Systemic Capillary Leak Syndrome: Report on 13 Patients With Special Focus on Course and Treatment

doi:10.1016/S0002-9343(97)00272-6

The American Journal of Medicine

Volume 103, Issue 6, December 1997, Pages 514-519

https://doi.org/10.1016/S0002-9343(97)00272-6 Get rights and content

Abstract

BACKGROUND: Systemic capillary leak syndrome (SCLS) is a rare condition characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse swelling, weight gain, and renal shut-down. From the first publication in 1960, only 34 cases have been reported.

OBJECTIVE: To collate enough patients to observe the natural history of the disease and evaluate the efficacy of empiric treatments.

DESIGN: Multicentric retrospective study.

RESULTS: Thirteen patients (6 women and 7 men) were collated with a mean follow-up of 6.4 years. Eight patients are still alive after a mean of 5.6 years (range 1 to 15). Three patients out of the 11 who were not lost to follow-up died; 1 during an attack and 2 because of a progression towards multiple myeloma.

CONCLUSIONS: Our series shows an improvement in the prognosis of SCLS due most likely to improved management during attacks. Some patients’ disease could evolve into a multiple myeloma. Treatment is still empiric and no prophylactic therapy, including terbutaline associated with aminophylline, has clearly proven its efficacy.

Section snippets

Design

The present series is based on a retrospective, cooperative survey of patient files from French departments of Internal Medicine, Nephrology, and Intensive Care Medicine. The patients were admitted over a 20-year period (from 1975 to 1995). Diagnosis of SCLS was made according to the following criteria: history of hypotensive shock with presence of a monoclonal component in the serum and transient hypoprotidemia or hypoalbuminemia with elevated hematocrit during a shock. Three cases have been

Patient 1

In November 1991, a white 49-year-old woman was admitted to an intensive care unit due to a shock following a flu-like illness of 2 days duration. On examination her systolic blood pressure was unmeasurable. In December 1993, she had another attack requiring resuscitation with intravenous fluid. Each episode began with the patient feeling anxious and irritable. Shocks were characterized by elevated hematocrit and decreased albumin serum level. Normal blood pressure was restored by intravenous

Discussion

We report a series of 13 patients with SCLS. The findings obtained in this series confirm and extend those previously reported in literature. First, SCLS appears to be a much more frequent disease than previously thought. Indeed since the first publication by Clarkson, only 34 cases have been published in the literature.[2]Our series adds 10 new cases, indicating that the real prevalence of the disease might have been underestimated. Most of these new cases occurred during the last 5 years;

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Cited by (135)

