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MEDLINE Abstracts: Treatment of Chronic Urticaria
Posted 09/16/2003
What's new concerning treatment of chronic urticaria? Find out in this
easy-to-navigate collection of recent MEDLINE abstracts compiled by the
editors at Medscape Allergy & Clinical Immunology.

Management of Chronic Urticaria. A Survey of Clinical Intentions of
Practice of Dermatologists, Allergologists and General Practitioners

Maurice-Tison S, Pouyanne J, Doutre MS
Ann Dermatol Venereol. 2003;130 Spec No 1:1S160-73

This report presents the results of a national study realized in June
and July 2002 to describe dermatologists, allergists, and general
practitioners' clinical intentions of practice in front of chronic
urticaria, before the consensus conference on this topic. A total of 75%
of general practitioners (112/148), 73% of dermatologists (131/180), and
90% of allergists (58/64) completed the interview by phone. Health
authorities and medical associations furnished the lists for drawing of
lots. General practitioners realize few diagnostic investigations and
prescribe in most cases antihistamines. In case of persistence, they
resort to specialists, dermatologists or allergists. Dermatologists and
allergists seemed to have similar practices for management of chronic
urticaria, even if allergists realize more allergy skin tests. Chronic
urticaria remains unexplained in about 60% of the observations. When an
aetiology was identified, it is a physical urticaria for allergists and
drug-induced urticaria for dermatologists. For all the physicians,
non-sedating and/or sedating anti-histamines are the principal
treatment, sometimes associated with others drugs, in case of
resistance. Most of the physicians perceived psychological factors as
important. Sometimes, they suggest a specific therapy. This
questionnaire survey will be done again some months after publication of
recommendations to appreciate its impact on physicians.

Management of Psychologic Factors in Chronic Urticaria. When and How?

Buffet M
Ann Dermatol Venereol. 2003;130 Spec No 1:1S145-59

Introduction: Chronic idiopathic urticaria (CIU) is a frequent disease
in which treatment is often disappointing. Psychological factors seem to
be frequently associated with it. In which cases should one consider
psychological treatment? And according to what modalities?
Method: This study was a review of the literature in search of articles
in both French and English concerning psychological factors associated
with chronic urticaria, either as responsible factors, or as aggravating
factors, or as a consequence of the urticaria, with the study of the
impact on the quality of life. We also studied articles ****yzing
various types of psychology-targeted treatments. We use a series of
keywords on following data banks: Medline (1970-2002), Embase, Pascal,
and Cochrane Library (period 1995-2002).
Results: Very few controlled studies were published. Various studies are
found reporting an association between stress, anxiety, or depressive
symptomatology and CIU, but none can assert a causality. Three
controlled, opened studies show significantly more anxiety and\or
depression in the chronic urticaria patients. Three studies ****yze the
psychopathological personalities of the patients with urticaria. Two
studies focus specifically on the impact of the CIU on the quality of
life. Various psychotropic drugs (mainly tricyclic antidepressants) have
been tested, mostly because of their anti-H1 activity. There is no study
on psychological support, psychotherapies, behavioral therapies,
technique of biofeedback, and group therapies. Particular attention is
focused on hypnosis and relaxation techniques because of the improvement
of the urticarial wheals reported in studies of cutaneous ability to
react in subcutaneous injections of histamine.
Conclusion: A complementary psychological treatment of patients
suffering from CIU seems necessary, because of the high frequency of
psychological symptoms. Published studies concern essentially the
prescription of psychotropic drugs and the use of therapies with
suggestion of relaxation under hypnosis. Prospective studies on the
impact of an adapted psychological treatment on the CIU evolution are
not available.

Treatment of Chronic Idiopathic Urticaria Unresponsive to Type 1
Antihistamines in Monotherapy

Mateus C
Ann Dermatol Venereol. 2003;130 Spec No 1:1S129-44

Treatment of CIU is a difficult and often frustrating problem for
physicians. Due to the lack of definitive medical the****utic programs
to relieve the symptoms and prevent from their recurrence, several
pharmacologic approaches to the management of CIU are proposed. The
chronic urticaria pharmacologic therapy is therefore fit to abrogate
effects of histamine and other mediators on cutaneous vasculature and
inflammatory cells that participate in the pathogenesis of the
urticaria. The most common approach is to avoid all aggravating factors
and to block histamine. The mainstay therapy is H1 antihistamines. A
significant number of patients may remain unresponsive even after an
increase in the dose or a change in the type of H1 antihistaminic drug.
In these cases, several therapies can be associated: combinations of H1
antihistamines, nonsedating one tablet (morning) and one sedating
(evening), this approach is very usual but no study has confirmed it
rational. The addition of an H2 antagonist to the previous treatment for
some patients may improve control of their symptoms; alternatively, the
tricyclic antidepressant, doxepin, is usually prescribed. The results of
other drugs reported in the literature are unpredictable, to include
them in a strategy therapy. The results with beta2-adrenergic agents,
nifedipine, ketotifen, leukotriene antagonists, and tranexamic acid are
variable and do not appear better than therapy with H1 antagonists. The
efficiency of danazol has to be confirmed by other controlled studies.
Warfarin, sulfasalazine, and ultraviolet radiation have been used
apparently successfully, but no controlled study has been published. If
the above treatments have failed then immunosuppresive therapies,
intravenous immunoglobulin, and plasmapheresis can be proposed for CIU.

