Pediatr Blood Cancer 2015;62:2232–2234
BRIEF REPORT Stem Cell Transplant-Associated Wernicke Encephalopathy in a Patient With High-Risk Neuroblastoma Wendy S. Darlington,
MD, MAPP,
Navin Pinto, MD, Hillary M. Hecktman, CPNP, Susan L. Cohn, James L. LaBelle, MD, PhD*
Children undergoing intense cancer treatment frequently require total parenteral nutrition (TPN). Rarely, vitamins are removed due to hypersensitivity to the carrier vehicle in the formulation. We present the case of a 5-year-old patient with stage 4, high-risk neuroblastoma who developed altered mental status, ataxia, and tachycardia during consolidative autologous stem cell transplantation. Skin findings and brain MRI were consistent with thiamine (vitamin B1) deficiency and
MD,
and
Wernicke encephalopathy. Vitamin B1 administration rapidly reversed all skin and neurologic symptoms. This case highlights the importance of close monitoring of micronutrients in pediatric patients receiving prolonged courses of chemotherapy and stem cell transplantation. Pediatr Blood Cancer 2015;62:2232–2234. © 2015 Wiley Periodicals, Inc.
Key words: neuroblastoma; total parenteral nutrition; vitamin B1; Wernicke encephalopathy
INTRODUCTION The outcome for children with cancer has improved dramatically during the past two decades with intensified therapies. This is particularly true for patients diagnosed with stage 4, high-risk neuroblastoma where the current standard of care includes multiple cycles of multi-agent chemotherapy, myeloablative chemotherapy with autologous stem rescue, immunotherapy, and cis-retinoic acid. [1,2] During this prolonged treatment, and often because of age, these patients frequently require caloric supplementation with total parenteral nutrition (TPN) because of limited enteral intake secondary to mucositis, prolonged nausea, and subsequent food aversion. Rarely, vitamins are removed from TPN due to hypersensitivity reactions to a carrier protein/compound.[3,4] These patients are at risk of developing vitamin deficiency syndromes when therapy is intensive enough to curtail adequate oral vitamin intake.
CASE PRESENTATION A 5-year-old female initially presented with widely disseminated unfavorable histology neuroblastoma.[5] The nutritional status of the patient at diagnosis was weight 19 kg (56% for age), height 112.5 cm (72% for age), and BMI 15.01 kg/m2 (45% for age). The patient was treated per the Children’s Oncology Group (COG) ANBL0532 protocol (NCT00567567). The patient developed severe mucositis and intermittent nausea during therapy. TPN was initiated with standard pediatric multivitamins, which the patient initially tolerated without incident. However, 48 hr following discharge from the hospital and still receiving TPN, the patient developed a hypersensitivity reaction with generalized erythema, pruritic urticaria, nausea, and vomiting. Both formulations of TPN given to the patient while inpatient and as an outpatient contained Infuvite Pediatric (Baxter Healthcare), an intravenous multivitamin preparation. Of note this formulation contains polysorbate 80, a hydrophilic emulsifier used to emulsify the oil-soluble vitamins A, D, E, and K. The multivitamins were suspected to be the cause of her hypersensitivity reaction and were subsequently discontinued. Over the next 21 weeks, the patient continued therapy and was admitted for stem cell transplantation. Upon admission for stem cell transplant her weight was 20.5 kg (60% for age), height 117.6 cm (81% for age), BMI 14.82 kg/m2 (39% C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25650 Published online 14 July 2015 in Wiley Online Library (wileyonlinelibrary.com).
