Pediatric vasculitis

Imaging of systemic vasculitis in childhood

Udomluck, Thorsang, Orawan R2

Systemic vasculitis

• Group of diseases • Inflammation of the blood vessels • Unclear etiology• In 2006, the European League Against Rheumatism (EULAR) and the

Pediatric Rheumatology European Society (PReS) proposed an updated classification of childhood vasculitis.

Takayasu arteritis

• Most common granulomatous inflammation of large arteries in children• Can be life-threatening• Early acute phase : nonspecific symptoms hypertension, fever,

arthralgia• Aorta and its main branches • Arterial wall inflammation concentric wall thickening fibrosis

consequent stenosis• Less commonly: aneurysm

Takayasu arteritis• EULAR/PReS criteria: angiographic abnormalities + at least 1/4

1. Decreased peripheral artery pulse or claudication of the extremities

2. Discrepancy of four limbs SBP > 10 mmHg difference in any limb

3. A bruit over the aorta or its major branches 4. Hypertension related to childhood

normative data criteria

The classification of Takayasu arteritis

• Type I : Supra-aortic arteries• Type IIa : Only the ascending aorta or aortic arch• Type IIb : Descending aorta with or without involvement of more

proximal portions of the aorta and aortic arch• Type III : Descending thoracic aorta and abdominal portion or renal

arteries• Type IV : Only the abdominal aorta or renal arteries• Type V : Generalized involvement with a combination of other types

Kawasaki disease

• Acute febrile vasculitic syndrome of early childhood• Predominantly between 6 months and 4 years of age• Children outside that range Lacked the classic clinical presentation

Delayed diagnosis• Medium-sized vessel systemic vasculitis : celiac, mesenteric, renal,

iliofemoral, proximal upper limb arteries, coronary artery • Small aneurysms or stenotic segments

The EULAR/PReS classification criteria

• Fever for 5 days (mandatory) + 4 of the following findings:

(1) peripheral changes in the hands and feet (erythema, edema, desquamation, rash) or perianal area(2) polymorphus exanthema(3) bilateral conjunctival injection(4) injection of oral and pharyngeal mucosa(5) Cervical lymphadenopathy

The American Heart Association

Consider the diagnosis of Kawasaki disease:

fever for 5 days or more and < 4 principal features disease + coronary artery disease (detected by 2-D echocardiography or coronary angiography)

A child with unexplained fever for 5 days or more + any of the principal features of Kawasaki disease

Role of imaging

• Delayed treatment with IV immunoglobulin beyond 10 days of onset of fever increases the risk of coronary aneurysms• Imaging does not have a pivotal role in the initial diagnosis of

Kawasaki disease• Important in the assessment of its more serious and potentially fatal

complications• Echocardiography = imaging technique of choice

Echocardiography

• Early phases : myo- and pericarditis & periluminal echogenicity • Subacute and convalescent phases : coronary artery aneurysms &

dilatation

Cardiac MRI• Combined benefits of demonstrating coronary artery lesions &

myocardial perfusion, function and viability in the same time• Detect distal coronary artery aneurysms might be missed in

echocardiography

MDCT angiography of the coronary arteries

• Limited high radiation dose, misleading data due to coronary calcifications (complication of longstanding coronary artery aneurysms)

• Prospective ECG-triggered dual-source CT coronary angiography alternative diagnostic modality

PET scans

• Limited to assess inflammation in the coronary artery wall Bec. increased glucose utilization within the heart muscle

Childhood polyarteritis nodosa (c-PAN)

• Nongranulomatous anti-neutrophil cytoplasmic auto-antibody(ANCA) negative vasculitis• Affects medium- or small sized muscular arteries

The EULAR/PReS classification criteria

• A positive biopsy or angiographic evidence of aneurysms or occlusion (mandatory) + 2/6 of the following findings:

(1) skin involvement (superficial and deep skin infarctions, tender subcutanous nodules and livedo reticularis, which is purplish reticular discoloration pattern of the skin)

(2) myalgia or muscle tenderness(3) systemic hypertension(4) mono- or polyneuropathy(5) renal involvement (proteinuria, haematuria)(6) testicular pain or tenderness

Conventional angiography using DSA

• Standard imaging modality for diagnosis of PAN• Aneurysms, stenoses or occlusions of a medium- or small sized artery • Color Doppler, MR angiography and CT angiography compared to

DSA, they are less sensitive and might result in false-negative • MR angiography considerable stenotic lesions in small arteries

might be overestimated and diagnosed as complete occlusion

• Childhood polyarteritis nodosa. Multiple aneurysms on arteriogram and autopsy specimen

ANCA (+)Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA)

• Wegener granulomatosis• Small-to-medium-sized vessel ANCA-associated systemic necrotizing

vasculitis • Granulomatous inflammation within arterial wall, perivascular, or

extravascular area• Affects nose+paranasal sinuses, respiratory tract and the kidneys• Abs are against serine proteinase-3 Ag

