Successful Treatment of Acquired Angioedema Using B

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Successful Treatment of Acquired Angioedema Using B-lymphocyte Depletion Therapy
Chang Na, MD, David Podell, MD, Christopher Randolph, David Dreyfus, Denise Kearney.
Yale Primary Care Program, Waterbury, CT1,2, Allergy, Asthma & Immunology, Waterbury, CT3,4,5
 Learning Objectives
Identify clinical manifestations of acquired C1
inhibitor (C1-INH) deficiency
Learn about the immunobiology underlying
acquired C1-INH deficiency
Make treatment decisions based on mechanism
of disease and the latest literature data
 Case Description Continued
 Discussion
 Discussion Continued
Patient B: A 37 year old woman with Crohn’s
disease and allergic asthma, presented with
angioedema associated with wheezing and urticaria.
Acquired C1-INH deficiency is a rare condition which
results in recurrent angioedema.
Rituximab has been effective as adjunctive
treatment of LPD, in particular B-cell lymphomas.
Even though there was no associated LPD in our
patients, they were successfully treated with B-
Laboratory tests showed elevated IgE levels and
positive aeroallergen skin testing. A hematologic
evaluation showed no evidence of lymphoma.
Patient C: A 41 year old
woman with myasthenia
gravis and antiphospholipids syndrome,
presented with
angioedema and
associated bowel and
laryngeal edema requiring
intubation.
 Case Description
Patient A: A 38 year old woman presented with
seropositive deforming erosive rheumatoid arthritis
(RA) and angioedema associated with acquired
C1-INH deficiency.
Laboratory tests showed decreased C1q, C3, C4,
and Ch50, worsening anemia, and elevated ESR.
She had a normal CT chest/abdomen/pelvis,
normal SPEP, and flow cytometry that showed
decreased CD4 and CD8 T cells but otherwise
normal lymphoid phenotype.
Advanced rheumatoid
arthritis with fusion of the
carpal bones (yellow
arrow). Metacarpal
phalangeal joint
subluxation (blue arrow).
Thickened ascending colon
The condition is characterized by reduced C1-INH
level or function, hyperactivation of the classical
complement pathway, and bradykinin mediated
recurrent angioedema.
Acquired C1-INH deficiency had been reported in
association with lymphoproliferative disease (LPD)
and autoimmune disorders.
The discovery of an auto-antibody IgG against C1INH in patients with angioedema demonstrates that an
auto-antibody mechanism may cause acquired C1INH deficiency.
Laboratory tests
showed low C1q, C2, C3,
C4 and anti-C1q antibody.
 Clinical Course
Rituximab appears to work by eliminating the
clonal B lymphocyte population expressing a
clonal Immunoglobulin G binding to C1 INH.
Anti-TNF agents such as adalizumab deplete
B lymphocytes via effects on follicular dendritic
cells and disruption of germinal center formation
and maintenance.
B-lymphocyte depletion with humanized
monoclonal antibodies such as rituximab or
adalizumab appears to be an effective, long
lasting therapy for acquired angioedema
associated with a variety of autoimmune
syndromes.
 Learning Points
After failure of other therapy including etanercept
and corticosteroids (A), xolair (B), and kallekrein
antagonist and corticosteroids (C), all three patients
responded with complete remission of symptoms
after B-lymphocyte depletion therapy with rituximab
(A, C) or adalizumab (B).
The patients have been symptom free for 5 years,
3 years and 6 months thus far.
lymphocyte depletion for acquired angioedema.
C1-INH deficiency is a rare condition resulting
in recurrent angioedema episodes.
A lymphoproliferative autoimmune mechanism
may cause acquired C1-INH deficiency.
B lymphocytes appear to play a key part in the
mechanism of action of acquired angioedema in a
variety of autoimmune syndromes.
Our cases highlight that B-lymphocyte depletion
may be an effective treatment for acquired C1-INH
deficiency
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