977 Stability of IgE Levels during Acute Asthma: Implications forInitiation of Omalizumab Therapy after the EmergencyDepartment Visit

C. J. Ahn1, B. M. Baumann2, R. F. Kysia3, M. S. Radeos4, K. Stiffler5,

C. A. Camargo, Jr, 1; 1Massachusetts General Hospital, Boston, MA,2Cooper University Hospital, Camden, NJ, 3Cook County Hospital,

Chicago, IL, 4Lincoln Medical and Mental Health Center, Bronx, NY,5Summa Health System, Akron, OH.

RATIONALE: Since serum IgE levels determine omalizumab eligibility

and dosage, we assessed potential variability of IgE levels during acute

asthma.

METHODS: Subjects were ages 18-54 years, and presented to the emer-

gency department (ED) with acute asthma. At the ED visit, we measured

serum IgE to common allergens to confirm allergic asthma. Serum total

IgE was measured at both the ED visit and a follow-up visit 4 weeks later.

RESULTS: The first 74 patients had a mean age of 37 years, 69% were

female, 85% were Black or Hispanic, and half were obese (median body

mass index 5 29.8 kg/m2). Only 41% of patients were on inhaled cortico-

steroids (ICS); no patient was on omalizumab. At the ED visit, 11% of pa-

tients had total IgE <30 IU/ml, 66% between 30-700, and 23% >700 (range:

723 to 5341). Most patients (76%) had�1 positive IgE antibody test to cat

(50%), dog (42%), D. farinae (49%), D. pteronyssinus (54%) or cockroach

(51%). Overall, 12 subjects (16%; 95%CI, 9-27%) were eligible at the ED

visit for omalizumab therapy (body weight 30-150 kg; on ICS; total IgE

30-700 IU/ml; positive allergy test). Among these 12 patients, total serum

IgE was minimally reduced at 4 weeks (median: 201 vs. 180 IU/ml) and all

patients remained eligible for omalizumab at the 4-week visit.

CONCLUSIONS: At least 16% of ED patients with acute asthma are

eligible for omalizumab therapy. For patients already on ICS with frequent

exacerbations, ED-initiated tests would facilitate initiation of omalizumab

at the post-ED follow-up visit.

Funding: Novartis

978 Prescribing of Fluticasone Propionate/Salmeterol Combinationsas Initial Therapy for Patients With Asthma in a Commercially-Insured Population

H. S. Friedman1, T. K. Wilcox2, G. Reardon3, S. Crespi4, B. P. Yawn5

1Analytic Solutions, LLC, New York, NY, 2United Biosource Corporation,

Bethesda, MD, 3Informagenics, LLC, Worthington, OH, 4Schering-Plough

Corporation, Kenilworth, NJ, 5Olmsted Medical Center, Rochester, MN.

RATIONALE: An FDA advisory states that long-acting beta2-agonists

(LABAs) should be prescribed only for patients not adequately controlled

on other asthma-controller medications (e.g., low- to medium-dose inhaled

corticosteroids) or whose disease severity clearly warrants initiation of

treatment with two maintenance therapies. This study examined whether

past prescribing of fluticasone propionate/salmeterol fixed combination

(FPS) adheres to current recommendations.

METHODS: This retrospective analysis examined a large commercial in-

surance database for patients starting therapy on FPS between October

2003-September 2005 (index date). Patients were excluded if they had

used FPS one year before index date, were <12 years, had any diagnosis

of COPD or pulmonary heart disease, or were not continuously enrolled

365 days before index date. Medical and pharmacy utilization was exam-

ined for 180 days prior to the index date (pre-index period). Patients were

identified as more-severe asthmatics if during the pre-index period they ei-

ther received �180 doses of short-acting beta2-agonists (SABAs), an oral

corticosteroid (OCS), an emergency department (ER) asthma visit with an

OCS prescription, or an asthma hospitalization.

RESULTS: Among 143,659 patients with new FPS claims, only 31% had

evidence of prior ICS monotherapy use or more-severe asthma: 5% used an

ICS, 16% had �180 doses of a SABA, 17% used an OCS, 1% had an ER

visit with an OCS prescription, and 1% were hospitalized. Sixty-nine per-

cent had not used an ICS or had milder asthma.

