Erythromelalgia (from Dermnet)

Erythromelalgia is characterised by intense burning pain, erythema (marked redness), and

increased skin temperature, primarily of the feet and hands.
It is classified into primary and secondary erythromelalgia.
Primary erythromelalgia with positive family history is known as Weir-Mitchell disease.
Primary erythromelalgia is more common in females while secondary form is more common in
men.
Causes of erythromelalgia:
- Primary erythromelalgia:
 Mutations in SCN9A, which encodes for the Nav1.7 sodium channel receptor.
Nav1.7 is expressed in nociceptive neurons and normally amplifies the
nociceptive pain signals. Mutations lead to dysregulation and
hyperexcitability’ of these neurons, with dilation of the small blood
vessels that become congested with blood
- Secondary erythromelalgia:
 commonly associated with myeloproliferative disorders. Erythromelalgia
presents before the appearance of the myeloproliferative disorder in 85% of
cases.
 Occasionally it can occur in association
with paraneoplastic disorders , autoimmune neuropathies and rarely
diabetes, rheumatological and infectious diseases.
Clinical features of erythromelalgia:

Primary erythromelalgia may develop at any age. Secondary erythromelalgia occurs most often
in those over 40 years of age.
Lower extremities such as the soles of feet and toes are most involved. Upper extremity
involvement includes the fingers and hands. It may affect one side of the body (unilateral),
particularly in secondary cases.

Less frequently, symptoms may also appear in the face, ears, and other parts of the body.

The classic description of erythromelalgia is red, painful, warm hands or feet, brought on by
warming or hanging the limb downward, and relieved with cooling and elevation.

 Some patients notice a continual burning, while others are troubled by intermittent
flare-ups.
 Flare-ups may last minutes to days and typically occur late in the day and continue
through the night.
 Usually attacks begin with an itching sensation, progressing to a more severe pain with a
burning sensation.
 During an attack the affected extremity becomes warm, tender, swollen, and appears
dusky red and sometimes mottled.
 Pain may be so intense that the patient cannot walk.
Diagnosis of Erythromelalgia

Primary erythromelalgia is a clinical diagnosis based on the presence of the triad

of recurrent redness, burning pain and warmth of extremities. Family history of erythromelalgia
can support a familial primary erythromelalgia

Investigation for underlying causes is essential to exclude secondary erythromelalgia.

Erythromelalgia may be an early sign of polycythaemia (raised red cells) or thrombocythaemia

(raised platelets), where symptoms may precede diagnosis of the myeloproliferative disorder by
2.5 years.

Diagnosis is based fairly much on the clinical picture, hence is often difficult because of the
intermittent nature of the disease.

If in doubt, a trial of immersing an affected area in hot water for 10–30 minutes may sometimes
provoke an attack and support the diagnosis.
Treatment of erythromelalgia (Dermnet)
- The underlying cause must be treated where possible in secondary erythromelalgia.
- Cooling
- Topical therapy: Capsaicin cream (varying results) , Amitriptyline-ketamine compound
- Oral medications:
 Aspirin: in case of thrombocytosis or polycythaemia vera
 Na channel blockers: Mexiletine
 Ca antagonists: nifedipine, diltiazem
 Prostaglandins: misoprostol
 IV infusions: Nitroprusside, lignocaine, prostaglandin
 Medications for neuropathic pain:
 SNRI
 TCA
 Gabapentinoids
 Carbamazepine
 Antihistamines: Cyproheptadine, pizotifen- non sedating antihistamine cetirizine
did not show improvement
- Novel Nav1.7 Agents
- Surgical interventions: sympathectomy (thoracic for hands and lumbar for feet)
- Injection of Botulinum toxin type A =>by blocking the release of substance P and glutamate