Successful Treatment of Acquired Angioedema Using B
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Transcript Successful Treatment of Acquired Angioedema Using B
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