• EULAR/PReS classification criteria includes 3/6

1. Hematuria or proteinuria2. Granulomatous inflammation on biopsy3. Nasal sinus inflammation4. Subglottic/tracheal/endobronchial stenosis5. Abnormal chest imaging6. Positive PR 3 ANCA or c-ANCA staining

Kidney

RS

Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA)

1. Hematuria/proteinuria2. Granulomatous inflammation3. Nasal sinus inflammation4. Subglottic/tracheal/

endobronchial stenosis5. Abnormal chest imaging6. PR 3 ANCA or c-ANCA staining

• Variable-sized lung nodules commonly > 5 mm (mms-10 cm)• Cavitation (common in nodules > 2 cm) with either thin or thick wall• Ground glass opacities and air space – hemorrhage/debris• Perivascular fluffy or hazy multifocal opacities • Mosaic perfusion

Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA)

1. Hematuria/proteinuria2. Granulomatous inflammation3. Nasal sinus inflammation4. Subglottic/tracheal/

endobronchial stenosis5. Abnormal chest imaging6. PR 3 ANCA or c-ANCA staining

• Subglottic tracheal and bronchial stenosis

• Focal/diffuse • DDx prolonged intubation, TB, amyloidosis or adenoid cystic

tumors• Long-standing bronchial stenosis >> recurrent chest infection and

lung collapse

Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA)

1. Hematuria/proteinuria2. Granulomatous inflammation3. Nasal sinus inflammation4. Subglottic/tracheal/

endobronchial stenosis5. Abnormal chest imaging6. PR 3 ANCA or c-ANCA staining

Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA)

• GPA >> necrotizing GN >> RPGN

• If absence of significant imaging findings >> rely on clinical+lab tests (e.g. Bx)

• CT, MRI, PET scan may reveal large-/medium-sized vessel involvement• Thrombosis, aneurysms, aortic dissection and aortic rupture

Granulomatosis with polyangiitis (GPA)

ANCA (+)Microscopic polyangiitis (MPA)

Microscopic polyangiitis (MPA)

• ANCA-associated vasculitis • Involves lungs and kidneys • No upper airway and non-granulomatous inflammation• p-ANCA; directed against the myeloperoxidase Ag• Pulmonary capillaritis >> pulmonary hemorrhage + renal dz

Microscopic polyangiitis (MPA)

http://pubs.rsna.org/doi/10.1148/radiol.10090105?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

ANCA (+)Eosinophilic granulomatosis with polyangiitis (EGPA)

Eosinophilic granulomatosis with polyangiitis (EGPA)• Churg-Strauss syndrome• Necrotizing granulomatous inflammation • Involves respiratory tract• predominately affects small and medium vessels

• associated with asthma and eosinophilia• ANCA positivity is more frequently seen with GN

• EULAR/PreS classification: 4/6

Eosinophilic granulomatosis with polyangiitis (EGPA)

1. Asthma2. > 10% Eo in WBC count3. Mono-/polyneuropathy from systemic vasculitis4. Migratory/transient pulmonary opacities5. Paranasal sinus abnormalities 6. Extravascular Eos in a biopsy

• Transient, bilateral consolidation with symmetrically peripheral location (90% of patients)• +/- Peribronchial or patchy random distribution • +/- Septal lines (50% of patients)

Eosinophilic granulomatosis with polyangiitis (EGPA)

Eosinophilic granulomatosis with polyangiitis (EGPA)

Eosinophilic granulomatosis with polyangiitis (EGPA)

http://pubs.rsna.org/doi/10.1148/radiol.10090105?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

Eosinophilic granulomatosis with polyangiitis (EGPA)

http://www.cellmoloto.net/index.php/acmo/article/view/27181

ANCA (-)Immune complex associated small-vessel vasculitis

Immune complex associated small-vessel vasculitis

• Ig A vasculitis (IgAV) • Non-granulomatous ANCA-negative vasculitis • IgA dominant immune complex deposits small vessels

(capillaries, venules and arterioles)• Purpuric eruption = Henoch-Schönlein purpura• gastrointestinal tract • Arthritis• GN

Ig A vasculitis

• The EULAR/ PReS classification

• Presence of a palpable purpura + 1/51. Diffuse abdominal pain2. Biopsy showing predominantly IgA deposition3. Arthritis or arthralgia4. Renal involvement (proteinuria/hematuria)5. Negative ANCA

• Imaging findings: scanty and non-specific• Patients are usually sent for imaging because of abdominal pain

• Ultrasound – small-sized mesenteric lymphadenopathy, bowel wall thickening and intraperitoneal fluid non-specific

Ig A vasculitis

Ig A vasculitis

• Main role of imaging >> to evaluate possible complications • Pancreatitis• GI perforation• Bile duct necrosis• Alveolar hemorrhage• Intussusception • Secondary to Peyer’s patch hypertrophy (ileo-ileal > ileocaecal junction)• US -- a pseudomass with a target sign

Ig A vasculitis

Other systemic vasculitides

• Behcet disease• Secondary vasculitis• Vasculitis associated with connective tissue

