of these disorders. Less frequently, biopsy reveals lymphocytic inflammation and fibrous thickening (15,20,22).Neurologic sequelae are common in patients with spinal cord pachymeningitis and vasculitic (hemorrhagic or ischemic) lesions and less frequent in those with cerebral pachymeningitis (16).

Brain Parenchyma

Cerebral small-vessel vasculitis, the most common parenchymal manifestation in patients with GPA, has been reported in approximately 4% of affected patients and is associated with intracerebral or subarachnoid hemorrhage, transient ischemic attacks, ischemic infarction (Fig 5), subdural hematoma (Fig 6), ischemic myelopathy, and arterial or venous thrombosis (Fig 7) (23,26,27). Cerebral infarcts may be caused by arterial occlusion secondary to a granulomatous mass that extends from nasal or paranasal sites into the skull base, whereas the least common forms of CNS involvement in GPA are remote granulomatous lesions in the brain parenchyma (Fig 8) (24). Clinical manifestations of cerebral vasculitis include paresis, seizures, altered consciousness, encephalopathy, cognitive impairment, visual loss, cortical blindness, and dementia (27).

Known GPA in a 40-year-old man who presented with visual disturbances.                     Axial diffusion-weighted image shows restricted diffusion (arrow) in the right                     occipital lobe.

Figure 5. Known GPA in a 40-year-old man who presented with visual disturbances. Axial diffusion-weighted image shows restricted diffusion (arrow) in the right occipital lobe.

GPA in a 50-year-old woman. Axial contrast-enhanced T1-weighted MR image                     shows diffuse pachymeningeal enhancement (arrows) and chronic subdural hematoma                     (*).

Figure 6. GPA in a 50-year-old woman. Axial contrast-enhanced T1-weighted MR image shows diffuse pachymeningeal enhancement (arrows) and chronic subdural hematoma (*).

GPA in a 27-year-old man who presented with headache. Sagittal                     contrast-enhanced T1-weighted maximum intensity projection MR venogram shows                     signal loss in the superior sagittal sinus (arrow) due to thrombosis.

Figure 7. GPA in a 27-year-old man who presented with headache. Sagittal contrast-enhanced T1-weighted maximum intensity projection MR venogram shows signal loss in the superior sagittal sinus (arrow) due to thrombosis.

GPA in an asymptomatic 34-year-old woman. Sagittal contrast-enhanced                     T1-weighted fat-saturated MR image shows a granulomatous lesion (arrow) near the                     Magendie foramina.

Figure 8. GPA in an asymptomatic 34-year-old woman. Sagittal contrast-enhanced T1-weighted fat-saturated MR image shows a granulomatous lesion (arrow) near the Magendie foramina.

Teaching Point Diagnosing CNS vasculitis is challenging, especially owing to the difficulty in distinguishing this condition from vascular atherosclerotic disease (27). MRI findings of cerebral vasculitis include multiple nonspecific white matter lesions with patchy high T2 signal intensity in a typical vascular distribution (periventricular, subcortical regions, basal ganglia, mesencephalon, and pons)
(26,28). Diffusion-weighted images can depict areas of infarction, and contrast-enhanced MR images may show patchy regions of enhancement (26). Hemorrhagic events occur less often and usually affect the brain parenchyma and subarachnoid space (28). Cerebral atrophy also is reported and is possibly associated with cerebral vasculitis and treatment with corticosteroids, whereas functional MRI studies in patients with GPA (24,29) have shown that fatigue may be related to the striatothalamofrontal structures of the brain.

Conventional angiography is not suitable for detecting small-vessel (50–300-µm) vasculitis since the size of the small vessels typically affected by GPA is below the resolution of conventional angiography (500 µm) (30). Therefore, negative cerebral angiography results are often seen. However, case reports (31) have shown involvement of the internal carotid, cerebral, and ophthalmic arteries, with improvement after treatment (Fig E1).

Posterior reversible encephalopathy syndrome is a rare complication that manifests clinically as an acute onset of encephalopathy, seizures, headache, and visual disturbance. Radiologically, posterior reversible encephalopathy syndrome manifests as vasogenic edema that involves predominantly the bilateral parieto-occipital regions (28). Moreover, isolated parenchymal masses are rare. They manifest clinically as seizures and radiologically as well-delineated granulomas with high signal intensity on T2-weighted MR images and enhancement on gadolinium-enhanced MR images (28).

Histologically confirmed vasculitis of the CNS is very rare, and biopsy for this disease is often impossible (30). Brain biopsy specimens from the dura, brain parenchyma, and leptomeninges reveal necrotizing vasculitis affecting small to medium vessels, granulomatosis with inflammatory cell (monocytes, plasma cells, eosinophils, and polymorphonuclear leukocytes) infiltration, fibrinoid necrosis, and edema (28).

Pituitary Gland

Pituitary gland involvement is reported in fewer than 1% of GPA cases, more commonly during the disease course than preceding the diagnosis, and in younger individuals, with a female predominance (32,33). In most patients with pituitary involvement, other organs are affected (34). The pituitary gland and the infundibulum may be involved in GPA by way of distant granulomas or direct spread from nasal, paranasal, or orbital disease and are therefore associated with the granulomatous rather than vasculitic component of the disease (24,33).

