A Case of Gastrointestinal Bleed due to Angiodysplasia in Primary Care treated with Thalidomide by Samar Zaki in Journal of Clinical Case Reports, Medical Images and Health Sciences

A Case of Gastrointestinal Bleed due to Angiodysplasia in Primary Care treated with Thalidomide by Samar Zaki in Journal of Clinical Case Reports, Medical Images and Health Sciences

Abstract:

Angiodysplasia is an important and frequent cause of long-term intermittent gastrointestinal (GI) bleed in elderly patients. Gastrointestinal angiodysplasia (GIAD) is one of the most common cause in the elderly, while tumors dominate in younger individuals (below 50 years of age). GIAD can present as hematochezia, malena or as iron deficiency anemia with intermittently positive occult blood in stools. Several methods have been invented and tried with no desired outcomes. Recurrent symptoms and requirement for blood transfusions despite endoscopic therapy necessitate the evaluation for a pharmacological intervention. Medical management in the past comprised of hormonal therapy and octreotide. The use of thalidomide for recurrent GIAD is not common thus in our case study we describe the use of thalidomide in an 81 years old man with GI bleed secondary to angiodysplasia, in which use of thalidomide showed favorable results

Key Words: Gastrointestinal angiodysplasia, thalidomide, vascular gastrointestinal bleed, pharmacological management.

Introduction:

 Angiodysplasia is a common vascular malformation of the gastrointestinal tract. These are small, dilated, and tortuous vessels, residing in the mucosa or submucosa. These vascular malformations are most commonly found in the right colon (78%), followed by the jejunum (10.5%), ileum (8.5%), and duodenum (2.5%). Although, frequently distributed in the colon, small intestine remains the most common source (66%) of occult gastrointestinal (GI) bleeding. GIAD is one of the most common cause in the older population (above 50 years of age), while tumors are more common in younger individuals (below 50 years of age). GIAD can present with symptoms of blood in stool, and iron deficiency anemia with intermittently positive occult blood in stools. In early 1950s, GIAD was managed with hormonal therapy such as estrogens. However, this treatment was not very effective in reducing the number of bleeding episodes or requirement for blood transfusions. The endoscopic treatment for GIAD has also been limited in its effectiveness because of presence of multiple vascular malformations at numerous sites and inability of endoscope to reach all the sites. Deep enteroscopy has better accessibility but higher complication rates (4%). Frequent requirements for blood transfusions despite endoscopic therapy, necessitate the evaluation for a pharmacological intervention. Medical management in the past comprised of hormonal therapy and octreotide. However, use of thalidomide for recurrent gastrointestinal angiodysplasia is a novel approach [1]. 

Case report :

A written consent was taken from the patient for publication of the case. An 81 years old man with a history of hypertension and diabetes, well controlled on medications presented to family physician with symptoms of shortness of breath, dizziness, and melena. On examination, he was pale but vitally

stable. Rest of his physical examination was normal. On investigations, he was found to have hemoglobin of 5.7 g/ dl with Hematocrit of 19.8%, MCV: 88.4 fl, MCH: 25.4 pg, MCHC 28.8 g/dl. His stool occult blood was positive. He was hospitalized for further evaluation and management. Three units of packed cells were transfused during admission. Investigations included endoscopy, which revealed mild gastritis, colonoscopy showed small colonic polyp which was removed, and histopathology revealed benign adenoma. Computerized Tomogram (CT scan) abdomen revealed no significant gastrointestinal pathology. Capsule endoscopy was performed which revealed vascular ectasias (angiodysplasia) predominantly in ileum. (Figure 1 & 2) He continued to experience melena with occasional periods of passing normal colored stools for maximum period of one week and he had to receive two units of packed cell every 3-4 weeks, when the hemoglobin dropped below cut off 9 g/dl. He was given a trial of tablet thalidomide (50 mg), which he discontinued after 2 months because of side effects of drowsiness and constipation. He switched to alternative medicine but continued to have malena despite the treatment. 

low dose thalidomide (50 mg once at night) for three months, there was significant decrease in Gastrointestinal bleeding episodes and frequency of packed cell transfusions was reduced to once in 6 to 8 weeks at 2 years of follow up.

Discussion :

Thalidomide is used for the treatment of gastrointestinal angiodysplasia, especially in cases that are refractory to other treatment modalities. The compliance and drug toxicity of this drug are dose dependent. Low dose thalidomide (50 mg) is a safe and effective option for bleeding related to GIAD [1]. Thalidomide is an antiangiogenic drug, which was first introduced in West Germany in 1950s. Initially it was used as a sedative agent, and for management of morning sickness but withdrawn from the market because of its teratogenic effects as well as side effects of neuropathy [2]. Thalidomide down regulates vascular endothelial growth factor (VEGF) through which it exerts its antiangiogenic effects. The drug was reintroduced for its antiangiogenic property in the management of erythema nodosum leprosum and vasculitis complications of leprosy. Since then, thalidomide has been used to treat diseases such as HIV1associated Kaposi sarcoma, multiple myeloma, crohn's disease, advanced prostate cancer, and recalcitrant erosive lichen planus [3,4,5,6]. In colonic angiogenesis, the expression of VGEF increases, hence thalidomide plays an important role 

in its management [1]. Thalidomide was used effectively for patients with cirrhosis and gastrointestinal bleeding related to vascular malformations but current information on the use of thalidomide in patients with cirrhosis is very limited and has to be interpreted with caution [7]. Thalidomide was also reported to be effective in rectal bleeding related to radiation-induced proctitis, where it was shown to improve multiple bleeding episodes [8]. Ge et al. (2011) conducted a randomized controlled trial (RCT) of thalidomide versus iron supplementation in 50 patients with GIAD. The study found that thalidomide was significantly more effective than iron supplementation in reducing the frequency of bleeding episodes [9]. In another study conducted on 15 patients with multiple comorbidities and GI bleeding secondary to GIAD and Gastric antral vascular ectasias, Thalidomide was shown to be an effective treatment in Western population with refractory GI bleed [10]. Therefore, it can be stated that Thalidomide is an effective and relatively safe treatment for patients with refractory bleeding from gastrointestinal vascular malformations. Similarly, in our patient, the bleeding episodes were significantly reduced with use of low dose of Thalidomide with mild side effects of constipation and drowsiness, which were managed with life style interventions.

Conclusion :

This case report presents the successful use of Thalidomide in an 81-year-old man with GI bleed secondary to angiodysplasia. The study highlights the efficacy of Thalidomide in managing recurrent GIAD and educates primary care and other physicians about the potential benefits of Thalidomide in managing gastrointestinal angiodysplasias in the elderly population. Further studies are warranted to confirm these findings and establish Thalidomide's role in the management of recurrent GIAD. Abbreviations: GI- Gastrointestinal, GIAD- Gastrointestinal Angiodysplasia, VEGF- Vascular endothelial growth factor Financial or other competing interests: None Acknowledgement: Dr Atif Majeed, Consultant Gastroenterologist & Hepatologist, Assistant Professor, Aga Khan Hospital, Karachi, Pakistan for his expert review and valuable feedback.

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