Initial presentation

A patient in his 70s with multiple myeloma being treated with chemotherapy and prior auto-stem cell transplant was seen in the hematology clinic for evaluation of neutropenia. Other past medical history included gastroesophageal reflux disease, Barrett’s esophagus, gastroparesis, and benign prostatic hyperplasia (BPH). White blood cell count at the time of hematology referral was 1.5 K/µL (neutrophil 29.2%), not fully attributable to his multiple myeloma or treatment-related effects, and hemoglobin ranging from 7.7 to 8.6 g/dL. As for symptoms, he reported progressive fatigue, nausea, and poor appetite for the past few weeks. He also stated having worsening numbness and tingling pain extending from the bilateral lower extremities to the thighs and new onset tingling in the bilateral hands for the past few weeks, in the background of known chemotherapy-induced peripheral neuropathy. His home medications included acyclovir 800 mg twice a day and sulfamethoxazole-trimethoprim 800 mg-160 mg three times a week for infection prophylaxis, amoxicillin-clavulanate 875 mg-125 mg twice a day following a recent hospitalization for fever, morphine sulfate immediate release 7.5 mg every 4 h as needed for cancer-related pain, alfuzosin 10 mg daily and finasteride 5 mg daily for BPH, and zinc sulfate 220 mg twice a day for dysgeusia initially prescribed approximately 2 years ago.

For the neutropenia, lab tests to investigate autoimmune etiologies (rheumatoid factor [RF], anti-neutrophil antibody [ANA]) and a copper level were ordered. The patient’s ANA and RF factors were undetectable. However, he was found to have a very low copper level of < 10 mcg/dL. Due to worsening lightheadedness, nausea, fatigue, and the finding of hypocupremia, he was instructed to present to the acute care center.

Hospital course

The patient was admitted to the hospital for further management. Zinc was discontinued. IV cupric chloride infusion of 4 mg daily was initiated with the plan to administer for a total of 10 days.

The supportive and palliative care team was consulted to assist with symptom management. The patient reported painful neuropathy with tingling and numbness in the bilateral lower extremities extending to the upper thighs and bilateral hands. He declined gabapentin or duloxetine; gabapentin had been ineffective, and he had discontinued duloxetine due to side effect concerns. He also reported increase in his chronic lower back pain related to vertebral compression fractures and lumbar facet arthropathy. Morphine immediate release oral solution 5 mg every 4 h as needed was prescribed to treat lower back pain and severe pain from neuropathy. Abdominal imaging revealed constipation, which was treated with senna tablets and polyethylene glycol daily. He reported that dysgeusia was no longer an issue.

For nausea with history of gastroparesis, gastroesophageal reflux disease, and Barrett’s esophagus, the gastrointestinal medicine team was consulted. It was determined that nausea was likely multifactorial due to severe copper deficiency exacerbating the known gastroparesis. He was given erythromycin three times a day for 3 days.

The neurology team was also consulted to assess the peripheral neuropathy. On further neurologic exam, he was found to have impaired gait, decreased vibration sense in the anterior superior iliac spine and ankles bilaterally, as well as a positive Romberg test. The findings were concerning for subacute combined degeneration of the spinal cord related to copper deficiency. Additional lab work to check a vitamin B12 level found this to be within normal range at 945 pg/mL. The neurology team recommended further copper repletion.

Outcome

The patient reported improvement in fatigue, nausea, and pain by hospital day 3, as seen in his Edmonton Symptom Assessment System (ESAS) scores (Table 1). He also reported mild improvement in paresthesia of the lower extremities during his hospital course. He received 5 days of IV cupric chloride inpatient. He was discharged with the plan to continue additional copper infusions in the outpatient setting for 5 more days.

Table 1.

Edmonton Symptom Assessment System (ESAS) scores

He was seen in the supportive care clinic 39 days post-discharge and reported some symptom improvement. Fatigue and pain remained improved overall from his hospital admission. He was not using any medications for pain or neuropathy. He reported the numbness and tingling in his lower extremities had diminished to the knee level. He denied dysgeusia but did report persistent issues with early satiety, nausea, and constipation. He was advised to increase laxatives and take metoclopramide 5 mg three times daily for nausea and early satiety.