Chronic Idiopathic Urticaria for the Generalist

Ortonne JP
Eur J Intern Med. 2003;14:148-157

Chronic idiopathic urticaria (CIU) manifests as frequently occurring,
short-lived wheals, surrounded by a bright-red flare, and often
accompanied by angioedema. The cause of CIU is undefined and its
diagnosis requires exclusion of other conditions with somewhat similar
symptoms. Recent evidence has indicated that immunoglobulin (Ig) G
autoantibodies directed against high-affinity IgE receptors
(FcepsilonRI) may be involved in the pathophysiology of CIU. Following
the release of mast cell or basophil-derived histamine, this mediator
binds to H1 and H2 receptors, leading to vasodilatation and increased
vascular permeability. Individuals with CIU may be unable to conduct
normal daily activities; therefore, prompt initiation of effective
treatment is essential. General management of patients should include
avoidance of substances likely to trigger or intensify episodes.
Treatment with antihistamines is the mainstay of pharmacotherapy for
CIU. Selection of antihistamine therapy for patients with CIU should be
based on the following key properties: (1) proven clinical efficacy in
providing a high rate of symptom improvement; (2) rapid onset of action
and a long-lasting response; and (3) an excellent safety profile and a
high degree of tolerability. The benefit of some second-generation
antihistamines is limited by sedation, drug-drug interactions, or a
variable the****utic response. The H(1)-receptor antagonist
desloratadine is a new, once-daily treatment option that is potent and
nonsedating, and has a low potential for drug-drug interactions.
Desloratadine has a rapid onset of action and has been shown to
effectively and safely reduce pruritus and the number and size of hives
in patients with CIU, leading to improvements in quality of life.

High-Dose Cetirizine: A Case Report

Nordness M, Zacharisen MC
Cutis. 2003;71:396

We report the case of a 46-year-old man who tolerated 50 mg per day of
cetirizine for the treatment of CIU. The patient denied any sedation or
somnolence and had no difficulty performing routine daily functions
including driving. He had tried other antihistamines, including
fexofenadine, loratadine, and hydroxyzine without improvement.

Chronic Urticaria: A Role for Newer Immunomodulatory Drugs?

Tedeschi A, Airaghi L, Lorini M, Asero R
Am J Clin Dermatol. 2003;4:297-305

Chronic urticaria is now recognized as an autoreactive disorder in a
substantial fraction of patients. A serologic mediator of whealing has
been demonstrated in 50% to 60% of patients with chronic urticaria; and
autoantibodies against the high-affinity IgE receptor or IgE have been
detected in about half of these patients. The demonstration that chronic
urticaria is frequently autoimmune has encouraged a more aggressive
the****utic approach, with the use of immunomodulatory drugs. A
step-by-step approach to the management of chronic urticaria is
proposed, based on our personal experience and review of current medical
literature, identified through Medline research and hand searching in
medical journals. The non- or low-sedating H1 receptor antagonists
(antihistamines), such as cetirizine, fexofenadine, loratadine,
mizolastine, and, more recently, levocetirizine, desloratadine, and
ebastine, represent the basic therapy for all chronic urticaria
patients. Older sedating antihistamines, such as hydroxyzine and
diphenhydramine, may be indicated if symptoms are severe, are associated
with angioedema, and if the patient is anxious and disturbed at night.
Corticosteroid therapy with prednisone or methylprednisolone can be
administered for a few days (7 to 14) if urticarial symptoms are not
controlled by antihistamines and a rapid clinical response is needed. In
cases of relapse after corticosteroid suspension, leukotriene receptor
antagonists, such as montelukast and zafirlukast, should be tried. In
our experience, remission of urticarial symptoms can be achieved in 20%
to 50% of chronic urticaria patients unresponsive to antihistamines
alone. When urticaria is unremitting and is not controlled by combined
therapy with antihistamines and leukotriene receptor antagonists,
prolonged corticosteroid therapy may be needed. Long-term corticosteroid
therapy should be administered at the lowest dose able to control
urticarial symptoms, in order to minimize adverse effects. In a few
patients, however, high-dose corticosteroid therapy may have to be
administered for long periods. In these patients, immunosuppressive
treatment with low-dose cyclosporine can be started. This type of
treatment has a corticosteroid-sparing effect and is also generally
effective in patients with severe, unremitting urticaria, but requires
careful monitoring of cyclosporine plasma concentration and possible
adverse effects. Other immunomodulating drugs that have been tried in
chronic urticaria patients include hydroxychloroquine, dapsone,
sulfasalazine, and methotrexate; but their efficacy has not been proven
in large controlled studies. Warfarin therapy may also be considered in
some patients with chronic urticaria and angioedema unresponsive to
antihistamines.