Behcet disease

• An immune-mediated vasculitis • Classic features: recurrent oral and genital aphthous ulcers, uveitis,

skin lesions and cardiovascular manifestations• Likely patients older than 20 years of age• All sizes of both arteries and veins >> aneurysms or thrombosis

Behcet disease

• Commonly seen in the pulmonary arterial tree>> Pulmonary artery aneurysms

highly suggestive of Behcet disease >> Thrombosis>> Pulmonary infarctions>> Ruptured aneurysm >> severe hemorrhage

• Brain• Cerebral artery -- stenotic segments >> ischemia• Thrombosis of the dural venous sinuses and venous infarcts

Behcet disease

MSK involvement in Behcet dz

• Asymmetrical, nonerosive, nondeforming arthralgia/arthritis in lower extremities esp. knees• May show joint effusion and soft tissue swelling

• Bone infarcts are less common

CNS findings in systemic vasculitis

• Primary form -- primary CNS vasculitis• Part of a systemic inflammatory process – more common• Manifestations• Direct findings -- narrowing of the cerebral arteries• Secondary to bleeding from the diseased small vessels• MRI usually demonstrates high signal white matter foci in FLAIR and T2W• Tumor mimic lesions • Post contrast enhancement of the arterial wall = active inflammation• MRA of the cerebral vessels might fail to identify vasculitis in small vessels

CNS findings in systemic vasculitis

• Normal MRI of the brain >> almost always excludes intracranial vasculitis

• No pathognomonic MRI findings in vasculitis

• Biopsy would be required for the diagnosis

CNS findings in systemic vasculitis: bleeding

CNS findings in systemic vasculitis

CNS findings in systemic vasculitis

• DWI -- restricted diffusion in active vasculitic lesions of the brain• Acute/subacute lesions may show elevated ADC -- the lesions disappear over

time suggesting a nonischemic mechanism • DDx posterior reversible encephalopathy syndrome

CNS vasculitis mimics

• Non-inflammatory vasculopathies• Moyamoya disease• Post irradiation• Thromboembolic disease• Hemoglobinopathies e.g. sickle cell disease• Vasculopathies from rare genetic/metabolic d/o

>> Brain biopsy is sometimes needed for a definite diagnosis

MSK findings in childhood systemic vasculitis

• Arthralgia and arthritis• up to 78% of patients with IgAV• MRI helps early diagnosis of musculoskeletal changes in vasculitis • BM edema• Bone infarctions• Synovitis, arthritis, joint effusion• Insufficiency fractures

Bone infarction from large-dosed steroid use

Arthritis/synovitis from systemic vasculitis

Pulmonary findings in childhood systemic vasculitis

• Wide spectrum of non-specific radiographic chest findings • Most are non-vasculitic lung diseases• Focal lesions, cavitary nodules, nodules with surrounding focal ground

glass pattern (halo sign) and early peribronchial thickening• Ground glass pattern detected with CT of the lungs is more commonly

seen with EGPA

Pulmonary findings in childhood systemic vasculitis• Hemoptysis + diffuse alveolar infiltrates + Hct drop• Imaging: alveolar opacities

Pulmonary vasculitis presented with peripheral ground glass densities

Differential diagnosis

• Diagnosis can be challenging because of overlapping signs/symptoms and non-specific imaging findings• Unusual group of clinical manifestations involving multiple organ systems

• Uveitis, rashes, arthritis or sinus troubles • RPGN • Pulmonary-renal syndrome

• Arterial wall thickening • Takayasu arteritis • Noninflammatory disorders e.g. fibromuscular dysplasia• Inflammatory diseases e.g. tuberculosis, Behcet dz

• Developmental disorders such as aortic coarctation, mid-aortic syndrome and Marfan syndrome can result in aortic stenosis and aneurysms• Diffuse ground glass pattern -- nonspecific for vasculitis• DDx HP, pulmonary edema, sarcoidosis, alveolitis due to systemic sclerosis,

drug toxicity, opportunistic infection

Differential diagnosis

• Attenuated/occluded cerebral vessels and hyperintense FLAIR/T2W white/gray matter foci• DDx vasculitis, other inflammatory diseases e.g. viral encephalitis, Moyamoya

dz

Differential diagnosis

Conclusion

• Systemic vasculitides are uncommon in childhood• No specific clinical features• Angiography is not of much value in evaluation of GPA, EGPA and IgAV• MRA is suggested in the assessment of Takayasu disease, Kawasaki disease

and C-PAN• Chest HRCT has a role in the evaluation of GPA and EGPA• CT of the sinuses in the evaluation of GPA and CTA in the evaluation of

Kawasaki disease• Color Doppler ultrasound is useful in the diagnosis and follow-up of IgAV

and C-PAN

http://pubs.rsna.org/doi/full/10.1148/rg.344135028

http://pubs.rsna.org/doi/full/10.1148/rg.344135028

http://pubs.rsna.org/doi/full/10.1148/rg.344135028

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