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Anais Brasileiros de Dermatologia

versão impressa ISSN 0365-0596versão On-line ISSN 1806-4841

An. Bras. Dermatol. vol.93 no.2 Rio de Janeiro mar./abr. 2018

http://dx.doi.org/10.1590/abd1806-4841.20187074 

CASE LETTERS

Urticaria and angioedema as possible reactions of omalizumab*

Ozlem Ozbagcivan1 

Sevgi Akarsu1 

Turna Ilknur1 

Emel Fetil1 

1Department of Dermatology, Faculty of Medicine, Dokuz Eylul University - Izmir, Turkey


Dear editor;

A 55-year-old man presented to our clinic with a 16-year history of chronic spontaneous urticaria (CSU). Given the poor response to H1-antihistamines at high doses alone or in combination with montelukast, he had started to receive omalizumab four months ago (300 mg/SC/every fourth week). He was referred to our clinic because of the exacerbation of his urticaria after this therapy. On physical examination, we detected the continuous eruption of short-lived hives on his body and extremities. He had no angioedema. His urticaria activity score-7 (UAS-7) was 14 in the preceding week. Complete blood count, liver, renal, and thyroid function tests, erythrocyte sedimentation rate, C3-C4 complement levels, and urine analysis were normal. Anti-thyroid and antinuclear antibodies, tests for human immunodeficiency, hepatitis B and C viruses, and stool examinations for parasitic infections were negative. Serum IgE level was 196 IU/mL (normal 0-87), and C-reactive protein (CRP) value was 2.2mg/L (normal<5 mg/L). His chest x-ray and abdominal ultrasonography were normal. Twenty-eight days after the last dose, we administered the fifth dose of omalizumab (300mg/SC) because of the ongoing symptoms. We also thought that the previous exacerbations should not be omalizumab-related. No acute reaction was observed following the administration, but an exaggeration of the urticaria and swelling of the lips and tongue were observed after about 12 hours (Figure 1). The CRP value measured in this period was 10.8mg/L. He was treated with antihistamines and systemic corticosteroids, but the UAS-7 was increased to 39 over the first week (Table 1). In the following period, the patient did not accept the diagnostic tests planned to determine the sensitizing compound of omalizumab.

Figure 1 Exacerbation of the urticaria after omalizumab administration in the patient 

Table 1 The UAS-7 values of the patient several weeks before and after omalizumab 

UAS-7 Before omali­zumab After the 1st dose After the 2nd dose After the 3rd dose After the 4th dose Afterthe 5th dose
1st week UN 38 32 32 36 39
2nd week UN 29 25 24 30 32
3rd week 18 20 21 18 22 26
4th week 16 15 12 13 14 15

UAS: Urticaria Activity Score; UN:Unkown

Omalizumab is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to human IgE. It was originally approved in 2003 for the treatment of persistent allergic asthma, and then was licensed in 2014 for the treatment of patients with antihistamine-refractory CSU. Over the past years, results of clinical studies and practical experience have shown its high efficiency with a rapid onset of action in CSU.1

Omalizumab has been known to be associated with serious adverse reactions in patients with allergic asthma, but it has a better tolerability profile in patients with CSU. Most adverse reactions in CSU patients are mild and temporary such as fever, headache, sinusitis and reactions at the injection site.2 Although the failure of therapy has been rarely mentioned in some reports, exacerbation of urticaria associated with omalizumab is an unusual complication.3,4 Recently, Ertaş et al. reported four patients with severe antihistamine-resistant CSU, who developed angioedema, anaphylaxis and/or flare-up of urticaria at different times following omalizumab therapy (Table 2).4 In our patient, the exacerbation of urticaria and development of angioedema after the administration of the drug made us think that it was a paradoxical adverse reaction.

Table 2 Exacerbation of urticaria and angioedema following omalizumab therapy 

Patient Age Gender Diagnosis Disease duration Omalizumab dosage Reaction
1* 68y Male CSU+angioedema 4 years 5th
6th Angioedema 29 25 24 30
Urticaria+angioedema 18 20 21 18 22
2* 49y Female CSU+angioedema 25 years 2nd Angioede­ma
3* 33y Female CSU+angioedema 7 years 1st
2nd Hypotension and weakness
Anaphylaxis
4* 38y Male CSU 5 years 1st Urticaria
Our patient 55y Male CSU 16 years 5th Urticaria+angioedema

*Cases in the report of Ertaş et al,2016. 4; CSU: Chronic spontaneous urticaria

Even though we were not able to make the diagnostic tests, exacerbation of the pre-existing urticaria, and development of angioedema in our patient may be related with the excipients in omalizumab such as polysorbat and histidine rather than the active ingredient. Especially polysorbat is one of the well-established sensitizers that may be involved in the development of severe non-immunological reactions. Anaphylactoid reactions with cutaneous symptoms have also previously been described in asthmatic patients being treated with omalizumab.5 As most commercial preparations include different excipients which are necessary to preserve and stabilize the product, it should be taken into consideration that these excipients may play a role in the development of such adverse reactions and in unsatisfactory responses to the omalizumab therapy.

*Work performed at the Department of Dermatology, Faculty of Medicine, Dokuz Eylul University - Izmir, Turkey.

Financial support: None

REFERENCES

1 Kaplan AP, Giménez-Arnau AM, Saini SS. Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. Allergy. 2017;72:519-533. [ Links ]

2 Termeer C, Staubach P, Kurzen H, Strömer K, Ostendorf R, Maurer M. Chronic spontaneous urticaria - a management pathway for patients with chronic spontaneous urticaria. J Dtsch Dermatol Ges. 2015;13:419-28. [ Links ]

3 Sabroe RA. Failure of omalizumab in cholinergic urticaria. Clin Exp Dermatol. 2010;35:e127-9. [ Links ]

4 Ertas R, Özyurt K, Yildiz S, Ulas Y, Turasan A, Avci A. Adverse reaction to omalizumab in patients with chronic urticaria: flare up or ineffectiveness? Iran J Allergy Asthma Immunol. 2016;15:82-6. [ Links ]

5 Price KS, Hamilton RG. Anaphylactoid reactions in two patients after omalizumab administration after successful long-term therapy. Allergy Asthma Proc. 2007;28:313-9. [ Links ]

Received: February 24, 2017; Accepted: August 06, 2017

Mailing address: Ozlem Ozbagcivan E-mail: ozlem.ozbagcivan@deu.edu.tr

Conflict of interests: None

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