successful treatment of 103 attacks of hereditary hngioedema (hae) with bradykinin b2 receptor...

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393 Neutrophilic Predominant Urticaria is Associated with More Resistance 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, for Acute 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 Hereditary Hngioedema (HAE) with Bradykinin B2 Receptor Antagonist Icatibant A. Malbran; Hospital Brita ´nico 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 Patients in Lithuania A. Blaziene 1 , A. Chomiciene 1 , J. Tursaite 1 , L. M. DuBuske 2 ; 1 Vilnius University Hospital, Vilnius, LITHUANIA, 2 Immunology 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. J ALLERGY CLIN IMMUNOL FEBRUARY 2008 S102 Abstracts SUNDAY

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Page 1: Successful Treatment of 103 Attacks of Hereditary Hngioedema (HAE) with Bradykinin B2 Receptor Antagonist Icatibant

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.