Chylothorax related to acute SARS-CoV-2 infection in a patient with Noonan syndrome with prior uncomplicated cardiac surgeries.

SARS-CoV-2 is a novel coronavirus that has rarely been associated with chylothorax. Patients with Noonan syndrome are at risk for developing chylothorax, especially after cardiothoracic interventions. We present the case of SARS-CoV-2 infection triggering the underlying tendency of a patient with Noonan syndrome to develop chylothorax who did not develop it even after prior cardiothoracic interventions. Patient presented in respiratory distress without hypoxia and was found, on imaging, to have a large right-sided pleural effusion, which was eventually classified as chylothorax. The patient was then started on a low-fat diet. Chest tube drainage substantially reduced the effusion in size, and it remained stable. Our report highlights that SARS-CoV-2 infection can cause the development of a chylothorax or a chylous effusion in patients with Noonan syndrome or among populations with a similar predisposition. A high index of suspicion in vulnerable patients or those not responding to traditional therapy should exist with providers, thus leading to the testing of the fluid to confirm the diagnosis.

Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome.

OBJECTIVE: To evaluate the effect of the RAS-MAPK pathway inhibitor trametinib on medically refractory chylous effusions in 3 hospitalized patients with Noonan syndrome. STUDY DESIGN: Pharmacologic MEK1/2 inhibition has been used to treat conditions associated with Noonan syndrome, given that activation of RAS-MAPK pathway variants leads to downstream MEK activation. We describe our experience with 3 patients with Noonan syndrome (owing to variants in 3 distinct genes) and refractory chylous effusions treated successfully with MEK inhibition. A monitoring protocol was established to standardize medication dosing and monitoring of outcome measures. RESULTS: Subjects demonstrated improvement in lymphatic leak with additional findings of improved growth and normalization of cardiac and hematologic measurements. Trametinib was administered safely, with only moderate skin irritation in 1 subject. CONCLUSIONS: Improvements in a variety of quantifiable measurements highlight the potential utility of MEK1/2 inhibition in patients with Noonan syndrome and life-threatening lymphatic disease. Larger, prospective studies are needed to confirm efficacy and assess long-term safety.

How we approach pediatric congenital chylous effusions and ascites.

Congenital lymphatic leak may develop in patients with maldeveloped lymphatics and result in life-threatening fluid and electrolyte imbalance, protein deficiency, and immunodeficiency. Rapid diagnosis and therapy are necessary to prevent these complications; however, the field lacks clinical trials to support standardized diagnostic treatment guidelines. We present our current multidisciplinary approach to the diagnosis and management of congenital lymphatic leak including chylous pleural effusions and ascites. Depending on the rate of lymphatic leak, therapy can range from observation with nutritional modifications to surgical and interventional procedures aimed to reduce lymphatic drainage. Modalities to image central and peripheral lymphatics have advanced considerably. Genetic variants and subsequent targets that drive lymphatic maldevelopment have expanded the repertoire of possible pharmacotherapeutic options.

[Differential diagnosis of chylothorax in therapeutic practice].

The article is devoted to the differential diagnosis of chylous pleural effusion. The spectrum of traumatic and non-traumatic causes of chylothorax is discussed in detail. Examples of necessary diagnostic measures are given for the accumulation of milky fluid in the pleural cavity in order to verify chylothorax.

Post-Traumatic Chylous Wrist Effusion: A Case Report.

Chylous joint effusion is a rare condition characterized by the presence of a milky, viscous synovial fluid with abnormal lipid concentrations. The thorax is the most common site of involvement. Only a handful of cases have been reported in the field of orthopedic surgery and even fewer have been reported involving uncommon locations such as the knee. Treatment of chylous joint effusion may require surgical intervention along with the use of somatostatin or octreotide and a low-fat diet. We present herein a case of post-traumatic chylous effusion in the wrist treated with surgical incision and drainage, octreotide, and a low-fat diet. There have been few reports of chylous effusion in the knee; however, to our knowledge, this is the first report of post-traumatic chylous effusion in the wrist.

Propranolol As a Treatment Option for Chylous Effusions and Chylous Ascites in Fetuses and Neonates: A Systematic Review.