CONCLUSIONS: The majority of patients starting FPS therapy had no

evidence of either prior ICS use or more-severe asthma.

Funding: Schering-Plough Corporation

979 Management of Patients with Bronchial Asthma, Elevated IgEand Eosinophilia Including Patients with Churg StraussSyndrome

V. V. Chopyak1, G. O. Potomkina1, K. O. Lishchuk-Yakymovych1,

R. R. Holovyn1, I. V. DuBuske2, L. M. DuBuske2; 1Lviv National Medical

University, Lviv, UKRAINE, 2Immunology Research Institute of New

England, Gardner, MA.

RATIONALE: Careful assessment of patients with bronchial asthma (BA)

may identify the rare patient who has the primary systemic vasculitic con-

dition Churg Strauss syndrome (CSS) along with the more common situa-

tion of BA associated with elevated IgE levels and eosinophilia.

METHODS: A protocol was developed for management of patients seen

in the West Ukrainian Regional Medical Center of Clinical Immunology

and Allergology. During 2005 a variety of allergic disease were diagnosed

in 2602 representing 30.2% of patients who were evaluated using clinical

and immunological laboratory assessments.

RESULTS: Among the evaluated patients, IgE-dependent allergic dis-

eases was seen in 52.3% of these patients and IgE-independent diseases

in 47.7%. Among patients with allergic diseases, 27.4% were diagnosed

with BA, 53.1% of whom had IgE-dependent disease, and 46.9% of

whom had IgE-independent disease. In 15.1% of the patients with IgE-de-

pendent BA, eosinophilia was seen (the number of eosinophils normally

being within the limits of 600-1600 cells/mL). In 12 (1.7%) patients with

BA further pathologic examination revealed CSS. In all patients with per-

sistent IgE-dependent BA having moderate to severe persistent disease and

eosinophilia, complex therapy with fluticasone/salmeterol along with

cetirizine was used. All patients with CSS additionally received systemic

corticosteroids (methylprednisolone). All of the patients had closely

monitored treatment under the care of an allergy specialist physician for

one year. Clinical remission following treatment was found in 78.3% of pa-

tients with bronchial asthma, with reduction of the IgE level in 81.2% of

these patients and normalization of the eosinophil counts in 53.8% of these

patients. In 8 (66.6%) patients with CSS clinical remission was obtained,

while in 3 (25.0%) patients the CSS remained under only partial control

and in 1 case (8.3%) the CSS resulted in fatality.

CONCLUSIONS: Patients with BA, elevated IgE and eosinophilia need

supervision of their management by physicians who have expertise in

allergy and clinical immunology. Complex treatment with inhaled cor-

ticosteroids, long-acting beta 2-agonists, antihistamines, and systemic

corticosteroids is typically necessary for patients with CSS.

980 Reversible Pan-hypogammaglobulinemia Associated WithThe Antiepileptic Levetiracetam (keppra)

A. E. Azar1,2, Z. K. Ballas1,2; 1University of Iowa Hospitals and Clinics,

Iowa City, IA, 2Veterans Affairs Medical Center, Iowa City, IA.

RATIONALE: We describe here the first case report of reversible hypo-

gammaglobulinemia occurring while on treatment with the antiepileptic

agent levetiracetam.

METHODS: Case report.

RESULTS: A 19 year-old white male patient was found to have a brain

abscess caused by Streptococcus milleri. He was treated with intravenous

ceftriaxone, and was started on oral levetiracetam for seizure prophylaxis.

Immunoglobulin levels at presentation were: IgG 1058 (694-1618), IgA

229 (66-378), and IgM 110 (60-263) mg/dL. His brain abscess resolved,

but his immunoglobulin levels decreased progressively so that by 2 months

he had: IgG 374, IgA 36, and IgM 32 mg/dL. B, T, and NK cells were nu-

merically normal. In vitro T cell responses to mitogens, alloantigen, and re-

call antigens were normal. Levetiracetam was replaced by topiramate.

