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Systemic Capillary Leak Syndrome

What is Systemic Capillary Leak Syndrome?

Systemic Capillary Leak Syndrome (SCLS) is an exceedingly rare, life- and limb-threatening disorder characterized by acute and severe recurrent attacks featuring a rapid fall in blood pressure due to the temporary leak of plasma out of the blood circulatory system.

This virtual community is dedicated to the memory of Judith (Judy) Lynne Davis (1958-2009) (judithdavis3), one of its founding members and a victim of a very severe episode of SCLS that took her life in November 2009.

We also mourn the death of seven other SCLS patient members of this community: Mario Gatto (mariogatto) from Naples, Italy, who passed away in December 2009; Denise Weston (mdweston) from Ohio, USA, who died in March 2011; Bruno Galien (bruno) from Nord-Pas-de-Calais, France, who passed on in February 2012; Guy Allen Overland (allenoverland) from the Washington DC area, USA, who died in January 2015; Marilyn Meaux (maire602) from Louisiana, USA, who passed away in March 2017; Julie Eady (jodono) from Perth, Australia, who died in September 2017; and Cara O'Hagan (Cara) from Dublin, Ireland, who passed on in February 2018.



  • Clarkson or Clarkson's Disease

Systemic Capillary Leak Syndrome (SCLS) is an exceedingly rare, life- and limb-threatening disorder characterized by acute and severe recurrent attacks featuring a rapid fall in blood pressure due to the temporary leak of plasma out of the blood circulatory system.

This virtual community is dedicated to the memory of Judith (Judy) Lynne Davis (1958-2009) (judithdavis3), one of its founding members and a victim of a very severe episode of SCLS that took her life in November 2009.

We also mourn the death of seven other SCLS patient members of this community: Mario Gatto (mariogatto) from Naples, Italy, who passed away in December 2009; Denise Weston (mdweston) from Ohio, USA, who died in March 2011; Bruno Galien (bruno) from Nord-Pas-de-Calais, France, who passed on in February 2012; Guy Allen Overland (allenoverland) from the Washington DC area, USA, who died in January 2015; Marilyn Meaux (maire602) from Louisiana, USA, who passed away in March 2017; Julie Eady (jodono) from Perth, Australia, who died in September 2017; and Cara O'Hagan (Cara) from Dublin, Ireland, who passed on in February 2018.

Acknowledgement of Systemic Capillary Leak Syndrome has not been added yet.

Less than one in 1 million people are affected by this disease. The onset of SCLS will usually occur in adults, however, SCLS can affect people of all ages.

Name Abbreviation
Clarkson or Clarkson's Disease Clarkson

Systemic Capillary Leak Syndrome (SCLS) is idiopathic, and thus, at present there are no known causes. Probably a mid-life gene mutation takes place that renders those affected vulnerable -- possibly immune-deficient in some way -- to these curiously self-reversing capillary leaks.

Many patients report having a runny nose, flu-like symptoms, gastro-intestinal disorders, a general weakness or pain in their limbs, swelling in the face or hands and feet, or very cold hands and feet, but others get no particular or consistent warning signs.

Name Description
Swelling swelling
Myalgia Myalgia is muscle pain
Rhinorrhea Rhinorrhea is a runny nose
Dizziness Dizziness
Lightheadedness Lightheadedness
Hypotension Hypotension is abnormally low blood pressure
Hemoconcentration Hemoconcentration is the decrease of the fluid content of the blood, with increased concentration of formed elements
Hypoalbuminemia Hypoalbuminemia is low levels of protein in the blood
Nausea Nausea
Excessive thirst Excessive thirst
Generalized edema Generalized edema
Decline in clinical picture Clinical picture declines rapidly within hours
Cold limbs and sweating Cold limbs and sweating
Rapid swelling and compartment syndrome Rapid swelling of all limbs with development of compartment syndrome, especially during IV fluid administration
Decreased urine output Decreased urine output
Vomiting Vomiting
Intestinal cramps Cramps
Diarrhea Diarrhea
Fatigue Fatigue
Headache Headache

The diagnosis of SCLS is made partly by exclusion, namely, by eliminating the possibility of other more common diseases, and is based on measurable, clinical symptoms such as hypotension or low blood pressure, hemoconcentration or decrease in blood volume, hypoalbuminemia or an abnormally low levels of a protein called albumin in urine, and the presence of a protein called Monoclonal Gammopathy of Unknown Significance (MGUS).

Some diagnostic tests may include blood and urine tests to check for abnormalities such as dark urine, concentrated blood, or low serum albumin in the blood.

  • Methylprednisolone 125 mg IV STAT, repeated as needed.
  • Judicious use of IVF boluses and drips to keep CVP above zero.
  • Phenylephrine or Norepinephrine for hypotension, early institution.
  • 50 ml of 25% albumin, repeated as needed.
  • Continuous CVP monitoring, stat and serial lab work including CPK and lactate.
  • Immediate Orthopedics consult and compartment pressure measurement; early, preventive limb fasciotomies if compartment pressures or CPK high. 
  • Venous Doppler for DVT, may need full anticoagulation.

Treatment of a fully developed SCLS episode requires recognition that there are two phases. The first phase, which often lasts a couple of days, is called the resuscitation phase because the dual aim of ER/ICU treatment is to stop or control the capillary leak and to raise the patient's blood pressure from near zero. In this initial phase, an albumin and fluid leak from the capillaries into the tissue spaces causes swelling, especially into the extremities rather than the abdomen or organs (such as the lungs). The blood pressure falls and the red cells concentrate. This loss of fluid has similar effects on the circulation as dehydration, slowing both the flow of oxygen carrying blood to tissues and the output of urine.

Glucocorticoids (steroids like methylprednisolone) are recommended to reduce or stop the capillary leak, and albumin and colloids usually help to increase the remaining blood flow to vital organs like the kidneys. Keeping up with the fluid loss is important because sustained low blood pressure can damage vital organs such as the kidneys. Even though blood pressure readings may reach and remain at very low levels, it is important to avoid overly aggressive intravenous fluid administration causing massive swelling of the extremities.

The goal of saline and vasopressors administered should NOT be to restore a "normal" blood pressure (or urine flow), but to maintain it at a minimal level sufficient to avoid permanent damage to vital organs. Measurement of central venous or arterial pressure in an ICU setting is often necessary to achieve this delicate balance. When too much fluid is administered, the result is excessive swelling, and the patient may well require surgical decompression of the limbs. In this procedure, known as a fasciotomy, the skin of the arms and/or legs is incised to release the compressive pressure the retained fluid is having on blood flow to and from the extremities.

The second phase of the treatment is known as the recruitment phase, when fluids and albumin are reabsorbed from the tissues during at least a couple of days. In this phase, the capillary leak has ended and the main threat is fluid overload. If intravenous fluids were given in excess, they usually cause an accumulation of fluid in the lungs and around other vital organs. Most of the patient deaths happen during this recruitment phase so it is important that diuretics be administered to help patients discharge all the fluid previously given -- and to keep them from backing up, especially into the lungs.

As concerns episode prevention, two approaches have been tried: β-agonists like theophylline and terbutaline, and a prophylaxis with IVIG infusions. In recent years, more and more patients have been migrated from the former to the latter in Canada, Europe, the United States and beyond, because IVIG therapy leads to superior results -- no episodes or fewer and lighter episodes than compared to no therapy or the other therapies -- and does not have as many adverse side effects as does treatment with β-agonists like theophylline and terbutaline.

The prognosis is uncertain and depends on (a) how well episodes are managed, in terms of preventing permanent damage to vital organs and extremities; and (b) the ability to prevent episodes altogether.

