Actas Dermo-Sifiliográficas (English Edition) Actas Dermo-Sifiliográficas (English Edition)
Actas Dermosifiliogr 2017;108:e53-5 - Vol. 108 Num.8 DOI: 10.1016/j.adengl.2016.08.019
e- Case Report
Response to Omalizumab in Solar Urticaria: Report of 3 Cases
Respuesta a omalizumab en 3 casos de urticaria solar
P. Rodríguez-Jiménez, , P. Chicharro, A. Pérez-Plaza, D. de Argila
Servicio de Dermatología, Hospital Universitario de La Princesa, Madrid, Spain
Abstract

We report 3 cases of solar urticaria in which there was no response or limited response to first-line treatments with high-dose H1 antihistamines or phototherapy. The patients were then treated with omalizumab. Symptoms improved in 2 patients, whose tolerance to sunlight increased considerably; quality of life clearly improved for 1 of these patients. The third experienced no improvement and developed a mild local reaction to the injected medication. We conclude that omalizumab may offer a potentially safe, useful alternative for patients with solar urticaria who do not respond to conventional therapy.

Resumen

Se presentan 3 pacientes con urticaria solar que o no habían respondido adecuadamente o presentaban limitaciones a los tratamientos de primera línea (antihistamínicos H1 a dosis altas o fototerapia), que fueron tratados con omalizumab. Dos de ellos mejoraron clínicamente con un aumento muy importante de la tolerancia a la luz, uno de ellos con clara mejoría de la calidad de vida. El otro paciente no mejoró y desarrolló una reacción local leve a la medicación inyectada. Omalizumab puede ser por tanto una alternativa terapéutica potencialmente útil y segura en urticarias solares graves no respondedoras al tratamiento convencional.

Keywords
Inducible chronic urticaria, Omalizumab, Solar urticaria
Palabras clave
Urticaria crónica inducible, Omalizumab, Urticaria solar
Introduction

Solar urticaria (SU) is an uncommon chronic inducible urticaria characterized by the development of wheals after exposure to sun radiation, visible light, or UV radiation. Because the condition is rare, there are no epidemiological data on incidence or prevalence rates,1 although varying figures of between 2.3% and 17.8% have been reported within the group of photodermatoses.1 Lesions typically appear within minutes of exposure and the most common action spectra are visible light and UV-A. Action spectrum and minimal urticaria dose (MUD) are important for diagnosis, treatment, and prognosis, and can be used to rule out other photodermatoses.2

Second-generation H1 antihistamines are the first-line treatment for inducible chronic SU, just as they are for other forms of inducible chronic urticaria. However, most patients require either high doses or combinations of different antihistamines.2 An alternative first-line approach is tolerance induction through phototherapy.2 The use of omalizumab has also been described in several case reports and small case series of patients in recent years, with varying results. The principle underlying this treatment is based on a hypothetic role for immunoglobulin (Ig) E in the pathogenesis of inducible chronic urticaria.3

Case Descriptions

The clinical data for 3 patients with severe SU refractory to H1 antihistamines treated in our department over a period of 5 years are summarized in Table 1.

Table 1.

Cases of Solar Urticaria Treated With Omalizumab.

Sex  Age, y  Com  TsO, y  PT  MUD  IgE  Dose During Treatment  Clinical Response 
53  ARC  H1A PT  Wheal after 30min with VL  502IU/mL  300mg/mo 12 mo  Complete with negative provocation test results 
65  PLE  10  H1Wheal after 30min with FL  17.2IU/mL  300mg/mo 6 mo  Partial 
50  Unr  25  H1UV-B, 10mj/cm2; UV-A, <0.6mj/cm2; SS, <10mj/cm2  1382IU/mL  150mg/2wk 1.5 mo  No clinical or objective response 
              300mg/mo 4 mo   

Abbreviations: ARC, allergic rhinoconjunctivitis; Com, comorbid conditions; FL, fluorescent light; H1A, H1 antihistamines; IgE, immunoglobulin E; MUD, minimal urticaria dose; PLE, polymorphic light eruption; PT, previous treatment; TsO, time since onset; Unr, unremarkable; VL, visible light.