The most frequent pituitary disorders in GPA are diabetes insipidus and secondary hypogonadism, although panhypopituitarism also may occur (34). Compressive symptoms of these disorders include headache, vomiting, and visual field defects. In contrast, hormonal abnormalities manifest as polyuria, polydipsia, asthenia, amenorrhea, galactorrhea, decreased libido, and muscular atrophy (34).

MRI of the pituitary gland reveals an enlarged gland with heterogeneous or homogeneous enhancement; cystic changes; increased enhancement and thickening of the infundibulum; and loss of posterior hyperintensity on T1-weighted MR images (especially in patients with central diabetes insipidus due to markedly decreased vasopressin content in the posterior pituitary gland). Thickening (>3.5-mm width), abnormal enhancement, and compression of the stalk (Fig 9) also can be seen at MRI (26,27,32,33). The resolution of MRI changes does not always correlate with clinical improvement in pituitary function, and vice versa. However, in up to 62%–86% of patients, hormone deficiency may persist despite an adequate systemic disease response, probably because of the permanent pituitary damage related to necrotizing granulomatous inflammation of the gland (3234). Cerebrospinal fluid analysis can be used to exclude other clinical conditions such as infection, lymphoma, and Langerhan cell histiocytosis (34).

Sagittal (A, C) and coronal (B, D) contrast-enhanced T1-weighted MR images                     in an 18-year-old man with newly diagnosed GPA and panhypopituitarism at                     presentation. (A, B) Pretreatment images show pituitary stalk thickening and                     enhancement (arrow in A) and pituitary enlargement (arrow in B). (C, D)                     Posttreatment images at 1-year follow-up show significant improvement                     (arrow).

Figure 9. Sagittal (A, C) and coronal (B, D) contrast-enhanced T1-weighted MR images in an 18-year-old man with newly diagnosed GPA and panhypopituitarism at presentation. (A, B) Pretreatment images show pituitary stalk thickening and enhancement (arrow in A) and pituitary enlargement (arrow in B). (C, D) Posttreatment images at 1-year follow-up show significant improvement (arrow).

Pituitary biopsy is not necessary to confirm GPA-related hypophysitis (18). Histopathologic analysis reveals polymorphous inflammatory changes and/or granulomas with lymphocytes and plasma cells (27).

Cranial Nerves

Cranial neuropathies are infrequent in GPA; they may occur as single or multiple abnormalities and are most often secondary to infiltration by granuloma from the paranasal sinuses (35). The frequencies of cranial neuropathies reported in several cohorts range from 2% to 10%, and it may be challenging to make the diagnosis, especially when these neuropathies occur as isolated manifestations (23,30,36).

The optic and olfactory nerves are the most frequently affected; peripheral cranial nerves (III to XII) are affected along their extracranial route, and palsies of cranial nerves III, V, VI, VII, and VIII are present in about 50% of patients with pachymeningitis (15). The optic nerve may be involved by vasculitis, direct inflammation of the neural sheath, or acute compression by granulomatous masses in the orbit that lead to atrophy and visual loss (15,37). Isolated or multiple cranial neuropathies in the absence of pachymeningitis are rare and usually attributed to a vasculitic process (23).

MRI reveals inflammatory changes with associated thickening and enhancement of the adjacent cranial nerves; specifically, acute optic neuritis manifests as signal hyperintensity in an enlarged enhancing optic nerve (26) (Fig 10). Short τ inversion-recovery and contrast-enhanced T1-weighted fat-suppressed MR images are needed to delineate the lesion.

GPA in a 58-year-old woman who presented with oppressive pain and diplopia                     in the right eye. T1-weighted contrast-enhanced fat-saturated MR image shows                     discrete right optic nerve enhancement (arrow) compared with the enhancement on                     the left side.

Figure 10. GPA in a 58-year-old woman who presented with oppressive pain and diplopia in the right eye. T1-weighted contrast-enhanced fat-saturated MR image shows discrete right optic nerve enhancement (arrow) compared with the enhancement on the left side.

Temporal Bones

The prevalence of otologic involvement varies from 19% to 61%. Otologic involvement is the presenting symptom in 20%–25% of cases of GPA and is almost always secondary to nasal involvement (3840). It is categorized as serous otitis media, chronic otitis media, sensorineural hearing loss, vertigo, or facial nerve palsy (41).

The middle ear is affected in 40%–70% of GPA cases (42). The most common manifestation is unilateral or bilateral serous otitis media due to granulomatous obstruction of the eustachian tube, which may be complicated by facial nerve palsy in 8%–10% of patients and by mastoiditis (14,39). In addition, destruction of the middle ear and mastoid cavity may occur (40).

Gradual or fluctuating hearing loss resulting from conductive (more common), sensorineural, or mixed hearing loss occurs in 6% of patients with GPA, and it may be bilateral in 60% of cases (38). Sensorineural hearing loss results from vasculitic involvement of the cochlear blood supply or deposition of immune complexes within the cochlea, whereas conductive hearing loss often persists because of a thickened, scarred, and often perforated tympanic membrane and middle ear adhesions (14,42).

