Major Inclusion Criteria:

• Chronic urticaria defined as symptoms >50% of the days or 3 days per week for more than 12 weeks
• Previous requirement for sustained or recurrent use of corticosteroids OR requirement for immunomodulatory treatment for urticaria (eg hydroxychloroquine, sulfasalazine, dapsone, cyclosporine, IVIg, etc) OR ongoing symptoms for at least 6 months duration with failure to respond at least maximally approved dosages of 2 different antihistamine therapies
• Chronic therapy with stable doses of antihistamines for at least 4 weeks. Patients may be taking more than one antihistamine or be taking combinations of antihistamines and leukotriene receptor antagonists
• High baseline score for pruritis (at least 2 on a 3 point scale)
• No underlying etiology clearly defined for urticaria
• Evidence of underlying autoimmunity as evidenced by clinical and laboratory criteria
• Concomitant use of hydroxychloroquine, sulfasalazine, or dapsone permitted if doses stable for at least 12 weeks
• Negative serum pregnancy test (for women of child-bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
• No planned elective surgical procedures for at least 6 months

Major Exclusion Criteria:

• Concomitant use of corticosteroids
• Current use of immunosuppressive medication (cyclosporine, IVIg, methotrexate, cyclophosphamide). Any such medication will be discontinued for at least 6 weeks before screening.
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
• Receipt of a live vaccine within 4 weeks prior to randomization
• Previous treatment with Rituximab (MabThera® / Rituxan®)
• Prior antibody therapy
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Known history of HIV seropositivity (testing will be performed at screening)
• History of Hepatitis B and/or Hepatitis C (Hep BsAg and Hep C Ab will be obtained at screening)
• History of recurrent significant infection or history of recurrent bacterial infections
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds)
• Any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• Known immunodeficiency syndrome, hypogammaglobulinemia, etc.
• Systemic lupus erythematosus
• Pregnancy (a negative serum pregnancy test will be performed for all women of childbearing potential within 7 days of treatment) or lactation
• Malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• Atopic dermatitis
• Clinically relevant medical conditions (cardiovascular including poorly controlled hypertension or coronary artery disease, pulmonary, metabolic, renal, hepatic, psychiatric) or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Plans or need to receive live viral vaccination over course of the study (e.g. Flu-Mist TM)