There are two main treatments to prevent episodes of SCLS. The oldest is the Mayo Clinic’s approach of a preventive therapy with theophylline (or aminophylline) and terbutaline tablets taken on a daily basis. However, these medications, meant to reduce endothelial hyperpermeability, have very unpleasant side effects, and often prove ineffective, providing partial and transient improvement.

The newest is the French preventive regimen, which involves monthly infusions of immunoglobulins (IVIG). There is growing evidence that IVIG (usually, 2 gr/kg per month, administered over two consecutive days) has worked for many patients in Europe for over 10 years now, and is proving extremely successful among patients who have tried it in North America and beyond in the past several years, thus having become the standard of care.

Name Description
Medical help

Find yourself a compassionate physician, preferably a specialist in internal medicine or hematology affiliated with a major university hospital, willing to do his/her homework on this rare disorder (namely, read the literature and follow the instructions), and willing to consult with the few SCLS experts available:

In the United States,
Dr. Mark S. Pecker,
Professor of Clinical Medicine;
Weill Cornell Medical College,
New York, NY,
tel. 646-962-2605,
email ;

in Europe:
Prof. Zahir Amoura,
Département de Médecine Interne,
Hôpital de la Pitié-Salpêtrière, Bd. de l'Hôpital 83, Paris 13e,
tél. 0033 1 42 17 80 81,
email :

Clinical Study Volunteer
Patients who have been diagnosed as having SCLS and who are at least 16 years old are wanted for participation in the only scientific study of the illness taking place anywhere in the world: at the National Institutes of Health in Bethesda, MD, right outside Washington DC. You must have a documented medical history including at least one acute episode of SCLS or else continuous symptoms of periodic hemoconcentration, hypotension and protein leakage. Have your primary doctor contact Ms. Linda Scott at, before sending in the requisite letter of referral with your medical history and laboratory studies to the lead clinical investigator, Dr. Kirk Druey,, tel. 301-435-8875. Once accepted into the clinical research study, you will be invited to come to NIH and spend about 4 days there for the purpose of being examined, donating blood, and being subjected to various tests (e.g., clinical digital photography of your blood vessels). Depending on circumstances, you probably will have time off to do sightseeing in the capital area during your stay at NIH. Those who wish to be greeted in person during their stay by this community's founder, please contact


Please see the Disorder Resources section.

United Healthcare Created by emouzon
Last updated 17 Sep 2019, 04:11 PM

Posted by Rita Wood
17 Sep 2019, 04:11 PM

I do I will get you info.

Posted by emouzon
17 Sep 2019, 04:07 PM

Hi, folks.  It looks as though Jeff is changing jobs again.  Does anyone have any experience with getting United Healthcare to approve IV/IG?

IVIG subcutaneous ? Created by AndreasGunsser
Last updated 9 Sep 2019, 03:56 PM

Posted by AndreasGunsser
9 Sep 2019, 03:56 PM



thanks for your posting. You mention basically the same  issues that the doctor that knows me since 2016 and who knows more than others here in Germany about SCLS also told me yesterday. Until two months ago I got my IVIG as an inpatient in the  hospital in which he works, about 3 hrs away from where I live. I had to stay at hospital for two nights.


Since July I get the Ivig in such a infusion center (for usually cancer patients), 40 minutes (public transportation) away from home. It takes three days, but I can go home at night. It is much more comfortable compared to how it used to be. So far, it is ok for me. 


I did not intend to switch to SCIG. But my new doctors asked if this could be a option, and I wanted to discuss the matter on a somehow rational basis.


Posted by aporzeca
9 Sep 2019, 08:07 AM

In principle it does not matter whether one receives the immunoglobulins one needs to prevent episodes of SCLS intravenously (IVIG) or subcutaneously (SCIG).  The practical issue is that SCIG is capable of delivering a much smaller amount of IG than IVIG can deliver.  There is only so much SCIG that a patient's skin and muscles can absorb at each spot without causing unbearable pain, and only so many times per week that patients are willing to shoot themselves with needles in order to receive the dose of SCIG they require -- especially when the body can absorb virtually unlimited amounts of IG when delivered intravenously.  This is why SCIG is usually only given to, and tolerated by, children with SCLS -- especially those for which lower doses have the desired effect.

For example, if a 10-year old child weighs a typical 30 kilos and needs 2 gr/kg/month, or a total of 60 grams, that is an amount that can reasonably be delivered either via IVIG (over two days) or SCIG (over many days).  Even better, of course, if the 30-kilo child only needs 1 gr/kg/month, in which case only 30 grams need to be delivered via IVIG (over two days) or SCIG (over many days).  That is usually tolerable and achievable either way.

However, if an adult weighs a typical 60-100 kilos and needs 2 gr/kg/month, or a total of 120-200 grams, that is an amount that usually cannot reasonably be delivered, absorbed, and thus tolerated via SCIG even when spread out over most days. 

Of course, you should not rely on what I just wrote, and you should discuss this practical aspect with your physician and infusion nurse -- especially now that you went through the trouble and risk of having a port, as per your other thread. 

If I were you, I would first make absolutely sure that I could not tolerate receiving my IVIG in two days rather than three, which is the normal, thereby cutting out one trip per month to your current infusion center.  And second, I would make sure that I could not receive my IVIG from an infusion center located closer to my home.  These centers typically cater to cancer patients -- and unfortunately there are a lot of cancer patients everywhere.

Posted by AndreasGunsser
8 Sep 2019, 07:43 AM


as mentioned in the „Port catheter“ thread, my doctors came up with another idea.

Could the immunoglobulin be given not info the veins, but subcutaneous? Does anyone has experience or an opinion to that?

The background of the question is, that I changed the institution and doctors that give me the monthly IVIG because I wanted to travel less. The new ones do not have any experience with SCLS, but they give immunoglobulin to other patients (mostly related with cancer). At least one patient of them does get it subcutaneous.

The doctor that basically treats the SCLS is still the same. I see him only once a year, so traveling to him is not such a problem . Of course also I asked him per email.

So far, I am against subcutaneous giving, unless there is experience with that and SCLS. 

If, from a medical perspective, the subcutaneous giving would be possible, the realization would also depend on the amount that has to be given and the health Insurance.





Port Catheter Created by AndreasGunsser
Last updated 8 Sep 2019, 06:56 AM

Posted by AndreasGunsser
8 Sep 2019, 06:56 AM



thank you very much for your advice and opinions, also to those, who sent me an email.

I finally decided to get a port. Since then, I had IVIG Infusions twice. It was very comfortable. No more hassle finding a vein, and the start was very fast - no more delays, what means, that I can go home much earlier. As I now get my infusions on three days and go home over night this is quite good for me.

For my daily life (e.g. sports, backpack,  sleeping) it is no problem.

As I changed the institution, where I get the monthly IVIG , they came up with another question. I will start a separate thread for this.


Posted by Barney
23 Aug 2019, 11:46 AM

Arturo, interesting that my nurses in the IV/Cancer center were lobbying for me to get a port for easier access and knowing I had to come every month, they could 'service' it and check it for any issues.  I talked to my doctors and they have both been less enthusiastic about it.  They left it up to me and gave me some pros and cons...pretty much which has been listed above along with some concern on my part on protecting it during physical activities. 

Posted by nwbsaw
16 Aug 2019, 11:56 AM

Nolan is on his second port. I advocated for it when he was having so many episodes. I never wanted to go with out easy veinous access. We have not had any serious problems. I think it is a life saver. Wendy

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1 IVIG treatment 9 weeks ago -no more chronic leak - thoughts? Created by kmiclon
Last updated 29 Aug 2019, 12:10 PM

Posted by stedrick
29 Aug 2019, 12:10 PM

I am also from Maine, though I spend winters receiving my infusions in Florida to avoid the ice and snow of medical travel. I have been very successful in reducing my IVIG side effects by splitting the dose, i.e., receiving 0.5 gram/kg every 14 days. It is time-consuming but my quality of life has improved as a result. Side effects may be unavoidable for some of us, but reducing them to a tolerable level and remaining on IVIG is definitely worth the increase in life expectancy.


