successful treatment of 103 attacks of hereditary hngioedema (hae) with bradykinin b2 receptor...
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J ALLERGY CLIN IMMUNOL
FEBRUARY 2008
S102 Abstracts
SU
ND
AY
393 Neutrophilic Predominant Urticaria is Associated with MoreResistance to Treatment with Antihistamines
B. Kim, A. Fiorillo, L. Fonacier; Winthrop University Hospital, Mineola,
NY.
RATIONALE: The polymorphonuclear predominant urticaria character-
ized by predominant neutrophilic and eosinophilic dermal infiltrate, tend
not to respond to antihistamines alone. Our study is designed to investigate
if histological findings on biopsy are associated with difficulty to treat
chronic urticaria (CU).
METHODS: This is a retrospective chart review of 43 CU patients (33
females and 10 males) who had skin biopsies done from 2001-2006.
Biopsies were taken from urticarial lesions with 4 mm diameter punch.
From the histological report, biopsies were classified as neutrophilic,
eosinophilic, combined neutrophilic and eosinophilic or lymphocytic
urticaria if predominant cells are neutrophils, eosinophils, combined or
lymphocytes respectively. For each group, treatment was reviewed to
determine which medications was required for improvement.
RESULTS: Of 43 patients with skin biopsies, 5 had predominant
neutrophils, 11 had predominant eosinophils, 9 had combined neutrophil-
s&eosinophils, 12 had predominant lymphocytes, and 6 had no predom-
inant cells. 71% of the patients with neutrophilic urticaria (NU) with or
without eosinophils required steroid or other immunomodulating agents as
compared with only 18% of the eosinophilic urticaria (EU) patients (p 5
0.0154), 58% of the lymphocytic urticaria patients, and 33% of patients
with no predominant cell infiltrate required steroid or immunomodulating
agents.
CONCLUSIONS: Our study indicates that a majority of patients with NU,
with or without eosinophils are likely to receive prednisone or immuno-
modulating agent, as compared to patients with EU, who are usually
responsive to antihistamines alone. Although most patients with CU are
treated based on clinical symptoms, our data show that skin biopsy helps to
identify more resistant cases that may require more aggressive treatment.
394 Icatibant, a New Bradykinin B2 Receptor Antagonist, forAcute Hereditary Angioedema Attacks
A. Reshef, I. Liebovich; Sheba Medical Center, Tel Hashomer, ISRAEL.
RATIONALE: We present our recent experience with Icatibant, a
selective bradykinin B2 receptor antagonist, for treatment of acute attacks
of hereditary angioedema (HAE).
METHODS: We administered Icatibant (30 mg subcutaneously) to 6
patients on 47 separate occasions. Selection criteria were: history of
clinical angioedema, documented low levels of functional or antigenic C1-
Inhibitor, or both. Icatibant was administered within 4-5 hours of onset of
an acute attack. Visual Analog Scale (VAS) of 0 to 100 mm was used by the
patient to assess the intensity of each key symptom: peripheral, facial,
laryngeal edema, pain and nausea. Severity of symptoms was recorded in a
personal diary at predetermined time points, until the symptoms fully
resolved, or at least 5 days after every treatment. The patients recorded the
time point when first symptom improvement was noticed.
RESULTS: Patient evaluation of the average onset of first symptom relief
for abdominal pain (N 5 25) was 40.6 minutes (SD 18.36, range: 19-90),
and for cutaneous and genital edema (N 5 25): 58 minutes (SD 26.5, range
15-150). 50% reduction of abdominal pain, nausea and peripheral edema
was obtained after 80, 70 and 165 minutes, respectively. Apart from local
pain at the injection site (abdominal skin) no significant early or late
adverse reactions were observed. No additional rescue medications were
needed during Icatibant treatment.
CONCLUSIONS: Icatibant is effective in abrogating ongoing angioe-
dema exacerbations, resulting in rapid onset of symptom relief, particularly
during abdominal and laryngeal attacks. The treatment is well tolerated and
leads to a good response in all the patients we treated so far.
