Abstract
Castleman disease is non-clonal lymphoproliferative disorders defined by hypertrophy of lymph nodes. The multicentric form (MCD), in which multiple lymph node stations are involved, is not associated with HHV8 infection, but considered idiopathic, although IL-6 appears to play a central role in its pathogenesis. Here, we report the case of a patient who presented with mixed autoimmune hemolytic anemia (AIHA) and adenopathy that was very challenging to diagnose due to very low values of hemoglobin and refractoriness of obtaining any improvement of AIHA with standard first and second lines of therapy (steroids, rituximab, immunoglobulin, erythropoietin, and cyclosporine). When we safely proceeded to lymph node biopsy, a diagnosis of MCD was established. This permitted the treatment with siltuximab, an anti-IL-6 monoclonal antibody. After only 1 week, hemoglobin raised and he was discharged. After 1 year, he was still in remission. This case underlines the challenges in diagnosis of MCD, and the first case of response to siltuximab after the failure of rituximab to relieve mixed AIHA.
Journal Section:
Anticancer Section / Case Report
References
1.
Dispenzieri
A
, Fajgenbaum
DC
. Overview of castleman disease
. Blood
. 2020
;135
(16
):1353
–64
.2.
Jiang
JP
, Shen
XF
, Du
JF
, Guan
WX
. A retrospective study of 34 patients with unicentric and multicentric castleman’s disease: experience from a single institution
. Oncol Lett
. 2018
;15
:2407
–12
.3.
Yu
JY
, Oh
IJ
, Kim
KS
, Kim
YI
, Lim
SC
, Kim
YC
et al. Castleman’s disease presenting as a tracheal mass
. Ann Thorac Surg
. 2014
;97
(5
):1798
–800
.4.
van Rhee
F
, Voorhees
P
, Dispenzieri
A
, Fosså
A
, Srkalovic
G
, Ide
M
et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease
. Blood
. 2018
;132
:2115
–24
.5.
Cronin
DMP
, Warnke
RA
. Castleman disease: an update on classification and the spectrum of associated lesions
. Adv Anat Pathol
. 2009
;16
(4
):236
–46
.6.
Soumerai
JD
, Sohani
AR
, Abramson
JS
. Diagnosis and management of Castleman disease
. Cancer Control
. 2014
;21
:266
–78
.7.
Fajgenbaum
DC
, Uldrick
TS
, Bagg
A
, Frank
D
, Wu
D
, Srkalovic
G
et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease
. Blood
. 2017
;129
(12
):1646
–57
.8.
Pierson
SK
, Stonestrom
AJ
, Ruth
JR
. Quantification of plasma proteins from idiopathic multicentric castleman disease flares and remissions reveals “chemokine storm” and separates clinical subtypes
. Blood
. 2017
;130
:3592
.9.
Palestro
G
, Turrini
F
, Pagano
M
, Chiusa
L
. Castleman’s disease
. Adv Clin Path
. 1999
3
1–2
11
22
.10.
Parravicini
C
, Corbellino
M
, Paulli
M
, Magrini
U
, Lazzarino
M
, Moore
PS
et al. Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman’s disease
. Am J Pathol
. 1997
;151
:1517
–22
.11.
Tabata
S
, Higuchi
T
, Tatsukawa
S
, Narimatsu
K
, Takeo
H
, Matsukuma
S
et al. Idiopathic multicentric castleman disease with autoimmune hemolytic anemia and production of anti-drug Antibody against Tocilizumab
. Intern Med
. 2019
;58
:3313
–8
.12.
Sun
DP
, Chen
WM
, Wang
L
, Wang
Z
, Liang
JH
, Zhu
HY
et al. Clinical characteristics and immunological abnormalities of Castleman disease complicated with autoimmune diseases
. J Cancer Res Clin Oncol
. 2021
;147
(7
):2107
–15
.13.
Ocio
EM
, Sanchez-Guijo
FM
, Diez-Campelo
M
. Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena
. Am J Hematol
. 2005
;78
:302
–5
.14.
Shahani
L
. Castleman’s disease in a patient with melanoma: the role of VEGF
. BMJ Case Rep
. 2012
2012
bcr0720114519
.15.
Liu
AY
, Nabel
CS
, Finkelman
BS
, Ruth
JR
, Kurzrock
R
, van Rhee
F
et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
. Lancet Haematol
. 2016
;3
(4
):e163
–75
.16.
Sudha Reddy
VR
, Samayam
P
, Ravichander
B
, Bai
U
. Autoimmune hemolytic anemia: mixed type - a case report
. Indian J Hematol Blood Transfus
. 2011
;27
(2
):107
–10
.17.
Webster
D
, Ritchie
B
, Mant
MJ
. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies
. Am J Hematol
. 2004
;75
(4
):258
–9
.18.
Marcelin
A-G
, Aaron
L
, Mateus
C
, Gyan
E
, Gorin
I
, Viard
JP
et al. Rituximab therapy for HIV-associated Castleman disease
. Blood
. 2003
;102
(8
):2786
–8
.19.
Berentsen
S
, Barcellini
W
. Autoimmune hemolytic anemias
. N Engl J Med
. 2021
;385
:1407
–19
.20.
Bower
M
, Newsom-Davis
T
, Naresh
K
, Merchant
S
, Lee
B
, Gazzard
B
et al. Clinical features and outcome in HIV-associated multicentric castleman’s disease
. J Clin Oncol
. 2011
;29
(18
):2481
–6
.21.
Pria
AD
, Pinato
D
, Roe
J
, Naresh
K
, Nelson
M
, Bower
M
. Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients
. Blood
. 2017
;129
(15
):2143
–7
.22.
Dong
Y
, Zhang
L
, Nong
L
, Wang
L
, Liang
Z
, Zhou
D
et al. Effectiveness of rituximab-containing treatment regimens in idiopathic multicentric Castleman disease
. Ann Hematol
. 2018
;97
(9
):1641
–7
.23.
van Rhee
F
, Wong
RS
, Munshi
N
, Rossi
JF
, Ke
XY
, Fosså
A
et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial
. Lancet Oncol
. 2014
;15
(9
):966
–74
.24.
van Rhee
F
, Casper
C
, Voorhees
PM
. Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials
. Lancet Haematol
. 2020
;7
:e209
17
.25.
Casper
C
, Chaturvedi
S
, Munshi
N
, Wong
R
, Qi
M
, Schaffer
M
et al. Analysis of inflammatory and anemia-related biomarkers in a randomized, double-blind, placebo-controlled study of siltuximab (anti-IL6 monoclonal antibody) in patients with multicentric castleman disease
. Clin Cancer Res
. 2015
;21
:4294
–304
.26.
Iskandar
A
, Hwang
A
, Dasanu
CA
. Severe warm-antibody autoimmune hemolytic anemia due to multicentric Castleman disease: responding to rituximab
. J Oncol Pharm Pract
. 2019
;25
(8
):2016
–8
.27.
Röth
A
, Barcellini
W
, D’Sa
S
, Miyakawa
Y
, Broome
CM
, Michel
M
et al. Sutimlimab in cold agglutinin disease
. N Engl J Med
. 2021
;384
(14
):1323
–34
.© 2023 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2023
You do not currently have access to this content.
