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80-6Pages: 0                                           2020-09-2020 | Published: 19-90-52020 | Accepted: 1-80-01Received:  

                                                                                                                                                                                           

Clinical Medicine Insights Page 6 
 

 

Rituximab treatment for chronic idiopathic urticaria with recurrent 

angioedema  

Dr. Vikola Yigovski 

Dept. Of  Medicine, Faculty of Medicine, China  

 

 Abstract : We report on 4 patients with severe chronic urticaria and idiopathic recurrence with angioedema 

attacks. Initially, they initially respond to high-dose corticosteroids but still recur on a high-protection dose. 

Next, test the use of steroid-sparking drugs i.e.. internal immunoglobulin then mycophenolate mofetil with 

hydroxychloroquine and tacrolimus could not sustain a quench. Therefore, Rituximab was given. One month 

after Rituximab infections, the Prednisone dose was successfully discontinued and discontinued. 

Subsequently, all patients remained in complete rest for 10-18 months.  

Key words: angioedema, prednisone, Rituximab, urticaria. 

 

Introduction :  

Urticaria is a common dermatological condition which typically presents with intensively pruritic, well-

circumscribed, raised wheels ranging from several millimeters to several centimeters or larger size.  

Urticaria can occur with angioedema, which is localized non-pitting edema of the subcutaneous tissue that 

can be painful and obstructs the air way.  Chronic urticaria (CU) is defined as urticaria persisting almost 

daily for more than six weeks [1].  It generally lasts 1 to 5 years, but can have a prolonged course beyond 5 

years in roughly 14% of patients [2].  The latter is considered a major health burden since the persistent 

pruritis impairs daily functions, disturbs sleep and hence the quality of life [3]. In general population the 

prevalence of CU is 0.5-5% [4]. According to the GRADE system, the mainstay of treatment of urticaria is 

avoidance of identified triggers, second-generation H1 antihistamines, Leukotriene antagonists, short course 

corticosteroids and Omalizumab if severe with or without angioedema [1].  In the present article, we 

describe our experience with treatment of systemic and idiopathic CU with Rituximab in patients who had 

failed multiple corticosteroid-sparing agents.   

Patients and methods: 

Inclusion criteria: 

All patients, with generalized purpuric wheals with surrounding erythema which persisted for > 6 weeks, 

were seen in the past 2 years.  All patients had the following criteria: (a) high IgE levels with/without 

previous history of atopy and/or bronchial asthma.  (b) none had secondary cause for allergy viz. 

malignancy, infections and parasitic infestations (c) no evidence of physical cause for their illness (heat, 

cold, solar, vibration, delayed-pressure, dermatographism, aquagenic and cholinergic induced urticaria) 

which was confirmed with skin testing.  The latter included; wet cloth, hot bath, prick/patch tests (d) no 

clinical evidence of food-association  (e) no evidence of new drug addition especially ACEI, ARB, oral 

contraceptives and all drugs were tested by a 2-weeks discontinuation period.  (f) skin biopsy that did not 

show vasculitis (g) normal TSH, CRP, IgA level, hepatitis B & C serology, Helicobacter antibodies, Anti-

microsomal antibodies, serum protein electrophoresis, RA, ANCA, ANA, and serum complements.   

Treatment protocol: 

All patients were treated with Prednisone 1 mg/kg for a minimum of 1 month.  Subsequently, the dose was 

decreased by 5 mg/week.  If fails to maintain a remission for > 2 weeks; intravenous immunoglobulin 

(IVIG) is used.  If the latter fails, another 2-weeks trial of Mycophenolate mofetil with Hydroxychloroquine 

and Tacrolimus is used.  If fails again; Rituximab infusions are to be given.  



Rituximab treatment for chronic idiopathic urticaria with recurrent angioedema  

 

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Rituximab infusions: 

The patients were treated with four weekly infusions of 500 mg of Rituximab (mabthera).  The patient was 

pre-medicated with two 500 mg Paracetamol and one Piriton tablets followed by an infusion of 125 mg of 

Solumedrol in 50 ml of D5W over 30 minutes before infusions.  The 500 mg of Rituximab was diluted in 

450 ml of NS leading to a concentration of 1 mg/ml.  The first infusion rate was 20 ml/h for the first 30 

minutes followed by 20 ml increments/hour every 30 minutes till the total dose is achieved.  The second 

infusion was a rate was started at 40 ml/hour, the third at 80 ml/hour and the fourth at 120 ml/hour.  Flow 

cytometry showed that her CD19 lymphocytes dropped to zero after one week of therapy and remained < 

0.5% for 8 months.  Interestingly, the patient is asymptomatic and up to 12 months after normalization of 

her CD19 i.e. total of 20 months following the start of Rituximab therapy.   

