Consult rounds: Hyperammonemic encephalopathy in the setting of myeloma

Can paraproteinemia cause an elevated ammonia level?

While liver disease and certain medications are known to cause hyperammonemia, myeloma is a rare cause of hyperammonemia. One of the first cases published on this topic was back in 2002 in NEJM.

Here are some cases published in the literature.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/

https://www.amjmed.com/article/S0002-9343(03)00630-2/fulltext

https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-022-01285-6

https://pubmed.ncbi.nlm.nih.gov/35871579/

 

 A retrospective study shed more light. In this study of individual patients diagnosed with ammonia related disease from myeloma was evaluated( 27 patients), interesting findings were noted. The mean age was 76 years with a 5:1 male-to-female ratio. All had stage III based on the International Staging Scale (ISS). Bone marrow biopsies demonstrated 54–98% (mean 69%) plasma cell infiltration. IgA subtype was the most common. The mean ammonia level was 113 umol/L. No intracranial processes were detected on imaging. Three patients had improvement in mental status and decreased ammonia levels after chemotherapy; the other three patients declined further interventions. Inpatient mortality was over 66%. 

    The authors also did a MEDLINE search revealing 20 articles originating from the United States and Japan detailing a total of 32 patients who were diagnosed with myeloma induced hyperammonemic encephalopathy. The mean age was 52 years  with an equal distribution between men and women. The average ammonia level amongst these patients was 121 umol/L with as high as 299umol/L.  All these patients had stage III disease by the ISS or the Durie-Salmon system. IgG was the most common subtype at 44% (n=12), followed by IgA with 37% (n=10), light chain multiple myeloma with 11% (n=3), and IgD with 7% (n=2). Of the 25 patients that received chemotherapy, 15 (60%) survived until discharge. The inpatient mortality was 40% (n=10). Those patients who did not receive chemotherapy had a lower rate of survival at 25%.

Some studies report beneficial effects in using hemodialysis to remove excess ammonia. Several others suggest that the initiation of aggressive chemotherapy is the most effective measure to achieve normal ammonia levels and clinical improvement.  Mechanism of this association is still unclear. 

It is important to consider myeloma as a cause of hyperammonemia.