Imaging findings in the temporal bones include middle ear or mastoid air cell opacification with thickening of the bone septa, and osseous demineralization or erosion (Fig 11) (26,43). Moreover, MRI findings include thickening and enhancement of adjacent cranial nerves, most frequently the mastoid and tympanic segments of cranial nerve VII, with effacement of the surrounding fat within the foramina of the skull base. Enhancement of the basal cochlear turn may be seen in patients with labyrinthitis, whereas vestibule enhancement is less commonly seen (44).

Recurrent otitis media and GPA in a 61-year-old woman. Axial noncontrast                     bone-window CT image shows soft-tissue opacification in the mastoid air cells                     (arrow) and middle ear (arrowhead).

Figure 11. Recurrent otitis media and GPA in a 61-year-old woman. Axial noncontrast bone-window CT image shows soft-tissue opacification in the mastoid air cells (arrow) and middle ear (arrowhead).

Biopsy specimens from the middle ear and mastoid are usually small, making it difficult to determine a diagnosis. Temporal bone histopathologic analysis in cases of deafness caused by GPA reveals tympanic granulation and inflammatory tissue invading the inner ear through the round window, atrophy of the stria vascularis, and preservation of the spiral ganglion cells (41).

Orbit and Eye

Orbital involvement occurs during the course of the disease in 45% of patients with GPA and as a presenting feature in 16% of these patients (45). Granulomatous masses arising from the nasal or paranasal cavities may perforate the bone and invade structures of the CNS such as the meninges, brain, and orbit. Moreover, orbital masses may arise primarily within the orbit, especially in the orbital apex (15). These masses may also spread intracranially along the skull base fissures or foramina (43).

Orbital masses are more frequently unilateral (86% of the cases), are extraconal or transspatial in distribution, and often coexist with sinus disease and/or bone destruction (15,26). Presenting features include severe orbital pain, proptosis (2% of the patients), diplopia, eyelid swelling, periorbital cellulitis, ocular movement impairment, and visual loss due to optic nerve compression and atrophy, which may be permanent in 8% of patients (15,42).

In 50%–60% of patients, ocular involvement occurs during the course of disease. Episcleritis is the most common ocular manifestation, present in 16%–38% of GPA cases (42). Uveitis, scleritis, eyelid ulceration and fistula, conjunctivitis, corneal ulcerations, choroidal granulomas, interstitial keratitis, retinal vascular ischemia or occlusion, and nasolacrimal duct obstruction with epiphora are additional eye manifestations (14,42,46,47). Optic perineuritis is more common than optic neuritis (Fig E2). Major causes of visual loss are compressive optic neuropathy, retinal and optic nerve vasculitis, and globe perforation from necrotizing scleritis and peripheral ulcerative keratitis (48).

At MRI, orbital masses are depicted as hypointense lesions on T1- and T2-weighted images, with gadolinium-based contrast medium uptake during the acute phase of inflammation (Fig 12) (15). Additional imaging findings include orbital socket contracture with radiologic evidence of fibrotic changes retracting the optic globe, lacrimal gland and extraocular muscle enlargement, and optic nerve sheath enhancement (15,43). Growth of inflammatory tissue leads to formation of an orbital pseudotumor (Fig 13) with resulting proptosis (26).

GPA in a 36-year-old man. (A, B) Axial (A) and coronal (B)                     contrast-enhanced T1-weighted MR images show a lesion surrounding the                     canalicular portion of the right optic nerve with heterogeneous enhancement                     (arrow). Dural enhancing nodular thickening (arrowheads in A) also is noted. (C)                     Orbit tissue biopsy specimen shows a panoramic appearance, with a dense                     inflammatory infiltrate in soft tissues and geographic necrosis with abscesses                     (arrowheads). (Hematoxylin-eosin [H-E] stain; original magnification,                     ×40.) (D) Photomicrograph shows a small vessel with an occluded lumen                     (*) and inflammatory infiltrate composed of epithelioid histiocytes,                     neutrophils, lymphocytes, scattered eosinophils, and karyorrhectic debris in the                     wall. (H-E stain; original magnification, ×400.)

Figure 12. GPA in a 36-year-old man. (A, B) Axial (A) and coronal (B) contrast-enhanced T1-weighted MR images show a lesion surrounding the canalicular portion of the right optic nerve with heterogeneous enhancement (arrow). Dural enhancing nodular thickening (arrowheads in A) also is noted. (C) Orbit tissue biopsy specimen shows a panoramic appearance, with a dense inflammatory infiltrate in soft tissues and geographic necrosis with abscesses (arrowheads). (Hematoxylin-eosin [H-E] stain; original magnification, ×40.) (D) Photomicrograph shows a small vessel with an occluded lumen (*) and inflammatory infiltrate composed of epithelioid histiocytes, neutrophils, lymphocytes, scattered eosinophils, and karyorrhectic debris in the wall. (H-E stain; original magnification, ×400.)

Orbital pseudotumor in a 51-year-old woman. (A, B) Axial (A) and coronal                     (B) contrast-enhanced CT images show a right orbital soft-tissue lesion with                     papyraceous lamina destruction (arrow) and obliteration of the middle meatus                     (arrowhead in B). Note the superior displacement of the medial rectus muscle                     (dashed oval in B). (C, D) Corresponding axial (C) and coronal (D)                     gadolinium-enhanced MR images better depict intense enhancement                     (arrow).

