If not angioedema, what is it? Diagnostic approach to facial edema.

Facial edema is a relatively frequent clinical presentation encountered in patients seen in allergology and dermatology clinics. The differential diagnosis is broad, and sometimes the definitive diagnosis can be a challenge for the clinician. Facial angioedema itself encompasses different etiopathologies (histaminergic, bradykinergic, etc.) that must be distinguished from other causes of facial edema, such as allergic contact dermatitis, granulomatous conditions, inflammatory causes, infections, neoplasms or paraneoplastic syndromes, autoimmune diseases, among other entities hereby referred as miscellanea. A proper diagnostic approach is essential to order the appropriate tests, as well as to prescribe a targeted treatment. This review focuses on entities that present with facial edema and summarize their characteristic clinical features.

Idiopathic systemic capillary leak syndrome, a unique complement and interferon mediated endotheliopathy syndrome: The role of the normal skin biopsy in establishing the diagnosis and elucidating pathogenetic mechanisms.

Idiopathic Systemic Capillary Leak Syndrome (ISCLS), also known as Clarkson's Syndrome, is due to primary fluid and protein leak across capillaries that leads to an accumulation of interstitial fluids and cardiovascular collapse from intravascular hypovolemia. Viral infections are a putative trigger of these episodes. ISCLS is typically associated with a monoclonal gammopathy. Here we present four patients with idiopathic systemic capillary leak syndrome. The cohort consists of three men and one woman who range in age from 55 to 72 years old. All of the patients had a monoclonal gammopathy. Two patients had viral triggers. Biopsies of normal skin were examined throughout all phases of the disease. During an acute attack, we identified perivascular mixed CD4+ and CD8+ T cell lymphocytic infiltrates in the superficial dermis. We observed significant microvascular deposits of C5b-9 and upregulation of type I interferon signaling in endothelium along with reduced serum levels of complement during very active disease. We also identified deposits of immunoglobulin along the dermal epidermal junction mirroring the monoclonal immunoglobulin isotype implicated in each patient. During a post treatment recovery or mild disease phase there was reduced inflammation and decreased amounts of C5b-9 and type I interferon expression. Sudden onset capillary leak syndrome reflects enhanced endothelial cell permeability as a unique form of endothelial injury mediated by the combined effects of complement pathway activation and upregulation of type I interferon signaling on endothelium.

Fatal Exacerbations of Systemic Capillary Leak Syndrome Complicating Coronavirus Disease.

We report 2 fatal exacerbations of systemic capillary leak syndrome (SCLS), also known as Clarkson disease, associated with coronavirus disease (COVID-19) in the United States. One patient carried an established diagnosis of SCLS and the other sought treatment for new-onset hypotensive shock, hemoconcentration, and anasarca, classic symptoms indicative of an SCLS flare. Both patients had only mild-to-moderate symptoms of COVID-19. This clinical picture suggests that these patients succumbed to complications of SCLS induced by infection with severe acute respiratory syndrome coronavirus 2. Persons with known or suspected SCLS may be at increased risk for developing a disease flare in the setting of mild-to-moderate COVID-19 infection.

Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2Vaccination in Patient with Multiple Myeloma.

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.

[Stakeholder Analysis of the Application of Artificial Intelligence in the Field of Primary Health Care].

The application of artificial intelligence in the field of primary health care can effectively improve diagnosis and treatment,avoid over-examination and over-medication,and make up for the shortage of high-quality medical resources in primary medical and health institutions.Focusing on the application of artificial intelligence in the field of primary health care,this paper analyzes the existing application modes and typical cases,studies its main stakeholders,interest demands and problems,and provides corresponding suggestions.

Myocardial oedema in an 8-year-old Chinese boy with Idiopathic systemic capillary leak syndrome.

