REVIEW
URRENT
C
OPINION

Advances in the pathogenesis representing definite
outcomes in chronic urticaria
Luis Felipe Ensina a,b, Ana Paula Cusato-Ensina c, and Ricardo Cardona d

Purpose of review
We reviewed in this article, the recent advances in CSU physiopathology and potential clinical and
laboratory biomarkers in CSU.
Recent findings
In addition to the central role of mast cells in urticaria physiopathology, increased interest in basophils has
arisen. Recent data corroborate the autoimmunity pathway as one of the main pathways in mast cell
activation. The association of inflammatory cytokines, heat shock proteins and staphylococcal infection with
CSU are also reviewed. C-reactive protein, D-dimers, autologous serum skin test, IgE levels and FceRI
expression in basophils have shown their potential as biomarkers for disease duration, activity, severity
and/or response to treatment.
Summary
A comprehensive understanding of chronic spontaneous urticaria mechanisms is essential to find novel
biomarkers and treatments. The use of these biomarkers in clinical practice will guide us in choosing the
best treatment option for our patients.
Keywords
biomarkers, therapeutics, urticaria

INTRODUCTION
Urticaria is a condition characterized by the development of wheals, angioedema or both. It is classified as chronic when symptoms persist for more
than 6 weeks, and spontaneous when there is
no specific eliciting factor. Chronic spontaneous
urticaria (CSU) must be differentiated from other
diseases that can manifest with wheals and/or
angioedema but have other pathophysiologic mechanisms, such as urticaria vasculitis, maculopapular
cutaneous mastocytosis, nonhistaminergic angioedema and autoinflammatory syndromes [1]. A
detailed history and physical examination are essential to identify significant aspects of the disease and
to guide any further laboratory assessment that may
be useful to confirm or exclude underlying causes or
diseases [2].
The diagnosed prevalence or chronic urticaria
has been estimated to be 0.53% in the United States,
0.63% in Europe and 0.41% in Brazil [3–5].
Although not life-threatening, chronic urticaria
has been associated with a negative impact in the
quality of life [6]. As CSU may last for many years, it
is imperative to control the disease until it is gone
[1]. A thorough understanding of its mechanisms
allows us to offer the best treatment approach for

each patient, considering the disease duration and
severity, as well as the response to each potential
treatment, in order to improve their quality of life.
In this article, we review the most recent findings
in urticaria physiopathology along with potential
clinical and laboratory biomarkers.

URTICARIA PHYSIOPATHOLOGY
Mast cells play a central role in CSU physiopathology and can be activated by different pathways.
On the other hand, increasing interest in basophils
has emerged as peripheral basophil’s number is
decreased in CSU and functional impairment
has been observed. After basophil stimulation with
anti-FceRI antibodies, two different groups of
patients were described: a reactive (67%) and a
a

Federal University of São Paulo, bHospital Sı́rio-Libanês, cCPAlpha
Clinical Research Center, Brazil and dUniversidad de Antioquia,
Colombia
Correspondence to Luis Felipe Ensina, MD, PhD, Rua Barata Ribeiro,
490, São Paulo, SP 01308-000, Brazil. Tel: +55 11 3123 5777;
e-mail: drluisensina@imunologiaealergia.com
Curr Opin Allergy Clin Immunol 2019, 19:193–197
DOI:10.1097/ACI.0000000000000519

1528-4050 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.

www.co-allergy.com

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Outcome measures

KEY POINTS
 Urticaria mechanisms are still not totally understood.
 The development of new therapies for urticaria is based
on new insights on its mechanisms.
 Biomarkers may be useful to predict disease duration,
severity and response to treatment.

