Multiple myeloma-associated amyloidosis manifesting as fulminant hepatic failure.

ABSTRACT: We report a case of amyloidosis associated with k light chain multiple myeloma in a 42-year-old African American man. The patient initially had mild dyspepsia, which rapidly progressed to include anorexia, fulminant hepatic failure, and death within 9 weeks. This is only the fourth reported case of hepatic failure from myeloma-associated amyloidosis and the second reported case of light chain myeloma with amyloidosis resulting in a progressive clinical course of hepatic failure. Our patient was unique in that, despite severe disease, he had mild symptoms without laboratory abnormalities until 2 weeks prior to death.

MULTIPLE MYELOMA is a malignant plasma cell disorder characterized by monoclonal immunoglobulin production with a peak incidence in the seventh decade of life. (1) Most patients have bone pain, renal insufficiency, or anemia. Ten to fifteen percent of myeloma patients have extracellular deposition of amyloid in tissues resulting in amyloidosis. (2) In these patients, symptoms will frequently manifest as nephrotic syndrome or heart failure. We report a case of multiple myeloma with amyloidosis manifesting as fulminant hepatic failure, resulting in refractory metabolic acidosis and fatal cardiac arrest.

CASE REPORT

A 42-year-old African American man was in excellent physical health until 9 weeks prior to hospital admission, when he had mild dyspepsia, nausea, and diarrhea. Outpatient treatment for gastroenteritis failed, and the patient was referred to our institution for persistent nausea, 25-lb weight loss, and dyspnea 8 weeks into the illness. Laboratory values on transfer were remarkable for the following: prothrombin time 45.8 seconds (normal, 10 to 15 seconds), alkaline phosphatase (ALK) 516 U/L, aspartate aminotransferase (AST) 229 U/L, alanine aminotransferase (ALT) 84 U/L, and total bilirubin 5.8 mg/dL. Serum urea nitrogen, creatinine, and complete blood count were all within normal limits, with the exception of 50% nucleated red blood cells on differential count. Physical examination was significant for jaundice, distended abdomen with hypoactive bowel sounds, and anasarca. There was no evidence of macroglossia or hepatosplenomegaly.

Electrocardiogram and echocardiogram were normal, with an ejection fraction of 65% and no evidence of inifitrative disease. Nuclear liver scan revealed cholestasis. Endoscopic retrograde cholangiopancreatography was attempted to rule out obstruction of the biliary tree but was aborted because of severe bowel edema. Computed tomographic scan of the chest, abdomen, and pelvis showed diffuse bowel edema, ascites, large bilateral pleural effusions, and no masses, adenopathy, or organomegaly.

Over the next 48 hours, laboratory values increased as follows: ALK 302 U/L, AST 3,104 U/L, ALT 652 U/L, total bilirubin 20.2 mg/dL, and direct bilirubin 17.2 mg/dL. The patient became obtunded and required endotracheal intubation with mechanical ventilation and continuous venovenous hemodialysis for progressive metabolic acidosis. Because of nucleated red cells on the peripheral smear, the patient had bilateral bone marrow aspiration and biopsies, which revealed extensive plasmacytic cell infiltrate comprising 70% of marrow cellularity, with the presence of homogenous eosinophilic material consistent with amyloid (Fig 1).

A liver biopsy the same day showed parenchymal eosinophilic material (Fig 2). Electron microscopy (Fig 3) and crystal violet stain confirmed the presence of amyloid. These results were consistent with multiple myeloma and amyloidosis. Serum protein electrophoresis lacked a monoclonal band but had low peaks in the light chain region. Urine protein electrophoresis revealed a monoclonal band in the light chain region consistent with Bence-Jones proteins. The patient died from fulminant hepatic failure shortly after confirmatory diagnosis of multiple myeloma and amyloidosis.

DISCUSSION

Multiple myeloma-associated amyloidosis occurs in less than 15% of myeloma cases. (1) Protein deposition commonly occurs in the kidneys and heart resulting in death from cardiac or renal failure. Amyloid deposition in the liver and other organs is common but usually asymptomatic. Elevation of liver-associated enzyme levels and intrahepatic cholestasis is extremely rare. (3) Jaundice, ascites, and liver enzyme abnormalities are ominous signs, which are present in 5% of reported cases. (4) Although there have been several cases of amyloidosis with hepatic involvement, few of these patients actually died from hepatic disease. Disease progression, is generally subacute. In fact, we could find only three reports of hepatic failure from myeloma-associated amyloidosis. Ours is the second reported case of k light chain myeloma with amyloidosis resulting in a progressive clinical course of hepatic failure. (5-7)

Our patient's case is unique in that, despite severe disease, he had mild symptoms without laboratory abnormalities until 2 weeks prior to death. Unlike others, our patient had no hepatomegaly on examination or on imaging studies. He did not have systemic signs of amyloidosis such as neuropathy, carpal tunnel syndrome, or signs of other organ involvement. He lacked systemic evidence of multiple myeloma, such as anemia or renal insufficiency.

This relatively quiescent case of myeloma with aggressive protein deposition in the liver and rapid progression to death supports earlier documentation suggesting that the severity of amyloidosis is independent of myeloma stage and the presence of active disease. (3) Indeed, the previously reported cases also had controlled myeloma at the time of death. In all cases, hepatitis A, B, and C serologies were negative, and there was no history of alcohol abuse or prior hepatic injury. The rapidly progressive course of hepatic failure in these three cases and in our patient suggest, however, that perhaps the mere presence of myeloma does play a role in the outcome of hepatic amyloidosis.

CONCLUSION

The presence of cases such as ours should prompt physicians to investigate even vague symptoms in all myeloma patients, especially those with hepatic dysfunction, for possible amyloidosis. Continued study and reporting of such cases, as well as consideration of myeloma-associated amyloidosis in the differential diagnosis of patients with myeloma, may allow discovery of additional cases and further investigation into therapeutic options for these patients.

References

(1.) Bataille R, Harousseau L: Multiple myeloma. N Engl J Med 1997; 334:16

(2.) Kyle RA, Gertz MA: Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995;32:45-59

(3.) Gertz MA, Kyle RA: Hepatic amyloidosis (primary [AL] immunoglobin light chain): the natural history in eighty patients. N Engl J Med 1998; 85:74-80

(4.) Hoffman MS, Stein BE, Davidian MM, et al: Hepatic amyloidosis presenting as severe intrahepatic cholestasis, a case report and review of the literature. Am] Gastroenterol 1988;83:783-785

(5.) Yamamoto T, Maeda N, Kawasaki H: Hepatic failure in a case of myeloma-associated amyloidosis (k-AL). J Gastroenterol 1995; 30:393-397

(6.) Okabe M, Heum G, Mineao K, et al: Hepatic failure due to myeloma-associated amyloidosis. J Gastroenterol 1998; 33:926927

(7.) Mainenti PP, Petrelli G, Lamanda R, et al: Primary systemic amyloidosis with giant hepatomegaly and a swiftly progressive course. J Clin Gastroenterol 1997; 24:173-175

KEY POINTS

* Multiple myeloma typically presents as bone pain, anemia, and renal insufficiency.

* Amyloidosis is an infrequent complication of multiple myeloma.

* Patients with multiple myeloma and liver function abnormalities should be investigated for underlying amyloidosis.

* Severity of amyloidosis may be independent of multiple myeloma stage.

* Currently, there are no therapeutic options for multiple myeloma-associated amyloidosis.