Persistent B Lymphocyte Depletion After an Ultralow Dose of Rituximab for Pemphigus Vulgaris

Abstract

Pemphigus vulgaris is an autoimmune bullous disease affecting the skin and mucosa. It is caused by autoantibodies targeting the adhesion molecules desmoglein 1 and desmoglein 3, which, respectively, mediate adhesion between keratinocytes in skin and mucosa, resulting in the formation of blisters and erosions. Early recognition and treatment are crucial for remission of this disorder. Treatment for severe pemphigus traditionally includes long-term corticosteroids and immunosuppressants [1]. Rituximab, a chimeric monoclonal antibody against the CD20 antigen of B lymphocytes, was recently introduced and has proven to be effective in resistant and life-threatening pemphigus [2]. Protocols for administration of rituximab are determined for use in non-Hodgkin lymphoma (375 mg/m 2 once a week, with duration depending on the type of lymphoma) and for rheumatoid arthritis (2 doses of 1000 mg given 2 weeks apart) [3]. A lower dose of rituximab (500 mg at 2 weeks interval) can be used in pemphigus [4][5][6].A 67-year-old woman was referred to our dermatology department for recent onset of erosive lesions of the oral cavity. The patient complained of severe difficulty swallowing, forcing her to feed almost exclusively with a liquid diet. The skin was not involved, showing only signs of previously active lesions. She denied trauma and application of topical drugs on the areas involved. Her medical history did not reveal any association with other immune-mediated diseases. Evaluation of circulating anti-DSG1, anti-DSG3, and anti-BP180 antibodies revealed a high anti-DSG3 autoantibody titer (192.13 U/mL, normal value <7 U/mL), which is consistent with a diagnosis of pemphigus vulgaris. Treatment was initially started with intravenous methylprednisolone 80 mg/d for 2 weeks, which was thereafter slowly tapered to 40 mg/d over 2 weeks, with complete remission. The patient was then treated with oral prednisone 50 mg/d for 1 month and 25 mg/d for a further month. At this time, the disease relapsed, with oral involvement only, and azathioprine 100 mg/d was combined with prednisone 25 mg/d for 3 months. The oral lesions did not resolve. Consequently, we decided to administer rituximab [7] in a 2-dose regimen (2 weeks apart) of 500 mg per dose. Prior to infusion of rituximab, the patient was premedicated with intravenous acetaminophen 1000 mg, chlorphenamine 10 mg, and methylprednisolone 20 mg diluted in 100 mL of normal saline. Rituximab 500 mg was then diluted in 500 mL of Manuscript

Pemphigus: Current and Future Therapeutic Strategies

“…On the other hand, high dose regimens should be preferred instead of low-dose regimens, due to longer disease response (163). Nowadays, one study recently reported on a pemphigus patient achieving successful disease remission with an ultra-low dose of RTX (200 mg in a single infusion), with persistent B-cell depletion after 6-month follow-up (172, 173). This highlights the need of further investigating individual factors that may influence RTX efficacy in an effort to personalize treatment schedules and optimize the safety.…”

Citrobacter freundiisepsis in an immunosuppressed patient with pemphigus vulgaris

“…Initially the most used regimen was the lymphoma protocol (375 mg/week for 4 weeks), nowadays some centres prefer two doses of 1000 mg given 2 weeks apart or 500 mg at 2 weeks interval because of the better side effect profile 10. In our experience, we observed the persistent suppression of B cell count for several months after a single very low dose of rituximab (200 mg) 11. Moreover, a recent study demonstrated that less than 1% of the conventional rituximab dose induced a nearly complete depletion of circulating B lymphocytes in healthy volunteers 12 13…”