Figure 13. Orbital pseudotumor in a 51-year-old woman. (A, B) Axial (A) and coronal (B) contrast-enhanced CT images show a right orbital soft-tissue lesion with papyraceous lamina destruction (arrow) and obliteration of the middle meatus (arrowhead in B). Note the superior displacement of the medial rectus muscle (dashed oval in B). (C, D) Corresponding axial (C) and coronal (D) gadolinium-enhanced MR images better depict intense enhancement (arrow).

In GPA, lacrimal gland involvement often accompanies orbital manifestations (Fig 14), and this involvement is usually unilateral. The clinical presentation includes eyelid swelling, orbital pain, proptosis, nasolacrimal duct obstruction, and limitation of extraocular movements with diplopia (45). Histopathologic analysis reveals poorly formed granulomas, necrotizing vasculitis, microabscesses, fibrinoid degeneration of collagen, or mixed inflammatory infiltrations in 50% of cases (15,45).

GPA in a 32-year-old man who presented with increased volume in the                     orbital region. Axial contrast-enhanced T1-weighted MR image shows bilateral                     lacrimal gland hypertrophy and enhancement (arrows) and diffuse dural                     enhancement (arrowheads).

Figure 14. GPA in a 32-year-old man who presented with increased volume in the orbital region. Axial contrast-enhanced T1-weighted MR image shows bilateral lacrimal gland hypertrophy and enhancement (arrows) and diffuse dural enhancement (arrowheads).

Oral Cavity and Salivary Glands

Oral cavity manifestations are rare and include “strawberry” gingival hyperplasia, ulcerative stomatitis, chronic inflammation, granulomata, oroantral fistula, osteonecrosis of palate, and labial mucosal nodules (42). The major salivary glands (parotid and submandibular glands) are an uncommon site of involvement in GPA and represent an early feature of the disease (13,49). In more than 40 case reports, the parotid glands were the most frequently affected (78%), and this involvement may be unilateral or bilateral (50). Imaging findings are nonspecific and consist of heterogeneous enlargement and hyperenhancement of the major salivary glands on CT and MR images (Fig 15); low signal intensity on T2-weighted MR images, suggestive of necrotic foci; and a circumscribed cystic or fluid-filled mass on US images, even in a clinically unaffected gland (13,50). Histopathologic findings of the salivary glands include geographic necrosis, granulomas, giant cells, microabscesses, necrotizing granulomatous inflammation, small-vessel vasculitis, xanthogranulomatous lesions, and fibrosis (13).

Increased volume in the parotid and submandibular regions in a 42-year-old                     woman. (A) Axial arterial phase CT image shows diffuse enlargement in both                     parotid glands (arrows). (B) Axial venous phase CT image shows the submandibular                     glands (arrows).

Figure 15. Increased volume in the parotid and submandibular regions in a 42-year-old woman. (A) Axial arterial phase CT image shows diffuse enlargement in both parotid glands (arrows). (B) Axial venous phase CT image shows the submandibular glands (arrows).

Upper and Lower Airways

Nose and Paranasal Sinuses

The nose and paranasal sinuses are the sites most frequently affected by GPA in the head and neck, with prevalences of nasal involvement of 64%–80% and 29%–36% of patients with generalized and localized disease, respectively (11,39). Nasal involvement manifests as frequent crust formation, serosanguineous discharge, obstruction, chronic rhinosinusitis symptoms, recurrent epistaxis, facial pain, hyposmia, anosmia, or cacosmia (11,39,46,51). Clinical examination reveals nasal crusting (more frequently in the turbinates and septum), friable erythematous mucosa, granulation, signs of sinusitis, an eroded and ulcerated vomer, mucosal cobblestoning, edema, septal perforation, and saddle-nose deformity (Fig 16C), with the latter present in 10%–25% of patients owing to destruction of the septal cartilage with resultant nasal collapse (11,14,39,42). The anterior nasal septum, known as the Kiesselbach plexus, is one of the most commonly involved regions (14). Chronic sinusitis occurs in 50% of cases of nasal involvement (42).

GPA in a 22-year-old man. (A) Axial noncontrast CT image shows total                         opacification of the maxillary sinus (arrows) with septal perforation                         (arrowhead) and bone erosion of the medial wall of the left maxillary sinus                         (*). (B) Follow-up CT image 4 years later shows sclerotic bone                         thickening and irregular borders of the inner walls (arrow). (C)                         Three-dimensional volume-rendered CT image shows saddle-nose deformity                         (arrow), a finding that reflects cartilage destruction.

Figure 16. GPA in a 22-year-old man. (A) Axial noncontrast CT image shows total opacification of the maxillary sinus (arrows) with septal perforation (arrowhead) and bone erosion of the medial wall of the left maxillary sinus (*). (B) Follow-up CT image 4 years later shows sclerotic bone thickening and irregular borders of the inner walls (arrow). (C) Three-dimensional volume-rendered CT image shows saddle-nose deformity (arrow), a finding that reflects cartilage destruction.

Teaching Point In the early stages of GPA, MRI of the nose and paranasal sinuses does not enable differentiation between mucosal inflammation and granulomatous tissue, whereas in the later stages, granulomas are seen as low-signal-intensity lesions at MRI (39). CT may be helpful in cases of bone destruction and intracranial extension of nasal lesions
(39). The most frequent CT findings are mucosal thickening (in 87% of patients) and bone destruction (in 59% of patients) (52).