OBJECTIVE: Chylous effusion and chylous ascites are rare but serious conditions that affect both fetuses and neonates. Previous studies have documented chylous effusions or chylous ascites treatment with medications as an adjunct to respiratory support and dietary modifications, but no formal recommendations have been made. New literature suggests propranolol as an effective and safe treatment option, though no randomized clinical studies have been published to date. This review aims to assess the efficacy and safety of propranolol in the treatment of chylous effusion and chylous ascites in fetuses and newborns from case reports. METHODS: A comprehensive search of 10 databases and grey literature was completed. The inclusion criteria for articles were age at diagnosis less than 40 days old and case report/series. Articles were excluded if they were animal studies or not published in English. RESULTS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 4 articles were ultimately included in the study for a total of 10 reported cases. Propranolol administered to mother and neonates was effective in 100% of cases. The most common oral dose for mothers was 20 mg, 4 times daily, titrated to 40 mg, 4 times daily. The maximum dosage varied for administration orally to neonates, with the median being 3 mg/kg/day. Side effects, including bradycardia and transient hypoglycemia, were seen in 20% of the cases and resolved with dose adjustment. CONCLUSION: Propranolol is a relatively effective and safe treatment option for chylous effusion and chylous ascites that can be administered prenatally or to neonates.

Rare scrotal chylous effusion: A case report.

Klippel-Trenaunay syndrome is a rare congenital malformation predominantly affecting lower limb. In most cases, it is characterized by a classic triad of cutaneous capillary malformation (port-wine stain), lymphatic and venous abnormalities, in association with variable soft tissue and bone overgrowths. We describe a 48-year-old male presenting on the genitalia several whitish vesicles discharging a milky fluid compatible with chyle. Extensive radiology workup revealed pelvic megalymphatic malformations. Pelvic lymphatic ligations and bleomycin sclerotherapy only allowed a partial improvement. Given the high potential of recurrence, the patient will soon undergo a genetic evaluation for PIK3CA gene mutation and may need further systemic treatment with Sirolimus. As this scrotal chylous effusion in the setting of Klippel-Trenaunay syndrome is rare and highly affects the quality of life, we wanted to raise awareness of this entity and its management.

Left Chylothorax Without Ascites in a Liver Transplant Patient.

Chylothorax is a rare condition that results from thoracic duct disruption with malignant and nonmalignant etiologies manifesting as a pleural effusion. Typically, chylothorax in the setting of cirrhosis is associated with the migration of chylous ascites. We present the case of a 64-year-old male with prior liver transplant who presented with new-onset transudative chylothorax without chylous ascites who responded to transjugular intrahepatic portosystemic shunt revision, diuresis, and serial thoracentesis.

Resolution of chyloabdomen following the removal of a projectile causing a granuloma.

A 2-year-old female neutered crossbreed dog was referred for investigation of a 10-day history of progressive abdominal distension. Diagnostic investigations included radiographs, abdominal ultrasound and computed tomography (CT) with lymphangiography. Fluid analysis was consistent with chylous effusion. CT revealed a metal object embedded in an ovoid homogenous soft tissue attenuating lesion, located ventral to the aorta and surrounding the roots of the celiac and cranial mesenteric arteries. At exploratory laparotomy the metallic object (projectile) was identified and retrieved under fluoroscopic guidance. Four weeks following the surgery, the abdominal distention resolved and the physical exam was unremarkable. Chyloabdomen is a rare presentation which usually carries a guarded prognosis. This is the first case report of chyloabdomen due to a foreign body granuloma, which showed that an excellent outcome can be achieved following the removal of the underlying cause.

Could the chylomicron marker apoB48 be of value in the diagnosis of chylous effusions?

