Reflex Sympathetic Dystrophy-Like Syndrome,Possibly Caused By Aripiprazole,in an Adolescent Patient

Case Report

MM was a 15-year-old female of Hispanic descent who presented to the outpatient psychiatry clinic with complaints of extreme anger, aggression, and impulsivity. Aripiprazole was accepted by the patient and her parents, to help with the presented symptoms, because of the relatively safe side effect profile. Patient was started on aripiprazole 2 mg orally at night, which she tolerated well. On third day, the dose of aripiprazole was increased to 4 mg orally at night. Two days after the aripiprazole dose was increased, the patient noticed redness on both her feet and gradually increasing swelling, so much so that she could not wear her regular footwear. She also noticed sharp shooting pain in her feet, the intensity of which varied from 5 to 8 on a 10 point scale. She described it as diffuse, intermittent, and mainly on the ventral surface of her feet. She reported that the pain was worse when she was walking, and was a bit better when she was at rest, although a dull achy feeling remained. She had no history of trauma or surgery in the recent past. She had a first degree relative with osteoarthritis, but there was no family history of any other joint problems (Murray et al. 2000).

Interestingly, the pain and swelling was localized to the feet, and her lower limbs were unaffected. Aripiprazole was discontinued, and patient was sent to her pediatrician for appropriate follow-up. After a thorough physical examination and laboratory testing consisting of a comprehensive metabolic profile, complete blood count, urine analysis, and urine drug screen, which revealed normal results, the symptoms were deemed to be a possible side effect of aripiprazole. Meanwhile the patient was advised to begin with gentle weight bearing, and slowly progress to active weight bearing, wearing comfortable footwear, and to take nonsteroidal anti-inflammatory drugs (NSAIDs) as needed for pain (Brunnekreef et al. 2009). Two days after discontinuing the medication, the patient felt relief of her symptoms, and they completely resolved within 1 week of discontinuation of aripiprazole. She did not take any medication for pain.

Discussion

In this case study, possible association of aripiprazole with RSD-like syndrome is made on clinical grounds. No specific diagnostic test is available and, hence, diagnosis is based mainly on history, clinical examination, and supportive laboratory findings (Albazaz et al. 2008).

This patient developed a possible adverse reaction to aripiprazole, as the symptoms resolved completely after discontinuation of the medication. RSDS is a diagnosis of exclusion made after ruling out vascular or inflammatory conditions, neuropathies, and tumors. The natural history of RSDS is still unclear, as it would appear that not all cases progress unremittingly, and resolution may occur at any stage (Marshall et al. 2000). Some cases seem to respond rapidly to treatment whereas others may be resistant (Marshall et al. 2000). Interestingly, recurrence may occur subsequently at the original, or at a completely separate, anatomical site (Marshall et al. 2000).

The natural history of RSD is variable and unpredictable, the pathogenesis is unknown, and few controlled treatment trials exist. Therefore, evidence-based treatment guidelines do not exist, and the approach depends largely on the specialty of the treating physician. Even if a disturbance in sympathetic nervous system function is important in the development of the clinical syndrome, not all patients respond to sympatholytic medications or to chemical or surgical sympathectomy (Viel et al. 1999).

Clinical experience teaches that early recognition and treatment are necessary to avoid permanent disability, and that the effectiveness of treatment is limited once the patient has reached the chronic fibrotic stage. Certainly, the incidence and severity of RSD can be greatly reduced by initiating prophylactic measures in situations that are known to be triggers (hemiplegic stroke, Colles fracture). These measures include immediate and aggressive mobilization of the involved extremity with passive and then active range-of-motion exercises. Similarly, in patients with established RSD, physical and occupational therapy are key components of any therapeutic regimen (Severens et al. 1999). Two major approaches to the medical treatment of early RSD exist: Sympathetic blockade and antiinflammatory therapy (Severens et al. 1999). Treatment aimed at pain reduction and rehabilitation of the affected limb form an important part of therapy (Albazaz et al. 2008). Comorbidities, if any, such as anxiety and depression, should be treated concurrently (Albazaz et al., 2008).

This case report points to a possible rare side effect of aripiprazole. Communication with the patient's family and coordination of care with the pediatrician enabled early intervention and treatment. As the use of psychiatric medications in children is on the rise, clinicians must be watchful of side effects that are not commonly listed, in order to prevent undue morbidity, and unnecessary investigations and treatment, which may exacerbate and prolong the condition. As aripiprazole is a relatively new drug, and is being used widely in the pediatric population, more research on its adverse effects will be extremely valuable.