Systemic capillary leak syndrome complicated by severe rhabdomyolysis

Case Report

Systemic capillary leak syndrome complicated bysevere rhabdomyolysis: A case report with reviewof literature

Sanjay Bhaumik a,*, Narayan Banerjee b

a Senior Consultant Neurologist, Apollo-Gleneagles Hospitals, Kolkata 700 054, Indiab Senior Consultant Internal Medicine, Apollo-Gleneagles Hospitals, Kolkata 700 054, India

a r t i c l e i n f o

Article history:

Received 2 August 2013

Accepted 7 August 2013

Available online xxx

Keywords:

Systemic capillary leakage

Myonecrosis

Hypoxemia

a b s t r a c t

Idiopathic systemic capillary leak syndrome is characterized by episodes of increased

capillary permeability resulting in severe hypovolemic shock, hem concentration and

hypoalbuminemia. Rarely, patient may develop compartment syndrome due to increased

interstitial fluid resulting severe myonecrosis. Here, we are reporting a case with review of

therapeutic aspects of this rare syndrome.

Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.

Key messages:

Idiopathic systemic capillary leak syndrome also known as

Clarkson’s disease is a potentially fatal disorder. Prompt insti-

tution of appropriate therapy as outlined here can reduce the

morbidity and prevent complication. A number of factors,

including under recognition in the medical community and

rarity of the syndrome, have precluded analysis by rational

clinical studies that are necessary to determine more targeted

and adequate therapy.

1. Introduction

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare

disorder that typically occurs in midlife. It is characterized by

development of severe hypotension, hem concentration and

hypoalbuminemia due to development of markedly increased

capillary permeability.1,2 Episode of ISCLS usually begin with

prodromal symptomsfollowedbyhypotensionandedema.The

hypotension and edema are due to extravasations, which

typicallyworsenover two to threedaysandmaybecomplicated

by a compartment syndrome. The termination of the attack

coincides with the return of the plasma constituents to the

vascular compartment, resulting in congestion and risk for

volume overload and pulmonary edema. Despite the impres-

sive weight gain and diffuse muscular swelling during the

period of capillary leakage, compartment syndrome and rhab-

domyolysis is not a usual feature for ISCLS and has been

described only in few patients.3

2. Case history

A 32 years old female initially was admitted in another hos-

pital with history of malaise, low grade fever for two to three

* Corresponding author.E-mail address: drsanjay_jogesh@hotmail.com (S. Bhaumik).

Available online at www.sciencedirect.com

journal homepage: www.elsevier .com/locate/apme

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Please cite this article in press as: Bhaumik S, Banerjee N, Systemic capillary leak syndrome complicated by severe rhabdo-myolysis: A case report with review of literature, Apollo Medicine (2013), http://dx.doi.org/10.1016/j.apme.2013.08.006

0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.http://dx.doi.org/10.1016/j.apme.2013.08.006

days followed by mild abdominal pain, decrease urine output

and lower limb weakness. Initial investigations showed in-

crease in creatine phosphokinase (1600 IU/L), normal nerve

conduction study and normalMRI dorso-lumber spine. Patient

was started on antibiotics and oral steroid. But in next 48 h her

condition deteriorated and she was transferred to our insti-

tute. During admission she was hypotensive with non

recordable peripheral pulses and central venous pressure of

3 cm of H2O, she was mildly tachypneic, had profound

weakness in limbswith hyporeflexia and swelling.With initial

clinical diagnosis of polymyositis/myoedema, septic shock

she was started on broad spectrum antibiotics and high dose

intravenous methyl prednisolone. After correction of hypo-

volemia her urine output increased and blood pressure sta-

bilized. But her limb swelling increased with development of

left foot drop. She also developed bilateral pleural effusion.

Her investigations showed features of hem concentration

(Hemoglobin: 17.3 mg%, Total leukocyte count e 28,200/L,

hypoalbuminemia-albumin: 1.9 mg%),progressively increasing

CPK level: from 22,155 IU/L to 46,843 IU/L within seven days,

normal renal parameters, absent urinary myogloblin, negative

collagen vascular disease work up, normal septic profile (done

twice), normal serum procalcitonin, negative malarial antigen,

dengueserology, leptospiraserology,normalCMVantibodytiter,

serum protein electrophoresis did not show any abnormality.

MRI leg muscle showed muscle swelling with increased

interstitial fluid. Muscle biopsy showed severe myonecrosis

without any inflammatory reaction. Patient was started on

intravenous immunoglobulin with the revised diagnosis of

non infective systemic capillary leak syndrome. After three

days of IV ig she started having remarkable clinical improve-

ment and CPK level also came down to 972 IU/L within next

seven days. Her left foot drop also improved partially. Patient

did not have further recurrence of symptoms for next six

months.