Funding: Jerini, Germany
395 Successful Treatment of 103 Attacks of HereditaryHngioedema (HAE) with Bradykinin B2 Receptor AntagonistIcatibant
A. Malbran; Hospital Britanico de Buenos Aires, Buenos Aires,
ARGENTINA.
RATIONALE: Bradykinin, via its B2 receptor, is the most important
mediator of HAE attacks. Icatibant is a highly specific antagonist for the B2
receptor and has been previously shown to be effective in the treatment of
HAE attacks.
METHODS: In a subset of an open-label extension phase of the pivotal
study FAST-1 103 moderate to severe HAE attacks in 19 patients (mean 5.4
attacks/patient, range 1-15) were treated subcutaneously with 30 mg
Icatibant. Time to first symptom improvement and symptom severity
measured by a visual analog scale (VAS) were recorded.
RESULTS: Fifty abdominal, 35 cutaneous, 10 abdominal/cutaneous, 6
laryngeal/cutaneous and 2 laryngeal attacks were analyzed. Time to first
symptom improvement was 40.4 6 35.3 minutes for all attacks. For
abdominal pain timepoint of symptom relief was 20.2 6 10.4 minutes (n 5
60); for cutaneous edema it was 69.2 6 40.6 (n 5 45) and for laryngeal
symptoms 62 6 49 minutes (n 5 8). In one attack (1%), a second Icatibant
dose was administered for insufficient response at 6 hr. Thirteen attacks
(12.7%) worsened within 48 hrs after treatment, six (5.8%) were success-
fully treated with a second dose of Icatibant and 7 resolved spontaneously
without further treatment.
Patients had an abdominal pain VAS score of 55.7 6 20.2 mm (n 5 50)
before treatment vs 23.7 6 12.5 mm (n 5 50) one hour after treatment, p <
0.001.
Adverse events were limited to mild injection site reactions (pruritus and
delayed local pain) which resolved spontaneously. No systemic adverse
events were observed.
CONCLUSIONS: HAE attacks were successfully treated with Icatibant
with rapid onset of symptom relief. Icatibant proved safe and was well
tolerated.
396 Autoimmune Disease and Chronic Urticaria in Adult Patientsin Lithuania
A. Blaziene1, A. Chomiciene1, J. Tursaite1, L. M. DuBuske2; 1Vilnius
University Hospital, Vilnius, LITHUANIA, 2Immunology Research Insti-
tute of New England, Gardner, MA.
RATIONALE: This study investigates the causes of chronic urticaria
(CU) in adults referred to our department in Vilnius, Lithuania.
METHODS: 101 patients with CU were studied (82 females, 19 males),
mean age 43.7 6 14.5 years old. Assessment included skin prick tests
(SPT), total serum IgE, specific food IgE, complete blood count, erythro-
cyte sedimentation rate (ESR), total serum IgA/IgM/IgG levels, autologous
serum skin tests (ASST) and Helicobacter pylori urease tests. Antinuclear
antibodies (ANA) were assessed if autoimmune disease was suspected.
Autoimmune thyroiditis was diagnosed by thyroid peroxidase antibodies
(TPO).
RESULTS: Increased IgE levels were found in 31 (30.7%) patients, 5 of
whom had a positive SPT to inhalant allergens. Specific IgE to food
allergens in patients with elevated IgE were negative. Elevated ESR was in
2 patients, one with SLE, and one with a dental infection. Total IgA, IgG,
IgM levels were unremarkable. 8 (7.9%) patients had positive Helicobacter
pylori tests. Positive antinuclear antibodies were found in 4 patients
including 1 with SLE, 1 positive on ASST, and 2 with autoimmune
thyroiditis. Elevated TPO were found in 30 (29.7%) patients only 10 of
whom had impaired thyroid function. 33 (32.7%) patients had positive
ASST, 6 (19.4%) with increased IgE (only one atopic) and 14 (46.6%)
patients with autoimmune thyroiditis. Sensitivity to NSAIDs occurred in 9
(8.9%) patients, 4 (44.4%) with positive ASST.
CONCLUSIONS: The most common cause of CU was autoimmunity.
About one-third of CU patients had positive ASST or autoimmune
thyroiditis.