BACKGROUND: Idiopathic systemic capillary leak syndrome (ISCLS) is rare, and there has been about 32 cases reported in children worldwide since this disorder was first described in 1960. Clinical guidelines on the management approach stemming from robust scientific evidence are lacking. This case report presents the first reported paediatric case of severe ISCLS with significant myocardial oedema and emphasizes this disease's impact on a child's cardiac function. CASE PRESENTATION: A Chinese boy had his first attack of severe hypovolaemic shock that responded to fluid resuscitation when he was 6 years of age. His second attack developed at 8 years of age. He was then transferred to our cardiac unit for refractory hypotensive shock. The patient's echocardiogram revealed ventricular wall thickening with significant cardiac dysfunction requiring extracorporeal membrane oxygenation support. Subsequently, he made a full recovery, including his myocardial wall thickness and function. The echocardiographic findings suggested myocardial oedema that was transient in nature. Clinical and laboratory investigation from both episodes were compatible with ISCLS. CONCLUSION: ISCLS is rare, and therefore there is only a limited understanding on the pathophysiology of this disorder. The current treatment approach is based on a few case reports and series. During the acute phase, optimal supportive management is paramount. Our case highlights the importance of early recognition and consideration for extracorporeal membrane oxygenation support in patients with a life-threatening presentation, as it was lifesaving for this child who suffered myocardial oedema and ventricular dysfunction.

[Investigation of Estimation Accuracy of Phantom Scatter Factor by Clarkson Method Considering Depth in MLC Irregular Field].

In monitor unit (MU) independent verification by calculation for irregular field (MLC field) using multileaf collimator in X-ray therapy, it has become common to use collimator scatter factor (Sc) and phantom scatter factor (Sp) instead of total scatter factor (Sc, p). It is usually expressed as Sc, p (A)=Sc (A)×Sp (A), and the field size A is considered but the depth d is not. Sc is data of in-air output, and measure with a mini-phantom at constant depth to remove electron contamination. On the other hand, Sp is obtained from measurement data of Sc, p and Sc, and can be expressed as Sc, p (d, A)=Sc (constant depth, A)×Sp (d, A) at an arbitrary depth d, thus Sp depends on the depth of Sc, p. Therefore, Sp needs to consider depth. In addition, a linear accelerator equipped with the tertiary MLC has two field sizes, that are collimator field by upper and lower collimators and MLC field by tertiary MLC below them. In MU independent verification by calculation, it is often used that the estimated value of Sp obtained by converting MLC field to equivalent square field and referring to data of Sp in square field. To convert the MLC field to equivalent square field, a conversion formula from sector radius r to equivalent square field L by Clarkson's sector integration (Clarkson method) is used. In this study, using 24 types of MLC fields to evaluate estimation accuracy due to the difference of conversion formula in Clarkson method, we estimated value of Sp using r=0.5611L of B-Clarkson method and using r=0.5580L of A-Clarkson method. And the difference with the measured value of Sp obtained by measuring Sc, p and Sc in the same MLC fields was compared. While, to evaluate estimation accuracy due to the different depths using these Clarkson methods, the difference between estimated value and measured value of Sp similarly obtained at depth of 5, 10 and 15 cm was compared. As results, estimated value of Sp using A-Clarkson method than using B-Clarkson method was close to measured value, and it was the same trend at depth of 5, 10 and 15 cm. Therefore, it was suggested that estimation accuracy of Sp by A-Clarkson method is higher than B-Clarkson method when verifying beams with different depths in MU independent verification by calculation for MLC field.

Convolution-based modified Clarkson integration (CMCI) for electron cutout factor calculation.

Electron therapy is widely used to treat shallow tumors because of its characteristic sharp dose fall-off beyond a certain range. A customized cutout is typically applied to block radiation to normal tissues. Determining the final monitor unit (MU) for electron treatment requires an output factor for the cutout, which is usually generated by measurement, especially for highly irregular cutouts. However, manual measurement requires a lengthy quality assurance process with possible errors. This work presents an accurate and efficient cutout output factor prediction model, convolution-based modified Clarkson integration (CMCI), to replace patient-specific output factor measurement. Like the Clarkson method, we decompose the field into basic sectors. Unlike the Clarkson integration method, we use annular sectors for output factor estimation. This decomposition method allows calculation via convolution. A 2D distribution of fluence is generated, and the output factor at any given point can be obtained. We applied our method to 10 irregularly shaped cutouts for breast patients for 6E, 9E, and 15E beams and compared the results with measurements and the electron Monte Carlo (eMC) calculation using the Eclipse planning system. While both the CMCI and eMC methods showed good agreement with chamber measurements and film measurements in relative distributions at the nominal source to surface distance (SSD) of 100 cm, eMC generated larger errors than the CMCI method at extended SSDs, with up to -9.28% deviations from the measurement for 6E beam. At extended SSD, the mean absolute errors of our method relative to measurements were 0.92 and 1.14, while the errors of eMC were 1.42 and 1.79 for SSD 105 cm and 110 cm, respectively. These results indicate that our method is more accurate than eMC, especially for low-energy beams, and can be used for MU calculation and as a QA tool for electron therapy.