Efficacy and Safety of Desloratadine 5 mg Once Daily in the Treatment of
Chronic Idiopathic Urticaria: A Double-Blind, Randomized,
Placebo-Controlled Trial

Monroe E, Finn A, Patel P, Guerrero R, Ratner P, Bernstein D;
Desloratadine Urticaria Study Group
J Am Acad Dermatol. 2003;48:535-541

Background: CIU has a major impact on patient well-being. Antihistamines
are the first-line treatment for CIU; however, some cause sedation.
Objective: Our purpose was to study the efficacy and safety of
desloratadine, 5 mg, a new H1-receptor antagonist, in patients with
moderate to severe CIU.
Methods: This study was a randomized, double-blind, placebo-controlled,
parallel-group, multicenter trial of 6 weeks' duration.
Results: Compared with placebo, desloratadine significantly improved the
total CIU symptom score as well as pruritus, the number of hives, and
the size of the largest hive. Overall the****utic response and global
CIU status improved significantly with desloratadine; interference with
sleep was reduced and the performance of daily activities improved.
Statistically and clinically significant improvements were seen within
the first 24 hours of treatment and were sustained throughout the full
duration of the study. The incidence of adverse events, including
somnolence, was similar in the desloratadine and placebo groups.
Conclusion: Desloratadine is a well-tolerated and effective treatment of
CIU.

Aspirin Sensitivity and Urticaria

Grattan CE
Clin Exp Dermatol. 2003;28:123-127

The relationship of aspirin sensitivity to urticaria is complex. Aspirin
sensitivity can cause acute urticaria in some individuals, aggravate
pre-existing chronic urticaria in others, or, rarely, act as a cofactor
with food or exercise to provoke anaphylaxis. Individuals who react with
urticaria appear to come from a different population to those who react
with asthma, although there is some overlap. Aspirin-sensitive chronic
urticaria patients may also react adversely to some food additives. The
pharmacological mechanisms of aspirin-sensitive urticaria are not fully
understood but probably involve diversion of arachidonic acid metabolism
from prostaglandin to cysteinyl leukotriene formation leading to direct
effects on blood vessels and delayed mast cell degranulation with
release of histamine. Cross-reactivity amongst all nonsteroidal drugs is
common in aspirin-aggravated chronic urticaria, but appears not to occur
with selective cyclo-oxygenase 2 inhibitors.

Blood Basophil Numbers in Chronic Ordinary Urticaria and Healthy
Controls: Diurnal Variation, Influence of Loratadine and Prednisolone
and Relationship to Disease Activity

Grattan CE, Dawn G, Gibbs S, Francis DM
Clin Exp Allergy. 2003;33:337-341

Background: The basopenia of chronic urticaria relates to histamine
releasing autoantibodies in the serum of patients with autoimmune
urticaria. This reduction in circulating basophils may be due to active
recruitment into weals. If so, it might be expected that numbers in
blood would be reduced when urticaria is active and increased after
treatment. The primary aim of this study was to look at diurnal
variation of basophil numbers in patients with chronic ordinary
urticaria (not physical or vasculitic) in relation to disease activity,
and the effect of treatment with antihistamines and corticosteroids, and
to compare the results with healthy controls. A secondary aim was to
compare a standard manual counting method with automated basophil counts
and to look at numbers of other circulating leucocytes that might be
relevant to urticaria pathogenesis.
Methods: Manual basophil counts using a toluidine blue stain and
automated 5-part differentials (Coulter Gen. S) were performed at
4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six
women, age 24 to 63 years) and seven chronic urticaria patients (five
women, 24 to 50 years). All chronic urticaria patients had severe daily
or almost daily urticaria. Only one of six chronic urticaria sera showed
in vitro basophil histamine releasing activity. Counts were performed
without treatment, after a week of taking loratadine 10 mg daily and
after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg).
Daily urticarial activity scores (UAS) were derived from weal numbers
and itch, maximum 7.
Results: There was no significant overall diurnal variation of basophil
numbers in healthy controls or chronic urticaria patients. Mean (SE)
manually counted basophils were higher in healthy controls than chronic
urticaria (43.4/ microL (2.1) vs. 4.4 (0.8), P < .001). Basophil counts
were reduced in healthy controls on steroids (19.2 (1.9), P < .001), but
increased in chronic urticaria (8.9 (1.9), P < .001). Loratadine did not
influence them. UAS fell on treatment (3.3 [0.4] baseline, 1.4 [0.5] on
loratadine and 0.5 [0.2] on prednisolone with loratadine, P < .001).
There was a negative linear correlation between basophil numbers and UAS
in untreated chronic urticaria patients (P = .001, Spearman rank
correlation). Manual and automated basophil counts showed poor
agreement. Lymphocyte numbers were lower in chronic urticaria than
healthy controls. Neutrophils increased whereas lymphocytes and
eosinophils decreased in all subjects on prednisolone. They were
unaffected by loratadine.
Conclusion: The results are consistent with the hypothesis that
circulating basophils may be recruited from blood into urticarial weals
during disease activity. Automated counts are not suitable for assessing
basophil numbers in chronic urticaria. The relevance of reduced
lymphocyte numbers in chronic urticaria needs to be explored.

http://www.medscape.com/viewarticle/461039?mpid=18738