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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Hematology

Subtypes, Triggers, and Blood Markers

At a Glance

Systemic capillary leak syndrome differs between adults and children: adults often have a monoclonal protein, while children usually do not, and viral infections commonly trigger flares. A missing monoclonal protein does not rule out SCLS.

While all cases of Systemic Capillary Leak Syndrome (SCLS) involve the same “leaky pipe” problem in the capillaries, the condition can look different depending on your age and the specific markers in your blood. Understanding these subtypes can help you and your doctors better predict and manage your risk [1][2].

Adult SCLS and the “M-Spike”

In adults, primary SCLS is frequently associated with an unusual protein in the blood called a monoclonal protein (or M-spike).

  • MGUS vs. M-Spike: Finding a monoclonal protein does not by itself establish a diagnosis of Monoclonal Gammopathy of Undetermined Significance (MGUS); further hematology testing is required to classify it. MGUS is generally benign but requires observation.
  • The SCLS Connection: In one Italian registry study, 20 out of 23 adults with SCLS had this monoclonal finding [3]. While researchers aren’t exactly sure why this protein is linked to capillary leaks, its presence is a key diagnostic clue for doctors.
  • Long-Term Monitoring: Because MGUS can occasionally progress to a more serious blood disorder, adults with SCLS typically need monitoring of these protein levels at risk-based intervals determined by a hematologist [2][4].

Pediatric SCLS: A Different Picture

Children with SCLS (pediatric SCLS) often have a different experience than adults.

  • No M-Spike: Unlike adults, children rarely have a monoclonal protein. In a systematic review of 32 children with SCLS, none had MGUS reported [1]. However, the absence of an M-protein does not exclude SCLS, in children or adults.
  • Heavy Viral Triggers: Pediatric flares are frequently triggered by an infection. The same systematic review found that about 75% of childhood episodes were preceded by a viral illness, most commonly the flu (influenza) [1][5].
  • Specific Risks: Children may be at a higher risk for certain complications during an attack, such as rhabdomyolysis (severe muscle breakdown) and compartment syndrome [5].

Common Triggers for an Attack

For many patients, identifying potential triggers is a major part of living with SCLS.

  1. Infections: Viral illnesses are a major recognized trigger. This includes the flu, common upper respiratory infections, and more recently, COVID-19 [6][7].
  2. Vaccinations: Isolated case reports have described SCLS flares shortly after vaccinations, including Japanese encephalitis vaccines and COVID-19 vaccines [8][9]. However, these temporal reports do not establish causation. Because infections are a major trigger for SCLS flares, avoiding indicated vaccinations can expose you to infections that commonly trigger attacks. Vaccination decisions should be individualized with your SCLS specialist, and indicated vaccines should not be avoided purely based on isolated reports.
  3. Physical Stressors: Intense physical exertion, surgery, or rare events like decompression sickness from deep diving have been reported in case studies as potential triggers [10][11].
  4. Medications: Certain cancer treatments, such as immune checkpoint inhibitors or “growth factor” drugs like pegfilgrastim, can trigger a secondary capillary leak [12][13].

Episodic vs. Chronic Presentations

Most people with SCLS have an episodic (relapsing-remitting) form. In this type, you have distinct attacks (flares) followed by a “recruitment” phase where you return to your normal baseline [14][15].

In some rare cases, patients present with persistent, long-term swelling (edema) and low albumin levels. This is sometimes referred to in literature as a “chronic” form of SCLS [16][17]. However, persistent edema and hypoalbuminemia require careful specialist reassessment to exclude other causes (such as heart or kidney disease). The evidence for a separate chronic subtype and its specific treatment is limited, and management must be highly individualized [16][18].

Common questions in this guide

What does an M-spike mean in systemic capillary leak syndrome?
An M-spike is an unusual monoclonal protein found in the blood and is a useful clue in many adults with SCLS. It does not by itself establish MGUS; a hematologist may use tests such as immunofixation and a serum free light chain assay to classify the finding and decide how often to monitor it.
Can children have SCLS without a monoclonal protein?
Yes. Children with SCLS rarely have a monoclonal protein, and its absence does not exclude SCLS in children or adults. Pediatric attacks are often preceded by a viral infection, especially influenza.
What can trigger a systemic capillary leak syndrome attack?
Commonly reported triggers include viral infections, intense physical exertion, surgery, and certain medications such as immune checkpoint inhibitors or pegfilgrastim. Isolated reports have described flares after some vaccines, but timing alone does not prove that a vaccine caused the attack.
Should I avoid vaccines if I have SCLS?
Not solely because of isolated case reports. Infections are important SCLS triggers, so vaccine decisions should be individualized with your SCLS specialist, and indicated vaccines should not be skipped without discussing the risks and benefits.
Is SCLS episodic or chronic?
Most patients have an episodic, relapsing-remitting pattern with attacks followed by a return to baseline. Persistent swelling or low albumin is sometimes called chronic SCLS, but it needs specialist evaluation to rule out heart, kidney, or other causes because evidence for a separate chronic subtype is limited.
How often should monoclonal proteins be monitored in adults with SCLS?
The monitoring interval depends on the protein finding and individual risk factors, so a hematologist should set the schedule. Monitoring can help identify changes associated with MGUS or another blood disorder, but finding a monoclonal protein alone does not establish a serious blood disease.

Questions For You

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Has a high-sensitivity test like immunofixation or a serum free light chain assay been used to check for monoclonal proteins?
  2. 2.Since I am an adult with a monoclonal protein, how often should we screen for progression based on my individualized risk factors?
  3. 3.What viral infections should I be particularly cautious about, given my history of flares?
  4. 4.Is my presentation considered 'relapsing-remitting' or do I have signs of a more persistent, chronic form?
  5. 5.How does the absence of a monoclonal protein (if applicable) change my long-term outlook or treatment plan?

