Systemic Capillary Leak Syndrome Case Study

Systemic capillary leak syndrome (SCLS) is a very rare disorder, characterized by recurrent episodes of severe hypotension, hypoalbuminemia and hemoconcentration.1 Attacks of SCLS occur in three phases: 1) prodrome; 2) hypovolemia with weight gain; and 3) hypervolemia with fluid overload and polyuria often complicated by pulmonary edema. Often, compartment syndrome can lead to rhabdomyolysis as a serious complication of SCLS.2

As of 2010, 126 cases of SCLS had been reported worldwide, and few cases have been reported since that time.3 No previous literature describes a case of SCLS in a patient with prior rheumatoid arthritis (RA).

Case Presentation

A 58-year-old man with past medical history of RA, gastrointestinal (GI) upset and asthma presented at the emergency department of George Washington Hospital at midnight one summer night in 2014 with severe nausea, vomiting and diffuse abdominal pain and bloating. He denied fever and diarrhea. He reported that he had experienced gastrointestinal upset for two or three days prior to his admission, but his full admitting symptoms had been present only since 6 p.m. the day before.

In 2009, the patient was diagnosed with RA (positive RF and negative cyclic citrullinated peptide). He first presented with hand pain. He was initially treated with methotrexate, but it was discontinued in July 2011 due to GI upset. The patient was then treated with leflunomide, which he was still using daily at time of admission.

In the emergency department, he was noted to have stable blood pressure of 112/74 and a pulse rate of 130. He received intravenous fluids, pain medications and anti-emetics. He had a CT scan of the abdomen notable for a possible early/partial small bowel obstruction.

While in the emergency department, his labs were notable for a white blood cell count of 14.92, hemoglobin 19.9, hematocrit 58.7 and platelet 353. His creatinine was 1.7, albumin 5.2, bicarbonate 17.2, anion gap 30 and lactate 4.3. (See Table 1)

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TABLE 1: Laboratory Data on Admission & Other Notable Subsequent Inpatient Labs

The patient received 4 liters of intravenous fluids, and within a short amount of time his blood pressure dropped to 69/51. He was immediately transferred to the intensive care unit (ICU). There was concern for sepsis due to ischemic bowel.

In the ICU, he was started on broad-spectrum antibiotics, intubated, given more intravenous fluids with little response, then started on vasopressors. He was taken to the operating room for an explorative laparotomy, which revealed no evidence of perforation.

Case Description

A 53-year-old woman was first admitted with a 5-day history of upper respiratory tract symptoms and a 1-day history of diarrhoea. At presentation she was alert and oriented with a pulse rate of 120 per minute and a systolic blood pressure of 85 mmHg. She developed progressive oedema to her mid-calves. The haemoglobin was 182 g/L with a haematocrit of 0.53. Initially her serum albumin was 37 g/L but fell over 2 days to 22 g/L. Her troponin was negative, ECG normal and echocardiogram revealed normal left ventricular function. The CRP was 15 mg/L and screen for sepsis was negative. Her serum creatinine was 225 µmol/L and she had 1+ protein in her urine with large numbers of hyaline casts. She had a low urine output. She was given 16 L of intravenous crystalloid solution over a period of 4 days with slowly improving blood pressure and urine output. She made a full recovery and was discharged 6 days after admission. No specific diagnosis was established.

Over the next 7 years the patient had 3 further admissions with profound hypotension, tachycardia and oedema, usually following trivial infections. The last of these admissions required a prolonged stay in the intensive care unit with intubation, ventilator and inotropic support, and transient dialysis. During each admission she was haemoconcentrated, hypoalbuminaemic and with evidence of pre-renal acute kidney injury. There was never any evidence of acute sepsis contributing to these events. Adrenal function was normal. Repeated echocardiograms showed normal systolic function. Serum protein electrophoresis showed the presence of an IgG kappa paraprotein with an estimated density of 3 g/L.

Based on the clinical features of the patients repeated presentations, a diagnosis of systemic capillary leak syndrome was made and the patient was commenced on oral theophylline. Over the subsequent 3 years she has had no further presentations with this disorder but has progressed to having multiple myeloma.

