Case Presentation: A 42-year-old African-American G8P5 woman with no significant past medical history developed tongue swelling the day after a preterm labor induction due to hydrops fetalis. The swelling initially resolved on the same day and the patient was discharged. However, during the following weeks, her tongue swelled almost every day. By the seventh week, it worsened to the point where her tongue was protruding out of her mouth, which she was unable to close completely. She came to the emergency department and received IV Benadryl, famotidine, and Salu-Medrol. A neck CT showed prominence of her tongue extending to the base with no organized fluid collections. Her laryngeal and pharyngeal structures were all normal. She was discharged home on the same day.
At primary care follow-up two days later, her symptoms had become worse. ANA with reflex, anti-double-stranded DNA, ESR, CRP, C4, C1 esterase inhibitor level, lactic dehydrogenase, and cryoglobulin levels were all ordered and eventually returned negative. Her primary sent her to the emergency department again where she received IV epinephrine, Benadryl, and Salu-Medrol. Her symptoms failed to subside and she was admitted and transferred to the ICU where she was intubated. She responded well to high-dose steroids and was extubated within 48 hours.
Further investigation of her angioedema revealed no new medications such as ACE-inhibitors, ARBs, estrogen, or NSAIDs. TSH, PT, PTT, INR, and platelet function tests were all within normal limits. DVT was also ruled out. Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) showed hypoalbuminemia and a faint band in the gamma region, respectively. A follow-up urine immunofixation showed a monoclonal three kappa light chain band. An abdominal/pelvis CT contrast showed splenomegaly suspicious for lymphoproliferative disorder and amyloidosis. A bone marrow biopsy showed 2% kappa restricted plasma cells, concerning for a monoclonal plasma cell neoplasm. The patient was diagnosed with MGUS-associated acquired angioedema and referred to a myeloma/plasma cell specialist.
Discussion: MGUS is most well-known for its potential to progress to multiple myeloma. However, recent case reports have demonstrated an association between MGUS and acquired angioedema. This case demonstrates an instance of undiagnosed MGUS that led to weeks of recurrent and at times life-threatening angioedema without an attributable cause. MGUS associated acquired angioedema is a very rare presentation. However, review of literature confirms that up to 1/3 of cases of acquired angioedema were associated with MGUS.
Conclusions: Investigation of M protein can serve as a valuable diagnostic clue in the evaluation of cases of acquired angioedema without an obvious etiology.