Post on 15-Apr-2017
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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