**Background:** Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by epistaxis, arteriovenous malformations, and mucocutaneous telangiectases. Gastrointestinal (GI) bleeding is a rare presenting symptom in children and is typically managed endoscopically. When the bleeding source is inaccessible, treatment becomes challenging. Previous reports in adults suggested tacrolimus may improve epistaxis and liver vascular malformations in HHT. This case describes the first pediatric HHT patient treated with tacrolimus for GI bleeding.
**Methods:** An 8-month-old boy presented with melena, iron deficiency anemia (hemoglobin 3.8 mmol/L, MCV 67 fl, ferritin 2.7 µg/L), and a family history of HHT. Extensive investigations (Meckelscan, gastroduodenoscopy, ultrasound, CT) were negative, but invasive angiography revealed telangiectases in jejunal branches of the superior mesenteric artery. Genetic testing confirmed HHT type 1 (heterozygous ENG c.247G>T; p.(Gln83*)) in the boy and his mother. The patient required frequent blood transfusions and experienced abdominal pain, fatigue, and behavioral problems. Endoscopic treatment was not possible. After discussion within the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), tacrolimus was started at age 2.5 years with target trough levels of 2–4 µg/L. The drug was used for 14 months, then stopped for 2 months due to unilateral viral parotitis, and subsequently restarted. Clinical outcomes (transfusion frequency, iron infusions, hemoglobin levels, symptoms) were monitored during and between treatment periods.
**Key Results:** During the initial 14-month tacrolimus period, GI bleeding persisted but decreased in frequency. The patient required no blood transfusions, though 3 iron infusions were given. Hemoglobin levels stabilized. Epistaxis occurred frequently but resolved after coagulation by an ENT doctor. Abdominal pain, fatigue, and behavioral problems decreased significantly. Adverse effects were mild recurrent ear infections. After tacrolimus withdrawal (2 months), GI bleeding increased, requiring 1 iron infusion and 3 blood transfusions. Symptoms returned to pre-treatment severity. Upon restarting tacrolimus, quality of life improved again, with decreased abdominal complaints. Over 9 months of follow-up after restart, 1 iron and 3 blood transfusions were needed. The mean interval between blood transfusions was 65 days during tacrolimus periods versus 34.5 days without tacrolimus.
**Clinical Implications:** This case suggests tacrolimus may reduce GI bleeding and transfusion requirements in pediatric HHT patients when endoscopic treatment is not feasible. The improvement in quality of life and the worsening upon withdrawal support a therapeutic effect. The mechanism likely involves upregulation of Smad 1/5/8 signaling and inhibition of VEGF signaling, counteracting the vascular disbalance in HHT. Compared to other targeted therapies like bevacizumab, which has been associated with severe side effects in children (malignant hypertension, proteinuria, lymphopenia, bleeding), tacrolimus appeared well-tolerated in this patient. However, this is a single case report, and larger studies are needed to confirm efficacy and safety. The findings align with adult HHT case reports and with pediatric vascular disease literature (e.g., sirolimus in blue rubber bleb syndrome). Tacrolimus may be considered for difficult-to-treat pediatric HHT with GI bleeding, but careful monitoring for infections and other adverse effects is warranted.