Background: Takayasu arteritis (TAK) is a rare large-vessel vasculitis with heterogeneous genetic background. Among other, TAK has been recently associated with a MLX gene mutation that leads to aberrant NLRP3 inflammasome activation.

Case presentation: A 32-year-old woman presented with high fever (39°C), diffuse mild abdominal pain and tenderness and an auscultated bruit over the right femoral artery. She had a 15-year history with multiple hospitalizations for recurring similar febrile episodes lasting 2-3 weeks. Tests for inflammatory markers, infections, systemic autoimmune rheumatic diseases and mutations in MEFV, MVK, and TNFRSF1A genes were normal or negative. Abdomen computed tomography scan (CT) and Doppler ultrasonography (U/S) revealed concentric abdominal aorta hypertrophy (dmax: 3mm), aorta, superior and lower mesenteric artery stenosis (approximately 50%, 60-65% and 55-60% lumen, respectively) and a small right iliac artery aneurysm. The diagnosis of TAK was established and the patient was started on methylprednisolone (1 mg/kg qd) with gradual tapering and oral cyclophosphamide (100 mg qd) for three months, followed by methotrexate (20 mg/week) and tapering of steroids, leading to overall improvement. Six months later, the febrile syndrome recurred with vascular deterioration (80% stenosis of superior and lower mesenteric arteries). Whole exome sequencing analysis revealed the novel likely pathogenic heterozygous splice-site variant (rs766603266) of the inflammation-regulating gene NLRP12, which is involved in suppressing the activity of NLRP3 inflammasome. Methotrexate was replaced by anakinra (100 mg qd sc) with only partial response. Hence, an off-label combination regimen was administered, consisted of tocilizumab (8 mg/kg/month iv), along with anakinra (100 mg sc qd, 5 days/week reduced to 3 days/week after a month). Over a 28-month follow-up period, this treatment led to sustained, corticosteroid-free clinical remission, as well as significant amelioration of stenotic inflammatory arterial findings on U/S imaging (reductions of abdominal aorta dmax to 1.5 mm and of superior and lower mesenteric artery stenosis to 50%, each). The combination treatment was well-tolerated, without significant adverse effects, except for a self-inflicted staphylococcus aureus-related left inguinal suppurative lymphadenitis caused by pubic hair shaving.

Learning points for clinical practice: Our case indicates that null NLRP12 gene mutants may contribute to the clinical phenotype of TAK, likely via improper regulation of the NLRP3 inflammasome activation. The combined therapeutic IL-1 and IL-6 receptors blockade was found safe and effective therapeutic modality. Also, in the setting of normal acute phase reactant values of the patient, U/S imaging has proved particularly helpful for the monitoring of inflammatory vascular lesions.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.