nonreactive group. Among the nonreactors, there is
a subgroup of patients with marked basopenia. This
group has a reduced surface expression of FceRI and
FcgRII, decreased binding of IgE and IgG, increased
serum reactivity and auto-antibodies against thyroid peroxidase, suggesting a possible autoimmune-associated mechanism [7].
Chronic spontaneous urticaria and its association with autoimmune diseases is well documented.
Immunoglobulin-G (IgG) autoantibodies to IgE or
the IgE receptor (FceRI) and IgE antibodies against
thyroid peroxidase have already been reported [8].
Two recent studies helped to corroborate those data
showing that 25–52% of CSU patients had IgG autoantibodies to FceRIa. This association was more
frequent in patients with a positive autologous
serum skin test (ASST) and autologous plasma skin
test (APST). No association was found with clinical
response to antihistamines [9,10].
In order to identify possible autoallergens as
targets for IgE in patients with CSU, Schmetzer
et al. evaluated sera of 1062 patients and compared
with 482 healthy controls. Thirty-one auto-antigens
were detected in more than 70% of patients. Eight
were soluble or membrane-bound and potentially
expressed on the skin, but only IgE against IL-24
was present in all CSU patients. Interestingly, IL-24
induced degranulation in mast cells preincubated
with IgE from CSU patients but not from healthy
controls, showing its functionality in CSU. Moreover,
IgE-anti-IL-24 levels were associated with disease
activity. Despite the presence of IgE anti-IL-24 in
some healthy donors, its concentration was markedly
lower in this group. New assays might help to better
explain the role of this cytokine in CSU [11 ].
To explore the role of other cytokines in CSU
physiopathology, Chen et al. selected IL-35, a suppressor of Th1 and Th17 cells, that play an essential
role in many autoimmune diseases. Serum levels of
IL-35 were investigated in CSU patients and compared with atopic dermatitis patients and healthy
controls, as well as IL-35 levels before and after
antihistamine treatment. CSU patients showed
significantly lower levels of IL-35 when compared
with the other groups, but increased levels after
&&

194

www.co-allergy.com

treatment, suggesting that this cytokine may play
a role in CSU pathogenesis [12]. Other cytokines
usually involved in immune responses as IL-17, IL31 and IL-33 were also found in higher plasma levels
in CSU patients when compared with controls [13].
Heat shock proteins (Hsp) are molecules that
play a role in inflammation and immune system
function. The 70 kDa Hsp (Hsp70) has been associated with many auto-immune diseases. Circulating
Hsp70 and anti-Hsp70 antibodies were evaluated in
patients with CSU and compared with controls.
Both plasma Hsp70 and serum anti-Hsp70 levels
were increased in CSU patients. Anti-Hsp70 antibodies levels were correlated with the grade of
inflammation and CRP concentration. Although
not clear if Hsp70 and its circulating antibodies have
a role in CSU or it is just an epiphenomenon, they
can be an attractive target for further studies [14].
Virus infection can be an important trigger in
acute urticaria or CSU exacerbation [15]. However,
there is no general agreement on the role of other
infections in CSU. Immunoglobulin-E antibodies to
Staphylococcus spp. have been demonstrated and
may play a role in diseases as atopic dermatitis
and allergic rhinitis. A retrospective study of sera
from 49 CSU patients was performed to address the
presence and functionality of these immunoglobulins in CSU patients. Levels of IgE against staphylococcal enterotoxin were higher but not statistically
significant in CSU patients than in healthy controls,
including staphylococcal enterotoxin B (SEB). SEB
could induce basophil histamine release in CSU
patients and be clinically correlated with disease
duration. These findings suggest that IgE against
staphylococcal antigens could trigger and perpetuate inflammation in a subgroup of CSU patients,
but more studies are necessary to clarify the role
of Staphylococcus spp. and other infections in this
disease [16].

BIOMARKERS FOR DISEASE ACTIVITY,
SEVERITY AND DURATION
A biomarker is a characteristic that is objectively
measured and evaluated as an indicator of a normal
biological process, pathogenic process or pharmacologic responses to a therapeutic intervention. They
can be useful in CSU to distinguish it from other
diseases, evaluate disease activity, severity and duration and predict response to treatment [17]. The
potential biomarkers reviewed in this article are
summarized in Tables 1 and 2.
Auto-immune thyroid disease patients have a
higher rate of CSU as well as antithyroid antibodies
prevalence is higher in CSU patients. In a retrospective analysis of outpatient CSU patients, around
Volume 19  Number 3  June 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Advances in the pathogenesis in chronic urticaria Ensina et al.
Table 1. Biomarkers for disease duration, severity, activity
and time to remission
Anti-TPO þ
Longer duration of disease
No association with severity
ASST and APSTþ

analyzed showing that one-third of patients had
elevated levels of CRP. These patients showed a
shorter duration of disease and higher disease activity based on the UAS7. CRP levels were also associated with ASST positivity and D-dimer levels,
confirming it as a useful biomarker for disease activity to monitor CSU patients [19 ].
Inflammatory conditions, such as metabolic
syndrome may contribute to the development of
CSU. Obesity and overweight were evaluated in
patients with CSU. A significant association was
demonstrated between heavyweight and older age
to disease onset. A trend to longer disease duration
was also observed in patients with higher BMI values. Obesity must be assessed and treated in CSU
patients, like in any other disease, but further studies
are necessary to consider it an excellent clinical
biomarker for disease duration [20].
&