BACKGROUND: Chylous effusions such as chylothorax, chylopericardium and chylous ascites are marked by the abnormal presence of chylomicrons in serous membranes. These relatively rare situations are associated with high morbidity and mortality rates. Given that a macroscopic assessment of the fluid is insufficient, the current gold standard method for chylous effusion is the electrophoretic separation of lipoproteins. Serous effusions are most frequently assayed for triglycerides, with a diagnostic threshold varying between studies. The present study is the first to assess the value of the apolipoprotein B48, specific of the chylomicron, in the diagnosis of chylous effusions. METHODS: A chemiluminescent sandwich enzyme immunoassay was used to measure levels of apoB48 in remnant samples of effusion fluid sent to our laboratory for chylomicron detection and lipid assays. The diagnostic values of apoB48 and triglyceride assays were compared with that of the gold standard method. RESULTS: The triglyceride and apoB48 levels and the triglyceride/cholesterol ratio in the effusion fluid were significantly higher in patients with chylous effusion. The threshold values for apoB48 were respectively 2.45, 0.25 and 19.00 µg/mL for a maximal Youden index, a sensitivity > 95 %, and a specificity > 95 %. The apoB48 assay's diagnostic value might be at least as high as that of a triglyceride assay (area under the receiver operating characteristic curve [95 % confidence interval]: 0.84 [0.72, 0.96]) and 0.80 [0.67, 0.94], respectively). CONCLUSION: ApoB48 appears to be a promising marker for the diagnosis of chylous effusions; the putative diagnostic improvement must be confirmed in larger studies.

Utility of 99mTc-Sulfur Colloid Lymphoscintigraphy and SPECT/CT in Chylothorax and Chylous Ascites.

Purpose: To assess the diagnostic efficacy of 99mTc-sulfur colloid lymphoscintigraphy in chylothorax and chylous ascites, and the utility of single-photon emission computed tomography-computed tomography (SPECT/CT) in localizing the sites of leaks. Methods: Data from patients who underwent lymphoscintigraphy for clinical suspicion of chylothorax or chylous ascites were retrospectively analyzed. Biochemical fluid analysis was taken as the reference standard. Pleural fluid triglyceride level > 110 mg/dL (with pleural fluid/serum ratio > 1) and a cholesterol level < 200 mg/dL (with pleural fluid/serum ratio < 1) were considered confirmatory for chylothorax. Ascitic fluid triglyceride level > 200 mg/dL with a low cholesterol level (ascites fluid/serum ratio < 1) was considered confirmatory for chylous ascites. Results: 26 patients (15 males, 57.7%) aged 9 months to 68 years were enrolled in the study. Based on the reference standard, 17 had chylothorax or chylous ascites (9 with surgical history). Lymphoscintigraphy was positive in 16 (with 1 false positive) and negative in 10 (with 2 false negatives). The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of lymphoscintigraphy were 88.2% (63.6-98.5%), 88.9% (51.8-99.7%), 80.0% (51.6-93.8%), 93.8% (70.1-99.0%), and 88.5% (69.9-97.6%), respectively. SPECT/CT could localize sites of leaks in 61.5% (8/13) with a localization rate of 77.8% (7/9) and 25.0% (1/4) in patients with surgical and nonsurgical causes, respectively. Conclusion: 99mTc-sulfur colloid lymphoscintigraphy is a highly efficacious noninvasive modality to diagnose chylothorax or chylous ascites with a high positive predictive value. SPECT/CT could localize the sites of leaks more frequently in patients with surgical causes.

Management of lymphoma-associated chylothorax by interventional radiology and chemotherapy: a report of five cases.

Chylous effusion is associated with lymphatic obstruction or leakage in mediastinal or abdominal lymph nodes, and is a rare but troublesome complication in patients with malignant lymphomas. Although there is no standard of care, it is often treated with simultaneous chemotherapeutic and non-chemotherapeutic interventions. Here, we describe the cases of five patients with lymphoma-associated chylothorax with the aim of clarifying an effective treatment strategy. All patients achieved a partial response or better for lymphoma. All patients underwent interventional radiology (IVR) procedures, including lymphangiography (LAG) and thoracic duct embolization (TDE). Complete resolution of chylothorax was eventually achieved by IVR procedures or pleurodesis in all patients. No patients experienced serious adverse events related to LAG/TDE. Treatment of chylous effusion required months for most patients (range: 0.2-4.8 months). Our data suggest that a combination of chemotherapy and LAG/TDE is effective for refractory lymphoma-related chylous effusion.

Propranolol treatment for chylothorax after congenital cardiac surgery.