Results 

A total of 4 patients fullfiled the inclusion criteria and hence were included in the study).  All patients were 

adults (26-50 years) and had CU for > 6-8 months prior to inclusion in the study All patients had recurrent 

attacks of angioneurotic oedema that had required multiple hospital admissions.  

Efficacy of Rituximab: 

The drug was tolerable on such dosage despite 4-6 hour infusion time.  There were no post-infusion 

immediate reactions and there was no report of delayed side effect.  One month after the last dose of 

Rituximab; Prednisone dose was tapered down and the drug was discontinued without relapse of their 

urticaria.   

Duration of follow up: 

The patients were followed up for > 14 months in the last patient and up to 24 months in the first patient.    

Discussion 

Urticaria is not a single disease but a reaction pattern that represents cutaneous mast cell degranulation. The 

latter results in extravasation of plasma into the dermis, forming the characteristic hives which are 

edematous pruritic pink wheals of variable size and shape.  The lesions may be associated with angioedema 

which is a swelling deeper than wheals and may affect mucosal surfaces with typical sites of predilection 

that include the eyelids, lips, and tongue [5].  Urticaria being defined as chronic if lesions recur for longer 

than 6 weeks.  CU includes physical urticaria, idiopathic urticaria, and urticarial vasculitis [1].  In our study, 

we included patients with idiopathic type of CU and excluded those with physical and vasculitic ones [6, 7].  

Idiopathic CU is the most common type, comprising up to 90% of all cases of CU.  It has been estimated 

that idiopathic CU affects between 0.6% to 5% of the population during their lifetime [8].  Over half of all 

cases of idiopathic CU are thought to be caused by an autoimmune mechanism. This is supported by the 

observation that 60% of patients with idiopathic CU will have a wheal and flare reaction to intradermal 

autologous serum injections in the autologous serum skin test (ASST) [9].  Approximately 50% of patients 

with idiopathic CU have IgG antibodies that are specific for the high affinity IgE receptor (FcεRI) [10, 11]. 

These autoantibodies activate mast cells in the skin, circulating basophils, and the complement system [9].  

Additional immunological causes in CU include IgG antibodies directed against IgE antibodies and the low 

affinity IgE receptor (FcεRII), antiendothelial antibodies, and complement C8 alpha-gamma (C8α-γ) 

deficiency [12].  Our patients had severe and persistent idiopathic CU and were hardly controlled with high-

dose corticosteroids.  The latter has significant long-term side effects viz. osteoporosis, hypertension, 

glucose intolerance, obesity, stria, cushinoid appearance, growth retardation, decreased immunity, poor 

wound healing [13].  To avoid Corticosteroids-toxicity, multiple drugs were proposed for such condition viz. 

intravenous immunoglobulin, 
 
Mycophenolate mofetil, Hydroxychloroquine, and Tacrolimus [1].  All those 

drugs were tried in our patients and, had failed to be even steroid-sparing agents.  Since CU is a disease of 

the mature B producing excessive amounts of autoantibodies [Vida supra], we elected to use Rituximab in 

such drug-refractory patients.  Rituximab is a murine antibody that destroys both normal and malignant B 

cells B that have CD20 on their surfaces and is therefore used to treat diseases which are characterized by 

having too many B cells, overactive B cells, or dysfunctional B cells.  The following effects have been 

found: (a) The Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC) and 



Rituximab treatment for chronic idiopathic urticaria with recurrent angioedema  

 

Clinical Medicine Insights Page 8 
 

complement-dependent cytotoxicity (CDC. (b) Rituximab has a general regulatory effect on the cell cycle. 

(c) It increases MHC II and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated 

antigen). (d) It elicits shedding of CD23. (e) It down regulates the B cell receptors (f) It induces apoptosis of 

the CD20+ cells [14].  The latter may be the basis of maintenance of long-term remission via generation of 

new cells without memory ones [15].   

In conclusion; our results are promising for a new hope in treatment of drug-refractory CU with Rituximab-

treatment.  The latter is safe and is able to produce a long-lasting remission of a disabling disease.    

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