Examining the Unanswered Questions in TSW: A Case Series of 16 Patients and Review of the Literature

<b>Background/Objectives:</b> Topical steroid withdrawal syndrome is an underrecognized (and at times controversial) diagnosis, predominantly seen in individuals with a history of prolonged medium- to high-potency steroid use with sudden cessation. We aim to present topical steroid withdrawal clinical cases along with a narrative review of the literature to better characterize this understudied phenomenon. <b>Methods:</b> A total of 16 patients with a history of topical steroid withdrawal were enrolled in an IRB-approved clinical trial (NCT04864886). Participants underwent clinical assessments at the National Institutes of Health, including a history and physical examination, photography, genome sequencing, and comprehensive blood work. A follow-up survey assessed symptom activity and functional impact. <b>Results:</b> All patients reported severe itch, heat and photosensitivity, erythema, skin dryness, and pain. A total of 11 patients exhibited elevated IgE levels, 9 patients noted metallic-smelling skin, and 4 had peripheral blood eosinophilia. Symptomatic relief was observed with dupilumab, berberine, naltrexone, and various home remedies including topical ointments, vitamins, and probiotics, though effectiveness varied and often required trial and error. At follow-up, most respondents reported partial but ongoing symptoms, with several describing residual itch and intermittent interference with daily activities. Some participants continued therapeutic interventions, such as berberine, over two years after their initial evaluation. <b>Conclusions:</b> Our findings report improvement in patient symptoms such as itch and detail emerging management strategies that have not been discussed before. Improved recognition, physician consensus, and systemic evaluation of therapeutic options are needed to guide care and enhance quality of life for affected patients.