Posted by kmiclon
28 Aug 2019, 02:50 PM

Thank you everyone for the added info - I am getting my 2nd IVIG on Friday and will definitely take the advice on fluids.  My husband was extremely hesitant about another treatment, so having this opportunity to hear others' experiences is definitely a blessing :-) 

Posted by DudeSCLS
25 Aug 2019, 12:32 PM

I just had my 18th straight month of IVIG. I have had no more episodes since I started the treatment. Basically, I made it through the winter without an episode. No flu to test it, though I did get some kind of virus/cold and managed to be ok without a visit to the ICCU. After my first infusion I had a serious migraine. Since then I’ve only experienced a migraine here and there (several times, but not every time). I’ve had diarrhea as well, just as few of times. It seemed like one or both of those symptoms might occur during my first few infusions. But I had my infusion 2 days ago and I’ve felt fine. All in all, the IVIG gives me peace of mind. So as long as my insurance is covering it I’m sticking to the plan, and advice from Dr. Druey at the NIH. It’s the only way I can convince myself that I am ok. And that I will be ok for a long time. Having a migraine or diarrhea is much better than being on life support and going through the physical and mental trauma.

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How many have a history of extensive air travel? Created by BPerry7
Last updated 25 Aug 2019, 01:07 PM

Posted by Arielbatt
25 Aug 2019, 01:07 PM

Hello, after two years of Ivig, I made my first long plane trip (13 hours) I had already made 3 test trips (1 hour) a year ago.  All without subsequent attacks.  I'm very happy.

a todos,... después de dos años de Ivig realice mí primer viaje largo (13 horas) , ya había realizado 3 viajes de prueba en avión ( 1 hora) de prueba, todos ellos con total éxito, creo que la Ivig, cumplió con su trabajo. Estoy muy contento de sentir que mis limitaciones son menores.

Posted by Hiltjo
5 May 2013, 12:44 PM

by the way: it would be interesting to know whether using oxygen masks during air plane travel could prevent attacks, but I 'm not willing to try at this moment..

Posted by Hiltjo
5 May 2013, 09:45 AM

Dear all, I experienced several (4-5) periods during or after being in the mountains ( cycling or skiing ). The last one intruduced à chronic persisting state of SCLS, with ongoing weekly swelling and disability to perform execise. Airplane travelling could be compared with staking at à level of 1600 mtrs attitude, but while just sitting not being very active. VEGF is problably one of the important agents of the body which play à role in SCLS. (Read Xie e.o, 2012). The accelated production of VEGF is highly dependend on hypoxemia, through HIF1alfa (hypoxemia inducable factor), so could be influenced by altitude and air plane travelling. Once being elevated, (HIF ->) VEGF problably influences cell metabolsm, and so prevents is own reduction. In that way air plane travelling could play à role in exacerbations, as well in the initiation of SCLS. In my personal situation the relation with altitude is evident. Maybe being Dutch and normally living at sea level plays à role. Others report not to experience à relation, which is intriouging. Best regards, Hiltjo

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Shortages of IVIG reported in the United States Created by aporzeca
Last updated 23 Aug 2019, 01:12 PM

Posted by DavidS
23 Aug 2019, 01:12 PM

Our infusion center hasn’t said anything to us about this. Maybe they’re putting my husband on the front of the line because they recognize SCLS is life threatening 

Posted by Barney
23 Aug 2019, 11:42 AM

I had been on Octagam and a few months back they moved me to Privigen.  Must be the reason why...???  Hopefully this gets resolved soon.

Posted by Lolaudesi
17 Aug 2019, 10:05 PM

Hi Arturo, hopefully it is solved

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Difficulties getting doctors to take diagnosis seriously Created by CaroleTT1222
Last updated 23 Aug 2019, 12:29 PM

Compartment Syndrome / pain control Created by CaroleTT1222
Last updated 15 Aug 2019, 01:52 PM

Posted by Arielbatt
9 Aug 2019, 03:16 PM

Hola Carole, ... siempre es doloroso saber de uno de nosotros que no funciona bien, cuéntanos como sigue hoy, adhiero a los comentarios de Arturo, tener la suerte de estar en los Estados Unidos es lo más recomendable. Lo intuitivamente lógico es que volví a IVIG ... no dejes de mantenernos al día. 

Posted by aporzeca
30 Jul 2019, 10:57 AM

Cases of chronic SCLS and related chronic swelling disorders are currently the most difficult to diagnose and treat. Given what you describe, I think you are right to worry and need expert medical attention ASAP.  If I were you, I would have made an urgent appointment with Dr. Druey and team at NIH, and also would go back to the Mayo Clinic for their advice.  It wouldn't surprise me if they told you to get back on IVIG and see if that helps.  Please fill out your profile page with these and other details of your medical history. We're still learning a great deal from one another.

Posted by CaroleTT1222
30 Jul 2019, 01:31 AM

Hi everyone.  I was diagnosed in 2010. Had about 20 episodes before diagnosis. The episodes increased in frequency after the first in 1999. Each "episode" required weeks in hospital. In between these attacks, the swelling and symptoms continued with varying degrees of severity. I started IVIG in 2010 after diagnosis at Mayo at Rochester. I received monthly infusions for about 5 years and had only one more hospital worthy attack. The rest have been more chronic, less defined, mostly legs. I stopped infusions 4 years ago.

Recently, swelling is back and pretty awful. Lots of vomiting, headaches, short of breath, weak etc. 

My question right now: my calves will get so tight that the skin breaks and they leak clear fluid. Socks get wet, often soaked. I've put off starting back on IVIG because the side effects were difficult, especially the needed pre med steroids. I had just recently felt "normal" again post steroids, etc.

The swelling in calves makes walking painful and walking increases swelling! My calves are very painful but traditional pain meds seem to worsen swelling. At present, I can't take any meds by mouth as it results in a ridiculous amount of vomiting and burning pain in chest. No thank you! Has anyone else noticed an increase in swelling almost immediately after taking any typical prescription pain med or aspirin or NSAID? 

During the first IVIG treatments, I was married. This go around, I live alone. No family to help. I'm scared to death of going back on IVIG and becoming even more "sickly" even if for only in the short run. At least right now, yes, my feet and legs hurt but I'm not feeling flu-like and miserable. 

I worry about Compartment Syndrome and possible Rhabdomyolisis  (sp?), from breakdown of muscle tissue. I've had a 25 lb weight loss since GI symptoms started about 3 months ago. Now, with increased swelling, I've had 15 lb weight gain in two weeks. The gain is clearly all fluid. The initial loss was some fluid but a lot of muscle loss. I was put on permanent disability right after diagnosis. At that time I practically lived in a hospital wing.  I got better after 5 years of ivig monthly and i felt more stable and healthier. No episodes for 4 consecutive years. Only chronic milder symptoms. After stopping IVIG 4 years ago, it took some time but i almost had a normal looking life rebuilt! Any pain management info or compartment syndrome or Rhabdomyolisis input would be so helpful. Thank you! (Sorry if this is sounds confused - I'm writing on my phone and can't really see what I'm typing too well)

Most recent attack Created by gandcburns
Last updated 9 Aug 2019, 03:41 PM

Posted by Arielbatt
9 Aug 2019, 03:41 PM

Hi Cristina, thank you for your detailed update, it is of enormous importance for the entire community and a wake-up call for those with a dose of 1g or 0,5gr. It would be very interesting that those who are or were with doses lower than those recommended update their experience.
Regards Ariel.

