Erythromelalgia

LAST UPDATED: Nov 22, 2021

Introduction

Erythromelalgia is rare skin condition characterised by an intense burning pain, warmth and erythema of the feet and hands resulting from small vessel vasodilatation. The condition is classified into primary erythromelalgia, and secondary erythromelalgia, which is most commonly associated with myeloproliferative disorders.

This chapter is set out as follows:


Aetiology

  • Most cases of erythromelalgia are primary
    • Primary erythromelalgia is defined as familial erythromelalgia (Weir Mitchell's disease) and is caused by an autosomal dominant mutation in the SCN9A gene. Most cases arise in the first decade   
  • Causes of secondary erythromelalgia include:
    • The most common cause are the myeloproliferative disorders, eg polycythaemia rubra vera. Myeloproliferative disorders are a heterogeneous group of conditions characterised by cellular proliferation of one or more haematologic cell lines in the peripheral blood, distinct from acute leukaemia. Erythromelalgia presents before the appearance of the myeloproliferative disorder in 85% of cases and by a median time of 2.5 years. Aspirin has been shown to dramatically relieve symptoms of erythromelalgia secondary to myeloproliferative disorders, but not other causes of secondary erythromelalgia
    • Connective tissue disorders eg lupus erythematosus
    • Medications such as calcium-channel blockers
    • Neoplasia especially of the colon or breast 
    • Metabolic - diabetes and lipid disorders 
    • Infection - influenza, recurrent bacterial infection, HIV, syphilis 
    • Peripheral neuropathy - neurofibromatosis, multiple sclerosis 
    • Peripheral vascular disease
    • Idiopathic 

History

  • The classic description of erythromelalgia is painful, red, warm hands or feet, precipitated by exercise, heat or hanging the limb downward, and relieved with cooling and elevation
  • Some patients notice a continual burning while others are troubled with flares, which may last minutes to days and typically occur late in the day and continue through the night  
  • Symptoms often become so bad that normal functioning and quality of life are greatly affected. Patients avoid warm weather and may even relocate to cooler climates. Many cannot wear socks or closed shoes even in winter. Some patients become virtually housebound by frequent flare-ups 
  • Given the association with myeloproliferative disorders, the clinician should inquire about a possible history of pruritus, thrombotic episodes (eg transient visual loss), constitutional symptoms, and abdominal discomfort that could accompany myeloproliferative disorders

Clinical findings

Distribution

  • Predominant sites:
    • Lower extremities such as the soles of feet and toes are the most commonly involved sites
    • Upper extremity involvement includes the fingers and hands
  • Much less frequently affected sites include upto the knees, the face, ears and other parts of the body
  • Primary erythromelalgia is confined to the lower legs
  • Symptoms are usually bilateral, although it may affect one side of the body, and occasionally one digit only, particularly in cases of secondary erythromelalgia

Morphology

  • During an attack the affected extremity becomes warm, tender, swollen, and appears dusky red and sometimes mottled 
  • Differential diagnosis - the diagnosis is usually straightforward, however, there are several dermatological conditions that can cause painful extremities, in addition to other conditions such peripheral neuropathy secondary to diabetes

Images

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Investigations

  • Secondary erythromelalgia
    • A thorough examination (including the breasts)
    • A general blood screen (including for neuropathy) 
    • CXR
    • Any relevant bowel symptoms, other abnormal systemic symptoms, or abnormal test results require further investigation
    • If no cause is found patients should continue to have periodic FBC given that myeloproliferative disorders have a median onset of 2.5 years after the onset of clinical symptoms
  • Primary erythromelalgia
    • ​Causes of secondary erythromelalgia (above) need to excluded
    • Once a diagnosis has been established some centres offer genetic testing as there is a 50% chance of passing on the mutation to offspring 

Management

Except for cases secondary to myeloproliferative disorders, erythromelalgia is a very difficult condition to treat, several medications may need to be tried with variable response and there is lack of evidence for the treatment ladder including which agent to use first. Consideration should be given at an early stage to refer patients to a pain clinic. 

Step 1: general measures

  • Provide a patient information leaflet
  • Cooling or elevating the painful limb
  • Care is needed around cold water immersions, although it will provide temporary relief, it can cause many other serious problems. Frequent immersion into cold water can create a vicious cycle as the changes in temperature may cause reactive flaring. This can also lead to infection, non-healing ulcers and tissue necrosis

Step 2: secondary erythromelalgia

  • Manage any underlying cause
  • Aspirin dramatically relieves symptoms of erythromelalgia secondary to myeloproliferative disorders, but not other causes of secondary erythromelalgia

Step 3: other medical treatments

  • Topical treatment with capsaicin cream
  • SSRI drugs
  • Anticonvulsants 
  • Calcium channel blockers 
  • Tricyclic antidepressants eg amitriptyline
  • Gabapentin

Step 4: other treatments occasionally used

  • Oral prostaglandins - misoprostol
  • Intravenous infusions of nitroprusside, or prostaglandin
  • Mexiletine, a non-selective sodium channel blocker has been found to be effective in some cases of primary erythromelalgia
  • More invasive procedures such as sympathetic blocks, epidurals and sympathectomy are occasionally used with varying success  

Prognosis

  • The prognosis varies
    • Patients who respond to aspirin have limited morbidity
    • Spontaneous remissions may occur
    • Early-onset disease is relatively unresponsive to treatment and generally unremitting
  • Ulceration and tissue necrosis is possible. Complications appear to be more frequent in patients who have platelet-mediated disease

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