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Background/Objective: Allergic reactions to insulin have decreased significantly since the introduction of human insulin preparation, but up to 2.4% of insulin-treated patients can still be affected. Rituximab is a monoclonal antibody against the surface antigen CD20 on B lymphocytes, and it is largely used to treat lymphoproliferative and rheumatological conditions. In a very few published case reports, rituximab has been used as an investigational drug to treat severe insulin allergy refractory to conventional therapy. Here, we present an unusual case of a 40-year-old woman with T1DM and severe insulin allergy that was successfully treated with rituximab. Case Report: The patient was diagnosed with T1DM at age 37. Three years later, skin reactions developed at insulin administration sites. These consisted of pruritic and painful erythema and wheals that appeared within 1 to 4 h of insulin administration, followed by induration, subcutaneous nodules, and surrounding lipodystrophy that lasted several days with spontaneous resolution in 1 to 2 weeks. Extensive immunologic evaluation suggested the reaction was related to insulin allergy. Skin biopsy revealed sublobular panniculitis. After failed conventional treatment with antihistamines, glucocorticoid, and various insulins, rituximab infusion as an investigational approach was initiated. This was very successful, leading to prolonged remission of her insulin allergy. Discussion: First-line management of insulin allergy should focus on second-generation antihistamines and switching insulin preparation. In refractory cases, systemic immunotherapy with rituximab can be a viable option. Conclusion: Practitioners should be aware that in patients with insulin allergy who fail conventional treatment, immunotherapy with rituximab can be a viable option.

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection. Niche function depended on moDC delivery of ligand GPNMB to the basal ESC receptor CD44 so that properly timed antibody blockade of ligand or receptor provided long-lasting correction of reprogramming and broad disease phenotypes. These same control points worked directly in mouse and human basal ESC organoids. Together, the findings identify a mechanism to explain and modify what is otherwise a stereotyped but sometimes detrimental response to epithelial injury., Introduction Epithelial barriers maintain a fundamental responsibility to respond to injuries from the full range of environmental toxins and infectious agents. This role depends critically on carefully controlled growth and [...]

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection. Niche function depended on moDC delivery of ligand GPNMB to the basal ESC receptor CD44 so that properly timed antibody blockade of ligand or receptor provided long-lasting correction of reprogramming and broad disease phenotypes. These same control points worked directly in mouse and human basal ESC organoids. Together, the findings identify a mechanism to explain and modify what is otherwise a stereotyped but sometimes detrimental response to epithelial injury. [ABSTRACT FROM AUTHOR]