Clinical heterogeneity and treatment optimization in anti-KLHL11 encephalitis: two case reports and literature review

This study aimed to investigate the clinical features, differential treatment responses, and management strategies of encephalitis associated with anti-Kelch-like protein 11 (KLHL11) antibodies.

We report two cases of anti-KLHL11 encephalitis that improved following immunotherapy and present a literature review of cases published in the last six years.

Case 1 involved a 52-year-old woman who tested positive for serum anti-KLHL11 antibodies at a 1:100 titer. The patient completely recovered following a treatment regimen comprising intravenous immunoglobulin administration at 400 mg/kg/day for 5 days, combined with low-dose rituximab (100 mg, weekly for three consecutive weeks). Extensive tumor screening revealed no underlying malignancies. In Case 2, a 65-year-old man tested positive for anti-KLHL11 antibodies in both serum (titer 1:320) and cerebrospinal fluid (titer 1:100). Initial high-dose intravenous glucocorticoid pulse therapy, starting at 1000 mg dose and tapered by halving the dose every 3 days until discontinuation, combined with low-dose rituximab (100 mg weekly for 3 consecutive weeks), resulted in a suboptimal response, with symptoms recurring after one month. Subsequent administration of efgartigimod (10 mg/kg) led to marked clinical improvement. A testicular ultrasound revealed an epididymal calcification, potentially indicating a burnt-out germ cell tumor.

Anti-KLHL11 encephalitis exhibits considerable clinical heterogeneity. A high serum anti-KLHL11 titer (1:320) was associated with treatment refractoriness, this association is a preliminary observation that requires validation in larger cohorts. Efgartigimod appears to be a promising therapeutic option for paraneoplastic neurological syndrome.