Imaging findings of sinonasal involvement include bone changes (septal destruction, scalloping, sclerosis, neo-osteogenesis, and calcification [Fig 16A] of the paranasal sinuses and greater wing of the sphenoid), opacification of the sinuses, and mucosal thickening with a nodular pattern, primarily of the maxillary sinuses (14,26,45). Granuloma formation (present in 14.5% of cases) may lead to osseous erosion (with a predilection for the anterior ethmoid region) and progressive destruction of cartilage (Fig 16) (26,43,52). The destructive process is initially localized to the midline septum and turbinates and spreads symmetrically to the adjacent antra and later to the rest of the sinuses, resulting in a large single sinus cavity (26). With use of bone windowing, sclerotic changes in the sinus walls can be seen as a slightly irregular double line to the sinus wall. This double line is made up of a new corticated edge inside the normal bone and is separated by an area of less dense bone (Fig 17) (53).

Axial noncontrast CT image in a 62-year-old man with chronic GPA shows                         extensive osseous erosion of the septum (*) and medial wall of both                         maxillary sinuses (arrows) and sclerotic bone thickening                         (arrowheads).

Figure 17. Axial noncontrast CT image in a 62-year-old man with chronic GPA shows extensive osseous erosion of the septum (*) and medial wall of both maxillary sinuses (arrows) and sclerotic bone thickening (arrowheads).

The sinonasal tissue is the best site for diagnosis in the head and neck region, with histopathologic analysis revealing leukocytoclastic vasculitis with geographic necrosis surrounded by palisaded histiocytes (26,54).

Larynx and Tracheobronchial Tree

Airway involvement occurs in 15%–55% of patients with GPA, usually in younger patients and in conjunction with other disease manifestations (55). Laryngeal involvement, a late manifestation of GPA, manifests as circumferential subglottic stenosis (9%–16% of patients) and smooth or nodular wall thickening, usually without involvement of the vocal cords or distal trachea (14,39,42).

The clinical presentation of airway involvement includes progressive dyspnea, acute stridor, and wheezing, and less frequently hemoptysis, cough, and hoarseness (42,51,55). Tracheobronchial involvement is usually associated with disease that affects the supraglottic structures, pulmonary parenchyma, and other organs, whereas involvement of the posterior membrane of the trachea helps to distinguish GPA from other entities (55).

Tracheobronchial tree involvement, along with pulmonary nodules or masses, is one of the main CT findings of GPA. CT findings also include focal (more common), segmental, multifocal, or elongated segments of stenosis; soft tissue medial to the cricoid cartilage (Fig 18); calcification and thickening of the tracheal rings; peribronchial thickening of the small airways at segmental and subsegmental bronchial levels; and less frequently, bronchiectasis (43,55).

Tracheal stenosis in a 26-year-old woman with a cough and stridor. (A,                         B) Axial (A) and sagittal (B) contrast-enhanced CT images show focal smooth                         circumferential stenosis (arrowheads) of the subglottic portion of the                         trachea. (C) Three-dimensional volume-rendered CT image better depicts the                         tracheal stenosis (arrow).

Figure 18. Tracheal stenosis in a 26-year-old woman with a cough and stridor. (A, B) Axial (A) and sagittal (B) contrast-enhanced CT images show focal smooth circumferential stenosis (arrowheads) of the subglottic portion of the trachea. (C) Three-dimensional volume-rendered CT image better depicts the tracheal stenosis (arrow).

MRI is a valuable diagnostic imaging tool in patients who have GPA with subglottic involvement. It is useful for assessing inflammatory subglottic activity, with sensitivity and specificity of 87.5% and 60.0%, respectively, and a negative predictive value of 85.7%. Specifically, T1-weighted MR images show thickening and narrowing of the subglottic area, whereas short τ inversion-recovery MR images show increased signal intensity when edema is present, with a sensitivity of 100% and a specificity of 60% for active inflammation (56).

Histopathologic analysis frequently reveals granulation tissue or nonspecific inflammation and less often reveals vasculitis, necrosis, microabscess formation, and scattered giant cells (55). Laryngeal and tracheal involvement may prove fatal if left untreated, whereas 50% of patients with laryngeal involvement will require tracheostomy at some point (Fig E3) (14,42). In addition to medication therapy, bronchoscopic interventions and surgery are required in the management of airway involvement (55).

Lungs

Teaching Point Pulmonary involvement occurs in more than 90% of patients with GPA during the course of disease and ranges from asymptomatic cavitating granulomatous lesions that appear as multiple pulmonary nodules or parenchymal bands, to pulmonary infiltrates and fulminating alveolar hemorrhage
(54,57) (Fig 19). Symptoms related to pulmonary involvement include cough, chest pain, dyspnea, and hemoptysis (42).

Drawing illustrates the main pulmonary manifestations of                         GPA.

Figure 19. Drawing illustrates the main pulmonary manifestations of GPA.