More severe disease
No association with time to remission
IL-17, IL-31 and IL-33 levels
High levels associated with a more severe disease
High levels of IL-31 associated with severe pruritus
CRP levels
High levels associated with shorter duration of disease
High levels associated with disease activity

12% had antibodies against thyroid peroxidase
(anti-TPO). These patients had a more prolonged
disease when compared with negative anti-TPO
patients. However, no differences were observed
regarding disease severity when comparing patients
with a positive or negative anti-TPO. ASST and
APTS were also performed in these patients to assess
autoreactivity, with positive results in 70%. Both
tests were associated with disease severity (attacks
>4 days/week). No differences in time to remission
were observed in patients with positive skin tests
when compared with those with negative results [18].
Inflammatory cytokines can be potential biomarkers for disease severity in CSU. In a study with
51 CSU patients and 20 controls, patients with a
severe disease (based on UAS7) had higher IL-17 and
IL-33 levels when compared with those with mild
disease. Pruritus severity was also associated with
higher levels of IL-31. A better understanding of the
role of these cytokines in urticaria may provide the
rational for new treatment strategies [13].
C-reactive protein (CRP) is a sensitive marker of
inflammation. Data from 1253 patients were
Table 2. Biomarkers for response to treatment
Antihistamines
APSTþ associated with nonresponse
CRP high levels associated with nonresponse
Omalizumab
Anti-TPO not associated with response to treatment
IgE lower levels in nonresponders
IgE not associated with time to response
FceRI expression in basophils increased in responders and
predict fast response
Cyclosporine
IgE lower levels predict better response
ASSTþ associated with a better response

BIOMARKERS FOR RESPONSE TO
TREATMENT
Considering the significant role of mast cells in
urticaria physiopathology, reducing mast cells activation, as well as its mediators (e.g. histamine)
effects in target organs, have been the suggested
approach to treat CSU. Nonsedating modern H1antihistamines in standard or high doses are recommended as first and second line treatment for CSU
[1]. However, up to 50% of patients are refractory to
high doses of antihistamines and require other
drugs to achieve complete symptom control [21].
Positivity to APST and high levels of CRP are related
with an inadequate response to antihistamines
[18,19 ]. On the other hand, anti-TPO levels were
not associated with response to treatment [18].
Omalizumab is an anti-IgE monoclonal antibody that reduces the levels of free IgE and downregulates FceRI expression on basophils and mast
cells, showing efficacy and safety in refractory CSU
treatment. Potential mechanisms include reducing
the activity of IgG autoantibodies against IgE or its
high-affinity receptor in mast cells and basophils
and reducing IgE activity against autoantigens.
However, its mechanism of action in urticaria is
not entirely understood, as omalizumab is effective
despite the presence of autoreactive antibodies [21].
In order to investigate the ability of omalizumab
in inhibiting mast cell and basophil degranulation
induced by sera from CSU patients, Serrano-Candelas et al. selected CSU sera able to induce expression
of CD63 in mast cells and basophils from healthy
donors and treated them with different concentrations of omalizumab or human IgG as a control.
Despite its effect in preventing IgE binding to its
receptor, omalizumab was unable to inhibit CSU

1528-4050 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.