Posted by HLOD
30 Jul 2019, 05:31 AM

Hi there,  just a comment regarding the 'tummy bug' that preceded your attack.  I am aware that bacterial infections of this type can also cause vascular leakiness through the action of 'bacterial endotoxins' in the bloodstream....which can potentially exacerbate an SCLS episode. Very nasty combination indeed.  I'm glad you have come through OK.   Helen 

Posted by ValeriaSpain
10 Jun 2019, 06:33 PM

Dear Cristina, 

Thank you very much for the update and I truly hope you finally tolerate infusions side effects ASAP.

Currently, I find myself in a very challenging situation since my doctors do not want to institute IVIG anymore upon stopping the infusions due to the intense common side effects I experienced on my 3rd initial infusion, (A daily 0.5g/kg infusion in 5 days was programmed. I weigh 50kg without edema), which I believe are a mere consequence of receiving a lower dose and a higher speed than the documented by Dr. Druey. 

So far, I am doing my best from the hospital to get my doctors contact both Dr. Druey and Prof. Amoura. It is a quite frustrating situation. 

I continuously experience an important lack of breath, dizziness, peripheral edema and extreme fatigue. The same reoccurs every three to four days when I suffer a mild episode along with drastic albumin level decrease, hypotension, +3 to 5 kg edema and high hematocrit - Arturo: I do not experience an hematocrit and Hgb increase in every episode, but in some. I use to be at 38%Hct/ 13-15Hgb and I can go from 41 to 51%Hct and 15-18Hgb in different episodes.

Moreover, I find it interesting that most “chronic leakers” we do not always experience an Hct and Hgb increase. 

Irrespective to the above mentioned, I would like to share the following case report (August 29th, 2018) in which Dr. Druey states the SCLS chronic presentation existence based on experience:



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Heftige aanval Created by Daan
Last updated 16 Jul 2019, 07:19 AM

Posted by Hiltjo
16 Jul 2019, 07:19 AM

Beste Daan en familie,

Wat een naar nieuws! Heel veel sterkte voor jou en je familieleden met het overlijden van je nicht Petra. 

Hiltjo Graafland.






Posted by aporzeca
15 Jul 2019, 11:53 AM

My sincere condolences!

Posted by krogers
15 Jul 2019, 09:10 AM

So sorry to hear that. My thoughts are with you.

View Full Thread (6 more posts)
Community Podcasts
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Arturo Porzecanski, a rare disease patient and advocate, gives us some tips on navigating decisions involved in choosing hospitals, doctors, and medical teams.
Featuring Arturo Porzecanski (American University). (Music

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Community Resources
Title Description Date Link
The Systemic Capillary Leak Syndrome

Narrative review: the systemic capillary leak syndrome

Abstract: The systemic capillary leak syndrome (SCLS) is a rare disease of reversible plasma extravasation and vascular collapse accompanied by hemoconcentration and hypoalbuminemia. Its cause is unknown, although it is believed to be a manifestation of transient endothelial dysfunction due to endothelial contraction, apoptosis, injury, or a combination of these. Fewer than 150 cases of SCLS have been reported, but the condition is probably underrecognized because of its nonspecific symptoms and signs and high mortality rate. Patients experience shock and massive edema, often after a nonspecific prodrome of weakness, fatigue, and myalgias, and are at risk for ischemia-induced organ failure, rhabdomyolysis and muscle compartment syndromes, and venous thromboembolism. Shock and edema reverse almost as quickly as they begin, at which time patients are at risk for death from flash pulmonary edema during rapid fluid remobilization. Diagnosis is made clinically and by exclusion of other diseases that cause similar symptoms and signs, most notably sepsis, anaphylaxis, and angioedema. Acute episodes are treated with vasopressor therapy and judicious fluid replacement, possibly with colloid solutions for their osmotic effects, to prevent the sequelae of underperfusion. Prognosis is uncertain, but patients who survive an initial severe SCLS episode are estimated to have a 10-year survival rate greater than 70%. Much remains to be learned about SCLS, and clinicians should consider the diagnosis in patients with unexplained edema, increased hematocrit, and hypotension.

IVIG as Treatment for SCLS

High-Dose Intravenous Immunoglobulins Dramatically Reverse Systemic Capillary Leak Syndrome.

Abstract: The objective of this study was to report the dramatic improvement of patients with systemic capillary leak syndrome obtained with high-dose intravenous immunoglobulins. Systemic capillary leak syndrome is a rare and life-threatening disorder characterized by hypotension that can lead to shock, weight gain, hypoalbuminemia, and elevated hematocrit secondary to unexplained episodic capillary fluid extravasation into the interstitial space. Because its cause is unknown, systemic capillary leak syndrome treatment has remained largely supportive. Intravenous immunoglobulins administration to a patient with refractory systemic capillary leak syndrome yielded dramatic improvement. The patient is still alive 11 yrs after systemic capillary leak syndrome diagnosis and receives intravenous immunoglobulins monthly. Later, based on that result, intravenous immunoglobulins were successfully given to two other patients during the acute phase of systemic capillary leak syndrome. Both are still alive 8 and 1.5 yrs after receiving intravenous immunoglobulins at the onset of each flare. In conclusion, intravenous immunoglobulins were effective against systemic capillary leak syndrome symptoms in three patients, but their exact mechanism remains unknown. Their immunomodulatory effect merits further investigation.

IVIG as Treatment for SCLS

Immunoglobulins for Treatment of Systemic Capillary Leak Syndrome

Abstract: A 43-year-old white woman in France diagnosed with SCLS was put on the recommended combination of Theophylline plus Terbutaline, but she nevertheless had 10 episodes of severe capillary leak during 2001-mid-2007, necessitating intensive care unit admission for her last 3 episodes. She was then put on IVIG administered every 6 weeks, and this yielded a dramatic improvement such that she has had no more episodes and has returned to her normal lifestyle.

Mayo Clinic write-up on SCLS

The Mayo Clinic's summary of the diagnosis and treatment of SCLS.

During an episode of systemic capillary leak syndrome, fluids are administered intravenously to maintain the patient's blood pressure and to prevent damage to vital organs such as the kidneys, heart and brain. The amount of fluid must be carefully controlled. An attempt to normalize blood pressure through aggressive fluid administration can cause destructive swelling of the body's extremities and overload the kidneys and lungs when the body needs to eliminate the excess fluids after the episode passes.

Glucocorticoids (steroids) are often injected during an acute capillary leak syndrome attack to reduce or stop the capillary leak. This is sometimes successful. Fluid pressure in muscles may be monitored. Emergency surgery may be needed to relieve pressure and minimize damage to muscles and nerves in the arms and legs.

Once the capillary walls stop leaking and fluids start to be reabsorbed, patients are usually given diuretics to speed up elimination of the fluids before they accumulate in the lungs and other vital organs, which can be a fatal complication.

Patients who avoid organ and limb damage in a capillary leak syndrome episode tend to recover their health after several days, once the capillary walls return to normal and the accumulated fluid is expelled from the body through urination.

Although no cure has been found for systemic capillary leak syndrome, the frequency and/or severity of episodes is often reduced by having patients take certain asthma medications: theophylline and terbutaline. Patients also may benefit from intravenous treatment with immunoglobulin or by taking thalidomide.

Patients may also be prescribed corticosteroid pills such as prednisone to be taken at the first sign of symptoms of another capillary leak.

Lessons from 28 European Patients with SCLS

The Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry.

