A swollen tongue
The patient complained of a swollen tongue. What are the possible causes? Hint: it's not an ace inhibitor, an arb, an allergy or hereditary angioedema.
This patient had acquired angioedema caused by lymphoma. 0.5 % of people with B cell lymphoproliferative disorders have acquired C1esterase inhibitor deficiency. Lymphoma, monoglonal gammopathyof uncertain significance (MGUS) , and cryoglobulinemia all have been reported to be associated with C1esterase inhibitor deficiency.
C1 esterase inhibitor blocks the activation of C1. When it is absent there is inappropriate activation of C1 and activation of C2 which results in kinin-like activity that increases vascular permeability. Edema can occur in the upper airway, GI tract (resulting in abdominal pain) or subcutaneous areas (often in the genitals). There is no urticarial with C1 esterase inhibitor deficiency because it is not IgE mediated.
Hereditary angioedema usually results from a deficiency of C1 esterase inhibitor (type I) or decreased biologic function ofC1 esterase inhibitor (type II). Acquired angioedema is complement mediated and is characterized by low levels of C4, C2 and C1 INH during and between attacks. C1q levels , however , are low only inacquired angioedema. There isa normal level of C1 in hereditary angioedema compared to a low level of C1 in acquired disease. In ACE inhibitor angioedema an excess of bradykinin occurs because of failure to break it down. Fresh frozen plasmacontains the enzyme ACE and is thought to degrade bradykinin by replacing the enzyme inhibited by the ACE inhibitor. Newer agents like ecalantide ( which is approved for hereditary angioedema) have been tried for ACE inhibitor angioedema with mixed results. It is designed to inhibit the production of bradykinin but does not increase its degradation. The cost of a single dose is $9,000.
Case conclusion
The pt had had a previous episode of tongue swelling requiring intubation six months pta. He his lymphoma had been recognized by an allergist in the community and he was started on chemo. He was treated with danazol which has been reported to be effective in acquired angioedema. When his C1 esterase level returned to normal; he was taken off danazol. On the night pta his tongue swelled again after he bit it. It became more swollen over the next 12 hours and he came to the ED.
The pt was scoped, awake, nasally and there was oropharyngeal edema and airway narrowing centered around the R tongue. He was intubated at that time over the scope. He was given Berinert but there was no significant improvement in his swelling and he remained in the ICU for two days. He was extubated and restarted on danazole. He was discharged from the hospital.
1 Geha RS, Quinti I, Austen KF, et al. Acquired C1-inhibitor deficiency associated with anti-idiotypic antibody to monoclonal immunoglobulins N Engl J Med 1985;312:534-540.
2 Bernstein JA, Moellman JJ, Collins SP. Et al. Effectiveness of ecallantide in treating angiotensin converting enzyme inhibitor-induced angioedema in the emergency department. Ann Allergy Asthma Immunol 2015: 114-245.
3 Lewis LM, Graffeo C. Crosley P et al Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Ann Emerg Med 2015; 65: 204.
4. Sonali S, Gunatilake C, Wimalaratna H. Angioedema as the first presentation of B-cell non-Hodgkin lymphoma—an unusual case with normal C1 esterase inhibitor level: a case report.
5. Gaur S, Cooley J, Aish L, Weinstein R.. Lymphoma-associated paraneoplastic angioedema with normal C1-inhibitor activity: does danazol work? American Journal of Hematology 2004; 77:296-298.