&

www.co-allergy.com

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

195

Outcome measures

patient sera-dependent cell degranulation. The
impact of in-vivo administration of omalizumab
on the activating capacity of sera was then evaluated
in patients participating in a placebo-controlled
randomized clinical trial. No changes in the activating capacity of sera on mast cells or basophils were
observed, and the clinical outcomes were similar
independently on the serum ability in cell activation. These data suggest that omalizumab efficacy
cannot be explained by the inhibition of sera activity in mast cells and basophils. Moreover, the capacity of CSU sera to activate basophils and mast cells is
not a good marker for predicting clinical response to
omalizumab [22].
On the other hand, there is increasing evidence
that total serum IgE can be used as a biomarker for
omalizumab response in CSU. Three recent studies
analyzed baseline IgE levels and response to omalizumab. It is noteworthy that the three studies considered a response to treatment based on the urticaria
activity score in 7 days (UAS7), as suggested by an
expert panel review [23]. In all studies, it was clear
that baseline IgE levels were lower in nonresponders
[24–26]. However, no differences were observed
when comparing IgE baseline levels in complete
(UAS7 of 0) and partial responders (minimum 30%
in UAS7 reduction) [25]. When stratifying patient’s
baseline IgE levels in quartiles, clinical response to
omalizumab differed significantly in another multicenter retrospective study. Patients with a serum IgE
higher than 168 IU/ml have an odds ratio of 13.81 for
a response when compared with patients with levels
of IgE below 15.2 IU/ml, suggesting that higher IgE
baseline levels predict a better response to omalizumab [27]. Interestingly, no differences in time to
response was observed when comparing patients
with normal or elevated IgE levels in a prospective
study with 93 CSU patients [28].
Baseline IgE levels and relapse after stopping
omalizumab were also analyzed. Nevertheless, here
the results are at odds. Marzano et al. in their retrospective study showed no correlation on IgE levels
and relapses within 2 months after drug withdrawal
and 3 months following drug withdrawal after a
second course of treatment. Differently, Ertas et al.
[28] showed that in complete responders (UAS 0),
the time to relapse was significantly shorter in
patients with IgE greater than 100 IU/ml when compared with those who have normal IgE levels.
Omalizumab prevents circulating IgE to bind on
its high-affinity receptors (FceRI) in mast cells and
basophils. Deza et al. demonstrated that baseline
expression of FceRI in CSU patient’s basophils was
higher than in healthy controls. Interesting, the
expression in omalizumab nonresponders was lower
than in responders. Moreover, clinical improvement
196

www.co-allergy.com

during therapy was associated with a reduction
in the FceRI expression and a positive correlation
between IgE levels and basophil FceRI expression
was observed. Lastly, these data suggest that baseline
FceRI expression in basophils could be used as a
predictor to treatment response in CSU patients,
with a 100% of sensitivity and 73.2% of specificity
[29 ]. In addition, data from the same group showed
a higher baseline basophil expression of FceRI in
patients that had an UAS7 6 or less during the first
4 weeks of treatment. Thus, FceRI expression in
basophils can be also a predictor of time to omalizumab response in CSU [30 ].
In a proof-of-concept study, a group of seven
antihistamines refractory CSU patients had their
basophil proteome examined. Results show that
all patient’s basophils are under stress, but the
response to stress is different accordingly to the
response to omalizumab. Responders overexpressed
intermediate filament proteins whereas nonresponders overexpressed proteins associated with catabolic processes, oxidative stress and unfolded
protein pathways. With these results, the authors
interrogate about possible differences in urticaria
mechanisms when comparing responders and nonresponders [31].
Regardless of its well known effects on total and
free IgE, there was a lack of data on the impact of
omalizumab treatment in other immunoglobulins
and inflammatory cells. Total baseline levels of
IgE, IgG, IgM and IgA, as well as blood eosinophil,
neutrophil, lymphocytes and platelets counts, were
compared with levels after a prospective 12-weektreatment of CSU patients with omalizumab or retrospectively in patients treated for a minimum of
3 months. No differences on immunoglobulin levels
were observed after omalizumab treatment, as well
as differences between complete or nonresponders.
Different groups reported a significant reduction in
neutrophils but different effects on eosinophil and
platelet numbers. Currently, neither of these parameters (immunoglobulin levels or blood cells count)
can be used to predict response to treatment [32,33].
The coagulation cascade is activated in CSU and
increased D-dimer levels are associated with disease
severity [34]. Omalizumab is effective in severe
refractory CSU, but whether D-dimer is a reliable
biomarker to response to treatment is still under
discussion, with recent studies showing divergent
results. Cugno et al. [25] observed that pretreatment
D-dimer levels were lower in nonresponders when
compared with partial and complete responders. In
opposition, Marzano et al. [24] reported no correlation of D-dimer levels and clinical response to
omalizumab, as well as any relation with relapse
after discontinuing the drug.
&

&

Volume 19  Number 3  June 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Advances in the pathogenesis in chronic urticaria Ensina et al.

Cyclosporine (CsA) is recommended for CSU
treatment when omalizumab fail or is contraindicated. Response to CsA is associated with lower IgE
levels, and the response is more effective (UAS 6) in
patients with a positive ASST. Both ASST and IgE
levels can be useful biomarkers to predict response
to CsA [35,36].