for age) similar to pre-treatment percentiles and indicating stable weight gain during treatment. She had no history of prolonged diarrhea or emesis during her treatment. Albumin was measured at diagnosis at 3.7 g/dl (nl 3.5–5 g/dl) and remained stable at the time of transplant at 4 g/dl. The patient had limited, but measurable, oral intake including an oral multivitamin per parental report up until transplantation and was therefore maintained on TPN without additional intravenous multivitamins. Eighteen days following stem cell infusion, the patient developed perioral superficial erosions and discoloration prompting dermatologic consultation (Fig. 1). The differential diagnoses at the time included infection, contact dermatitis, and vitamin deficiency. HSV PCR and cultures for bacteria and fungus returned negative. Hydrocortisone 2.5% ointment was applied to the skin lesions without improvement. On day 26 post-transplant, the patient developed rapid onset altered mental status, ataxia, and tachycardia. A brain MRI demonstrated bilateral enhancement of the medial thalami, hippocampi, and mammillary bodies, consistent with Wernicke encephalopathy (WE) (Fig. 2). The patient was immediately started on 7 days of intramuscular vitamin B1/thiamine (100 mg daily) replacement. Within 24 hr of the initial dose of thiamine, the patient’s tachycardia and neurologic symptoms improved and after the 7 day course her neurologic symptoms completely resolved. The patient tolerated the thiamine without any complications. Vitamin Abbreviations: CT, computed-tomography; MRI, magnetic resonance imaging; TPN, total parenteral nutrition; WE, Wernicke encephalopathy Department of Pediatrics, Section of Hematology/Oncology/Stem Cell Transplantation, Comer Children’s Hospital, University of Chicago, Chicago, Illinois Ethics statement: This report contains photographs of a human subject. We affirm that informed consent for the use of these images was granted prior to this submission. Conflict of interest: Nothing to declare.
Correspondence to: James L. LaBelle, Department of Pediatrics, Comer Children’s Hospital, 900 East 57th Street, KCBD 5122, Chicago, IL 60637. E-mail: [email protected] Received 16 February 2015; Accepted 1 June 2015
Vitamin B1 Deficiency During Stem Cell Transplant
2233
Fig. 1. Facial rash, day þ18 following autologous stem cell infusion. A: Geometric angular erythematous thin plaques on bilateral corners of mouth, right more than left, erosion on cutaneous upper lip near nasal ala. B: Hyperpigmented thin plaques on right cheek.
measurements obtained at the onset of rash returned with normal serum zinc of 1.08 mcg/ml (nl 0.6–1.2 mcg/ml) but an abnormally low vitamin B6 level of
BRIEF REPORT Stem Cell Transplant-Associated Wernicke Encephalopathy in a Patient With High-Risk Neuroblastoma Wendy S. Darlington,
MD, MAPP,
Navin Pinto, MD, Hillary M. Hecktman, CPNP, Susan L. Cohn, James L. LaBelle, MD, PhD*
Children undergoing intense cancer treatment frequently require total parenteral nutrition (TPN). Rarely, vitamins are removed due to hypersensitivity to the carrier vehicle in the formulation. We present the case of a 5-year-old patient with stage 4, high-risk neuroblastoma who developed altered mental status, ataxia, and tachycardia during consolidative autologous stem cell transplantation. Skin findings and brain MRI were consistent with thiamine (vitamin B1) deficiency and
MD,
and
Wernicke encephalopathy. Vitamin B1 administration rapidly reversed all skin and neurologic symptoms. This case highlights the importance of close monitoring of micronutrients in pediatric patients receiving prolonged courses of chemotherapy and stem cell transplantation. Pediatr Blood Cancer 2015;62:2232–2234. © 2015 Wiley Periodicals, Inc.
Key words: neuroblastoma; total parenteral nutrition; vitamin B1; Wernicke encephalopathy
INTRODUCTION The outcome for children with cancer has improved dramatically during the past two decades with intensified therapies. This is particularly true for patients diagnosed with stage 4, high-risk neuroblastoma where the current standard of care includes multiple cycles of multi-agent chemotherapy, myeloablative chemotherapy with autologous stem rescue, immunotherapy, and cis-retinoic acid. [1,2] During this prolonged treatment, and often because of age, these patients frequently require caloric supplementation with total parenteral nutrition (TPN) because of limited enteral intake secondary to mucositis, prolonged nausea, and subsequent food aversion. Rarely, vitamins are removed from TPN due to hypersensitivity reactions to a carrier protein/compound.[3,4] These patients are at risk of developing vitamin deficiency syndromes when therapy is intensive enough to curtail adequate oral vitamin intake.