Autologous hematopoietic stem cell transplantation in Clarkson disease
2023, Journal of Allergy and Clinical Immunology: In Practice
Intravenous Immunoglobulins Tapering and Withdrawal in Systemic Capillary Leak Syndrome (Clarkson Disease)
2022, Journal of Allergy and Clinical Immunology: In Practice
The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown.
We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS.
We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy–associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal.
Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W– group). Cumulative probabilities of 10-year survival in W+ versus W– groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W– groups were 72% versus 58% (P = 0.3) and 2.5 (0.3–4) versus 1 (0–2) (P = .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model.
The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients.
Protein Electrophoresis, Serum Free Light Chain Assay and Other Biomarkers in Diagnosis and Monitoring of Monoclonal Protein Associated Disease
2022, Encyclopedia of Infection and Immunity
This article discusses electrophoretic patterns and methodologies, especially descriptions of the methods with some historical content, weaknesses of the techniques and exact recommended collection and procedural processes. Many electrophoretic patterns are presented as an introduction to those who are gaining familiarity with the techniques and as advanced information for practitioners. The basis of humeral immunology is discussed to improve the understanding of where, why and how monoclonal gammopathies develop. Methodological topics discussed include serum and urine electrophoresis and immunoelectrophoresis, nephelometric and turbidometric measurement, serum free light chain assays, cryoglobulins isolation and measurement, interference from circulating immune complexes and other interferences. Clinical topics discussed include multiple myeloma, including both active and asymptomatic (smoldering), monoclonal gammopathy of undetermined significance, amyloidosis, Waldenstrom macroglobulinemia, cryoglobulinemia, circulating immune complexes, and POEMS syndrome as well as other neurological conditions associated with monoclonal proteins. Criteria for diagnosis defined by the international Myeloma Working Group are discussed. There is also an over view of associated workup for diagnosing, monitoring progress and therapy and defining status of persons with or suspected of having monoclonal gammopathies, and some information on treatments to put the concepts in a more complete perspective. The article also focused on why these methods are implicit in diagnosing, monitoring, treating and defining status of these conditions.
Consider systemic capillary leak syndrome in monoclonal gammopathy with shock
2021, Annals of Medicine and Surgery
Citation Excerpt :
Cadherin internalization and actin fiber formation are evidence of a vascular stress state altering capillary permeability, vascular endotheal growth factor (VEGF) and angioprotein 2 were higher during seizures justifying that treatment by an angioprotein 2 inhibitor and intravenous immunoglogbulin significantly decreasing capillary permeability while the VEGF inhibitor (bevacizumab) exerted a minimal effect [4]. Since the first description of Clarkson's syndrome several treatments have been tried, initially beta mimetic treatment combined with theophylline was administered without consistent results, Recently, intra venous Immuno Globulin (IVIG) treatment for seizure prophylaxis at a dose of 2g/kg/month over 48 hours has reduced the frequency and severity of seizures and is recommended by the authors of this study of patients in the European registry [5,6]. In addition, IVIG treatment may be effective during attacks according to limited data [7].
The cappilary leacking syndrome is a very rare disease that can be idiopathic (clarkson syndrome) or secondary to other pathologys.
We report a case of 37-year-old women who was admitted in the emergency room for a hemodynamic shock of neither cardiac nor septic cause, and the patient wasn't presenting any bleeding. The investigations showed that the diagnosis was a Clarkson syndrome crisis and the patient was having supportive treatment containing fluid therapy, vasoactive drugs, and ECMO. And died after 48h of hospitalization.
the cappilary leacking syndrome is a very fatal affection, its physiopathologis remains unknown. It evoluate by crisis made by hypotension and anasarca, in severe cases it is presented as fatal hypovolemic schock. Biological investigations show hemoconcentration associated with hypoalbunemia which is pathognomonic of the disease. The treatment is essentially based on crisis treatment support by fluid therapy, vasoactives drugs, some practicien report the use of theophilyn for prevention but without any proven efficiency.
For all this reasons we are in the obligation of investing in fundamental studies to better understand this fatal disease.
Idiopathic systemic capillary leak syndrome: 2 cases with misleading presentation
2021, Revue de Medecine Interne
Le syndrome de fuite capillaire idiopathique (SFCI), ou syndrome de Clarkson, est rare et met brutalement en jeu le prognostic vital. Trois phases évolutives sont décrites. La phase prodromique est aspécifique, souvent sous la forme d’un syndrome pseudo-grippal. La phase d’état, marquée par une fuite capillaire majeure et un état de choc hypovolémique, fait la gravité de la maladie par la survenue rapide d’une défaillance multiviscérale (DMV). L’hypovolémie contraste avec les oedèmes, et l’hémoconcentration contraste avec l’hypoalbuminémie. La phase de résolution spontanée est marquée par la restauration des défaillances d’organes.
Nous rapportons deux cas de SFCI pris en charge en réanimation dont l’errance diagnostique initiale a probablement grevé le pronostic. La première patiente, âgée de 28 ans a d’abord été prise en charge pour une « polyglobulie ». Il s’agissait pourtant d’une hémoconcentration secondaire à une hypovolémie. Elle a présenté un arrêt cardiocirculatoire lors de la deuxième saignée avant de développer une DMV. Des immunoglobulines polyvalentes intraveineuses ont été prescrites. L’évolution a été favorable en réanimation. Le second patient, âgé de 57 ans, a d’abord été pris en charge pour une « myosite » (douleurs musculaires et rhabdomyolyse). Il s’agissait pourtant d’un syndrome de loges (œdème musculaire lié à la fuite capillaire). Un état de choc brutal évoluant vers une DMV conduisait au décès du patient en réanimation.
