Case Reports in Pediatrics / 2018 / Article / Tab 1

Case Report

Successful Management of Blue Rubber Bleb Nevus Syndrome (BRBNS) with Sirolimus

Table 1

Articles on BRBNS with Sirolimus therapy.

Article authorsArticle titleArticle journalArticle yearPatientResponse to SirolimusSirolimus doseSirolimus levelTime to improvement

Yuksekkaya H, Ozbek O, keser M, Toy H [4]Blue rubber bleb nevus syndrome: successful treatment with SirolimusPediatrics20128 yo F; GI bleeding, not responsive to prednisolone, propranolol, aminocaproic acid, and alpha-interferon therapyHemoglobin improved from 7 gm/dL to 14 gm/dL (with iron supplement);0.05–0.1 mg/kg1–5 ng/mL2 months. Symptoms returned if sirolimus discontinued
Taddio A, Benelli E, Pierobon C, Martelossi S, Berti I, Ventura A [6]From skin to gutJ Pediatr20133 yo M; severe iron deficiency anemia, large subcutaneous swelling on right ankle, and multiple skin lesionsHemoglobin improved from 6.4 gm/dL to 'stable'not available (NA)NA6 months
Ozgonenel B, Martin A [9]Low-dose sirolimus controls recurrent iron deficiency in a patient with blue rubber bleb nevus syndromePediatr Blood Cancer201518 yo F; GI bleeding and iron deficiency anemiaHemoglobin improved from 5 gm/dL to ∼14 gm/dL1.6 mg/m2/day divided BID; reduced to 0.6 mg/m2/day10–15 ng/mL, then goal levels reduced <2.0–3.1 ng/mL“after starting sirolimus”
Ferrés-Ramis L, knöpfel N, Salinas-Sanz J, Martín-Santiago A [8]Rapamycin in the treatment of blue rubber bleb nevus syndromeActas Dermo-Sifiliográficas (English Edition)20158 yo with congenital cutaneous and GI vascular malformationsDecreased size of lesions, normalized hemoglobinInitial dose 0.05 mg/kg, reduced to 0.02 mg/kgWithin a month
Warner B, Butt A, cairns S [7]Sirolimus is a successful treatment for recurrent iron deficiency anemia in blue rubber bleb nevus syndromeJ Pediatr Gastroenterol Nutr201518 yo M; hemangioma, tracheostomy, anemic; thalidomide—discontinued due to side effects; multiple bowel resections to remove vascular malformationsHemoglobin 6.9 gm/dL, anemia resolved4 mg daily
Salloum R, Fox CE, Alvarez-Allende CR, et al. [3]Response of blue rubber bleb nevus syndrome to sirolimus treatment.Pediatr Blood Cancer20162–16 yo, cutaneous, GI tract, visceral and muscular lesionsDecreased size of lesions, decreased pain, normalized hemoglobin0.8 mg/m2 every 12 hourdose titrated to target trough level between 10 and 13 ng/mLless than 3 months
Cardoso H, Dias JA, Silva M, et al. [10]Gastrointestinal: successful treatment with sirolimus of a patient with blue rubber bleb nevus syndromeJ Gastroenterol Hepatol201619 yo M; multiple visceral, muscular, and subcutaneous vascular lesions, complicated with chronic local pain and GI bleeding requiring RBC transfusion (total of 74); treatment with thermal argon ablation and sclerosis and segmental jejunoileal surgical resections, propranolol and ferric carboxymaltoseimproved blood loss, asthenia, and decreased size of lesions; hemoglobin improved by 6 gm/dL2 gm/dayabout 5 months
Ünlüsoy Aksu A, Sari S, Eğritaş Gürkan Ö, Dalgiç B [11]Favorable response to sirolimus in a child with blue rubber bleb nevus syndrome in the gastrointestinal tractJ Pediatr Hematol Oncol201711 yo M with vascular malformation in GI tractNormalized hemoglobin in 2.5 months, decreased lesions in 5 months0.1 mg/kg/d1–5 ng/mL2.5–5 months
Akyuz C, Susam-Sen H, Aydin B [12]Blue rubber bleb nevus syndrome: promising response to sirolimusINDIAN Pediatr20176 yo F with skin lesions, GI tract and consumptive coagulopathy (platelets 77K, fibrinogen 104 mg/dL, d-dimer >40 mg/dL); oral steroids without success; bleeding requiring transfusions (hemoglobin 6.1 gm/dL)improved size and number of lesions, no further GI bleeding or anemia1.6 to 2 mg/m2/day5–12 ng/mLLess than 1 month. Disconintued sirolimus and at 4 months off therapy- no evidence of microscopic blood in stool and normal hemaglobin levels, stable lesions
Wang KL, Ma SF, Pang LY, Zhang MN, Hu LY, Liu MJ, Zou LP [13]Sirolimus alternative to blood transfusion as a life saver in blue rubber bleb nevus syndromeMedicine (Baltimore)201812 yo F with multiple hemangiomas on head and neck, limbs and trunk, tip of tongue and digestive tract. Severe anemia, requiring red cell transfusion every 2 weeks. Mutation in exon 15 of TEK geneImproved hemoglobin, skin and digestive tract hemangiomas, no further transfusions1 mg/m2/d, average 0.7 mg/d6.2–11.89 ug/L1 month
Kizilocak H, Dikme G, celkan T [14]Sirolimus experience in blue rubber bleb nevus syndromeJ Pediatr Hematol Oncol2018Four children, ages 4–15 years. Three with GI lesions, one with respiratory tract lesionsNormalized hemoglobin, decreased pain, decreased size of lesions1.2 mg/m2/d2 months

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