Abstract: The article describes the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. These European patients with SCLS were treated and monitored from the start of 1997 until end-July 2010. Survival rates were 89% at 1 year and 73% at 5 years; instances of death were directly related to SCLS attacks in 6 cases (75% of total). Treatments of various kinds increased the chances of survival: Five years after diagnosis, survival rates were 85% in 23 patients who had received a treatment and just 20% in 5 patients who had not. The authors provide additional evidence that a prophylactic treatment with IVIG tends to reduce the frequency and severity of attacks, and may improve the survival of patients with SCLS.

IVIG: A Promising Approach to SCLS

High-dose intravenous immunoglobulins: A promising therapeutic approach for idiopathic systemic capillary leak syndrome.

Abstract: The article reports the case of a 40-year-old woman with chronic SCLS treated in Berne, Switzerland, with high-dose intravenous immunoglobulins (IVIG) after a prophylactic therapy with theophylline and terbutaline (T&T) was poorly tolerated and failed to decrease the frequency and severity of the attacks. During the 5 years she was on T&T the patient suffered from about 20 similar episodes of mild to moderate shock, often requiring hospital re-admission and supportive therapy. So far, 10 months of prophylactic therapy with IVIG (2gr/kg/month) have resulted in an impressive reduction of intensity and frequency of attacks, confirming the finding of other case studies.

Comment on SCLS

Comment on The Systemic Capillary Leak Syndrome.

Abstract: The authors report on 2 additional patients from the United States with SCLS in whom prophylaxis with terbutaline and theophylline failed, but who had no further episodes after the initiation of IVIG therapy. There are additional published reports of successful prophylaxis with IVIG cited, and the authors are also aware of yet another case. Given the present state of knowledge and despite the high cost, the authors strongly believe that IVIG is the optimal prophylaxis and should be the initial choice to prevent attacks in patients with SCLS.

Successful Treatment of SCLS with IVIG

Successful Treatment of Systemic Capillary Leak Syndrome with Intravenous Immunoglobulins.

Abstract: The authors report on a 48-year-old woman in Spain who had her 1st episode of SCLS in 1997 and was initially put on a regimen of terbutaline and aminophylline, but went on to endure 20 additional episodes in the subsequent 3 years. She was then treated with melphalan-prednisone for a year and the frequency and intensity of her episodes diminished and even disappeared. In 2005, however, the episodes returned and in 2008 she was finally put on a regimen of IVIG (2 g/kg) every 6 weeks. She has had no more episodes since then.

Laboratory Evidence of SCLS and of the Effectiveness of IVIG

Vascular Endothelial Hyperpermeability Induces The Clinical Symptoms of Clarkson Disease (The Systemic Capillary Leak Syndrome)

Abstract: The authors report clinical and molecular findings on 23 subjects, the largest SCLS case series to date. Application of episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera obtained from subjects during remission, to human microvascular endothelial cells caused vascular endothelial cadherin (VE-cadherin) internalization, disruption of inter-endothelial junctions, actin stress fiber formation, and increased permeability in complementary functional assays without inducing endothelial apoptosis. Intravenous immunoglobulin (IVIG), one promising therapy for SCLS, mitigated the permeability effects of episodic sera directly. Consistent with the presence of endogenous, non-immunoglobulin, circulating permeability factor(s) constrained to SCLS episodes, we found that two such proteins, vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission sera. Antibody-based inhibition of Ang2 counteracted permeability induced by episodic SCLS sera. Comparable experiments with anti-VEGF antibody (bevacizumab) yielded less interpretable results, likely due to endothelial toxicity of VEGF withdrawal. Our results support a model of SCLS pathogenesis in which non-immunoglobulin humoral factors such as VEGF and Ang2 contribute to transient endothelial contraction, suggesting a molecular mechanism for this highly lethal disorder.

Systemic capillary leak syndrome: recognition prevents morbidity and mortality

Systemic capillary leak syndrome: recognition prevents morbidity and mortality.

Abstract: The authors report on a case of SCLS in Australia involving a 61-year-old male who was properly diagnosed after his third episode, to increase awareness of the condition and to highlight the benefits of prophylactic intravenous immunoglobulin (IVIG) in this condition. The diagnosis was made by exclusion and clinically by a classic triad of hypotension, hypoalbuminaemia and haemoconcentration. There have been recent advances in understanding the pathophysiological basis for SCLS and in effective prophylaxis, and the authors and patient benefitted from said advances.

SCLS in Children

Idiopathic Systemic Capillary Leak Syndrome in Children

Abstract: Adult subjects with systemic capillary leak syndrome (SCLS) present with acute and recurrent episodes of vascular leak manifesting as severe hypotension, hypoalbuminemia, hemoconcentration, and generalized edema. We studied clinical disease characteristics, serum cytokine profiles, and treatment modalities in a cohort of children with documented SCLS. Six children with SCLS were recruited from the United States, Australia, Canada, and Italy. Serum cytokines from SCLS subjects and a group of 10 healthy children were analyzed. Children with SCLS (aged 5-11 years old) presented with at least 1 acute, severe episode of hypotension, hypoalbuminemia, and hemoconcentration in the absence of underlying causes for these abnormalities. In contrast to what is observed in adult SCLS, identifiable infectious triggers precipitated most episodes in these children, and none of them had a monoclonal gammopathy. We found elevated levels of chemokine (C-C motif) ligand 2 (CCL2), interleukin-8, and tumor necrosis factor α in baseline SCLS sera compared with the control group. All patients are alive and well on prophylactic therapy, with 4 patients receiving intravenous or subcutaneous immunoglobulins at regular intervals. The clinical manifestations of pediatric and adult SCLS are similar, with the notable exceptions of frequent association with infections and the lack of monoclonal gammopathy. Prophylactic medication, including high dose immunoglobulins or theophylline plus verapamil, appears to be safe and efficacious therapy for SCLS in children.

High-Dose IVIG Therapy for SCLS

High-Dose IVIG Therapy for SCLS.

Abstract: We evaluated IVIG prophylactic therapy in a cohort of 29 patients with Systemic Capillary Leak Syndrome in a longitudinal follow up study. All patients received treatments at the discretion of their primary providers and retrospectively via questionnaire recorded symptoms beginning with their first documented episode of the SCLS until May 31, 2014. Twenty-two out of 29 patients responded to the questionnaire, and 18 out of the 22 respondents received monthly prophylaxis with IVIG during the study period for a median interval of 32 months. The median annual attack frequency was 2.6/patient prior to IVIG therapy and 0/patient following initiation of IVIG prophylaxis (P = 0.001). 15 out of 18 subjects with a history of one or more acute SCLS episodes experienced no further symptoms while on IVIG therapy. In conclusion, IVIG prophylaxis is associated with a dramatic reduction in the occurrence of SCLS attacks in most patients, with minimal side effects.

Mechanistic Classification of SCLS

Mechanistic Classification of SCLS.

Abstract: The authors analyzed circulating mediators of vascular permeability and proinflammatory cytokines in acute episodic sera from 14 patients with SCLS, and sera from 37 healthy control subjects. They monitored barrier function of human microvascular endothelial cells (HMVEC) after treatment with SCLS sera using transendothelial electrical resistance assays. Consistent with their previous study, the permeability factor vascular endothelial growth factor (VEGF) was increased in sera from acutely ill subjects with SCLS. An analysis of samples from one SCLS patient who has not responded to any preventive therapies (and who is a member of this Community), suggests that SCLS may have clinically varying forms, and that within the group of patients with SCLS, different cytokines may mediate the capillary leak. Therefore, quantitative molecular and humanized cell-based assays for humoral mediators of permeability should improve diagnostic specificity for SCLS and enable clinicians to screen for effective therapies.