Patient 1 had SU induced by visible light in which neither H1 antihistamines nor phototherapy proved effective. Following treatment with omalizumab, however, she exhibited clear signs of clinical improvement (she was able to tolerate sunlight for 10 times longer than before) and improved test results after photoprovocation testing. Patient 2 had SU to visible light triggered by indoor lights (fluorescents and LEDs) that prevented her from spending time in the sun. After treatment with omalizumab, she experienced an increase in tolerance of exposure to both indoor lights and sunlight. She is now able to remain in the sun for up to 5hours, something that she had not been able to do for 15 years. She also showed improved objective health-related quality of life scores on the Skindex-29 compared with baseline, with a 23% improvement noted for overall quality of life, and additional improvements in the Symptoms, Emotions, and Functioning domains. Patient 3, whose case has been previously published,4 had SU due to UV-B and UV-A and a very low MUD that limited the use of phototherapy. She had responded poorly to H1 antihistamines. She was treated twice with omalizumab but showed no response on either occasion. In addition, she developed a mild local reaction after the first injection in the form of pruritic wheals that resolved spontaneously.

Discussion

In our review of the literature, we identified 16 patients with SU treated with omalizumab (8 case reports and 3 case series).3–14 Fourteen of the patients were adults and 2 were children.5,6 The treatment doses varied between 150mg/mo7 and 800mg/mo.8 Varying measures of clinical response were used, and not all authors reported on this aspect of treatment. Most authors used subjective criteria based on patient-reported manifestations or other health-related quality of life measures. Others used phototesting6–9 or the Urticaria Activity Score 7, which is a validated tool for evaluating chronic urticaria.10 Of the 16 patients, 12 (75%) responded either partially or completely to treatment and 5 of these (31.2%) additionally showed negative provocation results. Follow-up time varied from 1 month, in a patient who showed complete response after a single dose,7 to 1 year, in a patient who received 12 monthly doses.6

On analyzing the cases reviewed, we observed a certain tendency towards an association between high total baseline IgE levels, albeit variable, and greater response to treatment. Seven of the 8 patients in this subgroup responded to treatment, although it should be noted that some of the responders had normal IgE levels, while some of the nonresponders (like patient #3 in our series) had elevated levels.

No severe adverse effects were mentioned in the cases reviewed, and it is noteworthy that the treatment proved safe in the 2 pediatric cases described.5,6

Finally, Aubin et al.15 recently reported on results from a phase II clinical trial investigating the use of omalizumab (300mg/mo for 2 months) in 10 patients with SU studied by phototesting and photoprovocation (action spectra: UV-A, UV-B, and polychromatic solar spectrum). The primary endpoint was the proportion of patients who did not develop SU lesions after photoprovocation with a UV radiation dose 10 times higher than the baseline MUD after 12 weeks of treatment. Approximately 40% of the patients showed an initial clinical improvement, but the efficacy results based on the primary endpoint showed no significant differences.

In conclusion, despite the limited data available from case reports and small case series on the characteristics and results of SU treatment with omalizumab, the clinical response rate of 75% based on reports in the literature to date is promising. The 3 patients described in our series are a selection of patients with severe SU treated at our department and omalizumab proved effective in 2 of them. Response was slower than that typically described for spontaneous chronic urticaria, with improvement observed after 3 doses (patient #1) or 5 doses (patient #2). Both patients are satisfied with the results and wish to continue treatment. Omalizumab may therefore be a potentially safe and useful treatment for patients with severe SU that is refractory to conventional treatment.

Ethical DisclosuresProtection of humans and animals

The authors declare that no tests were carried out in humans or animals for the purpose of this study.

Confidentiality of data

The authors declare that they have followed their hospital's protocol on the publication of data concerning patients.

Right to privacy and informed consent

The authors declare that no private patient data appear in this article.

Conflicts of Interest

Dr de Argila has worked as a clinical advisor for Novartis and also participated in clinical trials sponsored by this company. The other authors declare no conflicts of interest.

