title: First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up.
abstract: BACKGROUND
  Conventional therapy for pemphigus vulgaris (PV) consists of high-dose systemic corticosteroids (CS) and immunosuppressive agents (ISA). This combination may be ineffective, cause serious adverse events or relapses in some patients.
  
  
  OBJECTIVE
  To determine if the combination of intravenous immunoglobulin (IVIg) therapy and rituximab (RTX) can be used as first-line therapy in PV patients in whom systemic CS and ISA are contraindicated and evaluate its ability to produce long-term sustained remissions.
  
  
  METHODS
  This a retrospective study of five male and five female patients (mean age 47.87 years). RTX was administered once weekly for eight consecutive weeks, followed by once monthly for four months (dose 375 mg/m(2)). Since CD20(+) B cells were undetectable, IVIg was infused until they reached normal levels (dose 2 g/kg/cycle). IVIg was then continued according to published protocol.
  
  
  RESULTS
  Initial clinical response and complete disease resolution occurred in a mean of 3.2 weeks and 7.4 weeks, respectively. Mean duration of rituximab therapy was 6.09 months and 33.7 months for IVIg therapy. Mean duration of follow-up after the last dose of rituximab was 86.08 months, during which all patients remained in complete remission. Mean length of total follow-up was 103.99 months. No relapses, infections, or hospitalizations were reported.
  
  
  CONCLUSIONS
  When systemic CS and ISA are contraindicated in PV patients, combination RTX and IVIg therapy can produce a prolonged, sustained remission without additional systemic therapy. This positive clinical outcome could be the consequence of pathogenic B cell depletion and restoration of immune regulation.
authors.affiliation: Center for Blistering Diseases, Department of Dermatology, Tufts University School of Medicine, Boston, MA, USA. Electronic address: arahmedmd@msn.com.
authors.forename: A Razzaque
authors.initials: AR
authors.lastname: Ahmed
authors.affiliation: Center for Blistering Diseases, Department of Dermatology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Tegan
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Université Pierre et Marie Curie, Paris, France.
authors.forename: Srini
authors.initials: S
authors.lastname: Kaveri
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Spigelman
mesh_terms: D000305:Adrenal Cortex Hormones; D000328:Adult; D000075202:Contraindications; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000188:drug therapy*; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D000069283:Rituximab
keywords: Corticosteroids; First-line therapy; Immunosuppressive agents contraindicated; Intravenous immunoglobulin; Long-term follow-up; Pemphigus vulgaris; Rituximab