IVIG in SCLS: A Case Report and Review of Literature

IVIG in SCLS: Report and Review of Literature.

Abstract: In recent years, IVIG has become a common first-line prophylactic therapy in most patients with benefits at the dose of 2 gr/kg once a month. Here the authors report the case of a 49-year-old male patient in Italy -- he is a member of this community -- with SCLS treated successfully with a lower dose of IVIG (1 gr/kg monthly) in the maintenance phase. He presented no acute episodes in a follow-up period of 28 months. The authors describe prophylactic treatments for SCLS in the literature and compare their patient to another 18 who received IVIG in follow-up.

Genome-Wide SNP Analysis of SCLS

Genome-Wide SNP Analysis of SCLS.

Abstract: Polymorphisms in genes whose functional annotations suggest involvement in cell junctions and signaling, cell adhesion, and cytoskeletal organization, correlate with our previous mechanistic studies of SCLS sera. Such annotations provide a framework for future allelic discrimination strategies to validate top-ranked SNPs discovered here, as well as novel SNPs unique to the SCLS cohort detected by exome capture sequencing. Although the findings must be corroborated in a larger cohort, they provide a springboard for discovery of underlying pathophysiological mechanisms, biomarkers, and avenues for therapy.

The Mayo Clinic Experience with SCLS

Idiopathic Systemic Capillary Leak Syndrome (Clarkson's Disease): The Mayo Clinic Experience

Abstract: Of the 34 patients whose records were reviewed, 25 fulfilled all diagnostic criteria for SCLS. The median age at diagnosis of SCLS was 44 years. Median follow-up of surviving patients was 4.9 years, and median time to diagnosis from symptom onset was 1.1 years (interquartile range, 0.5-4.1 years). Flulike illness or myalgia was reported by 14 patients (56%) at onset of an acute attack of SCLS, and rhabdomyolysis developed in 9 patients (36%). Patients with a greater decrease in albumin level had a higher likelihood of developing rhabdomyolysis (P=.03). Monoclonal gammopathy, predominantly of the IgG-kappa type, was found in 19 patients (76%). The progression rate to multiple myeloma was 0.7% per person-year of follow-up. The overall response rate to the different therapies was 76%, and 24% of patients sustained durable (>2 years) complete remission. The estimated 5-year overall survival rate was 76% (95% confidence interval, 59%-97%). In conclusion, SCLS, a rare disease that occurs in those of middle age, is usually diagnosed after a considerable delay from onset of symptoms. The degree of albumin decrement during an attack correlates with development of rhabdomyolysis. A reduction in the frequency and/or the severity of attacks was seen in nearly three-fourths of patients who were offered empiric therapies. The rate of progression to multiple myeloma appears to be comparable to that of monoclonal gammopathy of undetermined significance.

Sharing the Pain [of living with SCLS]

Sharing the Pain [of living with SCLS]

This article from The Washington Post newspaper tells the story of how this SCLS virtual community was created, the story of its founder and, more generally, of this fantastic RareShare site.


Idiopathic systemic capillary leak syndrome (Clarkson disease)

Idiopathic systemic capillary leak syndrome (Clarkson disease)

Abstract: The enigmatic systemic capillary leak syndrome (SCLS) named for Dr Clarkson is characterized by transient and severe but reversible hemoconcentration and hypoalbuminemia caused by leakage of fluids and macromolecules into tissues. Although less than 500 cases of SCLS have been reported in the literature since 1960, the condition is probably underdiagnosed because of a lack of awareness and a high mortality without treatment. Treatment of acute SCLS remains primarily supportive. Prophylaxis with IVIG appears promising, but this therapy is nonspecific and expensive. Mechanistic understanding of SCLS is in its infancy. As a result, clinicians today cannot predict when or how badly SCLS will flare; targeted therapies do not yet exist, and prolonged remission or cure remains elusive. Our working hypothesis invokes exaggerated microvascular endothelial responses to surges of otherwise routinely encountered inflammatory mediators. This emerging disease model lends itself to innovative patient-centered translational research in the ways highlighted above. It is our hope that detailed and personalized investigation of intraendothelial responses among individual patients with SCLS might illuminate novel genetic and molecular control mechanisms. In turn, such advances could deliver the diagnostic, prognostic, and therapeutic tools sorely needed to combat this devastating disease.

Capillary leak syndrome: etiologies, pathophysiology, and management

Capillary leak syndrome: etiologies, pathophysiology, and management

Abstract: In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a “sepsis-like” syndrome with manifestations of  diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson’s disease, engraftment syndrome, differentiation syndrome, the ovarian  hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome;  hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.

Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated SCLS

Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated SCLS

Abstract: We conducted a cohort analysis of all patients included in the European Clarkson disease registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (e.g., the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%).Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Preventive treatment with IVIg and terbutaline were the only factors significantly associated with survival in multivariate analysis. Neither the use of thalidomide nor theophylline was associated with improved survival. Five- and 10-year survival rates in patients treated with IVIg were 91% and 77%, respectively, compared to 47% and 37% in patients not treated with IVIg. Patients treated with IVIg were more likely to be free of recurrence, severe recurrence, and alive at the end of follow-up. Furthermore, all but one patient who did not experience a severe relapse were treated with IVIg. Since preventive treatment with IVIg was the strongest factor associated with survival, the use of IVIg is suggested as the first line in prevention therapy.

The Clinical Picture of Severe SCLS Episodes Requiring ICU Admission

The Clinical Picture of Severe SCLS Episodes Requiring ICU Admission

Abstract: SCLS is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission.  This study was undertaken to describe the clinical pictures and ICU management of severe SCLS episodes.  This multicenter retrospective analysis concerned patients entered in the European Clarkson's disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016.  Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included.  Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains.  ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9-22 g/dL) and 50 g/L (36.5-58.5 g/L).  IVIG was infused during 15 episodes (25.4%).  A compartment syndrome developed during 12 episodes (20.3%).  Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients' last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2-140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6-180]; p = 0.02) as independent predictors of hospital mortality.  In conclusion, high-volume fluid therapy was independently associated with poorer outcomes.  IVIG use was not associated with improved survival; hence, its use in an ICU setting should be considered prudently and needs further evaluation in future studies.

Clinical Presentation, Management, and Prognostic Factors of SCLS

Clinical Presentation, Management, and Prognostic Factors of Idiopathic Systemic Capillary Leak Syndrome: A Systematic Review

Abstract: A total of 133 case reports (161 patients) and 5 case series (102 patients) of idiopathic SCLS were included in a survey of articles published through end-2016. The findings include that patients had hypotension (81.4%), edema (64.6%), and previous flu-like illness (34.2%). They were often misdiagnosed as having hypovolemic shock, septic shock, polycythemia vera, or angioedema. Thirty-seven patients died (23%) mainly because of complications from SCLS (78.4%). There were significant differences in the survival rates between patients who were treated with prophylactic b2 agonists, methylxanthines, and intravenous immunoglobulins and those who were not. The estimated 1-, 5-, and 10-year survival rate of patients treated with intravenous immunoglobulins was 100%, 94%, and 94%, respectively. The results of this review suggest that prophylactic use of intravenous immunoglobulins is the most effective treatment in reducing the mortality rate of SCLS patients.

