The burning sensation of erythromelalgia is matched by a burning desire to help these patients. According to Tang et al: “This rare and debilitating disorder was first reported and named “erythromelalgia” according to its main symptoms (erythros-red, melos-limbs, algos-pain) by Mitchel in 1878. Later the name “erythromelalgia” and “erythermalgia” were used respectively for cases secondary to myeloproliferative disorders and idiopathic cases that were refractory to aspirin. At present, erythromelalgia is classified into PE [primary erythromelalgia] and secondary erythromelalgia, based on the absence or presence of diseases or drugs that may associate with the onset or precipitation of its symptoms. PE is exclusively caused by mutations in SCN9A, the encoding gene of sodium channel subtype Nav1.7 and can be sub-classified into familial (inherited erythromelalgia) and sporadic forms. Secondary erythromelalgia is often associated with myeloproliferateive disorders. In some cases, secondary erythromelalgia occurs in paraneoplastic diseases and autoimmune neuropathies. Though very rare, secondary erythromelalgia can also appear in diabetes, rheumatologic diseases and infectious diseases.” (1)
Last week, I met a 64-year-old woman with a very recent onset of burning of her feet at night, necessitating keeping the bed linen off her legs. Her physical examination was unremarkable. My presumptive diagnosis was erythromelalgia; I asked her to check a CBC, ESR, ANA, and SPEP. I advised her to take a NSAID and we would see what transpires. Never once did I think of considering prednisone.
Pagani-Estévez et al retrospectively identified 31 patients with erythromelalgia who received corticosteroids (CS) and were stratified into corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs), complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs + CSRs). The median age was 47 years (26-57 years), and 22 (71%) were female. Fourteen (45%) were NRs, 17 (55%) SRs, 8 (26%) PSRs, and 9 (29%) CSRs. A subacute temporal profile to disease zenith (<21 days) was described in 15 (48%) patients, of whom 13 (87%) were SRs, a statistically significant finding. Six (67%) CSRs reported a disease precipitant (eg, surgery, trauma, or infection; also significant). SR patients received CS sooner than NR at 3 (3-12) versus 24 (17-45) months (P = .003). A high-dose CS trial (≥200 mg prednisone cumulatively) was administered to 17 (55%) patients, of whom 13 (76%) were SRs (statistically significant).
The authors state: “SR patients could have presented sooner than NR patients because of more fulminant disease. Alternatively, NR may have been more difficult to diagnose because of a different disease presentation. However, a “golden window” may exist in some patients; if not treated promptly enough, irreversible damage to peripheral nociceptors with neuropathic sensitization may occur. Chronic neuropathic pain has been shown to involve morphologic changes at the cutaneous nociceptor level histologically, thereby perpetuating the chronic pain process. There could exist a time-dependency between the 2 ends of this spectrum, with an initially reversible process becoming irreversible in the presence of untreated disease”. This “golden window” of opportunity for steroids in erythromelalgia may only exist for a short while prior to permanent nocioceptive remodeling.” (2)
Dabby et al reported on four patients with acute onset neuropathic pain, normal nerve conduction studies, and evidence of small-fiber dysfunction in quantitative sensory testing and skin biopsy. Symptoms were distal and symmetrical in three patients and generalized in one patient. In two cases, the neuropathy presented as an erythromelalgia-like syndrome. Marked clinical improvement occurred 1–2 weeks after oral prednisone therapy was initiated. Three patients remained symptom free, and one patient experienced recurrence of neuropathy after prednisone was tapered (3).
The list of therapeutic agents for erythromelalgia is long, reflecting the chronic nature and recalcitrance of the disorder. A partial list includes analgesics, antidepressants, calcium channel blockers, and gabapentin (4). I just got off the phone with my patient and explained my rationale to try prednisone, assuming that her laboratory studies come back normal and if there is no immediate benefit to the NSAID. I do not wish to be Dr. Nero as my patient burns. Should steroids be prescribed, as I anticipate they will, I hope they extinguish the fire of erythromelagia quickly.
- Tang Z, et al. Primary erythromelalgia: A review. Orphanet J Rare Dis 2015; 10: 127.
- Pagani-Estévez GL, et al. Erythromelalgia : Identification of a corticosteroid-responsive subset. J Am Acad Dermatol 2017 ; 76 : 506-511.
- Dabby R, et al: Acute steroid responsive small-fiber sensory neuropathy: A new entity? J Periph Nerv Syst 2006; 11: 47-52.
- Mork C, Kvernebo K. Erythromelalgia. In Lewohl MG, Heymann WR, Berth-Jones J, Coulson I (eds). Treatment of Skin Disease, fourth edition. Elsevier 2014, pp 242-4.