Discussion

Systemic capillary leak syndrome (SCLS) is due to recurrent episodes of generalised increased capillary permeability.1 This results in the rapid accumulation of fluids and proteins into the extravascular space, causing a rapid fall in blood pressure and subsequent hypovolemic shock. Episodes of SCLS are characterised by generalised oedema associated with an elevated haemotocrit (haemoconcentration) and hypoalbuminaemia, usually in the absence of albuminuria.2

The progression of a typical episode of SCLS can be divided into three phases: prodromal, acute leak and late post-leak phases.3 During the prodromal phase, individuals often complain of weakness, malaise, myalgias and abdominal pain, which can last hours to days. This is followed by the leak phase, during which marked hypoperfusion, hypotension and oedema occur as a result of extravasation of fluid and protein. This typically lasts several days. The post leak phase occurs after the repair of capillary barrier function and involves the restoration of intravascular volume via reabsorption of extravasated fluids and proteins, and subsequent diuresis.3

Capillary permeability is normal during quiescent periods.4 Although the precise mechanism behind the increased capillary permeability has not yet been established, several hypotheses have been proposed. These include activation of the classical complement pathway, endothelial damage due to cytokines such as interleukins 2 and 6, interferon gamma and tumour necrosis factor alpha and raised plasma concentrations of vascular endothelial growth factor.4

SCLS is a clinical diagnosis and requires the exclusion of other conditions that can result in increased capillary permeability, such as sepsis. The majority of patients with SCLS also have a monoclonal gammopathy present and testing for this can be useful when the condition is suspected. During quiescent periods this is generally the only notable laboratory abnormality.5 The class of this paraproteinaemia is predominantly IgG with either kappa or gamma light chains.

During an acute episode, careful use of intravenous fluid support is recommended to maintain adequate perfusion of the kidneys, brain, and other vital organs. However sufficient fluids to normalise blood pressure often exacerbates the oedema and can predispose the patient to pulmonary oedema.4 During the post-leak phase there is mass reabsorption of extravasated fluids and proteins. This can result in acute intravascular fluid overload if the patient’s kidneys are unable to compensate via diuresis. Therefore it is important that clinicians recognise the switch from the leak phase to the post-leak phase so they may alter patient management accordingly. This can been achieved with the use of loop diuretics if renal function is intact, otherwise haemodialysis or haemofiltration can be utilised.4

While no curative treatment exists for SCLS, several therapies have shown some success. Treatment with selective β2 stimulants (terbutaline) has been shown to inhibit the histamine and bradykinin-dependent macromolecular capillary leakage during acute episodes.6 In addition, combination treatment with theophylline and terbutaline reduces the incidence of, or completely abates, acute episodes of SCLS. More recently treatment with intravenous immunoglobulins has been used successfully as a prophylactic treatment.7 Several cases of SCLS-diagnosed patients progressing to multiple myeloma, as seen in our patient, have been described and therefore referral to a haematologist for surveillance is advised.6

Author Information

Thomas Manning, Research Assistant, Patrick Manning, Associate Professor, Department of Medicine, Dunedin School of Medicine, Dunedin; Anna Manning, Senior House Officer, Tauranga Hospital, Tauranga.

Correspondence

Associate Professor Patrick Manning, Department of Medicine, Dunedin, New Zealand.

Correspondence Email

patrickmanning@healthotago.co.nz

Competing Interests

Nil

References

1.       Clarkson B, Thompson D, Horwith M, Luckey EH. Cyclical edema and shock due to increased capillary permeability. The American journal of medicine. 1960;29:193-216.

2.       Atkinson JP, Waldmann TA, Stein SF, Gelfand JA, Macdonald WJ, Heck LW, et al. Systemic capillary leak syndrome and monoclonal IgG gammopathy; studies in a sixth patient and a review of the literature. Medicine. 1977;56(3):225-39.

3.       Druey KM, Greipp PR. Narrative review: the systemic capillary leak syndrome. Annals of internal medicine. 2010;153(2):90-8.

4.       Tahirkheli NK, Greipp PR. Treatment of the systemic capillary leak syndrome with terbutaline and theophylline. A case series. Annals of internal medicine. 1999;130(11):905-9.

5.       Vigneau C, Haymann JP, Khoury N, Sraer JD, Rondeau E. An unusual evolution of the systemic capillary leak syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2002;17(3):492-4.

6.       Kapoor P, Greipp PT, Schaefer EW, Mandrekar SJ, Kamal AH, Gonzalez-Paz NC, et al. Idiopathic systemic capillary leak syndrome (Clarkson’s disease): the Mayo clinic experience. Mayo Clinic proceedings. 2010;85(10):905-12.

7.       Marra AM, Gigante A, Rosato E. Intravenous immunoglobulin in systemic capillary leak syndrome: a case report and review of the literature. Expert Rev Clin Immunol 2014; 10:349.

 

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