CONCLUSION
Urticaria mechanism is still not totally understood.
However, with the current knowledge is already
possible to suggest some useful biomarkers for disease activity, severity, duration and response to
treatment. With new insights into urticaria mechanisms, other potential biomarkers will come out to
be used in clinical practice.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.

REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
&
of special interest
&& of outstanding interest
1. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA2LEN/EDF/WAO
guideline for the definition, classification, diagnosis and management of
urticaria. Allergy 2018; 73:1393–1414.
2. Cherrez-Ojeda I, Robles-Velasco K, Bedoya-Riofrı́o P, et al. Checklist for a
complete chronic urticaria medical history: an easy tool. World Allergy Organ J
2017; 10:34.
3. Vietri J, Turner SJ, Tian H, et al. Effect of chronic urticaria on US patients:
analysis of the National Health and Wellness Survey. Ann Allergy Asthma
Immunol 2015; 115:306–311.
4. Balp M-M, Vietri J, Tian H, Isherwood G. The impact of chronic urticaria from
the patient’s perspective: a survey in five European Countries. Patient 2015;
8:551–558.
5. Balp M-M, da Silva NL, Vietri J, et al. The burden of chronic urticaria from
Brazilian patients’ perspective. Dermatol Ther (Heidelb) 2017; 69:1–11.
6. Dias GAC, Pires GV, Valle SORD, et al. Impact of chronic urticaria on the
quality of life of patients followed up at a university hospital. An Bras Dermatol
2016; 91:754–759.
7. Rauber MM, Pickert J, Holiangu L, et al. Functional and phenotypic analysis of
basophils allows determining distinct subtypes in patients with chronic
urticaria. Allergy 2017; 72:1904–1911.
8. Kolkhir P, Borzova E, Grattan C, et al. Autoimmune comorbidity in chronic
spontaneous urticaria: a systematic review. Autoimmun Rev 2017; 16:
1196–1208.
9. Ulambayar B, Chen Y-H, Ban G-Y, et al. Detection of circulating IgG autoantibody to FceRIa in sera from chronic spontaneous urticaria patients. J Microbiol Immunol Infec 2017. (in press).
10. Baioumy SA, Esawy MM, Shabana MA. Assessment of circulating FceRIa in
chronic spontaneous urticaria patients and its correlation with clinical and
immunological variables. Immunobiology 2018; 223:807–811.
11. Schmetzer O, Lakin E, Topal FA, et al. IL-24 is a common and specific
&&
autoantigen of IgE in patients with chronic spontaneous urticaria. J Allergy
Clin Immunol 2018; 142:876–882.
The article describes an autoallergen (IL-24) that helps to validate the type I
autoimmunity mechanism in CSU.

