P3.I167: An Apple a Day Keeps the Doctor Away: Symptomatic Management of Persistent Hiccups in a Patient Undergoing Hematopoietic Stem Cell Transplant

Introduction: Mucositis is a common symptom in patients undergoing hematopoietic stem cell transplant (HSCT). Mucositis causes pain, alters taste, impairs intake, and can be a source of serious infection, treatment delays, dose-reductions, and need for parenteral nutrition. Although not classically associated with HSCT, hiccups carry a broad differential and can exacerbate pain, impede oral intake, and disrupt sleep, potentially contributing to delirium (Table 1).

Case Description: A 21-year-old male with pervasive developmental disorder (PDD) was diagnosed with refractory acute myeloid leukemia (AML) and underwent allogeneic HSCT. He developed mucositis two days post-HSCT infusion, earlier and more severe than expected for his conditioning regimen. Intermittent hiccups arose on day +3. A morphine patient-controlled analgesia (PCA) pump was initiated to treat pain. Hiccup frequency increased (~20-30 hiccups/min) and did not abate with sleep, increased sedation, speaking, or eating. Deep breathing and acupressure were ineffective. A stepwise pharmacologic treatment approach was used over the next four days including: (1) PCA opioid rotation to hydromorphone; (2) continuation of an intravenous proton pump inhibitor; (3) baclofen up to 10mg three times daily (TID); (4) wean of lorazepam dosing; (5) ketamine infusion to potentiate opioid effects; and (6) titration of gabapentin up to 200mg TID (~3mg/kg/dose). Hiccups persisted, and after six days, the patient developed altered mental status (AMS), worsening mucositis, and extensive oral epitheliolysis. Physical exam was notable for longstanding perifollicular petechiae on his legs (Figure 1). The skin findings, in conjunction with AMS, prompted a broad evaluation, including infectious, neurologic, and metabolic, which were initially unrevealing. He was started on TPN with a multivitamin; four days later, hiccups abated and sleep and pain improved. His vitamin C level sent prior to TPN-initiation returned undetectable a week later (due to processing time), revealing the diagnosis of scurvy.

Discussion: Many patients are at risk for limited diet before, during, and after HSCT, increasing the risk for nutritional deficiencies. Scurvy can present post-HSCT with vague, overlapping symptoms, including petechiae and oral changes. We hypothesize that scurvy led to more significant mucositis and esophageal inflammation, stimulating thoracic branches of the vagus nerve and causing hiccups. Vitamin C is also reported to aid in myelination, and deficiency may have exacerbated the hiccup reflex arc. This hypothesis is supported by hiccups improving after 36 hours of vitamin C supplementation, with complete cessation after four days. Eight evidence-based interventions for persistent hiccups (Table 1) were trialed without effect, suggesting that interventions did not target the underlying symptom cause, leading to pain/distress, delirium, overmedicalization, polypharmacy, and prolonged hospitalization

Conclusion: Scurvy may exacerbate symptoms distressing to patients undergoing HSCT, including mucositis, hiccups, delirium, bleeding/bruising, and hair growth. When an atypical symptom does not respond to typical interventions, it is critical to consider the zebra, not just the horse.