Idiopathic systemic capillary leak syndrome also known as Clarkson’s disease is a potentially fatal disorder. Prompt institution of appropriate therapy as outlined here can reduce the morbidity and prevent complication.

1. Systemic capillary leak syndrome complicated by severe rhabdomyolysis

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Case Report
Systemic capillary leak syndrome complicated by
severe rhabdomyolysis: A case report with review
of literature
Sanjay Bhaumik a,*, Narayan Banerjee b
a
b
Senior Consultant Neurologist, Apollo-Gleneagles Hospitals, Kolkata 700 054, India
Senior Consultant Internal Medicine, Apollo-Gleneagles Hospitals, Kolkata 700 054, India
article info
abstract
Article history:
Idiopathic systemic capillary leak syndrome is characterized by episodes of increased
Received 2 August 2013
capillary permeability resulting in severe hypovolemic shock, hem concentration and
Accepted 7 August 2013
hypoalbuminemia. Rarely, patient may develop compartment syndrome due to increased
Available online xxx
interstitial fluid resulting severe myonecrosis. Here, we are reporting a case with review of
therapeutic aspects of this rare syndrome.
Keywords:
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
Systemic capillary leakage
Myonecrosis
Hypoxemia
Key messages:
Idiopathic systemic capillary leak syndrome also known as
Clarkson’s disease is a potentially fatal disorder. Prompt institution 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.
capillary permeability.1,2 Episode of ISCLS usually begin with
prodromal symptoms followed by hypotension and edema. The
hypotension and edema are due to extravasations, which
typically worsen over two to three days and may be complicated
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 impressive weight gain and diffuse muscular swelling during the
period of capillary leakage, compartment syndrome and rhabdomyolysis is not a usual feature for ISCLS and has been
described only in few patients.3
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
2.
Case history
A 32 years old female initially was admitted in another hospital with history of malaise, low grade fever for two to three
* Corresponding author.
E-mail address: drsanjay_jogesh@hotmail.com (S. Bhaumik).
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
Please cite this article in press as: Bhaumik S, Banerjee N, Systemic capillary leak syndrome complicated by severe rhabdomyolysis: A case report with review of literature, Apollo Medicine (2013), http://dx.doi.org/10.1016/j.apme.2013.08.006

3. 2
a p o l l o m e d i c i n e x x x ( 2 0 1 3 ) 1 e2
days followed by mild abdominal pain, decrease urine output
and lower limb weakness. Initial investigations showed increase in creatine phosphokinase (1600 IU/L), normal nerve
conduction study and normal MRI 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 institute. 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 limbs with 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 hypovolemia her urine output increased and blood pressure stabilized. 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,
dengue serology, leptospira serology, normal CMV antibody titer,
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 improvement 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 permeability in the capillary bed of skeletal muscles and connective
tissues. Several studies have found a monoclonal gammopathy,6 elevated levels of vascular endothelial growth factor
(VGEF) and angioprotein 2 in few case series. Involvement of
IL2 and several inflammatory mediators including leukotrienes and tumor necrosis factor alpha are also implicated in
several series.7,8
ISCLS is a diagnosis of exclusion that is made when a patient 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. Compartment syndrome can lead to rhabdomyolysis, with moderate 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 concentration (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 airways, correcting hypoxemia and tissue hypo perfusion. Patients 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 reports 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 endothelial 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.
references
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edema and shock due to increased capillary permeability. Am
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leak syndrome. Q J Med. 1990;75:515e524.
4. Druey KM, Greipp PR. Narrate review: the systemic capillary
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5. Foeldvari I, Waida E, Junker AK. Systemic capillary leak
syndrome in a child. J Pediatr. 1995;127:739.
6. Zhang W, Ewan PW, Lachmann PJ. The para proteins in
systemic capillary leak syndrome. Clin Exp Immunol.
1993;93:424.
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8. Cicardi M, Gardinali M, Bisiani G, et al. The systemic capillary
leak syndrome: appearance of interleukin-2-receptor-positive
cells during attacks. Ann Intern Med. 1990;113:475.
9. Lambert M, Launay D, Hachulla E, et al. High-dose
intravenous immunoglobulin dramatically reverse systemic
capillary leak syndrome. Crit Care Med. 2008;36:2184.
10. Dowdwn AM, Rullo OJ, Aziz N, et al. Idiopathic systemic
capillary leak syndrome: novel therapy for acute attacks. J
Allergy Clin Immunol. 2009;124:1111.
Please cite this article in press as: Bhaumik S, Banerjee N, Systemic capillary leak syndrome complicated by severe rhabdomyolysis: 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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