Innov Clin Neurosci. 2018;15(5–6):11–12
Dr. Majeed is an attending psychiatrist with Department of Psychiatry, Natchaug Hospital in Norwich, Connecticut. Dr. Ubaidulhaq is a Pain Medicine Fellow and Dr. Gusa Attending Physician with the Department of Anesthesiology at the University of Mississippi Medical Center in Jackson, Mississippi.
Funding/financial disclosures. The authors have no conflicts of interest relevant to the content of this letter. No funding was received for the preparation of this letter.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic autosomal dominant disorder arising from a de novo genetic mutation of the lamin A gene on chromosome 11.1 The estimated prevalence is approximately 1 in 8 million live births, with more than 100 known current living cases in the world.2 These patients show premature aging characteristics, linked with cardiovascular and central nervous system complications, growth impairment, skin abnormalities, bone development problems, and abnormal fat distribution patterns.3 The average life expectancy for patients is 13 years, and the most common causes of mortality are cardiovascular events. These patients frequently require pain management due to of common unintentional injuries, spontaneous fractures, and end-of-life/palliative care issues. To our knowledge, no literature has been published regarding safe prescription of opioid medications in patients with HGPS. In the present case, our treatment team faced the clinical challenge of adjusting pain medications for effective and safe analgesia.
Case report. A 17-year-old woman with a history of progeria-like-syndrome, pulmonary embolism, decubitus ulcers, multiple contractures of the extremities, hip dislocation, osteoporosis, and knee chronic osteomyelitis was referred to us for pain management. The patient reported multiple areas of pain, including the hip, knee, hands, wrist, and forearm. Spasticity and contractures made her somatic pain worse. She also reported significant pain due to an open ulcer from osteomyelitis of the knee.
Her medication regimen was evaluated. She was prescribed baclofen and nortriptyline for muscle spasms and neuropathic pain, respectively. A fentanyl patch, 25mcg once every 72 hours, was prescribed for acute pain, and an oxycodone tablet 5mg four times daily was prescribed for breakthrough pain. After starting the medications, her pain was under control for the first two days. On the third day, she complained of unbearable pain. Fentanyl patch frequency was increased to 25mcg every 48 hours and a slow taper of oxycodone was started. The patient reported better and more stable pain control with this regimen for several months.
Discussion. Patients with HGPS frequently suffer from acute and chronic pain because of musculoskeletal abnormalities and unintentional injuries. These injuries occur because of bone deformities, malfunctioning joints, and gait problems.2 Opioid pain medications are frequently used to treat acute pain conditions and for palliative care management in these cases.4
Clinicians should be aware that, because of accelerated aging, individuals with HGPS differ in their response to specific opioid analgesics. The metabolism and the rate of elimination of opioids from the body could vary significantly in these patients. They might require higher-than-usual doses of some opioids for effective and safe analgesic effects, while other opioids should be avoided due to poor elimination and risk of toxicity.
Primarily, the liver enzymes CYP2D6 and CYM3A4 metabolize opioids.5 With the early aging of the liver, HGPS patients might experience a reduced efficacy of codeine as the liver loses its ability to metabolize codeine into the active molecule morphine. In patients treated with oxycodone, poor metabolism can lead to an increase in noroxycodone levels and a reduction in active metabolite oxymorphone production. This could result in a poor efficacy of drugs and an unsatisfactory treatment response. Nortriptyline is a preferred drug to treat pain in patients with HGPS because it does not need to be metabolized in the liver to become active.
Patients with HGPS have reduced stores of adipose tissue.3 This leads to reduced distribution and storage areas for lipophilic drugs such as opioids. This can cause a faster elimination of opioids, resulting in a shorter half-life. Patients might also require more frequent doses of the medication for sustained analgesic control.
Effective and safe pain control in patients with HGPS requires knowledge of the pharmacokinetics of individual opioid medications. Because of the frequent use of opioids to treat common pain symptoms and end-of-life/palliative care issues, studies are urgently needed to understand the opioid metabolism among patients with HGPS.
- Eriksson M, Brown WT, Gordon LB, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423(6937):293–298.
- Coppedè F. The epidemiology of premature aging and associated comorbidities. Clin Interv Aging. 2013;8:1023–1032.
- Merideth MA, Gordon LB, Clauss S, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008;358(6):592–604.
- Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. JAMA. 2016;315(15):1624–1645.
- Smith HS. Opioid metabolism. Mayo Clin Proc. 2009;84(7):613–624.
Muhammad Hassan Majeed, MD; Muhammad Ubaidulhaq, MD; and William E. Gusa, MD