Individual approach for treatment of primary intestinal lymphangiectasia in children: single-center experience and review of the literature.

BACKGROUND: Intestinal lymphangiectasia is a rare disease. Thus, prospective studies are impossible, and therapy is still controversial. Several medicines are suggested for treatment but there are no existing indications for drug choice and treatment guidelines. We aimed to introduce the action mechanism of each drug and treatment overview in a single-center experience and a review of the literature on second-line therapy for primary intestinal lymphangiectasia. METHOD: Children under 18 years old diagnosed with intestinal lymphangiectasia from June 2000 to June 2020 were included and retrospectively reviewed in the study. Capsule endoscopy, MR lymphangiography, or whole-body MRI for investigating the extent of abnormal lymphatic vessels in addition to endoscopy and biopsy were conducted. The individual treatment approaches depended upon the lymphangiectasis locations involved. RESULTS: Only one patient showed a response to dietary therapy. One patient was successfully cured after two therapeutic lymphatic embolization. Octreotide was tried for two patients who had extensive lymphangiectasis. Lymphangiectasis recurred when octreotide was used for 3 months in one patient, and there was no effect in the other patient. Sirolimus was tried for four patients. Two of them had abnormal lymphatic lesions only in the intestine, and the others had extensive lymphangiectasis. The former group showed clinical improvement after 3-4 months of sirolimus treatment, whereas the latter group showed clinical improvement only after 1 month of sirolimus treatment. CONCLUSION: Surgery or embolization is a potential therapeutic option for patients with focal abnormal lymphatic lesions. Octreotide is not an optimal choice for patients with extensive lymphangiectasis. Sirolimus is an effective and safe drug and can be the first drug of choice for patients with extensive lymphangiectasis.

Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial.

BACKGROUND: Cutaneous microcystic lymphatic malformations (CMLMs) are rare conditions in children and adults. They present as clusters of vesicles full of lymph and blood to various extents, inducing maceration, esthetic impairment, pain, and impaired quality of life. The treatment is challenging. Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Topical sirolimus has recently been reported as effective in a few reports of patients with CMLMs. The objective is to compare the efficacy and safety of a 12-week application of 0.1% topical sirolimus versus topical vehicle in CMLMs in children and adults. METHODS: This French blinded multicenter within-person randomized controlled phase 2 trial aims to include 55 patients aged ≥ 6 years who have a primary CMLM. The CMLM will be divided into two equal areas that will be randomly allocated to 0.1% topical sirolimus or topical vehicle applied for 12 weeks. At the end of the 12-week period, the patient/parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for eight more weeks. Patients will be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy. The primary outcome will be improvement of the CMLM in the area treated with topical sirolimus compared to the area treated with topical vehicle by the investigator physician (blinded to the treatment) with the Physician Global Assessment score at week 12. Secondary outcomes will include: assessment of efficacy by independent experts on the basis of standardized photographs; impact on quality of life; efficacy for oozing, bleeding, erythema, and thickness evaluated by the investigators; and global efficacy as well as efficacy for functional and aesthetic impairment evaluated by the patient. Systemic passage of sirolimus will be measured at weeks 6, 12, and 20, and at week 16 for CMLMs ≥ 900 cm2. DISCUSSION: For patients with CMLMs, topical sirolimus could be a non-invasive and well-tolerated therapeutic option. If the trial demonstrates efficacy and safety of this treatment, this result will lead to a real change in the management of this condition, and 0.1% sirolimus cream would become the first-line treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03972592. Registered on 3 June 2019. EU Clinical Trials Register EudraCT, 2018-001359-11.

Thoracic involvement of diffuse lymphangiomatosis successfully treated with sildenafil.

General lymphatic anomaly (GLA) is a very rare disorder, characterised by multifocal lymphatic malformations into various tissues that is due to congenital abnormalities of lymphatic development. No treatment has ever proved its efficiency.We report a 22-year-old man with recurrent bronchial casts due to thoracic involvement of GLA. After a 6-month treatment with sildenafil (20 mg three times a day), a phosphodiesterase 5 inhibitor, chest CT scan showed a complete regression of ground-glass opacities and lung function test results improved substantially and remained stable for 1 year. The treatment was well tolerated.This observation suggests that sildenafil may be a therapeutic approach to be tested in thoracic involvement of GLA.

Cutaneous alternariosis in an immunocompromised dog successfully treated with cold plasma and cessation of immunosuppressive medication.

