Erythromelalgia

Erythromelalgia (or erythermalgia) is a paroxysmal vascular acrosyndrome characterized by episodes of painful erythema of the extremities. It is very rare, with an incidence of less than 2 per 100,000 inhabitants per year, so its epidemiological characteristics remain uncertain. Based on small recent series, it appears to predominate in women in developed countries (sex ratio of four women to one man), and the median age of diagnosis is 61. However, it can occur at any age. Secondary forms are the most frequent and should be systematically investigated.

Etiologies

A distinction is made between :

• Primary ("idiopathic") and hereditary (exceptional) erythromelalgias.
• Secondary erythromelalgia :
  • Myelodysplasias (the majority of cases): primary polycythemia, essential thrombocythemia >> myeloid metaplasia, chronic myeloid leukemia,...
  • Iatrogenic (controversial): calcium channel blockers, bromocriptine, fluorouracil, doxorubicin, etc.
  • Miscellaneous: rheumatoid arthritis, systemic lupus erythematosus, vasculitis, etc.

As a rule, myelodysplastic syndrome should always be suspected and investigated in the presence of erythromelalgia.

Classically, primary erythromelalgias are attributed to micro-circulatory disorders. More recently, however, arguments have been put forward in favor of small-fiber neuropathies as associated or causative in a proportion of cases. As the sensitivity of neurographic examinations is poor in cases of small-fiber neuropathy, this remains uncertain at present.

Diagnosis and clinic

Positive diagnosis is exclusively clinical. The syndrome is characterized by :

• Progression in attacks, lasting from a few minutes to a few hours, characterized by erythema of the extremities associated with pain, sensations of heat or paresthesias of variable intensity. Attacks preferentially affect the feet, and may extend to the knees. Clinical features are generally relatively symmetrical. Associated edema may be present.
  • Exceptionally, symptoms may be constant. The face may also be affected.
• Triggering and/or aggravating factors: walking, declivity, prolonged standing, heat, physical exercise, alcohol consumption, certain foods, etc.
• Relieving factors: cold, lifting the limb, acetylsalicylic acid.

DIAGNOSTIC CRITERIA
Major criteria	Minor criteria
evolution by attacks burning, biting, grinding pain in hands and/or feet during attacks redness of affected areas during attacks	triggered by heat, physical exercise and/or orthostatism relief by cold, rest or elevation of the limb local heat during attacks symptomatic improvement with acetylsalicylic acid
Diagnosis established if all major criteria + minimum 2 minor criteria

Secondary forms have no characteristic clinical features. However, the following are suggestive: presence of trophic disorders, onset over the age of 40, mild to moderate intensity, incomplete clinical course, unilateral or asymmetric attacks, etc.

On clinical examination, look for signs of macro-arteriopathy (palpation of all pulses, etc.) and polyneuropathy (reflexes, sensitivity, etc.).

Erythromelalgia - feet

Erythromelalgia - hand

Additional tests

Their sole purpose is to diagnose the etiology (mainly myelodysplasia).

• Systematic biology: hemogram, ESR, FR, FAN, ANCA, (may be supplemented in the event of biological abnormalities or other tests).
• Osteo-medullary puncture or biopsy and other tests to be discussed according to biological results and degree of clinical suspicion.
• Systematic nerve conduction velocity testing for polyneuropathy is not standardized, but seems reasonable.

Other examinations (biological, capillaroscopy, ankle-arm Doppler index, angiography, etc.), in search of differential diagnoses, can only be justified in cases of atypical clinical features and reasonable diagnostic doubt.

Therapeutic management - Treatments

• Secondary erythromelalgia → etiological treatment
• Symptomatic :
  • Primary erythromelalgia : reassurance that the phenomenon is benign
  • First-line symptomatic treatment: acetylsalicylic acid 500 mg/day (possibly 1 g during attacks) and avoidance of triggering factors.
  • Second-line treatment: indomethacin 25 mg in the event of an attack.
  • Third-line treatment: propranolol 40 to 120 mg/day.
  • Non-specific analgesics can also be tried, as well as standard treatments for neuropathic pain (amitriptyline, venlafaxine, duloxetine, gabapentin, carbamazepine, etc.).

Author(s)

Dr Shanan Khairi, MD

Bibliography

EMC, Traité d'Angéiologie, Elsevier, 2014

EMC, Traité de médecine AKOS, Elsevier, 2018

Creager M et al., Vascular Medicine: A Companion to Braunwald’s Heart Disease, Saunders, 2013

Davis MDP et al., Erythromelalgia: vasculopathy, neuropathy, or both? a prospective study of vascular and neurophysiologic studies in erythromelalgia, Arch Dermatol. 2003; 139: 1337-1343

Davis MDP et al., Erythromelgalgia, UpToDate, 2022

Lazareth I, Erythermalgies : nosologie et évolution des concepts, Journal de médecine vasculaire, vol 43 n°2, mars 2018

Longo DL et al., Harrison - Principes de médecine interne, 18e éd., Lavoisier, 2013