OBJECTIVE: Postoperative chylothorax causes significant morbidities in pediatric patients with cardiac disease. New treatment approaches based on evolving understanding of underlying lymphatic dysfunction are being developed. We hypothesized that propranolol reduces morbidities and duration of chest tube requirement in high-output chylous effusion. METHODS: The postoperative courses of 50 pediatric patients with cardiac disease and high-output chylous effusion (control, n = 25; propranolol-treated, n = 25) were reviewed, including morbidities, length of hospitalization, and duration of chest tube requirement. Statistical analysis was performed using Welch's t test, Kruskal-Wallis tests for continuous variables, and chi-square and Fisher exact tests for categorical variables. Univariable logistic regression was used to determine predictors of response. RESULTS: Propranolol response was defined as 80% or more drainage reduction in 9 days or less. Treated patients were grouped into responders (<9 days) and nonresponders (>10 days). Neither initial amount of drainage (P = .12) nor day of propranolol initiation (P = .17) correlated with response. When compared with controls and nonresponders, responders had significantly fewer days with chest tube requirement (P < .01), infection (P < .0002), and thrombus (P = .005), and shorter hospitalization (P < .05). All patients had low serum albumin, although nonresponders had significantly decreased serum albumin when compared with responders and control patients (P < .002), and were more likely to receive albumin replacement (P < .01). Malnutrition was prevalent in all patient groups. CONCLUSIONS: Responders to propranolol had significantly less morbidity and duration of chest tube requirement when compared with control patients and nonresponders. Nonresponders did not have worse outcomes than control patients. We conclude that propranolol may be an effective treatment of patients with refractory chylothorax.

Serous fluid: Reactive conditions.

This chapter highlights the steps that would help to analyze any fluid. It highlights importance of knowing gross analysis of fluid along with biochemical information. These parameters along with clinical information are very important in arriving at a differential diagnosis. Morphologic appearances in the fluid can often become challenging and occasionally reactive conditions can reveal changes that may mimic malignancies. This chapter provides not only a framework of approach to assessment of fluid cytology but also shows how to distinguish some of the challenging reactive conditions from the diagnosis of carcinoma. The chapter also utilizes two cases to demonstrate approach to reactive conditions. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Cytopathologic Diagnosis of Serous Fluids.

Recurrent Chylous Pleural Effusions in a Patient Treated With Dasatinib.

Dasatinib is a second-generation BCR-ABL tyrosine kinase inhibitor (TKI) that is approved for the treatment of chronic myeloid leukemia (CML), a myeloproliferative disorder seen commonly in adults over the age of 50. Dasatinib is superior in tolerance and efficacy to first-generation TKIs such as imatinib, given its ability to target mutation products that are resistant to first-generation TKIs. One of the common side effects of dasatinib includes pleural effusion which can be seen in up to 25% of patients on treatment. These effusions are predominantly exudative; however, they tend to resolve upon discontinuation of the drug. While infrequent, chylous effusions have been reported with the use of dasatinib; they tend to resolve following discontinuation of the drug. We present a case of a patient who was treated with dasatinib and developed a chylous effusion which was refractory to the discontinuation of the medication. Our patient was switched to imatinib and since his first episode, he has had multiple reaccumulation requiring thoracentesis, all of which have revealed chylous pleural fluid as per fluid analysis. We present this case to highlight a rare adverse effect of dasatinib which, via an unknown mechanism, can potentially lead to irreversible damage to the lymphatic duct resulting in recurrent chylous effusions.

Outcomes of neonatal chylous effusions: A 20-year west-Australian tertiary center experience.

Neonatal chylous effusions are rare entity with limited evidence-based management. We conducted a retrospective review of neonates admitted to King Edward Memorial and Princess Margaret/Perth Children's Hospital over 20 years with laboratory-confirmed chylous effusions. A total of 51 infants with chylous effusion were identified. Median gestational age and birth weight were 35.5 weeks and 2620 grams respectively. Congenital [27/ 51] and acquired [24/51] cases were included. Antenatal interventions were performed in 17/22 with antenatal hydrops and 50/51 needed postnatal drains. Effusions were monitored with serial (≥2) chest ultrasounds in 29/51 infants and multiple (≥5) x-rays in 45/51 infants. Median duration of mechanical ventilation, oxygen requirement, and hospital stay was 294.5 hours, 400 hours, and 49 days respectively. 39/51 received medium chain triglyceride (MCT) diet while 8/51 received octreotide. Six infants died during hospital stay. 12/19 had normal developmental assessment at one-year. The acquired group had higher number of xrays done, need for MCT diet and inotropes, and hospital stay vs congenital group. Duration of drains, radiological investigations and immunoglobulin administration were higher in neonates who received octreotide. Syndromic association, duration of ventilation and oxygenation were risk factors for mortality. In our setting, neonatal chylous effusions are associated with significant morbidity and mortality.