A cutaneous infection with Alternaria spp. was diagnosed in a 2-year-old male intact Irish setter dog, presenting with multifocal papules, plaques and ulcerations involving all four distal limbs, shoulder blades, scrotum, pinnae and nasal mucous membranes. The dog had been treated for inflammatory bowel disease and lymphangiectasia with immunosuppressive doses of cyclosporine and prednisolone for approximately 3 months. The diagnosis was based on clinical signs, the demonstration of fungal elements within skin biopsies, deep fungal culture and fungal PCR from a formalin-fixed tissue specimen. Complete clinical remission was achieved by tapering and cessation of the immunosuppressive medication, treatment with cold atmospheric-pressure plasma (CAPP) and topical enilconazole within 8 weeks.

Successful Treatment of Conjunctival Lymphangiectasia With Subconjunctival Injection of Bevacizumab.

PURPOSE: To report a novel intervention for the treatment of conjunctival lymphangiectasia-subconjunctival injection of bevacizumab. METHODS: A 53-year-old white male presented with a 3-month history of right ocular discomfort and redness unresponsive to conventional topical treatment of lubricants and steroids. A clinical diagnosis of conjunctival lymphangiectasia was confirmed by biopsy. Bevacizumab (25 mg/mL) was injected subconjunctivally into the affected area. RESULTS: An improvement in the degree of conjunctival chemosis was evident at 5 days postinjection. At 1-month follow-up, symptoms had fully resolved. No recurrence had been observed at 3 years' follow-up. CONCLUSIONS: Subconjunctival bevacizumab injection may be an effective treatment for conjunctival lymphangiectasia.

Congenital chylothorax treated with oral sildenafil: a case report and review of the literature.

Congenital chylothorax (CC) can result from a congenital malformation or an acquired obstruction or disruption of the thoracic duct. Recently, oral administration of the phosphodiesterase-5 inhibitor, sildenafil, was reported to be effective in resolving non-pulmonary lymphatic malformations in infants and young children. We report a case of CC in a late preterm infant with congenital pulmonary lymphangiectasia where octreotide was not effective, but management with oral sildenafil was successful.

Treatment of congenital pulmonary lymphangiectasia using ethiodized oil lymphangiography.

Historically, congenital pulmonary lymphangiectasia (CPL) has had poor treatment outcomes despite aggressive therapy. There are recent reports of ethiodized oil (Lipiodol) lymphangiography successfully treating lymphatic leakage in adults. In this report, we describe two infants with CPL complicated by chylothoraces successfully treated by instillation of ethiodized oil into the lymphatic system. Congenital atresia of the thoracic duct was demonstrated on the lymphangiogram in both patients before treatment. Both patients have shown good short-term outcomes without supplemental oxygen or fat restricted diets at 9 months of age. Ethiodized oil lymphangiography represents a new treatment modality for some patients with CPL.

Treatment of congenital generalized lymphangiectasia with propranolol in a preterm infant.

Generalized lymphangiectasia is a rare congenital disorder characterized by dilated lymphatic vessels with a fatal prognosis, especially in cases with thoracic involvement. We describe the use of propranolol in the therapy of generalized lymphangiectasia in a preterm infant with hydrops fetalis. Propranolol was well tolerated and effective within the first months. It remains to be shown whether propranolol is a treatment option for infants with generalized lymphangiectasia.

Renal lymphangiectasia.

Renal lymphangiectasia is a benign disorder of renal lymphatics. Seldom observed, the pathophysiology is unclear. The clinical course may vary, and management alternatives range from percutaneous drainage in symptomatic cases to pharmacological substitutes in the form of anti-hypertensives and diuretics. We present a case of bilateral perinephric collections on imaging, which presented with gross ascites, abdominal pain and reversible hypertension. Ultrasound examination indicated ascites. Computerized tomography revealed bilateral symmetrical large perinephric collections. This is consistent with the appearance of renal lymphangiectasis (enlarged kidneys with fluid collections seen to be abutting the surrounding structures) reported in the literature. Needle aspiration of the perinephric fluid was undertaken, and laboratory analysis was carried out, which revealed a protein level of 643 mg dl(-1) and a total leucocyte count of 50, of which 80% were lymphocytes. Thereafter, a diagnosis of renal lymphangiectasia was made, and conservative treatment with diuretics and anti-hypertensives was initiated. Reassessment at subsequent follow up visits showed improvement in the patient's clinical condition.

Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.