References

References (18)
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    Idiopathic systemic capillary leak syndrome (Clarkson syndrome) in childhood: systematic literature review.

    Bozzini MA, Milani GP, Bianchetti MG, et al.

    European journal of pediatrics 2018; (177(8)):1149-1154 doi:10.1007/s00431-018-3189-8.

    PMID: 29936591
  2. 2

    Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease).

    Xie Z, Chen WS, Yin Y, et al.

    Journal of leukocyte biology 2018; (103(4)):749-759 doi:10.1002/JLB.5A0817-324R.

    PMID: 29360169
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    Clarkson disease in critically and non-critically ill patients: insights from the Italian IRIS-CLS registry.

    Colombo R, Montomoli J, Lanzi T, et al.

    Internal and emergency medicine 2025; (20(4)):991-1001 doi:10.1007/s11739-025-03890-x.

    PMID: 40057670
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    [Idiopathic and secondary capillary leak syndromes: A systematic review of the literature].

    Duron L, Delestre F, Amoura Z, Arnaud L

    La Revue de medecine interne 2015; (36(6)):386-94.

    PMID: 25600329
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    Idiopathic systemic capillary leak syndrome and related shock in PICU: an underdiagnosed disease?

    Piastra M, Portaccio I, Dondi A, et al.

    Journal of anesthesia, analgesia and critical care 2026; (6(1)):22 doi:10.1186/s44158-026-00337-3.

    PMID: 41514342
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    Clinical Presentation, Management, and Prognostic Factors of Idiopathic Systemic Capillary Leak Syndrome: A Systematic Review.

    Eo TS, Chun KJ, Hong SJ, et al.

    The journal of allergy and clinical immunology. In practice 2018; (6(2)):609-618 doi:10.1016/j.jaip.2017.07.021.

    PMID: 28939140
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    Systemic Capillary Leak Syndrome triggered by SARS-CoV2 infection: Case Report and Systematic Review.

    Beber A, Dellai F, Abdel Jaber M, et al.

    Scandinavian journal of rheumatology 2022; (51(1)):67-69 doi:10.1080/03009742.2021.1917145.

    PMID: 34169783
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    A rare cause of shock in cases of refractory hypotension, hypoproteinaemia and haemoconcentration.

    Elhassan O, Williams S, Joseph F

    Clinical medicine (London, England) 2026; (26(2)):100550 doi:10.1016/j.clinme.2025.100550.

    PMID: 41500395
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    A Case of Systemic Capillary Leak Syndrome With Severe Cardiac Dysfunction After mRNA Vaccination for COVID-19.

    Araki T, Morimoto R, Ito R, et al.

    CJC open 2022; (4(7)):656-659 doi:10.1016/j.cjco.2022.03.008.

    PMID: 35345835
  10. 10

    A case report of idiopathic systemic capillary leak syndrome that occurred during the postoperative period of abdominoperineal resection for colorectal cancer.

    Ozawa T, Yamaguchi H, Kiyomatsu T, et al.

    International surgery 2015; (100(1)):58-62 doi:10.9738/INTSURG-D-13-00206.1.

    PMID: 25594640
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    Systemic capillary leak syndrome secondary to decompression sickness.

    Mathavan A, Mathavan A, Jones K, Ataya A

    BMJ case reports 2023; (16(7)) doi:10.1136/bcr-2022-253045.

    PMID: 37407231
  12. 12

    Denileukin diftitox-induced systemic capillary leak syndrome with acute kidney injury.

    Horino T, Okada D, Inotani S, et al.

    CEN case reports 2023; (12(1)):63-67 doi:10.1007/s13730-022-00720-3.

    PMID: 35870043
  13. 13

    A Case of Concurrent Leukocytosis and Systemic Capillary Leak Syndrome Due to Pegfilgrastim.

    Gotera N, Hasan S, Shrestha P, et al.

    Cureus 2022; (14(5)):e24640 doi:10.7759/cureus.24640.

    PMID: 35663724
  14. 14

    A fatal case of acute progression of generalized edema and simultaneous flash pulmonary edema in a patient with idiopathic systemic capillary leak syndrome: a case report.

    Hirosaki Y, Hayashidani S, Ouchi S, et al.

    Journal of medical case reports 2015; (9()):90 doi:10.1186/s13256-015-0544-5.

    PMID: 25928289
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    Anesthetic Considerations for a Patient With Chronic Systemic Capillary Leak Syndrome: A Case Report.

    Datta R, Panchamia JK

    A&A practice 2018; (11(10)):276-278 doi:10.1213/XAA.0000000000000808.

    PMID: 29894349
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    Chronic systemic capillary leak syndrome treatment with intravenous immune globulin: Case report and review of the literature
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    Mullane R, Langewisch E, Florescu M, Plumb T

    Clinical nephrology 2019; (91(1)):59-63 doi:10.5414/CN109467.

    PMID: 30431430
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    Chronic systemic capillary leak syndrome with lymphatic capillaries involvement and MYOF mutation: case report and literature review.

    Gao D, Zhong W, Zhang W, et al.

    Frontiers in genetics 2023; (14()):1282711 doi:10.3389/fgene.2023.1282711.

    PMID: 38054026
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    Chronic idiopathic systemic capillary leak syndrome: a case report.

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    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 2019; (15()):34 doi:10.1186/s13223-019-0347-0.

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This page explains SCLS subtypes, possible triggers, and blood-marker findings for education only; it is not medical advice. A hematologist or SCLS specialist should interpret your tests and guide monitoring, vaccination, and flare planning.