Managing late onset primary erythromelalgia with oral pregabalin

Introductıon Erythromelalgia (EM), a rare and chronic condition of unknown etiology, is characterized by recurrent intense burning pain in extremities associated with erythema and increased skin temperature. Warmth or heat intensifies the discomfort, while cold provides symptomatic relief.1 The pathogenesis of erythromelalgia has been a matter of debate. The primary EM may occur due to mutation of voltage-gated sodium channel α-subunit gene SCN9A and the secondary may be associated with various disorders like thrombocytopenia, essential thrombocytosis, polycythemia, mushroom or mercury poisoning, myeloproliferative disorders, hypertension, vasculitis, systemic lupus erythematous, scleroderma, rheumatoid arthritis, Raynaud’s disease, HIV and gout.2 The disease is not associated with any sexual preponderance and is often intermittent in nature.

was non-diabetic, non-hypertensive, and euthyroid with no significant family history of similar pain.
Blood investigations were unremarkable.Anti-nuclear antibodies, CRP, ANA, RA factor, anti-CCP, uric acid, prothrombin time, activated partial thromboplastin time, serum fibrinogen, and platelet count were within the normal limits.There was no evidence of liver and kidney dysfunctions.There was no abnormal electrocardiographic pattern and history of radiation exposure.
Based on these findings, the diagnosis was concluded as late onset primary erythromelalgia of unknown origin.Treatment of the patient was initiated with a short course of oral deflazacort 6 mg twice daily for 1 week and oral pregabalin 150 mg daily in divided doses.From the ergonomic point of view, he was transferred from infantry division to administration.After 7 days, the patient reported a reduction in VAS score (from 7/10 to 2/10), and relief in erythema, swelling and tenderness.For the subsequent weeks, he was only on oral pregabalin 150 mg and his symptoms continued to improve, and within 1 month, the dose was reduced to 75 mg.For the past 4 months, the patient was receiving pregabalin 75 mg and it helped in reducing the frequency of duration and intensity of pain and erythema.

Discussion
Erythromelalgia (erythro = red, melos = limb, algos = pain) is characterized by burning discomfort, warmth and dermal erythema of the feet and/or the hands.Despite many proposed etiologies, the exact etiopathogenesis remains poorly understood.Drenth and Michiels classified the condition into 3 categories i.e, erythromelalgia (plateletmediated and aspirin-sensitive), primary erythromelalgia, and secondary erythromelalgia. 3Symptoms are often triggered by minor trauma, exercises or heat exposure and relieved by cooling and elevation of the limb.Pain due to erythromelalgia is often resistant to a range of analgesic therapies.[6][7][8] The involvement of secondary causes must be ruled out in cases with confirmed diagnosis.Erythromelalgia can be associated with SLE, Raynaud's disease, pernicious anemia, thrombotic thrombocytopenic purpura, infectious mononucleosis, metabolic, endocrine, and vascular origin and diabetic neuropathy.In the present case, appropriate testing was done to exclude all these conditions.Factors that may contribute to primary erythromelalgia include: postganglionic sympathetic dysfunction, hypersensitivity of C-fibers or/and maldistribution of skin perfusion caused by arteriovenous shunting. 9esence of mechanical allodynia/hyperalgesia in affected area and ineffectiveness of opiate analgesics raised the suspicion of neuropathic pain mechanism.Pregabalin is a relatively safe anticonvulsant indicated for managing neuropathic and chronic pain conditions.The most common adverse events of pregabalin are dizziness, peripheral edema, weight gain and somnolence.The patients generally develop tolerance to these events.
The mechanism of action of pregabalin and gabapentin are almost similar, i.e inhibiting calcium influx and subsequent release of excitatory neurotransmitters.But pregabalin possess definite advantages over gabapentin.Bockbrader et  al. have noted that pregabalin is found to have approximately 2.5 times greater potency than gabapentin based on plasma concentrations to treat neuropathic pain.The efficacy of pregabalin is comparable to gabapentin, however, at much lower doses.The probable reasons for the lower doses are much higher bioavailability (90% versus 33-66%) and rapid absorption (peak: 1 hr).Moreover, plasma concentrations increase linearly with dose.However, these do not hold true for gabapentin.The absorption rate of gabapentin is comparatively slower (peak: 3 to 4 hours post dose) and the association between plasma concentrations and increasing doses has been found to be non-linear. 10e present patient demonstrated immediate as well as long-term response to pregabalin administration in erythromelalgia.The initial and dramatic response to deflazacort and pregabalin might be due to placebo or steroid effect.However, long-term maintenance was achieved by pregabalin.The disappearance of tenderness over erythematous area (allodynia/hyperalgesia symptoms) shows that pregabalin is useful for managing neuropathic pain mechanism.
In conclusion, we report a successful management of erythromelalgia pain with pregabalin.Since the drug is relatively safe and well tolerated, it is better to initiate the treatment of erythromelalgia with pregabalin before considering more aggressive alternatives.