The following Comment has been published in the 6 September 2011 issue of _The Annals of Internal Medicine,_ in response to an earlier article discussing the effectiveness of IVIG versus beta-agonists like theophylline and terbutaline based on European experience:
*The Systemic Capillary Leak Syndrome*
We read the article by Gousseff and colleagues (#1) on the systemic capillary leak syndrome (SCLS) with great interest. However, we differ with their conclusion implying that beta-agonists and intravenous immunoglobulin (IVIG) provide equivalent prophylaxis.
The data presented by Gousseff and colleagues show that none of the 8 patients who died in the study were receiving prophylactic treatment at the time of death. Eleven of the 20 remaining patients were initially treated with beta-agonists, but almost all of the survivors were migrated to prophylaxis with IVIG over time. Eight of the 18 patients receiving IVIG had no additional episodes of SCLS. Only 1 patient of the 14 who received the recommended IVIG dosage of 2 g/kg per month had a severe episode. Other patients had either mild episodes or no episodes at all, and most patients had no episodes or far fewer episodes than the number before they received IVIG therapy. Two of the 3 patients receiving a low dosage of IVIG had no further episodes.
We report on 2 additional patients with SCLS in whom prophylaxis with terbutaline and theophylline failed, but who had no further episodes after initiation of IVIG therapy. Patient 1 is a 56-year-old man who had his first episode of SCLS when he presented with severe hypotension, oliguria, and a hemoglobin level of 23 g/L. A monoclonal gammopathy of undermined significance (MGUS) was present. Complications included compartment syndromes in the arms and legs, deep venous thrombosis, and acute renal failure. Therapy with terbutaline and theophylline was initiated and continued despite ensuing personality changes. A second severe episode occurred 16 months later, again requiring fasciotomies. Despite continued therapy, 8 additional episodes occurred in the 2 years after the first. Theophylline levels were within the therapeutic range (10 to 20 mg) 80% of the time during this period. Levels did not correlate with the occurrence or severity of the attacks. After the last attack, 2 g/kg of IVIG was given over 2 days every 4 weeks. Terbutaline and theophylline therapy was stopped 5 months later. No episodes have occurred in more than 16 months since IVIG therapy was initiated.
Patient 2 is a 53-year-old man who had his first episode of SCLS when he presented with hypotension and a hematocrit of 58.2%. Over the next 6 months, multiple episodes of hypotension ensued, with hematocrits as high as 65.6%. Treatment with cetirizine, ranitidine, and zafirlukast was ineffective. An MGUS was discovered, and SCLS was diagnosed on the seventh hospitalization, 6 months after the initial attack. Therapy with terbutaline and theophylline was initiated. The patient had 25 episodes over the next 19 months, with complications that included atrial flutter, pericardial tamponade, recurrent pulmonary emboli, renal failure, pulmonary edema, and forearm compartment syndromes. A daily dose of prednisone, 5 mg, and thalidomide was administered at 5 months and 17 months after diagnosis, without obvious effect. Nineteen months after diagnosis, IVIG therapy at a dosage of 2 g/kg over 2 days on a monthly basis was initiated. The patient has had no episodes for more than 20 months, but renal failure has progressed, and he is now receiving permanent dialysis.
There are additional published reports of successful prophylaxis with IVIG (#2–5). We are also aware of another case (Barrett J. Personal communication). In at least 2 of these patients, instability occurred 5 weeks after treatment with IVIG, suggesting that the dosing interval may be important.
We agree with Gousseff and colleagues that patients with SCLS require prophylactic therapy. However, given the present state of knowledge and despite the high cost, we strongly believe that IVIG is the optimal prophylaxis and should be the initial choice to prevent attacks in patients with SCLS. That we are not alone is implied by the authors’ observation that “IVIG became a common first-line treatment in more recent years.”
_Mark Pecker, MD
Weill Cornell Medical College, New York, NY 10021
Michael Adams, MD
Georgetown University School of Medicine, Washington, DC 20057_
_Walter Graham, MD
Cassia Regional Medical Center, Burley, ID 83318_
Potential Conflicts of Interest: None disclosed.
*References*
1. Gousseff M, Arnaud L, Lambert M, Hot A, Hamidou M, Duhaut P, et al; Capillary Leak Syndrome Registry. _The systemic capillary leak syndrome: a case series of 28 patients from a European registry._ Ann Intern Med. 2011;154:464-71. [PMID: 21464348]
2. Lambert M, Launay D, Hachulla E, Morell-Dubois S, Soland V, Queyrel V, et al. _High-dose intravenous immunoglobulins dramatically reverse systemic capillary leak syndrome._ Crit Care Med. 2008;36:2184-7. [PMID: 18552679]
3. Abguueguen P, Chennebault JM, Pichard E. _Immunoglobulins for treatment of systemic capillary leak syndrome._ Am J Med. 2010;123:e3-4. [PMID: 20569743]
4. Govig BA, Javaheri S. _The systemic capillary leak syndrome_ [Letter]. Ann Intern Med. 2010;153:764. [PMID: 21135305]
5. Zipponi M, Eugster R, Birrenbach T. _High-dose intravenous immunoglobulins: a promising therapeutic approach for idiopathic systemic capillary leak syndrome._ BMJ Case Reports. 2011.