In this episode of Derms and Conditions, host James Q. Del Rosso, DO, welcomes David Altman, MD, dermatologist at Midwest Center of Dermatology in Warren, MI, to review recent case studies that highlight unexpected presentations, treatment responses, and immune system interplay in dermatology. The first case focuses on a 34-year-old patient with severe, recalcitrant Hailey-Hailey disease. After multiple failed therapies, including antibiotics, corticosteroids, apremilast, and low-dose naltrexone, she achieved near-complete clearance within 12 weeks on dupilumab. Drs Altman and Del Rosso share their thoughts on why a drug targeting type 2 inflammation might be effective in a condition traditionally considered structural, drawing parallels to reports in Darier disease. Next, the conversation shifts to an unusual immune response observed in a patient with well-controlled psoriasis on IL-17 inhibitors who developed widespread atopic dermatitis. Dr Altman describes this as a “cytokine shift,” where suppression of IL-17 may upregulate IL-4 pathways, mirroring the reverse effect sometimes seen with IL-4 inhibition. While uncommon, such effects are now recognized in prescribing information, and the patient improved after transitioning to a broader-acting JAK inhibitor (upadacitinib). In the final case, a patient with Crohn’s disease developed rapidly progressing alopecia areata while on infliximab. Switching to tofacitinib improved hair growth but worsened gastrointestinal symptoms. Following colectomy, both the Crohn’s disease and alopecia resolved, highlighting the role of systemic inflammation in driving skin disease. Tune in to the full episode to hear more about these unique cases, the underlying immunologic mechanisms, and how lessons from complex cases can inform everyday dermatologic practice.