La physiopathologie du SFCI est inconnue et impliquerait une dysfonction endothéliale transitoire. Devant l’impossibilité de réaliser des essais contrôlés randomisés pour le traitement de cette pathologie exceptionnelle, les thérapeutiques symptomatiques (expansion volémique prudente, amines vasopressives) et spécifiques (aminophylline intraveineuse) restent empiriques et peu efficaces. Présentant des effets controversés voire délétères en phase de fuite, les immunoglobulines polyvalentes sont néanmoins bénéfiques en prophylaxie secondaire. Le diagnostic syndromique est difficile mais sa précocité est probablement l’élément clef permettant une prise en charge immédiate en réanimation, avant le stade des défaillances d’organe.
Idiopathic systemic capillary leak syndrome (ISCLS) also known as Clarkson syndrome is a rare and sudden life-threatening entity. Three consecutive phases are described. A first non-specific prodromal phase often manifests as “flu-like” symptoms and precedes capillary leak phase with major hypovolemic and distributive shock leading to serious and frequent multiorgan dysfunction syndrome (MODS). Severe hypovolemia contrasts with edema, and hemoconcentration with hypoalbuminemia. ISCLS is characterized by these two clinical and biological paradoxes. Subsequent recovery phase exhibits organ function restoration along with interstitial/intravascular volumes normalization. The latter occurs spontaneously and systematically in patients surviving from leak phase.
We report here two ISCLS cases admitted in intensive care unit (ICU) both enhancing initial misdiagnosis possibly lowering prognosis and outcome. Our first 28-year-old female patient was admitted for « polycythemia vera » although hemoconcentration was attributable to hypovolemia. She presented circulatory arrest during the second bloodletting session and complicated with MODS. In and out ICU favorable outcome was noted on intravenous immunoglobulin therapy. A second 57-year-old male patient was admitted in ICU for severe “myositis” (myalgia and rhabdomyolysis) although rectified diagnosis retained compartment syndrome (muscular severe edema following capillary leak). Rapid and refractory hypovolemic shock appeared with subsequent MODS leading to death.
ISCLS pathophysiology remains unknown but certainly implies transitory endothelial dysfunction. Impossibility of randomized controlled trial for this exceptional disease led to based-on-experience therapeutic guidelines implying symptomatic care (cardiac output surveillance, nephroprotection, prudent fluid intake, prudent vasoactive amine use) and specific therapies (intravenous aminophylline during severe flares). Although enhancing controversial and even deleterious effects during the acute phase, polyvalent immunoglobulins are effective for relapse prevention. Syndromic diagnosis is difficult, but its precocious finding constitutes a key-element in better outcome before organ failure.
Acitretin-induced capillary leak syndrome: Case report and literature review
2020, Annales de Dermatologie et de Venereologie
Les rétinoïdes sont d’utilisation courante en dermatologie. Leurs effets indésirables sont fréquents et rendent nécessaire une surveillance clinique et biologique. Nous rapportons l’observation d’un syndrome de fuite capillaire secondaire (SFCS) chez une patiente traitée par acitrétine et présentons une revue de la littérature sur les rétinoïdes systémiques et le SFCS.
Une patiente de 57 ans consultait pour l’apparition d’un pityriasis rubra pilaire de type I sévère. Un traitement par dermocorticoïdes d’activité forte, associé à un traitement systémique par acitrétine à la dose de 0,5 mg/kg/j était débuté. Au huitième jour de traitement apparaissaient de volumineux œdèmes, une prise de poids de 8 kg en 48 h et une hypotension artérielle. Le bilan biologique montrait une hypoalbuminémie et une hémoconcentration. Devant la triade hémoconcentration, hypoalbuminémie et hypotension et l’amélioration rapide à l’arrêt de l’acitrétine, un SFCS à l’acitrétine était évoqué.
Nous avons colligé au total 7 observations de SFCS aux rétinoïdes entre 1981 et 2018, incluant notre cas. L’indication des rétinoïdes correspondait à des maladies dermatologiques sévères, le délai d’apparition moyen était de 9,8 jours et celui du retour à la normale à l’arrêt du rétinoïde de 17 jours. Le syndrome de fuite capillaire est un syndrome clinicobiologique rare et sous-diagnostiqué, qui nécessite d’être reconnu pour éviter les prises en charge inadaptées potentiellement fatales. Il s’agit d’un effet indésirable rare des rétinoïdes utilisés en dermatologie, dont la physiopathologie reste méconnue.
Retinoids are widely used in dermatology. Adverse effects are frequent and require clinical and laboratory monitoring. Herein we report the case of a patient with secondary capillary leak syndrome (SCLS) associated with acitretin. We then present a review of the literature on systemic retinoids and SFCS.
A 57-year-old patient consulted following the onset of severe type I pityriasis rubra pilaris. Treatment was initiated comprising topical corticosteroids combined with acitretin at a dose of 0.5 mg/kg/day. On the eighth day, voluminous edema appeared, accompanied by weight gain of 8 kg in 48 h and hypotension. The laboratory assessment showed hypoalbuminemia and hemoconcentration. Acitretin-induced SCLS was diagnosed based on the triple signs of hemoconcentration, hypoalbuminemia and hypotension, as well as rapid improvement following discontinuation of acitretin.
We collected 7 published clinical cases between 1981 and 2018, including our own case report. Retinoids were indicated only in severe cutaneous diseases. The mean time to onset of SLCS is 9.8 days, with a return to normal 17 days after discontinuation of retinoids. Capillary leak syndrome is a rare and under-diagnosed clinical-laboratory syndrome that must be recognized in order to avoid potentially fatal inappropriate management. It is a rare adverse effect of retinoids used in dermatology and the pathophysiology remains unclear.

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^☆: This work was supported by Société Nationale Française de Médecine Interne, Société Française de Néphrologie, and Société Française de Réanimation.

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Clinical StudiesSystemic Capillary Leak Syndrome: Report on 13 Patients With Special Focus on Course and Treatment☆

Abstract

Section snippets

Design

Patient 1

Discussion

Am J Med.

Rev Med Interne.

Ann Fr Anesth Reanim.

Am J Med.

Lancet.

Le syndrome d’hyperperméabilité capillaire idiopathique

STV.

Choc cyclique par exagération de la perméabilité capillaire: responsabilité probable d’une immunoglobuline G

Presse Med.

Systemic capillary leak syndrome and monoclonal IgG gammopathy

Medicine.

The paraproteins in systemic capillary leak syndrome

Clin Exp Immunol.

Clinical Studies
Systemic Capillary Leak Syndrome: Report on 13 Patients With Special Focus on Course and Treatment☆