Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a rare CNS inflammation mainly affecting the pons and cerebellum. It responds to corticosteroids, but alternative diagnoses should be considered if there is no improvement. We present a case of Erdheim-Chester Disease (ECD), a histiocytosis that can mimic CLIPPERS, highlighting diagnostic and treatment challenges.

61-year-old woman with an 8-month history of gradually worsening symptoms, including slurred speech, diplopia, and ataxia, was found to have multifocal enhancing lesions in the pons (Figure 1). She was treated with pulse steroids based on a presumed diagnosis of CLIPPERS, followed by a prolonged steroid taper. One month later, she reported worsening gait difficulty that required support with a walker. Repeat brain imaging showed persistent enhancement and the emergence of new atypical patchy, instead of curvilinear lesions with increased perfusion (Figure 2), prompting further investigation for an alternative diagnosis as findings suggest lack of improvement despite steroid treatment. FDG PET imaging revealed increased radiotracer uptake in multiple areas, including the bones and kidneys (Figure 3). A biopsy of an iliac crest lesion showed histiocyte infiltration of the bone marrow, suggesting Erdheim-Chester disease. Negative results for the BRAF-V600 mutation prompted additional biopsies of lesions in the mandible and kidney, which did not yield different results. She was empirically treated with cobimetinib, a MEK inhibitor. Her clinical course stabilized after starting treatment, and she is currently undergoing restorative physical therapy.

EDC can resemble CLIPPERS, presenting with a clinical phenotype consistent with infratentorial lesions. This case emphasizes the need to consider alternative diagnoses when pontine lesions are patchy instead of curvilinear, unresponsive to steroids, and show increased perfusion. Diagnosing EDC requires tissue analysis and BRAF-V600E testing; if these are negative with nervous system involvement, empiric MEK inhibitor treatment is recommended.