Treatment of Complex Regional Pain Syndrome (CRPS) Using Low Dose Naltrexone (LDN)
A female patient, currently 12 years old, has a genetic disorder, Ehlers-Danlos Syndrome (EDS) hypermobility type 1, dysautonomia, non-epileptic seizures, chronic gastritis, mitochondrial dysfunction, asthma, vision loss, thyroid tumor and anti-cardiolipin antibodies. As a result of her EDS, the patient has had repeated dislocations of her right shoulder, as well as her right ankle. The patient first developed CRPS in her lower right extremity in 2008. In 2009, the patient developed dystonic muscle spasms in the upper extremities, which were interpreted by her physicians as evidence of a conversion disorder.\nThe patient was first seen by one of us (PC) in February of 2011. Her symptoms of CRPS included color change, increased temperature in the right foot (90 °C) versus (82 °C) in the left foot, allodynia over the dorsum of right foot, and patchy areas of dysesthesia over her right leg. She also had areas of allodynia and dysesthesia in the left lower extremity and both upper extremities, as well as distorted nails on the right foot. When first seen, the patient’s medications were levetiracetam, midodrine, baclofen, trazodone, diphenhydramine, lansoprazole, budesonide, levalbuterol, L-Carnitine, coenzyme Q10, vitamin D, vitamin C, magnesium, and vitamin B complex. She rated her pain on a NRS (Numerical Rating Scale) as 8/10 at its lowest and 10/10 at its worst. In early 2011, the patient experienced a subluxation of her right ankle. The lower right leg and ankle subsequently developed fixed dystonia, with plantar flexion and varus (Fig. ).\nIn June 2011, the patient was started on low dose naltrexone (LDN) of 3 mg once a day and ketamine troches (sublingual) 10 mg on as needed basis. The LDN was increased to 4.5 mg per day, 4 weeks after starting it. LDN was started as a lower dose to gauge tolerability. She tolerated the LDN very well with no reports of adverse effects. Her pain scores dropped from NRS (7–10)/10, to (3–5)/10. She also reported a decrease in allodynia, as well as a decrease in sensitivity to touch and temperature change. There was no effect on the dystonia. Two months after starting LDN, she underwent 400 units of botulinum toxin A injections to the right gastrocnemius group of muscles with minimal relief of her dystonia. The right lower extremity was placed in an above knee cast for 6 weeks. Several weeks after the cast was removed, the patient subluxated her right ankle again. She underwent a 400 units injection of botulinum toxin, and a cast was applied again. The patient used ketamine troches (10 mg) for 3 weeks after the LDN was started, as needed for pain. She was taking ketamine troches on as needed basis for acute flare-ups of her CRPS pain. This was limited to no more than 30 mg of ketamine troches per day. The patient progressively reduced her use of ketamine troches 3 weeks after starting LDN, and by 8 weeks was taking them rarely.\nIn December of 2011, she underwent percutaneous pinning of the right ankle to stabilize the joint. The pins were removed 6 weeks later and the ankle joint subluxated again. In February of 2012, the patient underwent reinforcement to the right ankle with cadaver ligaments. She continued to be on low dose naltrexone during this time, except for 4 perioperative days, during which the LDN was discontinued. As per institutional protocol, LDN was stopped for 24 h before surgery. After surgery, she was given oral opioids (hydrocodone with acetaminophen) for 1 week. The oral opioids were then discontinued, and LDN treatment was resumed 24 h, after her last dose of opioid. The patient noticed a decrease in her post-operative pain, ranging from (4–6)/10, 3 weeks after resuming LDN. Skin discoloration and allodynia could not be assessed after the surgery because her leg was in a cast.\nAt the time of cast removal, the patient’s lower leg and ankle had a normal range of motion, indicating a remission of the leg’s fixed dystonia (Fig. ). The leg had a slight red color at the time of cast removal, but no allodynia. Ten months after surgery, the patient’s gait was normal.\nRemarkably, the patient did not experience any spread of her CRPS, despite undergoing multiple invasive procedures, including surgery. One of the known triggers for a CRPS flare-up, or spread of CRPS symptoms, is trauma (Schwartzman et al. ; van Rijn et al. ). The patient still has a chronic shoulder dislocation, associated with her EDS. However, her CRPS symptoms have resolved completely. The patient has been maintained on LDN for 18 months. No side effects of LDN have been noted.