Background and Clinical Significance: Dermato-neuro syndrome is a rare, potentially fatal complication of scleromyxedema, characterized by a prodrome of flu-like symptoms, and a triad of fever, confusion, and seizures. Intravenous immunoglobulin (IVIG) has become first-line treatment for both scleromyxedema and dermato-neuro syndrome based on case reports and case series data showing variable treatment responses. Case Presentation: In this report, we describe a Black, female patient with scleromyxedema and lambda-restricted IgG monoclonal gammopathy who developed suspected dermato-neuro syndrome within a week of her first round of IVIG infusions. Conclusions: To our knowledge, this is the second case report of dermato-neuro syndrome temporally linked to a recent IVIG infusion, a paradoxical reaction that may complicate clinical decision making. Furthermore, we highlight the dermatologic manifestations of scleromyxedema in dark skin tones and emphasize the need for heightened clinical suspicion of dermato-neuro syndrome in patients with scleromyxedema presenting with acute neurological symptoms.