Chest radiographs combined with chest CT images show abnormalities during the disease course in 85% of patients with GPA, whereas CT has higher sensitivity in the detection of pulmonary nodules, cavities, and alveolar opacities (4). The most common imaging findings, occurring in 40%–70% of patients, are pulmonary nodules and masses, which are usually multiple, bilateral, and random, and rounded or oval, and range in diameter from a few millimeters to 10 cm (Fig 20A). When these lesions are larger than 2 cm, cavitation occurs in 25% of cases (57,58). The walls of the cavities may be thin or thick and nodular (Fig 20B), and hemorrhage around the nodules appears on high-resolution CT images as ground-glass opacity surrounding the consolidated nodule, referred to as the “halo” sign (Fig 20C) (58). The “reverse halo,” or “atoll,” sign reflects an organizing pneumonia reaction at the periphery of focal hemorrhage (59). In addition, the feeding vessel sign (ie, vessels heading to nodular lesions), suggesting angiocentric distribution, may be seen frequently (Fig 20D) (60). Additional findings include radiating linear scarring, pleural tags, consolidation, increased bronchovascular lines involving the lung parenchyma, bronchial wall thickening in the segmental or subsegmental bronchi, and less frequently, pleural disease, mediastinal or hilar lymphadenopathy, and interstitial disease (55,61). Subpleural and wedge-shaped, focal parenchymal, or peribronchoarterial consolidation may reflect granulomatous changes and pneumonia (Fig 21A) (57). Patchy bilateral airspace consolidation and ground-glass opacities are seen in 25%–50% of cases, are more prominent in the perihilar areas and the middle and lower lung zones, and represent diffuse alveolar hemorrhage due to necrotizing capillaritis (Fig 21B) (61). Involvement of pulmonary arterioles manifests as mosaic attenuation or the “tree-in-bud” pattern (62). Pulmonary nodules and masses, ground-glass opacities, and consolidations may wax and wane regardless of the therapy used (59).

GPA with pulmonary involvement at axial noncontrast CT (lung window)                         in three patients. (A) Image in a 56-year-old woman with a cough shows                         multiple pulmonary nodules in a random distribution (arrowheads), a right                         upper lobe consolidation (arrow), and bilateral atelectasis (*). (B,                         C) Images in a 51-year-old man show multiple bilateral cavitary masses with                         irregular and thick walls measuring more than 2 cm (arrows in B), and                         ground-glass opacity in the right upper lobe (halo sign) (arrowheads in C).                         (D) Image in a 42-year-old man with GPA and hemoptysis shows ground-glass                         opacity (arrowhead) surrounding a consolidated nodule (white arrow) and a                         pulmonary vessel heading to the nodule in the left superior lobe (feeding                         vessel sign) (black arrow).

Figure 20. GPA with pulmonary involvement at axial noncontrast CT (lung window) in three patients. (A) Image in a 56-year-old woman with a cough shows multiple pulmonary nodules in a random distribution (arrowheads), a right upper lobe consolidation (arrow), and bilateral atelectasis (*). (B, C) Images in a 51-year-old man show multiple bilateral cavitary masses with irregular and thick walls measuring more than 2 cm (arrows in B), and ground-glass opacity in the right upper lobe (halo sign) (arrowheads in C). (D) Image in a 42-year-old man with GPA and hemoptysis shows ground-glass opacity (arrowhead) surrounding a consolidated nodule (white arrow) and a pulmonary vessel heading to the nodule in the left superior lobe (feeding vessel sign) (black arrow).

(A) Axial noncontrast CT image (lung window) in a 31-year-old woman                         with a cough and fever shows bilateral diffuse consolidation and                         ground-glass opacity. (B) Axial CT image in a 57-year-old woman with GPA and                         hemoglobin descent shows diffuse and extensive bilateral ground-glass                         opacities and consolidations, with sparing of the subpleural lung. Diffuse                         alveolar hemorrhage was confirmed at bronchoscopy.

Figure 21. (A) Axial noncontrast CT image (lung window) in a 31-year-old woman with a cough and fever shows bilateral diffuse consolidation and ground-glass opacity. (B) Axial CT image in a 57-year-old woman with GPA and hemoglobin descent shows diffuse and extensive bilateral ground-glass opacities and consolidations, with sparing of the subpleural lung. Diffuse alveolar hemorrhage was confirmed at bronchoscopy.

Histopathologic analysis reveals large areas of parenchymal necrosis in the form of neutrophilic microabscesses or a large zone of geographic necrosis, granulomatous inflammation, and vasculitis, with a mixed cellular infiltration of neutrophils, lymphocytes, plasma cells, histiocytes, and eosinophils (Fig 22) (60,61).

Histopathologic pulmonary findings of GPA in a 42-year-old man (same                         patient as in Fig 20D) who underwent partial left-lung excision. (A) Gross                         specimen shows a poorly circumscribed lesion with a necrotic appearance. (B)                         Photomicrograph highlights the presence of vascular thrombosis and pulmonary                         parenchyma trapped by fibrosis, chronic inflammation with abundant                         macrophages, and fibrosis. (Elastic tissue fibers–Masson stain;                         original magnification, ×40.) (C) Photomicrograph of pulmonary                         parenchyma specimen shows a cavitated lesion (*) with geographic                         necrosis of the serpiginous border. The periphery of the lesion is lined by                         palisade histiocytes and some multinucleated giant cells (arrowheads). (H-E                         stain; original magnification, ×10.)

