The findings were consistent with chronic urticaria. on long-term venlafaxine Mouse monoclonal to CD15 and dexamphetamine for a mood disorder. There was no history to suggest an allergic reaction to current medications. Differential blood count, C-reactive protein, and erythrocyte sedimentation rate did not suggest any chronic or recurrent infections triggering urticaria. Specific IgE to dust mite, grass pollen mix, and staple food was unfavorable. A clinical diagnosis of chronic spontaneous urticaria (CSU) was made, and she was treated with a maximal dose of histamine (H1/H2) receptor blockade (cetirizine 20 mg bis die and ranitidine 150 mg bis die). Despite this treatment, she continued to have breakthrough urticaria and required intermittent high dose prednisolone (1 mg/kg/d) while still scoring 42 around the Urticaria Activity Score over 7 Days scale. Therapy was intensified with omalizumab (300 mg monthly), because of its exhibited KU-55933 efficacy in CSU1 and low side-effect profile as compared to other agents used in treatment of alemtuzumab-related secondary autoimmunity. This resulted in a dramatic (but incomplete) reduction in urticaria, with burdensome breakthrough lesions typically in the week before her next omalizumab dose. No clinical relapses or new signs of radiologic MS activity occurred over this period; her MS continued to improve throughout omalizumab therapy with the Expanded Disability Status Scale score improving from 2 to 0, over 18 months of monitoring. A skin biopsy was performed that excluded other causes of immune-mediated urticaria, securing the diagnosis of CSU2 (see physique 1 and physique e-1, links.lww.com/NXI/A186). Montelukast was initiated at 10 mg/d and advised to adhere to a strict 28-day dosing of omalizumab to minimize the breakthrough period. Open in a separate window Physique A perilesional skin biopsy showed moderate, superficial, dermal perivascular lymphocytic infiltrate and moderate dermal oedema with dilated lymphaticsNeutrophils were seen within the lumen of the vessels and scattered in small numbers through interstitium together with occasional mast cells. The findings were consistent with chronic urticaria. No evidence of vasculitis was seen. Discussion Alemtuzumab is a monoclonal antibody directed against the CD52 antigen. It is used therapeutically in chronic lymphocytic leukemia and increasingly in MS. The CD52 antigen is usually expressed on 95% of peripheral B and T lymphocytes, monocytes, macrophages, and thymocytes. Binding of alemtuzumab to the CD52 antigen causes lysis of the target cell, and its clinical efficacy is because of B and T lymphocyte, monocyte, and natural killer KU-55933 cell depletion.3 Immune dysregulation after alemtuzumab has been reported at rates up to 30%, with common manifestations being thyroid diseases and autoimmune hematologic conditions.3 Autoimmune side effects manifested at 6 months with a peak incidence in year 3 after the first course.4 It is postulated the autoimmune sequelae arise from reconstitution of cells after T-cell lymphopenia along with additional insults including the depletion of Tregs and overproduction of interleukin-21.5 T cells undergo homeostatic proliferation to reconstitute the immune system relying on stimulation through the T-cell receptor-self peptide-major histocompatibility complex and leads to generation of self-reactive T cells.5 CSU is the appearance of wheals and/or angioedema for longer than 6 weeks.1 It can be because of autoantibodies or idiopathy.2 The treatment paradigm is high-dose H1-antagonists (up to 4 times the usual recommended dose), H-2 antagonists, KU-55933 and adjuvants such as leukotriene antagonists. If symptoms remain refractory, the most effective next-line agent is usually omalizumab. Omalizumab is a humanized immunoglobulin G directed against immunoglobulin E and is thought to not only bind serum IgE but also downregulate its cognate receptor (Fc ?R-1) on mast cells; it has exhibited efficacy in severe, autoimmune CSU.6 We believe that this is the first reported case of CSU in the context of immune dysregulation within the typical time period after alemtuzumab and thus adds to the expanding repertoire of alemtuzumab-related immune-mediated side effects. Previous reports of urticaria were solely acute infusion-related side effects.7 It is important to consider CSU as a cause of recurrent rashes and angioedema after alemtuzumab because disease specific therapy is effective and available. Appendix.?Authors Open in a separate window Study funding No targeted funding reported. Disclosure Disclosures available: Neurology.org/NN..