I am pleased to report that a group of U.S. and European physicians has published, in the medical journal Annals of Internal Medicine: Clinical Cases, the results of first experiences with managing episodes of SCLS by giving patients a full dose of IVIG as soon as possible.  (At least 3 members of RareShare, myself included, are featured in this article.)  It is titled "Management of Acute Episodes of Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome) With Intravenous Immunoglobulins."

I recommend that you download this article from https://www.acpjournals.org/doi/epdf/10.7326/aimcc.2022.0496; that you email it, or print it out and give it, to your main physician and also to your family members; and that you print a copy for yourself and carry it with you wherever you go, so that you can give it to the first nurse or doctor you meet the next time you experience an episode of SCLS.

Summary: Monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS, Clarkson disease) is a rare disorder defined by transient but recurrent bouts of hypotensive shock and anasarca resulting from plasma extravasation. Although prophylactic treatment with high-dose intravenous immunoglobulins (IVIG, 1–2 g/kg/mo) prevents most disease flares, its utility for acute episodes of ISCLS is unclear. Here we report the results of a retrospective study of subjects with acute ISCLS treated at or near the onset of symptoms with IVIG. We found that administration of IVIG with minimal additional intravenous fluids was safe and associated with rapid clinical improvement. IVIG given close to the onset of ISCLS-related symptoms is associated with a favorable outcome.

Main points: Clarkson disease is characterized by acute episodes of hypotension, hemoconcentration (elevated hemoglobin/hematocrit), and hypoalbuminemia. This “leak” phase is associated with multiorgan dysfunction syndrome, anasarca, and thrombosis but is usually self-limited. This is followed by a “recruitment” phase during which edema is resorbed, which may result in intravascular volume overload and pulmonary edema. Although most patients are treated with large amounts of intravenous (IV) fluids, cumulative fluid therapy is significantly associated with mortality because of compartment syndromes and rhabdomyolysis. IV immunoglobulin (IVIG) has typically been given during the later stages of the episode as a “rescue” therapy, if at all. Although Lambert et al. reported in 2008 that IVIG administered at or near the onset of flares resulted in rapid symptom resolution in 3 patients, this approach has not been widely embraced. Here, we report the usefulness of IVIG as initial therapy for ISCLS episodes in lieu of IV fluid resuscitation.

The clinical course and laboratory abnormalities in 6 patients and 9 attacks treated with IVIG at or near the onset of idiopathic systemic capillary leak syndrome (ISCLS) episodes are summarized in Tables 1 and 2 of the article.  The beneficial effects of IVIG may depend on the timing of administration; the benefits are maximal within the first 24 hours of the flare onset rather than days later when used as rescue therapy. We did not observe any change in renal function associated with IVIG. The mechanism by which IVIG rapidly reverses acute ISCLS episodes is unclear. Several patients had rapid diuresis and stable creatinine levels, suggesting that it leads to improved clinical outcomes through mechanisms other than simple restoration of plasma volume.

Because acute ISCLS episodes and responses to IVIG prophylaxis are similar in patients with and without monoclonal gammopathy of undetermined significance (MGUS), early administration of IVIG for acute ISCLS episodes in patients lacking an MGUS should be strongly considered.

Arturo,

Thank you for sharing this report. As recommended I downloaded it, made a print, I have a copy on my (and my family members') smartphone and sent it to my physician. But let us hope that we will never have to use it.

Hans 

Wonderful information, Arturo! Thank you once again for your leadership in this research.

Susan Tedrick