Immunoglobulin levels gradually increased and normalized 25 months

later. Secondary hypogammaglobulinemia has been described with the

use of several antiepileptic agents (carbamazepine, phenytoin, oxcarbaze-

pine, valproate, lamotrigine, and zonisamide), and antiinflammatory medi-

cations (gold, penicillamine, sulfasalazine, fenclofenac). It is not duration or

dose dependent, and may take up to 6 years to recover. The mechanisms of

hypogammaglobulinemia remain unclear. These agents do not share a sim-

ilar chemical structure that would suggest a common molecular mechanism.

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CONCLUSIONS: Hypogammaglobulinemia secondary to medications

should always be considered before making a diagnosis of primary immu-

nodeficiency, especially in patients receiving antiepileptic agents.

Levetiracetam should be added to the list of agents that could potentially

cause reversible hypogammaglobulinemia.

981 Efficacy of IGIV in Patients With IgG Subclass Deficiencyand/or Antibody Deficiency in a One-Year Open Label Study ofQuality of Life, Innate Immunity, and Correction of Subclass/Antibody Levels

C. A. Greenwell1, R. Mehta2, J. D. Hester3, G. V. Yamshchikov3, J. F.

Halsey3, N. I. Abdou1; 1Center for Rheumatic Disease, Allergy, and Im-

munology, Kansas City, MO, 2University of Missouri Kansas City School

of Medicine, Kansas City, MO, 3IBT Reference Lab, Lenexa, KS.

RATIONALE: Efficacy of prolonged IGIV therapy in patients with recur-

rent sinupulmonary infections, deficiencies in IgG subclass levels and/or

functional antibody (anti-Pneumococcal/Tetanus Toxoid) production has

not been thoroughly studied. Due to link between adaptive and innate im-

munity, key proteins and receptors of the innate immune system were

investigated.

METHODS: Ten adults were treated with monthly IGIV (Gamunex,

400 mg/kg) for twelve months and were followed for three months post-

therapy, and were given Quality of Life Questionnaires. Mannose-binding

lectin (MBL) serum concentration and genetic polymorphisms in MBL,

MASP-2, and the toll-like receptors (TLR) 2,4,5,9 were evalulated.

RESULTS: All patients showed marked improvement in quality of life

(p<0.001). Seven of the patients had their IgG subclass and functional

antibody levels increase to normal ranges. One patient required frequent

antibiotics, and had a significant MBL protein deficiency (<100 ng/ml).

Genetic analysis of common TLR and MASP-2 polymorphisms indicates

a significant deficiency in these key proteins is not likely.

CONCLUSIONS: IGIV therapy improved patient’s quality of life, correct-

ing IgG subclass and functional antibody deficiency in majority of patients.

Clinical significance and efficacy of IGIVand MBL deficiency as a co-factor

needs to be studied in a double blind cross-over study with a larger cohort.

Funding: Talecris Biotherapeutics

982 Why Are Patients Referred to A Non HIV AdultImmunodeficiency Clinic?

J. B. Hagan, R. S. Abraham, M. A. Park, G. W. Volcheck, D. E. Maddox,

J. H. Butterfield, J. T. C. Li; Mayo, Rochester, MN.

RATIONALE: Fifty thousand diagnosed cases of primary immunodefi-

ciency (PID) exist in the United States with 60% reported in adults. Yet,

the indications for referral to an adult PID clinic are not well established.

We reviewed the indications for physician referred patients to our adult PID

clinic.

METHODS: A retrospective review of the indications for referral to an

adult PID Clinic. Electronic patient records of active staff in the PID clinic

as of March 2006 were reviewed for major indications of referral in accor-

dance with the Mayo Institutional Review Board.

RESULTS: Two hundred fifty-three patients (male 91, female 162; median

age 51 with range 15-85) were referred for evaluation with each patient

having one or more stated indications for referral. Of these there were

300 major reasons for referral with 174 for previous immune findings or

diagnoses (non-specific immune findings, hypogammaglobulinemia, IgG

subclass deficiency, other specific immune finding, common variable hypo-

gammaglobulinemia, IgA deficiency, previous malignancy, IgM defi-

ciency, elevated total IgE, and rheumatologic disease); 97 for recurrent

infections (recurrent sinusitis, non-categorized infection, other specific

infection, recurrent pneumonias, and bronchiectasis); and 29 with other

non-characterized reasons.

CONCLUSIONS: Health care providers refer adult patients to immunol-

ogy specialists for a variety of concerns. This initial report of indications

may help the allergy/immunology community focus attention to specific

areas for research and education for adult PID patients.

