Coupled plasma filtration adsorption (CPFA) is an extracorporeal supportive therapy based on nonspecific adsorption of pro- and anti-inflammatory mediators combined with continuous renal replacement therapy. The main field of CPFA application is septic shock, and there are limited data about its efficacy in the treatment of other acute conditions characterized by a dysregulation in immune homeostasis. Capillary leak syndrome (CLS) defines a life-threatening condition sustained by hypercytokinemia and characterized by abrupt onset of increased capillary permeability leading to severe generalized edema and hypovolemic shock refractory to fluid administration. Therapy for CLS is not specific and, at present time, it consists in the use of steroids or intravenous immunoglobulins. We present the case of a 34-year-old woman who developed CLS superimposed to acute generalized exanthematous pustulosis after initiating therapy with hydroxychloroquine for undifferentiated connective tissue disease. CLS did not respond to steroids and intravenous immunoglobulins, while it was successfully treated with CPFA. This observation supports the possible role of CPFA in restoring a proper immunologic homeostasis not only in sepsis but also in other devastating conditions sustained by hypercytokinemia.

1.
Ronco C, Brendolan A, d’Intini V, Ricci Z, Wratten ML, Bellomo R. Coupled plasma filtration adsorption: rationale, technical development and early clinical experience.
Blood Purif
. 2003;21(6):409–16.
2.
La Manna G, Donati G. Coupled Plasma Filtration Adsorption: A Multipurpose Extracorporeal Detoxification Therapy.
Blood Purif
. 2018;46(3):228–38.
3.
Feldmeyer L, Heidemeyer K, Yawalkar N. Acute generalized exanthematous pustulosis: Pathogenesis, genetic background, clinical variants and therapy.
Int J Mol Sci
. 2016 Jul;17(8):E1214.
4.
Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP): A review and update.
J Am Acad Dermatol
. 2015 Nov;73(5):843–8.
5.
Britschgi M, Pichler WJ. Acute generalized exanthematous pustulosis, a clue to neutrophil-mediated inflammatory processes orchestrated by T cells.
Curr Opin Allergy Clin Immunol
. 2002 Aug;2(4):325–31.
6.
Alniemi DT, Wetter DA, Bridges AG, El-Azhary RA, Davis MD, Camilleri MJ, et al. Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013.
Int J Dermatol
. 2017 Apr;56(4):405–14.
7.
Siddall E, Khatri M, Radhakrishnan J. Capillary leak syndrome: etiologies, pathophysiology, and management.
Kidney Int
. 2017 Jul;92(1):37–46.
8.
Druey KM, Parikh SM. Idiopathic systemic capillary leak syndrome (Clarkson disease).
J Allergy Clin Immunol
. 2017 Sep;140(3):663–70.
9.
Lambert M, Launay D, Hachulla E, Morell-Dubois S, Soland V, Queyrel V, et al. High-dose intravenous immunoglobulins dramatically reverse systemic capillary leak syndrome. Crit Care Med. 2008 Jul;36(7):2184–7.
10.
Ronco C, Bonello M, Bordoni V, Ricci Z, D’Intini V, Bellomo R, et al. Extracorporeal therapies in non-renal disease: treatment of sepsis and the peak concentration hypothesis.
Blood Purif
. 2004;22(1):164–74.
11.
Tetta C, Bellomo R, Inguaggiato P, Wratten ML, Ronco C. Endotoxin and cytokine removal in sepsis. Ther Apher. 2002 Apr;6(2):109–15.
12.
Ankawi G, Neri M, Zhang J, Breglia A, Ricci Z, Ronco C. Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls.
Crit Care
. 2018 Oct;22(1):262.
13.
Schmid S, Kuechler PC, Britschgi M, Steiner UC, Yawalkar N, Limat A, et al. Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation.
Am J Pathol
. 2002 Dec;161(6):2079–86.
14.
Kakeda M, Schlapbach C, Danelon G, Tang MM, Cecchinato V, Yawalkar N, et al. Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis.
Arch Dermatol Res
. 2014 Dec;306(10):933–8.
15.
Navarini AA, Simpson MA, Borradori L, Yawalkar N, Schlapbach C. Homozygous missense mutation in IL36RN in generalized pustular dermatosis with intraoral involvement compatible with both AGEP and generalized pustular psoriasis.
JAMA Dermatol
. 2015 Apr;151(4):452–3.
16.
Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)—a clinical reaction pattern. J Cutan Pathol. 2001 Mar;28(3):113–9.
17.
Orime M. Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions.
J Immunol Res
. 2017;2017:6928363.
18.
Ledochowski S, Freichet M, Prieur C, Friggeri A, Lega JC. An uncommon cause of distributive shock: lessons from two consecutive cases of idiopathic systemic capillary leak syndrome (Clarkson’s disease).
Anaesth Crit Care Pain Med
. 2015 Aug;34(4):251–3.
19.
Kapoor P, Greipp PT, Schaefer EW, Mandrekar SJ, Kamal AH, Gonzalez-Paz NC, et al. Idiopathic systemic capillary leak syndrome (Clarkson’s disease): the Mayo clinic experience. Mayo Clin Proc. 2010 Oct;85(10):905–12.
20.
Xie Z, Chan E, Yin Y, Ghosh CC, Wisch L, Nelson C, et al. Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).
J Clin Cell Immunol
. 2014;5(02):1000213.
21.
Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8).
Blood
. 1999 Oct;94(7):2217–24.
22.
Dejana E, Tournier-Lasserve E, Weinstein BM. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications.
Dev Cell
. 2009 Feb;16(2):209–21.
23.
Corada M, Mariotti M, Thurston G, Smith K, Kunkel R, Brockhaus M, et al. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci USA. 1999 Aug;96(17):9815–20.
24.
De Pas T, Curigliano G, Franceschelli L, Catania C, Spaggiari L, de Braud F. Gemcitabine-induced systemic capillary leak syndrome. Ann Oncol. 2001 Nov;12(11):1651–2.
25.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome.
Blood
. 2014 Jul;124(2):188–95.
26.
Sheehan JR, Keating L, Chan A, Walden A. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression.
BMJ Case Rep
. 2013 Apr;2013:pii:bcr2013009048.
27.
El-Azhary RA, Wang MZ, Wentworth AB, Hickson LJ. Treatment of severe drug reactions by hemodialysis.
Int J Dermatol
. 2018 Feb;57(2):177–82.
28.
Pezzi M, Renda S, Giglio AM, Scozzafava AM, Tiburzi SP, Casella P, et al. The Use of Coupled Plasma Filtration Adsorption in Traumatic Rhabdomyolysis.
Case Rep Crit Care
. 2017;2017:5764961.
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.
You do not currently have access to this content.