Mimicking pneumonia with septic shock: A case report and literature review.

Hydrochlorothiazide (HCTZ) is a commonly used diuretic antihypertensive drug that can cause electrolyte disorders, hyperglycemia and hyperuricemia as well as rare life-threatening adverse drug reactions. These include non-cardiogenic pulmonary edema, interstitial pneumonia, angioedema and aplastic anemia. The present report describes a case of a 59-year-old man who developed a hypersensitivity reaction to HCTZ. Specifically, the patient presented with symptoms of cough, chest tightness and shortness of breath, with pneumonic consolidation on chest CT and elevated levels of white blood cell count, neutrophil percentage, C-reactive protein and procalcitonin. A presumptive diagnosis of severe pneumonia was made initially. However, during the gradual recovery of the patient through treatment, he mistakenly ingested HCTZ containing losartan potassium intended for another patient, which resulted in symptoms similar to those observed upon admission. Upon further inquiry into the medical history, it was revealed that the patient had also taken irbesartan/HCTZ 4 h prior to hospitalization. There was no evidence of a pathogenic infection. Therefore, HCTZ-induced anaphylactic reaction was considered to be the most likely etiology for his severe shock. Treatments including epinephrine, methylprednisolone and respiratory support were administered. After 7 days, the patient was transferred from the Respiratory Intensive Care Unit [The Affiliated Jiangning Hospital of Nanjing Medical University (Nanjing, China)] to a general ward. During the follow-up, 12 months after advising the patient to discontinue HCTZ, there had been no recurrence of the aforementioned symptoms. At the time of publication, the patient is currently alive.

Sorafenib-Induced Capillary Leak Syndrome.

Capillary leak syndrome is a rare life-threatening disorder of acute endothelial hyperpermeability. It consists of initial fluid extravasation resulting in hypotension, hypoalbuminemia, and hemoconcentration, followed by noncardiogenic pulmonary edema from rapid fluid remobilization into intravascular compartment. Drug-induced etiology is an important diagnostic consideration in cancer patients, particularly with use of antimetabolites, immunostimulants, and monoclonal antibodies. Sorafenib-mediated capillary leak syndrome has never been reported. Here, we present the case of a 29-year-old female patient with a desmoid tumor of the thigh, who was admitted for acute hypoxic respiratory failure after recent initiation of sorafenib. She was found to have extensive pulmonary edema, bilateral pleural effusions, and hemoconcentration, all of which stabilized on supportive care with noninvasive mechanical ventilation and intravenous diuresis. Her infectious and cardiac work-up were negative. Given the temporal relationship between sorafenib use and symptom onset as well as a lack of an alternative etiology of her findings, patient was deemed to have sorafenib-induced acute capillary leak syndrome. Importantly, she did not become hypotensive prior to or during this hospitalization. To our knowledge, we reported for the first time an atypical presentation of acute capillary leak syndrome due to sorafenib use without hemodynamic instability.

Idiopathic Systemic Capillary Leak Syndrome: A Clinical Case.

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare condition caused by the extravasation of intravascular fluids and proteins into the interstitial space due to increased vascular endothelium permeability. It is characterized by episodes of hypotension, hypoalbuminemia, and hemoconcentration with generalized edema. Its etiopathogenesis is unknown. However, it is associated with monoclonal gammopathy in more than 80% of cases. There is currently no targeted treatment, and the approach during a crisis is supportive, mainly to control blood pressure, maintain perfusion of vital organs, and prevent complications, such as acute pulmonary edema and organ failure due to ischemia, which are the primary causes of death. We present the case of a 72-year-old man with generalized edema and pleural, pericardial, and peritoneal effusions whose laboratory results showed hypoalbuminemia, hypoproteinemia, and immunoglobulin G kappa monoclonal gammopathy. Other etiologies for severe hypoalbuminemia with anasarca were excluded after an exhaustive complementary study, leading to the diagnosis of ISCLS associated with monoclonal gammopathy. The patient showed progressive clinical improvement with albumin and diuretic therapy. However, they were readmitted to the hospital due to hypotension with multiorgan dysfunction and died a few hours later.

Systemic Capillary Leak Syndrome as a Rare, Potentially Fatal Complication of COVID-19: A Case Report and Literature Review.

Systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare and potentially lethal condition characterized by hypotension, hemoconcentration, and hypoalbuminemia; however, the cause of SCLS is still uncertain. We present the case of a 62-year-old male with flu-like symptoms who presented to the emergency department with shock. Initial evaluation revealed hemoconcentration, hypoalbuminemia, acute kidney failure, and positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite aggressive fluid resuscitation, the shock persisted, and the patient's condition deteriorated. After ruling out ischemia and septic shock, the patient was diagnosed with coronavirus disease 2019 (COVID-19)-associated SCLS. Treatment with remdesivir and intravenous immunoglobulin (IVIG), along with the restoration of intravascular volume, led to the gradual improvement of the patient's condition. The patient experienced pulmonary edema, which was managed by correcting the fluid balance through continuous hemodiafiltration. Eventually, the patient recovered without any residual organ complications. SCLS is often misdiagnosed because of its rarity and non-specific symptoms. Accurate diagnosis and understanding of the disease's pathophysiology are crucial for effective management. This report contributes to the existing literature by presenting a case of COVID-19-associated SCLS and emphasizes the need for further research on its occurrence and outcomes.

Capillary hyperpermeability syndrome: A fatal complication of acute leukaemia: Case report and review.

INTRODUCTION: The capillary hyperpermeability syndrome is a rare disease that should be suspected in the presence of recurrent generalized edema without obvious cause, which may be idiopathic or secondary. CASE PRESENTATION: In this case, we report a Clarkson syndrome secondary to an acute leukemia affecting a 4-year-old child admitted to the emergency room in respiratory and hemodynamic distress with a generalized oedematous syndrome and a bone marrow failure syndrome. Laboratory tests concluded that the patient was suffering from an acute lymphoblastic leukemia, hypoalbuminemia, pericardial effusion, and the absence of any other cause that is in favor of a capillary leak syndrome.In spite of the filling and the introduction of drugs, the cardio respiratory arrest could not be recovered and the child died 24h after his admission. DISCUSSION: It is a rare pathology described for the first time in 1960, generally secondary to a pathological state and more rarely idiopathic, to be evoked in front of clinical and biological parameters which are hypoalbuminemia, hemiconcentration and hypoperfusion, after having eliminated a sepsis in the first place.The treatment is based on the management of the acute phase by filling with crystalloids, drugs or even steroids, and as a preventive treatment of relapses immunoglobulins or theophylline are used. CONCLUSION: The evolution can be quickly fatal, that's why it is necessary to know how to evoke this syndrome in front of a similar clinical presentation.

A Rare Case of Idiopathic Systemic Capillary Leak Syndrome.

Idiopathic systemic capillary leak syndrome (SCLS) is characterized by an increased capillary hyperpermeability with subsequent hemoconcentration, hypoproteinemia, and hypovolemia. Patients present with diffuse swelling, weight gain, low blood pressure, and shock. We present our case of idiopathic SCLS in a 50-year-old man presenting with prodromal flu-like illness associated with shock that was complicated by compartment syndrome requiring four limb fasciotomies, disseminated intravascular coagulation, acute kidney injury requiring dialysis, and cardiac arrest.

Intravenous Immunoglobulins Tapering and Withdrawal in Systemic Capillary Leak Syndrome (Clarkson Disease).

BACKGROUND: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown. OBJECTIVE: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS. METHODS: We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal. RESULTS: Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W- group). Cumulative probabilities of 10-year survival in W+ versus W- groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W- groups were 72% versus 58% (P = 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P = .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model. CONCLUSIONS: The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients.

A deadly capillary leak attack. Clarkson's disease: a narrative review.

A previously 42-year-old healthy man was brought in by an ambulance to the emergency department with symptoms of a distributive shock. He experienced a rapid decline in his clinical state that evolved into a cardiac arrest. Despite all the performed measures and a prolonged resuscitation, the patient died a few hours later without an initial clear diagnosis. Lab results showed an extremely high haemoconcentration leading to further investigations which suggested the possibility of Clarkson's disease, although septic shock as an alternative diagnosis could not be excluded. Nevertheless, because of its presentation, especially emergency and intensive care physicians should be aware of the existence of this condition in the event of an unexplained refractory distributive shock in combination with haemoconcentration and hypoalbuminemia given its possible fatal outcome.