Figure 22. Histopathologic pulmonary findings of GPA in a 42-year-old man (same patient as in Fig 20D) who underwent partial left-lung excision. (A) Gross specimen shows a poorly circumscribed lesion with a necrotic appearance. (B) Photomicrograph highlights the presence of vascular thrombosis and pulmonary parenchyma trapped by fibrosis, chronic inflammation with abundant macrophages, and fibrosis. (Elastic tissue fibers–Masson stain; original magnification, ×40.) (C) Photomicrograph of pulmonary parenchyma specimen shows a cavitated lesion (*) with geographic necrosis of the serpiginous border. The periphery of the lesion is lined by palisade histiocytes and some multinucleated giant cells (arrowheads). (H-E stain; original magnification, ×10.)

Cardiovascular and Aortic Involvement

Cardiac involvement occurs in 6%–30% of patients with GPA; it manifests as pericarditis, pericardial effusion, pancarditis, focal myocarditis, noninfectious endocarditis, cardiomyopathy, coronary vasculitis that may cause myocardial ischemia, granulomas on valves that may cause insufficiency or conduction defects, granulomatous infiltration, and heart failure (41,57,63,64).

Case reports of GPA with large-vessel involvement include those of periaortitis, with resultant aortic aneurysm and intramural wall dissection. Periaortic inflammation manifests as abdominal pain and is believed to result from the extension of granulomatous tissue through the vessel wall, in contrast to granulomatous inflammation limited to the layers of the wall (in Takayasu arteritis), or vasa vasorum vasculitis (in polyarteritis nodosa) (59,64). The main imaging finding of GPA with large-vessel involvement at CT and MRI is thickening of the aortic wall (Fig E4).

Breast

Breast involvement by GPA is very unusual, occurring in 2.3% of cases, mainly in women. Breast involvement occurs as a presenting symptom or in the setting of systemic disease (65). It manifests clinically as a unilateral or bilateral painful or nonpainful breast mass; skin inflammation or ulcerations; and/or nipple discharge (66). Breast involvement manifests mammographically as skin or trabecular thickening. Biopsy should be performed to rule out breast cancer and other forms of autoimmune or infectious mastitis (66). Histologic analysis reveals necrotizing granulomatous inflammation with central necrosis, vasculitis, multinucleated giant cells, plasma cells, lymphocytes, scattered neutrophils, and eosinophils (Fig 23) (65).

GPA in a 37-year-old woman with right breast skin changes. (A) Axial                     noncontrast CT image shows a right breast mass (arrow). (B) Photomicrograph of                     biopsy specimen shows chronic inflammatory infiltrate that destroys the terminal                     lobular duct unit (arrowheads), with abundant histiocytes, lymphocytes, and                     multinucleated giant cells (*). (H-E stain; original magnification,                     ×200.) (C) Photomicrograph shows residual acini of the breast (*)                     and stroma with vasculitis (arrowheads). (H-E stain; original magnification,                     ×600.)

Figure 23. GPA in a 37-year-old woman with right breast skin changes. (A) Axial noncontrast CT image shows a right breast mass (arrow). (B) Photomicrograph of biopsy specimen shows chronic inflammatory infiltrate that destroys the terminal lobular duct unit (arrowheads), with abundant histiocytes, lymphocytes, and multinucleated giant cells (*). (H-E stain; original magnification, ×200.) (C) Photomicrograph shows residual acini of the breast (*) and stroma with vasculitis (arrowheads). (H-E stain; original magnification, ×600.)

Abdomen

Gastrointestinal involvement is uncommon; it is discovered at presentation or occurs during the disease course in 10%–12% of patients (63). The small intestine is the most frequently affected. Ulcerations mimicking inflammatory bowel disease with hemorrhage, as well as arterial microaneurysms of small and medium-sized arteries at the mesenteric, hepatic, and splenic vessels, may occur (67). Acute abdomen secondary to peritonitis, bowel ischemia secondary to mesenteric vasculitis, infarction, and perforation are rare manifestations (41,63). CT findings of bowel involvement include bowel dilatation, focal or diffuse bowel wall thickening, abnormal bowel wall enhancement, mesenteric vessels in a comblike configuration, ascites, and lymphadenopathy (68).

Hepatic involvement by GPA is described mainly in case series; it comprises elevated liver enzymes (cholestatic and hepatocellular patterns) and rarely, vasculitis on the portal spaces and centrolobular territories (67,69).

Splenic involvement also is infrequent in GPA. Segmental splenic infarction may be a consequence of diffuse arteritis resulting in occlusion of distal parenchymal splenic arteries. Findings at CT include a peripheral wedge-shaped area of low attenuation, as well as subcapsular or diffuse hypoattenuation in larger infarctions (57). Pancreatic involvement has been reported in 11% of autopsy series; manifestations include recurrent acute pancreatitis and pseudotumoral pancreatic masses. Cholecystitis and gallbladder infarction are rare (67).

Renal and Urogenital Organs

Renal involvement occurs in 25%–75% of patients with GPA, usually as a necrotizing glomerulonephritis, and its presence heralds a more severe outcome (11). The classic manifestation of renal involvement is rapidly progressive glomerulonephritis, with hematuria, proteinuria, edema, decreased urine output, and rapid progressive deterioration of renal function (70). Despite treatment, 20%–30% of patients who have ANCA-associated vasculitis with renal involvement will develop end-stage renal disease within 5 years, and those who undergo kidney transplantation show similar 10-year patient and transplant survivals compared with matched control groups with other causes of renal failure (71).