Idiopathic SCLS (Clarkson syndrome) in childhood

Idiopathic systemic capillary leak syndrome (Clarkson syndrome) in childhood: systematic literature review

Abstract: The authors performed a systematic review of the literature on Clarkson syndrome in subjects less than 18 years of age, and identified 24 reports, published since 1989, providing data on 32 otherwise healthy subjects, who experienced 67 well-documented episodes of SCLS. The condition affected more frequently girls (21, 66%) than boys, presented throughout childhood, and was preceded by a mostly viral illness in 75% of cases. The presence of a monoclonal gammopathy (MGUS) was never reported. Uncompensated circulatory shock, muscle compartment syndrome, acute kidney injury, pulmonary edema, and either pleural or pericardial effusion were, in decreasing order of frequency, the most common complications. Four patients died. In sum, SCLS develops not only in adulthood but also in childhood, but of potential significance is that in this age group the condition is not linked to an MGUS, and thus it could be that it does not play a pivotal pathogenic role.

Whole Exome Sequencing of SCLS Patients

Whole Exome Sequencing of Adult and Pediatric Cohorts of the Rare Vascular Disorder Systemic Capillary Leak Syndrome

Abstract: The extent to which genetic abnormalities contribute to SCLS is unknown. The authors identified pediatric and adult cohorts with characteristic clinical courses and sought to identify a possible genetic contribution to SCLS through the application of Whole Exome Sequencing (WES). On the basis of 9 adult and 8 pediatric SCLS patients and available unaffected first-degree relatives, they did not identify a uniform germline exomic genetic etiology for SCLS. However, WES did identify several candidate genes for future research.

Chronic SCLS treatment with IVIG: Case & literature

Chronic systemic capillary leak syndrome treatment with intravenous immune globulin: Case report and review of the literature

Abstract: A rarely described chronic form of SCLS (cSCLS) presents as refractory edema, with pleural and/or pericardial effusions and hypoalbuminemia. These entities are differentiated by massive and periodic episodes of capillary leak, which can result in shock in SCLS, and chronic refractory edema in cSCLS. The etiologies of these disorders are poorly understood, but both acute and chronic forms often present with an associated monoclonal gammopathy. Flares of the SCLS have been reduced by treatment with intravenous immune globulin (IVIG). Only six cases of cSCLS have been reported, and previous treatments have included steroids, terbutaline, and theophylline. Based upon the reported responses of SCLS to IVIG, we present the case of a 54-year-old man with cSCLS where ongoing treatment with IVIG resulted in a marked and sustained improvement in the signs and symptoms of the capillary leak syndrome.

Handling Shock in SCLS: Less Is More

Handling shock in idiopathic systemic capillary leak syndrome (Clarkson’s disease): less is more

Abstract: SCLS presents with recurrent potentially life-threatening episodes of hypovolemic shock associated with severe hemoconcentration and hypoproteinemia. Here the authors summarize 40 years’ experience in treating shock in Italian SCLS patients to derive a therapeutic algorithm. Records from 12 patients were informative for treatment modalities and outcome of 66 episodes of shock. Episodes are divided in 3 phases and treatment recommendations are the following: (1) prodromal symptoms-signs (growing malaise, oligo-anuria, orthostatic
dizziness) last 6-12 hours and patients should maintain rigorous bed rest. (2) The acute shock phase lasts 24-36 hours; patients should be admitted to ICU, placed on restrictive infusion of fluids favoring cautious boluses of high-molecular-weight plasma expanders when SAP < 70 mmHg; and monitored for cerebral/cardiac perfusion, myocardial edema and signs of compartment syndrome. (3) The post-acute (recovery) phase may last from 48 hours to 1 week; monitor for cardiac overload to prevent cardiac failure; in case of persistent renal failure, hemodialysis may be necessary; consider albumin infusion. Complications listed by frequency in our patients were acute renal failure, compartment syndrome and neuropathy, rhabdomyolysis, myocardial edema, pericardial-pleural-abdominal effusion, cerebral involvement, acute pulmonary edema and deep vein thrombosis.


Clinical Trials

Cords registry

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access.

Enrolling is easy.

  1. Complete the screening form.
  2. Review the informed consent.
  3. Answer the permission and data sharing questions.

After these steps, the enrollment process is complete. All other questions are voluntary. However, these questions are important to patients and their families to create awareness as well as to researchers to study rare diseases. This is why we ask our participants to update their information annually or anytime changes to their information occur.

Researchers can contact CoRDS to determine if the registry contains participants with the rare disease they are researching. If the researcher determines there is a sufficient number of participants or data on the rare disease of interest within the registry, the researcher can apply for access. Upon approval from the CoRDS Scientific Advisory Board, CoRDS staff will reach out to participants on behalf of the researcher. It is then up to the participant to determine if they would like to join the study.

Visit to enroll.

Community Leaders


I had my first episode of what turned out to be SCLS in November 2005, and was very lucky to have survived it (though with permanent disabilities in arms and legs, and thus in hands and feet) and to have been diagnosed correctly within days.

I went on to have 2 other life- and limb-threatening episodes in April 2007 and March 2009, requiring 2+ weeks of Intensive Care hospitalization to keep my organs alive and emergency fasciotomies to preserve the muscles and nerves I still have in my extremities.

I also had 7 episodes of lesser severity (Dec. 2007, June 2008, June 2009, July 2009, September 2009, and two in November 2009), because I realized I was having them early on, which allowed me to get a massive dose of steroids (Prednisone pills and/or injections of Solu-Medrol and Albumin) that effectively stopped the capillary leak phase of SCLS.

Given the increased frequency of my episodes of SCLS, despite having taken the recommended doses of the traditional medications (e.g., Theophylline, Terbutaline and Singulair), I was given my first infusion of IVIG in November 2009 and have had monthly infusions since then with no adverse side effects whatsoever. So far, so very good: I have had no more episodes of SCLS.

While I was among the first SCLS patients in the United States to benefit from an IVIG therapy, most other patients who had previously been getting this medication in Europe, and virtually all patients around the world who have since received IVIG, have stopped having episodes of SCLS.

Our stories are now told in a number of case studies published in various medical journals, and there is also a scientific article showing the efficacy of IVIG in countering SCLS in laboratory conditions based on our blood samples before and after receiving IVIG, as well as several articles with the results of surveys of SCLS patients who have been on IVIG.  The evidence that IVIG is the best and almost always successful therapy for the prevention of episodes of SCLS is now overwhelming.

My address is


Expert Questions

Ask a question

kbas719 Message
25 Jan 2010, 01:37 AM

Hello, I am new to RareShare. My 16-year-old daughter is currently in the ICU diagnosed with SCLS. When do you start these traditional medications?


I'm so sorry to hear about your teenage daughter. SCLS in young people is very rare, so once she is discharged from the hospital, I suggest you get a 2nd opinion to make sure she was diagnosed correctly. I see that you live in the state of New York. If by chance you are within driving distance of Manhattan, I recommend you seek an appointment with Dr. Mark Pecker of Weill Cornell/New York Presbyterian Hospital, tel. 212-746-2210. Once confirmed, your MD will probably suggest that she start taking Theophylline and Singulair, perhaps with a tranquilizer to offset the side effects of the former. If she still has episodes despite taking those meds, the treatment of last resort is IVIG. In the meantime, you must educate her, yourself, and your personal doctor and the ICU staff at the hospital nearest your home about how to treat an episode of SCLS without causing any collateral damage. To start, have them go through this site (see Disorder Details and Disorder Resources).

heptagona Message
27 Sep 2009, 04:03 PM




How many people have received the loading dose of IVIG 1-2 gm/kg over 2 days without it being during an acute attack? I have only seen literature (one article) supporting it given during an acute attack. I have tried every drug out there to no avail. Since I live in Minnesota I have been to Mayo twice to see Dr. Greipp. Our last discussion we talked about IVIG and Revlimid but decided that IVIG might be the next drug to try. Thank you for your help.





Heptagona (Steve)



P.S. At a later date I will share my SCLS story with the group.