Percutaneous Venous Reconstruction for Central Thrombosis-Associated Chylothorax: A Safe and Efficacious Option.

Central thrombosis-associated chylothorax is underrecognized in children and frequently refractory to conservative management. Central venous catheterizations are the predominate cause. We present 3 cases highlighting endovascular techniques used to treat persistent chylous effusions. (Level of Difficulty: Advanced.).

Propranolol for the Treatment of Lymphatic Malformations in a Neonate - A Case Report and Review of Literature.

Lymphatic malformations in neonates often manifest as a chylothorax, and although rare, morbidity and mortality can be significant. First-line treatment with medium-chain triglyceride-enriched formulas, or enteric rest with total parenteral nutrition, are not always successful. We describe the case of a premature neonate with trisomy 21 who presented with bilateral pleural effusions and a pericardial effusion that worsened with the initiation of enteral nutrition. Clinical improvement was not seen until the initiation of treatment with oral propranolol at a maximum dosage of 0.5 mg/kg/day divided every 8 hours with extubation 8 days after propranolol initiation. Two case reports have described the use of propranolol in similar patients receiving 2 mg/kg/day; however, our experience is the first to report treatment success at a much lower dose. A review of the literature for alternative medication treatments uncovered numerous case reports and series documenting variable results with incongruent definitions of treatment success in a diverse patient population. The rarity of this disease state makes accrual of patients difficult and more robust treatment data unlikely. Therefore, selection of the optimal adjunctive treatment must be based on individual patient and disease state characteristics as well as safety and efficacy profile of the medication.

Clinical approach and review of causes of a chylothorax.

A chylothorax, also known as chylous pleural effusion, is an uncommon cause of pleural effusion with a wide differential diagnosis characterized by the accumulation of bacteriostatic chyle in the pleural space. The pleural fluid will have either or both triglycerides >110 mg/dL and the presence of chylomicrons. It may be encountered following a surgical intervention, usually in the chest, or underlying disease process. Management of a chylothorax requires a multidisciplinary approach employing medical therapy and possibly surgical intervention for post-operative patients and patients who have failed medical therapy. In this review, we aim to discuss the anatomy, fluid characteristics, etiology, and approach to the diagnosis of a chylothorax.

Complete resolution of chylopericardium after chemotherapy for chronic lymphocytic leukemia.

Nontraumatic chylous pleural effusions (chylothorax) and pericardial effusions (chylopericardium) are rare. They can, however, accompany intrathoracic malignancies and, most commonly, lymphomas. An association of chronic lymphocytic leukemia (cll) with chylopericardium has rarely been reported. A 68-year-old woman with cll, previously treated with single-agent fludarabine in the community, developed pleuritic chest pain and a new pericardial effusion. Computed tomography (ct) imaging of her chest revealed a large pericardial effusion with progressive lymphadenopathy. Pericardiocentesis identified a chylous effusion, and complete evacuation was achieved by catheter drainage. The cll was not treated. An asymptomatic pericardial effusion subsequently recurred. Pericardiocentesis was not repeated. Lymph node biopsy and flow cytometry revealed no evidence of large-cell lymphoma transformation. The patient was treated with 6 cycles of chlorambucil and obinutuzumab. Imaging of her chest by ct between cycles 2 and 3 revealed a marked resolution of the intrathoracic lymphadenopathy, with complete disappearance of the pericardial effusion. Repeat imaging at 5 months and again at 3 years after completion of chemotherapy demonstrated no recurrence of either the lymphadenopathy or the pericardial effusion. The mechanism of production and the treatment of chylous effusions are poorly defined. In this case, resolution of the pericardial effusion with effective chemotherapy is postulated to have alleviated obstruction of anterograde lymphatic flow facilitating drainage into the systemic venous system and allowing for spontaneous complete resolution of the pericardial effusion without surgical intervention.