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Systemic capillary leak syndrome complicated by severe rhabdomyolysis: A case report with review of literature
a p o l l o m e d i c i n e x x x ( 2 0 1 3 ) 1 e2
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
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: [email protected] (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
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
1. Clarkson B, Thompson D, Horwith M, Luckey EH. Cyclical edema and shock due to increased capillary permeability. Am J Med. 1960;29:193. 2. Marks J, Shuster S. Disorders of capillary permeability. Br J Dermatol. 1973;88:619. 3. Teelucksingh S, Padfield PL, Edwards CRW. Systemic capillary leak syndrome. Q J Med. 1990;75:515e524. 4. Druey KM, Greipp PR. Narrate review: the systemic capillary leak syndrome. Ann Intern Med. 2010;153:90. 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. 7. Nagao Y, Harada H, Yamanaka H, Fukuda K. Possible mediators for systemic capillary leak syndrome. Am J Med. 2011;124:e7. 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
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
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: [email protected] (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
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
1. Clarkson B, Thompson D, Horwith M, Luckey EH. Cyclical edema and shock due to increased capillary permeability. Am J Med. 1960;29:193. 2. Marks J, Shuster S. Disorders of capillary permeability. Br J Dermatol. 1973;88:619. 3. Teelucksingh S, Padfield PL, Edwards CRW. Systemic capillary leak syndrome. Q J Med. 1990;75:515e524. 4. Druey KM, Greipp PR. Narrate review: the systemic capillary leak syndrome. Ann Intern Med. 2010;153:90. 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. 7. Nagao Y, Harada H, Yamanaka H, Fukuda K. Possible mediators for systemic capillary leak syndrome. Am J Med. 2011;124:e7. 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