3. Discussion

Idiopathic systemic capillary leak syndrome was first

described by Clarkson in 1960, since then approximately 150

cases have been reported worldwide.4 Though it primarily

affects middle aged adults, cases in children as young as five

months old has been reported.5 The patho physiologic

mechanisms are partially understood. An unknown trigger

causes a temporary increase in the macromolecular perme-

ability in the capillary bed of skeletal muscles and connective

tissues. Several studies have found a monoclonal gammop-

athy,6 elevated levels of vascular endothelial growth factor

(VGEF) and angioprotein 2 in few case series. Involvement of

IL2 and several inflammatory mediators including leukotri-

enes and tumor necrosis factor alpha are also implicated in

several series.7,8

ISCLS is a diagnosis of exclusion that is made when a pa-

tient manifests intravascular hypovolemia, generalized

edema and the triad of hypotension, hem concentration, and

hypoalbuminemia in the absence of an identifiable alternative

cause. The initial differential diagnosis for a patient with

ISCLS is likely to include typical causes of distributive shock

complicated by a systemic capillary leak (eg. severe sepsis,

septic shock, toxic shock syndrome, anaphylaxis and certain

drug reaction). Despite intensive investigations no identifiable

cause could be detected in our patient. Plasma leakage into

muscles in SCLS can cause increase intra compartmental

pressure, with pressure induced muscle damage. Compart-

ment syndrome can lead to rhabdomyolysis, withmoderate to

severe elevation of creatine phosphokinase. There have been

few reports of moderate elevated CPK concentration with

SCLS, however our patient had extremely elevated CPK con-

centration (46,843 IU/L). Fluid resuscitation may exacerbate

the problem. This explains why our patient had progressively

increasing CPK levels during resuscitatory phase.

Initial management of ISCLS is aimed at securing the air-

ways, correcting hypoxemia and tissue hypo perfusion. Pa-

tients with hypo perfusion should have their tissue perfusion

restored using a strategy similar to that use for septic shock.

After initial resuscitation and stabilization, treatment should

be redirected towards the prevention of intravascular volume

overload and its complication (eg. pulmonary edema). There is

no acute pharmacologic therapy for ISCLS, although case re-

ports described several treatment modalities eg. intravenous

immunoglobulin,9 combination of terbutaline (5 mg four

times daily) and sustained release Theophylline (with serum

concentration of 10e20 mcg/ml),10 and anti-vascular endo-

thelial growth factors antibody, i.e. bevacizumab. Our patient

responded very well to intravenous immunoglobulin and fluid

resuscitation.

Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

1. Clarkson B, Thompson D, Horwith M, Luckey EH. Cyclicaledema and shock due to increased capillary permeability. AmJ Med. 1960;29:193.

2. Marks J, Shuster S. Disorders of capillary permeability. Br JDermatol. 1973;88:619.

3. Teelucksingh S, Padfield PL, Edwards CRW. Systemic capillaryleak syndrome. Q J Med. 1990;75:515e524.

4. Druey KM, Greipp PR. Narrate review: the systemic capillaryleak syndrome. Ann Intern Med. 2010;153:90.

5. Foeldvari I, Waida E, Junker AK. Systemic capillary leaksyndrome in a child. J Pediatr. 1995;127:739.

6. Zhang W, Ewan PW, Lachmann PJ. The para proteins insystemic capillary leak syndrome. Clin Exp Immunol.1993;93:424.

7. Nagao Y, Harada H, Yamanaka H, Fukuda K. Possiblemediators for systemic capillary leak syndrome. Am J Med.2011;124:e7.

8. Cicardi M, Gardinali M, Bisiani G, et al. The systemic capillaryleak syndrome: appearance of interleukin-2-receptor-positivecells during attacks. Ann Intern Med. 1990;113:475.

9. Lambert M, Launay D, Hachulla E, et al. High-doseintravenous immunoglobulin dramatically reverse systemiccapillary leak syndrome. Crit Care Med. 2008;36:2184.

10. Dowdwn AM, Rullo OJ, Aziz N, et al. Idiopathic systemiccapillary leak syndrome: novel therapy for acute attacks. JAllergy Clin Immunol. 2009;124:1111.

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Please cite this article in press as: Bhaumik S, Banerjee N, Systemic capillary leak syndrome complicated by severe rhabdo-myolysis: A case report with review of literature, Apollo Medicine (2013), http://dx.doi.org/10.1016/j.apme.2013.08.006

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