Dear Steve:



The only U.S. patient we've heard from who has just started to get IVIg on a monthly basis is Nolan, who lives in Idaho. Check out the Discussion Forum topic "IVIG" and you will read all about it.



It appears that monthly infusions of IVIg have become the treatment of choice in Europe and in Quebec, and as you will read, our (few) community members from those parts of the world are very pleased with the results.



A recent article published in France in French mentions that many European patients have been on IVIg in recent years, but unfortunately does not say what the success rate has been. If you'd like a copy, send me a private email to and I'll send it to you.



Here in the U.S. we have the practical problem that IVIg infusions are very expensive (about $10,000/month), and thus most insurance companies will not cover it unless there is published evidence that it works. However, you could explore the possibility by getting your own MDs and also Mayo's Dr. Greipp to write letters of support to your insurance company, appealing for coverage and explaining that nothing else has worked. After all, Nolan succeeded, so his precedent may be useful.

josee Message
29 Aug 2009, 04:22 AM

Bonjour Arturo.


j'ai une petite question.


Je me demandais combien il y a de personnes environs dans le monde qui ont été diagnostiqué avec le Syndrome de fuite capillaire systémique?



c'est que c'est la collect de sang dans ma municipalité et je veux faire écrire un article sur moi dans le journal local afin d'inciter les gens à donner du sang.


alors, je veux inscrire quelques statistiques dans l'article.







Bonjour Josée!



Nous ne savons pas combien de personnes souffrent de SCLS, mais comme vous pouvez le voir partir de ce site Web, nous sont découvrir plus en plus chaque semaine qui enfin obtenir le bon diagnostic. Pour l'instant, je dirais que nous savons de moins de 1 000 patients qui ont SCLS.

clswalt Message
4 Mar 2009, 09:43 PM

Arturo, please accept my thanks for pursuing the SCLS story. I have been running blind with very little knowledge of my condition since 2005, and was unaware of what I had until recently. Until today, I have had no contact with others who have SCLS. I am scheduling a first-time visit to Dr. Greipp in April. Have you visited Mayo?


I'm very glad you found your way to RareShare, and feel free to contact me directly at with whatever other personal questions you have. As a matter of fact, no, I've never been to the Mayo Clinic to see Dr. Greipp, but that is because my doctors took the initiative to speak to him on the phone and to read up on what he and others have published on SCLS. I am very grateful to Dr. Greipp that he has been willing to give his best advice -- at no charge -- to my doctors and to others around the world.

clswalt Message
4 Mar 2009, 05:42 PM

Arturo, does any one group or person keep track of SCLS patients? What is the count of SCLS patients?




No, there is no official national or international registry of SCLS patients as of yet, though I'm working on that. As the stories told in this virtual community demonstrate, many of us have only recently been properly diagnosed, and have only recently found a means to make our existence known to each other and the world. Chances are that many victims of SCLS die during their first episode -- before they are properly diagnosed. Even so, SCLS is likely to be a rare disease among rare diseases. It was first described in the medical literature in an article published in 1960.

rnuara Message
26 Feb 2009, 02:26 AM



I recently have been diagnosed with severe capillary leak syndrome. My first attack was 20 years ago. My fifth and most recent attack occured this past July. During the years, I was misdiagnosed and given little hope of ever finding out what was wrong with me. Since my diagnosis, I have met with Dr. Greipp and Dr. Druey at NIH. Dr. Druey sent me the link to the Washington Post article speaking about your advocacy for SCLS. I applaud your dogmatic persistence with NIH so that they allocated funding for this research project. I want to help raise awareness and funding for additional research. Are you still actively pursuing this? Please let me know how I can help.




Welcome to this SCLS community Robert! I am very glad that you were finally diagnosed properly. God only knows how many others there are out there who have yet to be diagnosed correctly -- hopefully before they die or suffer irreparable damage to organs and/or limbs. Write to me at so that I may follow up with you privately.

claude53 Message
11 Feb 2009, 12:31 PM

I thank Rick for his comment on the G-suits for the pilots. I myself found an anti-G suit of the Swiss Air Force. I used it twice, in 2 different cases of serious shocks (undetectable blood pressure) in my residence, to try to mobilize blood remaining in the venous compartment of the legs and the lower abdomen and to support its return towards the heart. This process is effective in the initial phase of the capillary leak, when there is still enough blood in the venous system particularly in the lower extremities. The overpressure which one can reach with these pilot suits allows a transport towards a hospital under good conditions but remains effective only for the extreme urgency of the initial shock. The fluid reanimation in an intensive care unit requires the monitoring with a central venous catheter and peripheral venous lanes for the careful perfusion of volumes of liquid to maintain an acceptable blood pressure around 80mmHg.


Claude Pfefferlé, Switzerland



Thank you very much, Dr. Pfefferlé!

frosty1151 Message
29 Jan 2009, 02:36 AM

My mother has SCLS. We live in Guatemala but here we have not met a specialist in this disorder. Can you help me please in Spanish if at all possible? Thank you.


En este sitio he colocado casi toda la información disponible sobre este muy raro Síndrome de Derrame Capilar Sistémico, pero Ud. tiene que pedirle a alguien que le traduzca este material al español, o de lo contrario ubicar un doctor en medicina interna o hematología que entienda inglés y se pueda beneficiar de este material.



Yo le solicito que Ud. ponga más detalles sobre el caso de su madre en su ficha, explicando por ejemplo cuántos episodios y con qué frecuencia ella ha tenido; qué daños físicos le han causado dichos episodios; y qué medicamentos está tomando -- por si es que le puedo dar algun otro consejo.

claude53 Message
13 Oct 2008, 12:02 PM

According to the french medical literature concerning the treatment of the SCLS by intravenous Immunoglobulines (IvIg), there are 2 different approaches: 1. preventive treatment (by monthly injection of Ig). 2. treatment of an acute crisis per perfusion of Ig as soon as the first symptoms appear. Which is the American experiment on this subject? Do You know how many Patients with SCLS profit from the treatment by IvIg in the USA? I am not informed of another Patient in Switzerland (7 million inhabitants) exept me. Which treatment do you have personally? I thank you for your answer.



As far as I know, there is no ongoing “American experiment” using IVIg either during acute episodes or for prevention purposes. There are 4 reasons for this: 1) Dr. Greipp of the Mayo Clinic, the country’s leading authority on SCLS with whom everyone consults, has not endorsed it; 2) no long-term, convincing study of experimental treatments (in Europe) has been published as of yet; 3) IVIg infusions often lead to unpleasant and costly medical complications; and 4) last but not least, the cost is prohibitive (at least $10,000/injection) and no U.S. insurance company is likely to cover it unless conditions 1-3 have been met. Thus, most patients take various combinations and dosages of Theophylline, Terbutaline and a leukotrine antagonist like Singulair to minimize the frequency and severity of episodes, and are given stress doses of steroids (e.g., Prednisone) as early as possible during an episode.

meldumais Message
27 Aug 2008, 03:10 AM

I see in your discussion you talk about the Mayo Clinic and Doctor Greipp, so how can we get in touch with him? Do we need to be referred to him by a Doctor? Do we know if they other people in Canada have this disease? Thank you so much.


Yes, the proper way to approach a consultation with Mayo's Dr. Greipp is to have your own doctor contact him directly by telephone, so that he/she may be able to tell him precisely what diagnostic, treatment, prevention or other issues need his expert help.



I don't recall from the literature that any doctors in Canada have published about SCLS cases in recent years, but that doesn't mean that there are no cases. For example, most of us survivors of SCLS have not been written about in the medical literature, so I'm sure the case you know about is not the first or only one. SCLS is very rare but also often misdiagnosed.

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