12. Chen T, Fu L-X, Sun Q-M, et al. Decreased interleukin-35 serum levels in
patients with chronic spontaneous urticaria. Ann Allergy Asthma Immunol
2018; 121:503–504.
13. Lin W, Zhou Q, Liu C, et al. Increased plasma IL-17, IL-31, and IL-33 levels in
chronic spontaneous urticaria. Sci Rep 2017; 7:17797.
14. Kasperska-Zaja˛c A, Damasiewicz-Bodzek A, Bieniek K, et al. Elevated
circulating heat shock protein 70 and its antibody concentrations in
chronic spontaneous urticaria. Int J Immunopathol Pharmacol 2018;
31:394632017750440.
15. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of
acute and chronic urticaria: 2014 update. J Allergy Clin Immunol 2014;
133:1270–1277.
16. Altrichter S, Hawro T, Liedtke M, et al. In chronic spontaneous urticaria, IgE
against staphylococcal enterotoxins is common and functional. Allergy 2018;
73:1497–1504.
17. Kolkhir P, André F, Church MK, et al. Potential blood biomarkers in chronic
spontaneous urticaria. Clin Exp Allergy 2016; 47:19–36.
18. Chanprapaph K, Iamsumang W, Wattanakrai P, Vachiramon V. Thyroid
autoimmunity and autoimmunity in chronic spontaneous urticaria linked to
disease severity, therapeutic response, and time to remission in patients with
chronic spontaneous urticaria. Biomed Res Int 2018; 2018:1–13.
19. Kolkhir P, Altrichter S, Hawro T, Maurer M. C-reactive protein is linked to
&
disease activity, impact, and response to treatment in patients with chronic
spontaneous urticaria. Allergy 2018; 73:940–948.
An important article supporting the use of CRP as a biomarker for CSU duration and
activity.
20. Zbiciak-Nylec M, Wcisło-Dziadecka D, Kasprzyk M, et al. Overweight and
obesity may play a role in the pathogenesis of chronic spontaneous urticaria.
Clin Exp Dermatol 2018; 43:525–528.
21. Kaplan AP. Chronic spontaneous urticaria: pathogenesis and treatment
considerations. Allergy Asthma Immunol Res 2017; 9:477–482.
22. Serrano-Candelas E, Martinez-Aranguren R, Vega O, et al. Omalizumab
efficacy in cases of chronic spontaneous urticaria is not explained by the
inhibition of sera activity in effector cells. Sci Rep 2017; 7:8985.
23. Ferrer M, Boccon-Gibod I, Gonçalo M, et al. Expert opinion: defining response
to omalizumab in patients with chronic spontaneous urticaria. Eur J Dermatol
2017; 27:455–463.
24. Marzano AV, Genovese G, Casazza G, et al. Predictors of response to
omalizumab and relapse in chronic spontaneous urticaria: a study of 470
patients. J Eur Acad Dermatol Venereol 2018. [Epub ahead of print]
25. Cugno M, Genovese G, Ferrucci S, et al. IgE and D-dimer baseline levels are
higher in responders than nonresponders to omalizumab in chronic spontaneous urticaria. Br J Dermatol 2018; 179:776–777.
26. Weller K, Ohanyan T, Hawro T, et al. Total IgE levels are linked to the response
of chronic spontaneous urticaria patients to omalizumab. Allergy 2018;
73:2406–2408.
27. Straesser MD, Oliver E, Palacios T, et al. Serum IgE as an immunological
marker to predict response to omalizumab treatment in symptomatic chronic
urticaria. J Allergy Clin Immunol Pract 2018; 6:1386.e1 –1388.e1.
28. Ertas R, Ozyurt K, Ozlu E, et al. Increased IgE levels are linked to faster relapse
in patients with omalizumab-discontinued chronic spontaneous urticaria. J
Allergy Clin Immunol 2017; 140:1749–1751.
29. Deza G, Bertolı́n-Colilla M, Pujol R, et al. Basophil FceRI expression in chronic
&
spontaneous urticaria: a potential immunological predictor of response to
omalizumab therapy. Acta Derm Venereol 2017; 97:698–704.
An important article supporting FceRI expression in basophils as a biomarker for
response to omalizumab in CSU.
30. Deza G, Bertolı́n-Colilla M, Sánchez S, et al. Basophil FceRI expression is
&
linked to time to omalizumab response in chronic spontaneous urticaria.
J Allergy Clin Immunol 2018; 141:2313–2316.
Another important article supporting FceRI expression in basophils as a biomarker
for response to omalizumab in CSU.
31. Stitt JM, Dzieciatkowska M, Edwards MG, et al. The basophil proteome in
chronic spontaneous urticaria distinguishes responders to omalizumab from
nonresponders. Clin Exp Allergy 2018; 48:898–901.
32. Çildağ S, ent€
urk T. The effect of omalizumab treatment on IgE and other
immunoglobulin levels in patients with chronic spontaneous urticaria and its
association with treatment response. Postepy Dermatol Alergol 2018;
35:516–519.
33. Acer E, Kaya Erdogan H, Y€
uksel Çanakçi N, Saracoglu ZN. The effect of
omalizumab on hematological and inflammatory parameters in patients with
chronic spontaneous urticaria. Cutan Ocul Toxicol 2018; 26:1–4.
34. Asero R. D-dimer: a biomarker for antihistamine-resistant chronic urticaria. J
Allergy Clin Immunol 2013; 132:983–986.
35. Santiago L, Ferreira B, Ramos L, Gonçalo M. IgE levels are negatively
correlated with clinical response to ciclosporin in chronic spontaneous
urticaria. Br J Dermatol 2018; 73:1393–1398.
36. Endo T, Toyoshima S, Kanegae K, et al. Identification of biomarkers for
predicting the response to cyclosporine A therapy in patients with chronic
spontaneous urticaria. Allergol Int 2018. [Epub ahead of print]

1528-4050 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.

www.co-allergy.com

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

197