References
1
N. Botto,E. Warshaw
Solar urticaria
J Am Acad Dermatol, 59 (2008), pp. 909-920 http://dx.doi.org/10.1016/j.jaad.2008.08.020
2
M. Magerl,S. Altrichter,E. Borzova,A. Giménez-Arnau,C. Grattan,F. Lawlor
The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA2LEN/EDF/UNEV consensus recommendations 2016 update and revision
Allergy, 71 (2016), pp. 780-802 http://dx.doi.org/10.1111/all.12884
3
M. Metz,S. Altrichter,E. Ardelean,B. Kessler,K. Krause,M. Magerl
Anti-immunoglobulin E treatment of patients with recalcitrant physical urticaria
Int Arch Allergy Immunol, 154 (2011), pp. 177-180 http://dx.doi.org/10.1159/000320233
4
A. Pérez-Plaza,M.J. Concha-Garzón,G. Solano-López,D. De Argila
Failure of omalizumab in ultraviolet-induced severe solar urticaria
Immunology, 33 (2014), pp. 147-148
5
S. Arasi,G. Crisafulli,L. Caminiti,F. Guarneri,T. Aversa,F. Porcaro
Treatment with omalizumab in a 16- year-old Caucasian girl with refractory solar urticaria
Pediatr Allergy Immunol, 26 (2015), pp. 583-585 http://dx.doi.org/10.1111/pai.12413
6
A. Levi,Y. Tal,Z. Dranitzki,M. Shalit,D.E. Claes
Successful omalizumab treatment of severe solar urticaria in a 6-year-old child
Pediatr Allergy Immunol, 26 (2015), pp. 588-590 http://dx.doi.org/10.1111/pai.12441
7
O. Güzelbey,E. Ardelean,M. Magerl,T. Zuberbier,M. Maurer,M. Metz
Successful treatment of solar urticaria with anti-immunoglobulin E therapy
8
K.H. Waibel,D.A. Reese,R.G. Hamilton,R. Devillez
Partial improvement of solar urticaria after omalizumab
J Allergy Clin Immunol, 125 (2010), pp. 490-491 http://dx.doi.org/10.1016/j.jaci.2009.11.007
9
A. De Dios-Velázquez,M. Gónzalez-De Arriba,V. Beteta-Gorriti,E. Macías,V. Campanón-Toro,I. Dávila
Effectiveness of omalizumab in severe solar urticaria
Ann Allergy Asthma Immunol, 116 (2016), pp. 256-264 http://dx.doi.org/10.1016/j.anai.2015.11.019
10
C. Baliu-Piqué,P. Aguilera-Peiró
Three cases of solar urticaria successfully treated with omalizumab
J Eur Acad Dermatol Venereol, 30 (2015), pp. 704-706 http://dx.doi.org/10.1111/jdv.13001
11
M. Metz,T. Ohanyan,M.K. Church,M. Maurer
Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: A retrospective clinical analysis
12
S. Zimmer,A. Pevelling-Oberhag,A. Weber,T.T. Gilfert,U. Rady-Pizarro,P. Staubach
Unique co-existence of cold and solar urticaria and its efficient treatment
Br J Dermatol, 174 (2016), pp. 1150-1152 http://dx.doi.org/10.1111/bjd.14354
13
G. Duchini,W. Bäumler,A.J. Bircher,K. Scherer
Failure of omalizumab (Xolair) in the treatment of a case of solar urticaria caused by ultraviolet A and visible light
Photodermatol Photoimmunol Photomed, 27 (2011), pp. 336-337 http://dx.doi.org/10.1111/j.1600-0781.2011.00624.x
14
S. Müller,C.M. Schempp,T. Jakob
Failure of omalizumab in the treatment of solar urticaria
J Eur Acad Dermatol Venereol, 30 (2016), pp. 524-525 http://dx.doi.org/10.1111/jdv.12922
15
F. Aubin,M. Avenel-Audran,M. Jeanmougin,H. Adamski,J.L. Peyron,M.C. Marguery
Omalizumab in patients with severe and refractory solar urticaria: A phase II multicentric study
J Am Acad Dermatol, 74 (2016), pp. 574-575 http://dx.doi.org/10.1016/j.jaad.2015.11.021

Please cite this article as: Rodríguez-Jiménez P, Chicharro P, Pérez-Plaza A, de Argila D. Respuesta a omalizumab en 3 casos de urticaria solar. Actas Dermosifiliogr. 2017;108:e53–e55.

Corresponding author. (P. Rodríguez-Jiménez pedro.rodriguez.jimenez90@gmail.com)
Copyright © 2017. Elsevier España, S.L.U. and AEDV
Actas Dermosifiliogr 2017;108:e53-5 - Vol. 108 Num.8 DOI: 10.1016/j.adengl.2016.08.019