Background/Purpose:
Granulomatosis with polyangiitis (GPA), a small-sized–vessel vasculitis, commonly involves ear, nose & throat (ENT), lungs and kidneys, and, more rarely, the central nervous system (CNS). Three different pathological CNS-involvement patterns are known: 1) a manifestation of generalized GPA, with vasculitis of small-sized brain or spinal cord vessels; 2) contiguous granulomatous CNS invasion from extracranial sites; 3) intracerebral (meninges (pachymeningitis) or brain) granulomatous lesions. We evaluated GPA CNS clinical features, imaging findings, treatments and outcomes.
Methods:
GPA patients with CNS (pachymeningitis, meningitis, stroke, spinal cord and/or hypophyseal) involvement who met ACR criteria and/or Chapel Hill definitions, after excluding other causes, were studied retrospectively. Patient characteristics, treatments and outcomes were analyzed. Neurological sequelae were evaluated with a simplified modified Rankin scale (mRS) by telephone interview at the last follow-up.
Results:
We included 31 patients (22 men), whose mean age at GPA diagnosis and onset of CNS involvement were 46±17 and 50±15 years, respectively. The latter was present in 14 (45%) patients at GPA diagnosis, and appeared in the other 17 (55%) after a median follow-up of 69 months. Headache was the main symptom (64%), along with motor (32%) and sensory impairments (41%). CNS lesions were: 19 pachymeningitis (16 cranial and 3 spinal cord), 14 ischemic or 3 hemorrhagic strokes, 5 cerebral vasculitides and/or 2 hypophyseal lesions. Extra-CNS manifestations affected ENT (81%), lungs (58%), peripheral nerves (48%) and kidneys (35%). ANCA detected in 27/31 (87%) patients had PR3 (n=22) or MPO (n=5) specificity.
Induction comprised corticosteroids (CS; 100%) combined with IV (61%) or oral (35%) cyclophosphamide (CYC), or rituximab (RTX; 3%). Maintenance therapy consisted of CS (100%) combined with azathioprine (58%), methotrexate (19%) or RTX (6%).
After 73±56 months of follow-up since GPA CNS onset, CNS manifestations had responded clinically in 26/31 (84%) patients, whereas 5 (16%) patients had refractory CNS GPA. Seven out of the 26 (27%) responders relapsed after a median of 13 months. Relapsed and/or refractory CNS GPA was seen in 9/14 (64%) of patients with initial vascular CNS manifestations but only in 5/19 (26%) of those with granulomatous lesions. Overall, relapsing and/or refractory CNS involvement was more frequently associated with vascular CNS manifestations (P=0.04).
Relapsing and/or refractory CNS (n=12) were treated with CS (100%) and RTX (58%), IV CYC (33%) or oral CYC (8%). All but one achieved remission after new induction regimen. One patient died. Neurological sequelae persisted in 10/31 (32%) patients. Diabetes insipidus related to hypophyseal GPA persisted after induction and maintenance regimens in the 2 patients.
Conclusion:
Our series highlights the heterogeneity of GPA CNS involvement. Despite initial severe disease, most patients improved under conventional therapy. Baseline vascular CNS manifestations were more frequently associated with relapsing and/or refractory disease than granulomatous lesions. RTX deserve to be evaluated to treat GPA patients with CNS involvement.
Disclosure:
G. De Luna,
None;
B. Terrier,
None;
P. Kaminsky,
None;
F. Maurier,
None;
R. Solans,
None;
R. Seror,
None;
X. Puéchal,
None;
L. Mouthon,
None;
L. Guillevin,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/granulomatosis-with-polyangiitis-central-nervous-system-involvement-presentation-and-management/