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An Unusual Case of Angioedema

Q: A 72 year old female patient was referred for evaluation of angioedema that started a couple months ago. She had developed a gradual swelling of the neck and face, along with diffuse pain in both arms. She was concerned that an allergy might be the root cause of the problem. However, patient denied any asthma history or other allergic disease history. A month prior to her evaluation, in addition to angioedema, she reported itchy, watery eyes, and rashes on the face and hands which seemed exacerbated by her cigarette smoking. At that point, she took antihistamines, which quelled the symptoms temporarily. Although the symptoms initially responded to antihistamines, over the course of the next couple weeks symptoms became refractory to all treatments. Her examination showed diffuse, symmetrical subcutaneous edema of the face, neck, and upper chest. She was also noted to have dilated spider veins on the right side of the chest. Labs demonstrated an IgE of 278 (normal: 0 – 158 IU/ml) and a histamine level of 3.68 (normal: < 1.00 ng/ml).

What additional workup should be obtained, and what could be causing these findings?

A: Angioedema of the face and neck which does not vary and is diffuse, symmetrical raises concerning possibilities in the differential diagnosis. In conjunction with elevated levels of IgE and histamines, it would be tempting to diagnose her as having an allergy-related ailment. However, this patient's presentation, other findings, and smoking history would raise the suspicion of a superior vena cava syndrome, in which an obstructing tumor limits venous drainage diffusely from the head, neck, upper chest and arms. A chest x-ray - or preferably chest CT - as soon as possible would be recommended in this situation.

Clinical follow-up:
A chest x-ray demonstrated a lesion in the upper quadrant of the right lung field. Chest CT scan did confirm the development of a superior vena cava syndrome secondary to this tumor. Bronchoscopy demonstrated positive staining for CD-56 and TTF-1 along with focal positive staining for AE1/AE3. There was no staining for chromogranin or synaptophysin. Results were consistent with a neuroendocrine tumor, and these tumors can be associated with histamine production. This patient’s symptoms and lab evaluation thus signaled a false “allergic response"!

 
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