Funding: Mayo Foundation

983 Autoimmune Lymphoproliferative Syndrome (ALPS) in aPatient with Common Variable Immunodeficiency (CVID):Fas Deficiency with Increased Apoptosis

M. B. Narra1, N. I. Abdou2; 1UMKC School of Medicine, Kansas City,

MO, 2Center for Rheumatic Disease, Allergy and Immunology, Saint

Luke’s Hospital, Kansas City, MO.

RATIONALE: ALPS is usually associated with hypergammaglobuline-

mia, defective apoptosis due to Fas deficiency. CVID is a disorder with

hypogammaglobulinemia, commonly associated with increased Fas

expression and increased spontaneous apoptosis. We report a case with

unique combination of panhypogammaglobulinemia and ALPS with Fas

deficiency but high spontaneous apoptosis.

METHODS: We describe a male patient diagnosed with CVID at age

10 years receiving monthly IgIV. The patient then developed ALPS at

age 21 manifested by persistent lymphadenopathy and hepatosplenomeg-

aly. Fas expression on freshly isolated lymphocytes was evaluated by im-

munofluorescence using polyclonal rabbit anti-Fas F(ab’)2 IgG antibody.

Apoptosis of cultured lymphocytes was quantitated by acidine orange

and ethidium bromide staining. Lymphocyte phenotypes were assayed

by flow cytometry.

RESULTS: Lymph node biopsies showed reactive hyperplasia without

malignancy. Double negative T lymphocytes (DNT, CD31CD4-CD8-)

were estimated to be 9%. Freshly isolated lymphocytes showed low Fas ex-

pression (3.6% patient; 11.2% normal control). Spontaneous apoptosis rate

was high (15% patient; 5% normal control). Addition of anti-Fas antibody

unexpectedly decreased apoptosis slightly in patient’s lymphocytes (from

15% to 12.5%) and as predicted, increased apoptosis in normal control

(from 5% to 10.5%).

CONCLUSIONS: ALPS can be associated with hypogammaglobuline-

mia and should be suspected in patients with CVID who develop chronic

lymphadenopathy with or without organomegaly. Testing for DNT cells

and Fas analysis should be considered. The increased spontaneous apopto-

sis rate with Fas deficiency observed in our patient could indicate the

involvement of a Fas-independent pathway in CVID.

984 A Pilot Study of Quality of Life, Mood, Sleepiness and Fatiguein Patients with Primary Immunodeficiency Receiving IVIG

A. S. Kanani, R. R. Schellenberg, D. F. Stark; University of British

Columbia, Vancouver, BC, CANADA.

RATIONALE: The objective of this pilot study is to assess quality of life

by measuring the responsiveness of the SF-36 health survey, the Profile of

Mood States (POMS), the Epworth Sleepiness Scale (ESS) and the Sleep

Questionnaire to changes in serum IgG levels in patients with hypogamma-

globulinemia receiving IVIG.

METHODS: This is a prospective, open, uncontrolled pilot study.

Participants are adults with a diagnosis of common variable immunodefi-

ciency or X-linked agammaglobulinemia. They are blinded to the study ob-

jective. Questionnaires were completed 10 days post IVIG infusion and on

the day of infusion. Serum IgG levels were obtained at day 10 post infusion

and on the day of infusion (trough levels). Data was obtained from three

infusion cycles. Questionnaire results were correlated with IgG levels.

RESULTS: Fourteen subjects completed the study.

POMS: Fatigue (p50.02), tension (p50.03), and vigor (p50.04) improved

from trough to day 10.

SF-36: Energy/fatigue (p < 0.01) and Role limitations due to physical

health problems (p<0.01) improved from trough to day 10.

ESS score was significantly lower 10 days post infusion than at trough

(p50.04).

Sleep Questionnaire: No significant change from trough to day 10.

The mean change from trough to day 10 was 1.8 6 1.2 g/l, representing an

increase of 21%.

CONCLUSIONS: All scales appear to be moving in the expected direc-

tion. The selected scales do appear to be sensitive to change over the period

from trough to day 10. A larger sample size will be needed to better estab-

lish their sensitivities to change.

Funding: Bayer Health Care

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