CASE PRESENTATION A 5-year-old female initially presented with widely disseminated unfavorable histology neuroblastoma.[5] The nutritional status of the patient at diagnosis was weight 19 kg (56% for age), height 112.5 cm (72% for age), and BMI 15.01 kg/m2 (45% for age). The patient was treated per the Children’s Oncology Group (COG) ANBL0532 protocol (NCT00567567). The patient developed severe mucositis and intermittent nausea during therapy. TPN was initiated with standard pediatric multivitamins, which the patient initially tolerated without incident. However, 48 hr following discharge from the hospital and still receiving TPN, the patient developed a hypersensitivity reaction with generalized erythema, pruritic urticaria, nausea, and vomiting. Both formulations of TPN given to the patient while inpatient and as an outpatient contained Infuvite Pediatric (Baxter Healthcare), an intravenous multivitamin preparation. Of note this formulation contains polysorbate 80, a hydrophilic emulsifier used to emulsify the oil-soluble vitamins A, D, E, and K. The multivitamins were suspected to be the cause of her hypersensitivity reaction and were subsequently discontinued. Over the next 21 weeks, the patient continued therapy and was admitted for stem cell transplantation. Upon admission for stem cell transplant her weight was 20.5 kg (60% for age), height 117.6 cm (81% for age), BMI 14.82 kg/m2 (39% C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25650 Published online 14 July 2015 in Wiley Online Library (wileyonlinelibrary.com).
for age) similar to pre-treatment percentiles and indicating stable weight gain during treatment. She had no history of prolonged diarrhea or emesis during her treatment. Albumin was measured at diagnosis at 3.7 g/dl (nl 3.5–5 g/dl) and remained stable at the time of transplant at 4 g/dl. The patient had limited, but measurable, oral intake including an oral multivitamin per parental report up until transplantation and was therefore maintained on TPN without additional intravenous multivitamins. Eighteen days following stem cell infusion, the patient developed perioral superficial erosions and discoloration prompting dermatologic consultation (Fig. 1). The differential diagnoses at the time included infection, contact dermatitis, and vitamin deficiency. HSV PCR and cultures for bacteria and fungus returned negative. Hydrocortisone 2.5% ointment was applied to the skin lesions without improvement. On day 26 post-transplant, the patient developed rapid onset altered mental status, ataxia, and tachycardia. A brain MRI demonstrated bilateral enhancement of the medial thalami, hippocampi, and mammillary bodies, consistent with Wernicke encephalopathy (WE) (Fig. 2). The patient was immediately started on 7 days of intramuscular vitamin B1/thiamine (100 mg daily) replacement. Within 24 hr of the initial dose of thiamine, the patient’s tachycardia and neurologic symptoms improved and after the 7 day course her neurologic symptoms completely resolved. The patient tolerated the thiamine without any complications. Vitamin Abbreviations: CT, computed-tomography; MRI, magnetic resonance imaging; TPN, total parenteral nutrition; WE, Wernicke encephalopathy Department of Pediatrics, Section of Hematology/Oncology/Stem Cell Transplantation, Comer Children’s Hospital, University of Chicago, Chicago, Illinois Ethics statement: This report contains photographs of a human subject. We affirm that informed consent for the use of these images was granted prior to this submission. Conflict of interest: Nothing to declare.
Correspondence to: James L. LaBelle, Department of Pediatrics, Comer Children’s Hospital, 900 East 57th Street, KCBD 5122, Chicago, IL 60637. E-mail: [email protected] Received 16 February 2015; Accepted 1 June 2015
Vitamin B1 Deficiency During Stem Cell Transplant
2233
Fig. 1. Facial rash, day þ18 following autologous stem cell infusion. A: Geometric angular erythematous thin plaques on bilateral corners of mouth, right more than left, erosion on cutaneous upper lip near nasal ala. B: Hyperpigmented thin plaques on right cheek.
measurements obtained at the onset of rash returned with normal serum zinc of 1.08 mcg/ml (nl 0.6–1.2 mcg/ml) but an abnormally low vitamin B6 level of
