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Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).

Xie Z, Chan E, Yin Y, Ghosh CC, Wisch L, Nelson C, Young M, Parikh SM, Druey KM - J Clin Cell Immunol (2014)

Bottom Line: We analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function.Several cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα.The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.

ABSTRACT

Objectives: The Systemic Capillary Leak Syndrome (SCLS) is a rare and potentially fatal disorder resembling systemic anaphylaxis that is characterized by transient episodes of hypotensive shock and peripheral edema. The pathogenesis of SCLS is unknown, and triggers for attacks are apparent only in a minority of patients. We introduce a clinical algorithm for the diagnosis of SCLS, and we investigated potential serum biomarkers of acute SCLS episodes.

Methods: We analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function. We investigated the cellular source(s) of CXCL10, a chemokine that was significantly elevated in both basal and acute SCLS sera, by flow cytometry.

Results: Several cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα. The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression. Monocytes appear to be the major source of serum CXCL10, and the percentage of CXLC10+ monocytes in response to IFNγ stimulation was increased in SCLS subjects compared to controls.

Conclusions: The presence of proinflammatory cytokines in acute SCLS sera suggests that inflammation or infection may have a role in triggering episodes. The enhanced capacity of monocytes from SCLS patients to produce CXCL10 suggests a new therapeutic avenue for SCLS.

No MeSH data available.


Related in: MedlinePlus

Clinical considerations in the prospective diagnosis of SCLS. After exclusion of primary cardiovascular and/or allergic causes, a diagnosis of SCLS should be entertained in patients with unexplained, transient hypotension and/or peripheral edema. Systemic anaphylaxis and hereditary and/or acquired angioedema can be excluded by measurement of serum tryptase during the acute episode and quantitative and functional assays for the complement component 1 esterase inhibitor (C1 INH). Although presumptive treatment for sepsis is prudent in the undiagnosed SCLS patient during the first severe episode, the hypotension and hemoconcentration of SCLS are typically refractory to intravenous fluid resuscitation, which exacerbates peripheral edema. Hypoalbuminemia due to protein extravasation is a hallmark of classic acute SCLS whereas low serum albumin levels and edema that does not resolve between episodes should prompt the diagnosis of “chronic” SCLS. MGUS is not universally present in SCLS and is therefore not required for the diagnosis.
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Figure 1: Clinical considerations in the prospective diagnosis of SCLS. After exclusion of primary cardiovascular and/or allergic causes, a diagnosis of SCLS should be entertained in patients with unexplained, transient hypotension and/or peripheral edema. Systemic anaphylaxis and hereditary and/or acquired angioedema can be excluded by measurement of serum tryptase during the acute episode and quantitative and functional assays for the complement component 1 esterase inhibitor (C1 INH). Although presumptive treatment for sepsis is prudent in the undiagnosed SCLS patient during the first severe episode, the hypotension and hemoconcentration of SCLS are typically refractory to intravenous fluid resuscitation, which exacerbates peripheral edema. Hypoalbuminemia due to protein extravasation is a hallmark of classic acute SCLS whereas low serum albumin levels and edema that does not resolve between episodes should prompt the diagnosis of “chronic” SCLS. MGUS is not universally present in SCLS and is therefore not required for the diagnosis.

Mentions: SCLS should be considered in a patient with unexplained, transient hypotension and/or peripheral edema (Figure 1). If a temporally linked exposure (e.g. food, insect venom, drug) is suspected, elevated serum tryptase should exclude systemic anaphylaxis. Although our experience and that of others [6,9] suggest that acute triggers for SCLS attacks are often absent, viral-type upper respiratory and/or systemic symptoms may be present in many patients with SCLS prior to the onset of an episode. While catastrophic SCLS attacks are typically accompanied by massive edema of the face, trunk, and peripheral extremities, swelling resembling angioedema may be confined to certain areas (periorbital, back, and abdomen) in less severe episodes. Thus, complement factor 1 esterase inhibitor (C1 INH) levels and function should be evaluated in all patients with suspected SCLS to rule out hereditary or acquired angioedema.


Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).

Xie Z, Chan E, Yin Y, Ghosh CC, Wisch L, Nelson C, Young M, Parikh SM, Druey KM - J Clin Cell Immunol (2014)

Clinical considerations in the prospective diagnosis of SCLS. After exclusion of primary cardiovascular and/or allergic causes, a diagnosis of SCLS should be entertained in patients with unexplained, transient hypotension and/or peripheral edema. Systemic anaphylaxis and hereditary and/or acquired angioedema can be excluded by measurement of serum tryptase during the acute episode and quantitative and functional assays for the complement component 1 esterase inhibitor (C1 INH). Although presumptive treatment for sepsis is prudent in the undiagnosed SCLS patient during the first severe episode, the hypotension and hemoconcentration of SCLS are typically refractory to intravenous fluid resuscitation, which exacerbates peripheral edema. Hypoalbuminemia due to protein extravasation is a hallmark of classic acute SCLS whereas low serum albumin levels and edema that does not resolve between episodes should prompt the diagnosis of “chronic” SCLS. MGUS is not universally present in SCLS and is therefore not required for the diagnosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232957&req=5

Figure 1: Clinical considerations in the prospective diagnosis of SCLS. After exclusion of primary cardiovascular and/or allergic causes, a diagnosis of SCLS should be entertained in patients with unexplained, transient hypotension and/or peripheral edema. Systemic anaphylaxis and hereditary and/or acquired angioedema can be excluded by measurement of serum tryptase during the acute episode and quantitative and functional assays for the complement component 1 esterase inhibitor (C1 INH). Although presumptive treatment for sepsis is prudent in the undiagnosed SCLS patient during the first severe episode, the hypotension and hemoconcentration of SCLS are typically refractory to intravenous fluid resuscitation, which exacerbates peripheral edema. Hypoalbuminemia due to protein extravasation is a hallmark of classic acute SCLS whereas low serum albumin levels and edema that does not resolve between episodes should prompt the diagnosis of “chronic” SCLS. MGUS is not universally present in SCLS and is therefore not required for the diagnosis.
Mentions: SCLS should be considered in a patient with unexplained, transient hypotension and/or peripheral edema (Figure 1). If a temporally linked exposure (e.g. food, insect venom, drug) is suspected, elevated serum tryptase should exclude systemic anaphylaxis. Although our experience and that of others [6,9] suggest that acute triggers for SCLS attacks are often absent, viral-type upper respiratory and/or systemic symptoms may be present in many patients with SCLS prior to the onset of an episode. While catastrophic SCLS attacks are typically accompanied by massive edema of the face, trunk, and peripheral extremities, swelling resembling angioedema may be confined to certain areas (periorbital, back, and abdomen) in less severe episodes. Thus, complement factor 1 esterase inhibitor (C1 INH) levels and function should be evaluated in all patients with suspected SCLS to rule out hereditary or acquired angioedema.

Bottom Line: We analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function.Several cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα.The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.

ABSTRACT

Objectives: The Systemic Capillary Leak Syndrome (SCLS) is a rare and potentially fatal disorder resembling systemic anaphylaxis that is characterized by transient episodes of hypotensive shock and peripheral edema. The pathogenesis of SCLS is unknown, and triggers for attacks are apparent only in a minority of patients. We introduce a clinical algorithm for the diagnosis of SCLS, and we investigated potential serum biomarkers of acute SCLS episodes.

Methods: We analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function. We investigated the cellular source(s) of CXCL10, a chemokine that was significantly elevated in both basal and acute SCLS sera, by flow cytometry.

Results: Several cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα. The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression. Monocytes appear to be the major source of serum CXCL10, and the percentage of CXLC10+ monocytes in response to IFNγ stimulation was increased in SCLS subjects compared to controls.

Conclusions: The presence of proinflammatory cytokines in acute SCLS sera suggests that inflammation or infection may have a role in triggering episodes. The enhanced capacity of monocytes from SCLS patients to produce CXCL10 suggests a new therapeutic avenue for SCLS.

No MeSH data available.


Related in: MedlinePlus