Capillary leak syndrome: State of the art in 2021.

Capillary leak syndrome (CLS) is an increasingly acknowledged multifaceted and potentially lethal disease. Initial nonspecific symptoms are followed by the intriguing CLS hallmark: the double paradox associating diffuse severe edema and hypovolemia, along with hemoconcentration and hypoalbuminemia. Spontaneous resolutive phase is often associated with poor outcome due to iatrogenic fluid overload during leak phase. CLS is mainly triggered by drugs (anti-tumoral therapies), malignancy, infections (mostly viruses) and inflammatory diseases. Its idiopathic form is named after its eponymous finder: Clarkson's disease. CLS pathophysiology involves a severe, transient and multifactorial endothelial disruption which mechanisms are still unclear. Empirical and based-on-experience treatment implies symptomatic care during the acute phase (with the eventual addition of drugs amplifying cAMP levels in the severest cases), and the prophylactic use of monthly polyvalent immunoglobulins to prevent relapses. As CLS literature is scattered, we aimed to collect and summarize the current knowledge on CLS to facilitate its diagnosis, understanding and management.

[Idiopathic systemic capillary leak syndrome: 2 cases with misleading presentation]. / Syndrome de fuite capillaire idiopathique : 2 cas cliniques de présentation trompeuse.

INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) also known as Clarkson syndrome is a rare and sudden life-threatening entity. Three consecutive phases are described. A first non-specific prodromal phase often manifests as "flu-like" symptoms and precedes capillary leak phase with major hypovolemic and distributive shock leading to serious and frequent multiorgan dysfunction syndrome (MODS). Severe hypovolemia contrasts with edema, and hemoconcentration with hypoalbuminemia. ISCLS is characterized by these two clinical and biological paradoxes. Subsequent recovery phase exhibits organ function restoration along with interstitial/intravascular volumes normalization. The latter occurs spontaneously and systematically in patients surviving from leak phase. OBSERVATIONS: We report here two ISCLS cases admitted in intensive care unit (ICU) both enhancing initial misdiagnosis possibly lowering prognosis and outcome. Our first 28-year-old female patient was admitted for « polycythemia vera ¼ although hemoconcentration was attributable to hypovolemia. She presented circulatory arrest during the second bloodletting session and complicated with MODS. In and out ICU favorable outcome was noted on intravenous immunoglobulin therapy. A second 57-year-old male patient was admitted in ICU for severe "myositis" (myalgia and rhabdomyolysis) although rectified diagnosis retained compartment syndrome (muscular severe edema following capillary leak). Rapid and refractory hypovolemic shock appeared with subsequent MODS leading to death. CONCLUSION: ISCLS pathophysiology remains unknown but certainly implies transitory endothelial dysfunction. Impossibility of randomized controlled trial for this exceptional disease led to based-on-experience therapeutic guidelines implying symptomatic care (cardiac output surveillance, nephroprotection, prudent fluid intake, prudent vasoactive amine use) and specific therapies (intravenous aminophylline during severe flares). Although enhancing controversial and even deleterious effects during the acute phase, polyvalent immunoglobulins are effective for relapse prevention. Syndromic diagnosis is difficult, but its precocious finding constitutes a key-element in better outcome before organ failure.

The sine-Gordon expansion method for higher-dimensional NLEEs and parametric analysis.

The Estevez-Mansfield-Clarkson (EMC) equation and the (2+1)-dimensional Riemann wave (RW) equation are important mathematical models in nonlinear science, engineering and mathematical physics which have remarkable applications in the field of plasma physics, fluid dynamics, optics, image processing etc. Generally, through the sine-Gordon expansion (SGE) method only the lower-dimensional nonlinear evolution equations (NLEEs) are examined. However, the method has not yet been extended of finding solutions to the higher-dimensional NLEEs. In this article, the SGE method has been developed to rummage the higher-dimensional NLEEs and established steady soliton solutions to the earlier stated NLEEs by putting in use the extended higher-dimensional sine-Gordon expansion method. Scores of soliton solutions are figure out which confirms the compatibility of the extended SGE method. The solutions are analyzed for both lower and higher-dimensional nonlinear evolution equations through sketching graphs for alternative values of the associated parameters. From the figures it is notable to perceive that the characteristic of the solutions depend upon the choice of the parameters. This study might play an impactful role in analyzing higher-dimensional NLEEs through the extended SGE approach.