Imaging can be helpful for differentiating medium-sized vessel vasculitis (ie, polyarteritis nodosa) from small-vessel vasculitis involving the kidneys and can be used to assess vascular complications and monitor response to treatment. For example, renal US can be used to evaluate the renal size and contour and therefore provides information on the chronicity of the disease (72) (Fig E5). Histologic evaluation reveals a pauci-immune necrotizing crescentic glomerulonephritis (Fig 24) (42). Interstitial granulomas are rare, with a frequency ranging from 5% to 12%. The presence of interstitial granulomas in association with pauci-immune crescentic glomerulonephritis strongly suggests the diagnosis of GPA (70).

Percutaneous kidney biopsy specimens in a 60-year-old woman with GPA who                     presented with findings of renal function impairment, active urinary sediment,                     and subnephrotic proteinuria. (A) Photomicrograph (Berden mixed-class renal                     biopsy) shows pauci-immune necrotizing crescentic glomerulonephritis                     (arrowheads). (H-E stain; original magnification, ×600.) (B)                     Photomicrograph shows interstitial fibrosis (40%) and moderate tubular atrophy                     (30%) (*). (H-E stain; original magnification, ×200.)

Figure 24. Percutaneous kidney biopsy specimens in a 60-year-old woman with GPA who presented with findings of renal function impairment, active urinary sediment, and subnephrotic proteinuria. (A) Photomicrograph (Berden mixed-class renal biopsy) shows pauci-immune necrotizing crescentic glomerulonephritis (arrowheads). (H-E stain; original magnification, ×600.) (B) Photomicrograph shows interstitial fibrosis (40%) and moderate tubular atrophy (30%) (*). (H-E stain; original magnification, ×200.)

Lower urogenital involvement is uncommon in GPA. It occurs in 0.7%–7.4% of cases and can affect any part of the urogenital tract, including the prostate, seminal vesicles, epididymis, testis (orchitis, embolic testicular infarction secondary to nonbacterial thrombotic endocarditis, and testicular infarction), penis, urethra, ureters, cervix, vagina, peritoneum, and retroperitoneum (73). Among these organs, the prostate is the most frequent site, with manifestations of increased urinary frequency, dysuria, and macroscopic hematuria, with a firm, enlarged, indurated prostate (73). Imaging studies reveal an enlarged prostate, mimicking abscess, whereas histologic findings include extravascular granulomas, fibrinoid necrosis, and inflammatory infiltrate composed of lymphocytes, histiocytes, and neutrophils (74) (Fig 25).

GPA in a 51-year-old man who presented with increased urinary frequency,                     macroscopic hematuria, and incontinence. (A) Axial noncontrast CT image shows a                     hypoattenuating lesion with peripheral calcifications in the prostate (arrows).                     (B) Photomicrograph of biopsy specimen shows prostatic stroma with inflammatory                     infiltrate composed of neutrophils, lymphocytes, plasma cells, macrophages, and                     small vessels (*) demonstrating necrosis and wall destruction                     (arrowheads). (H-E stain; original magnification, ×200.)

Figure 25. GPA in a 51-year-old man who presented with increased urinary frequency, macroscopic hematuria, and incontinence. (A) Axial noncontrast CT image shows a hypoattenuating lesion with peripheral calcifications in the prostate (arrows). (B) Photomicrograph of biopsy specimen shows prostatic stroma with inflammatory infiltrate composed of neutrophils, lymphocytes, plasma cells, macrophages, and small vessels (*) demonstrating necrosis and wall destruction (arrowheads). (H-E stain; original magnification, ×200.)

Extremities

Peripheral nervous system involvement occurs in up to 67% of patients with GPA, manifesting as sensorimotor polyneuropathy (55%) or mononeuritis multiplex (45%). It occurs especially during the first 2 years of disease onset, in men of older age, and in the setting of other clinical manifestations (15). On the other hand, skin involvement is present in 10%–50% of patients, with palpable purpura being the most common lesion (especially in the lower limbs, with a histopathologic hallmark of leukocytoclastic vasculitis with fibrinoid necrosis). Papules, subcutaneous nodules, vesicles, blisters, necrotic-ulcerative lesions, and livedo reticularis also may be seen, whereas gangrene of the digits and pyoderma gangrenosum-like ulcers are less frequent (75).

Conclusion

The heterogeneous manifestations of GPA represent a significant challenge in the diagnosis of this rare disease. By recognizing the common and unusual imaging findings of GPA, radiologists have an important role in the diagnosis and follow-up of patients with GPA and aid clinicians in distinguishing between disease activity and damage, which ultimately affects therapeutic decisions.

Acknowledgments

The authors thank Luis A. Sosa-Lozano, MD, Division of Diagnostic Radiology, Medical College of Wisconsin, Milwaukee, Wis, and Antonio Carlos Hernández-Villegas, MD, Department of Radiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico, for assistance in interpreting the radiologic images.

For this journal-based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant relationships.

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Article History

Received: Apr 16 2021
Revision requested: May 25 2021
Revision received: June 18 2021
Accepted: June 23 2021
Published online: Oct 15 2021
Published in print: Nov 2021