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History and Physical Examination 

The importance of a thorough history and physical examination cannot be overemphasized in the evaluation of a patient with obscure GI bleeding. The nature of the exact presenting symptom is important in deciding a practical, efficient, and cost-effective evaluation plan. For example, recurrent hematemesis from an unknown source usually signifies a bleeding lesion above the ligament of Treitz, and lower GI evaluations are generally not warranted in such a scenario. Severity and temporal pattern of the associated anemia should have a significant impact on subsequent management decisions. For example, in a patient with mild anemia and a very slow decrease in hematocrit who has multiple severe comorbidities, a conservative workup may be prudent, although little information is available on the safety and efficacy of such a strategy. Also, the degree of severity of anemia has a bearing on planning endoscopic evaluation in terms of potential complications related to sedation.

Although abdominal symptoms may sometimes help in targeting focused evaluation, conclusions from few available studies are too divergent to recommend targeted evaluation based on abdominal symptoms.¹ A thorough history of consumption of prescription and over-the-counter medications is very important to exclude medication-related mucosal lesions that may precipitate or exacerbate bleeding.

A recent review stresses the importance of skin signs that may enable a clinician to make a diagnosis of the etiology of obscure GI bleeding.³³ In HHT, the vascular lesions develop primarily on the lips, nasal mucosa, tongue, palms, and palate, but they also can be found under the nails, on the soles of the feet, and even on the tympanic membrane. They appear as dark red, slightly elevated lesions with an ill-defined border and one or more legs radiating from an eccentrically placed punctum. The lesions are often more prominent after blood transfusion and may be missed in an anemic patient.³³ In patients with blue rubber bleb nevus syndrome, classically the skin lesions present in childhood but can develop later in life. They are usually blue in color and easily compressible with light palpation. Complete compression classically results in an empty, slowly refilling sac.³³

Other rare causes of obscure GI bleeding with cutaneous stigma are celiac disease (dermatitis herpetiformis), acquired immunodeficiency syndrome (Kaposi’s sarcoma), Plummer–Vinson syndrome, tylosis, pseudoxanthoma elasticum (brittle spoon nails), Ehlers–Danlos syndrome (chicken skin appearance, angioid streaks in retina), Schoenlein–Henoch purpura, neurofibromatosis, malignant atrophic papulosis (painless papules), and inherited polyposis syndromes. Reports of severe GI bleeding in patients with Klippel–Trénaunay–Weber syndrome exist³⁴, ³⁵; these patients can be identified during physical examination because of the presence of hemihypertrophy involving the extremities and external genitalia.