Erythromelalgia - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Erythromelalgia is a rarely occurring clinical disease characterized by three symptoms of redness, warmness, and burning pain. Erythromelalgia most commonly affects the extremities. Symptoms will be resolved by cooling. Other terms for erythromelalgia are burning feet syndrome, erythermalgia, Gerhardt disease, and Mitchell disease.

What Is Erythromelalgia?

Erythromelalgia is a greek word meaning erythros called” red” Melos means “limp”, and algia means “pain".Initially, erythromelalgia is described as “Mitchell disease” by Silas weir Mitchell in 1878. The term erythermalgia was proposed by Smith and Allen in 1938. The term erythromelalgia was proposed by Drench and Michiels in 1990.

Erythromelalgia is of two types.

1. Primary erythromelalgia.

2. Secondary erythromelalgia.

Primary erythromelalgia is an autosomal dominant neuropathy caused by the mutation in genes or may be idiopathic. Secondary erythromelalgia is due to systemic conditions with myeloproliferative disorders and myelofibrosis.

What Are the Causes of Erythromelalgia?

Primary erythromelalgia has a genetic etiology. Secondary erythromelalgia has systemic causes, which include several infections, autoimmune diseases, endocrine diseases, neoplastic conditions, medications, gout, high blood pressure, multiple sclerosis, and hematological disorders like pernicious anemia, thrombotic thrombocytopenic purpura, and also by mushroom intoxication and mercury poisoning.

Causes of Secondary Erythromelalgia.

• Essential thrombocytosis.

• Polycythemia vera.

• Infections include human immunodeficiency virus or HIV, Influenza, syphilis, and poxvirus.

• Autoimmune disorders such as Rheumatoid arthritis, systemic lupus erythematosus.

• Endocrine disorders: Diabetes mellitus includes both type1 and type 2.

• Neoplastic conditions: Breast cancer, colon cancer, astrocytoma.

• Medications include Nifedipine, Verapamil, Bromocriptine, topical Isopropanol, and Pergolide.

• Hypertension.

• Venous insufficiency.

• Anemia: Pernicious anemia.

• Platelet Disorders: Thrombotic thrombocytopenic purpura.

What Are the Symptoms of Erythromelalgia?

Erythromelalgia shows classic triad symptoms: redness, warmness, and recurrent burning pain. Erythromelalgia most commonly affects the feet and the upper extremities including the hands and the fingers. Other less commonly involved areas are the head, neck region, and genitals. At the beginning of erythromelalgia, the affected area shows an itching sensation and progresses to severe burning. symptoms are bilateral and asymmetrical. In between the episodes of erythromelalgia, the affected area shows no signs of redness, warmth, and pain and it remains normal.

Symptoms of Erythromelalgia

• Redness.

• Warmness.

• Burning pain.

• Other symptoms include swelling, sweating, and discoloration of the skin.

What Are the Disorders Associated With Erythromelalgia?

Hematologic Disorders.

• Polycythemia.

• Thrombocythemia.

• Pernicious anemia.

Cardiovascular Disorders.

• Hypertension.

• Atherosclerosis.

• Venous insufficiency.

Embolic Disease.

• Cholesterol crystal embolism syndrome.

• Familial nephritis.

• Diabetic Mellitus includes type 1 and type2.

• Gout.

• Hypercholesterolemia.

• Familial nephritis.

Connective Tissue Disorders.

• Rheumatoid arthritis.

• Systemic Lupus Erythematosus or SLE.

• Sjogren's syndrome.

• Vasculitis.

Infectious Diseases:

• Acquired Immunodeficiency Virus or AIDS.

• Viral infections.

• Syphilis.

Musculoskeletal Disorders:

• Neuropathies.

• Multiple sclerosis.

Drug-Induced:

• Iodide contrast injection.

• Vaccines: hepatitis, influenza.

Neoplasm :

• Carcinoma in abdomen, colon, thymoma, and astrocytoma.

Other:

• Frostbite.

• Mercury poisoning.

How to Diagnose Erythromelalgia?

The diagnosis of erythromelalgia involves a thorough evaluation of classical triad symptoms and signs. It is advisable to take photographs of the affected region during the episode of symptoms. By screening the mutation of gene SCN94 the primary erythromelalgia is diagnosed. A complete blood count examination is done to rule out myeloproliferative disorder and cellulitis. Serology is also done. Bone scanning is done in the case of trauma. Electromyography and nerve conduction tests are also considered.

Various diagnoses include:

• A physical examination of the patient to evaluate classic signs.

• Proper personal history.

• Complete blood count (CBC): increased white blood cell count (WBC), increased neutrophils.

• Serological tests for antinuclear antibody(ANA) and human immunodeficiency virus(HIV).

• Rheumatoid factor(RF) for systemic lupus erythematosus(SLE).

• Blood uric acid level for gout.

• Triple-phase technetium bone scanning for the history of trauma.

• Electromyography.

• Nerve conduction velocity test(NCV).

How to Manage Erythromelalgia?

Erythromelalgia management includes patient education, lifestyle modifications, and avoiding the causative triggers. We can avoid triggers. The triggers of erythromelalgia are heat, exercise, and standing. Topical lidocaine patches and topical capsaicin helps in relieving burning pain.

What Is the Treatment for Erythromelalgia?

Aspirin is the drug of choice in the treatment of erythromelalgia in association with thrombocytopenia or myeloproliferative disorder. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used as an alternative method of treatment. Erythromelalgia patients with polycythemia vera can be treated by phlebotomy. Medicines found to be effective in both types of Erythromelalgia are gabapentin, pregabalin, venlafaxine and misoprostol, calcium channel blockers, and beta-blockers. Alternative for refractory cases includes transdermal infusions of bupivacaine and ropivacaine. Botox(botulinum toxin A can be injected subcutaneously. Thoracic or lumbar sympathectomy can also be done. Improvement is also obtained with rehabilitation programs and patient counseling.

• Triggers should be avoided.

• Treatment is done for one month with aspirin.

• Topical medications can also be given.

• Systemic infusion of gabapentin or venlafaxine for 2 to 3months.

• Rehabilitation programs.

• Patient education is done.

• Regular follow-up.

Topical Treatment:

• Capsaicin cream.

• Doxepin cream.

Oral Medications:

• Aspirin.

• Venlafaxine.

• Sertraline.

• Tramadol.

• Tricyclic antidepressants(TCA) include Amitriptyline and Imipramine.

• Anticonvulsants : Gabapentin and Carbamazepine.

• Calcium antagonists: Nifedipine.

• Misoprostol.

Parenteral Approach:

• Nitofusside infusions.

• Lidocaine infusions.

• Prostaglandin infusions.

Invasive Approach:

• Sympathetic blocks and epidurals.

• Sympathectomies.

• Dorsal column stimulator.

• Neurosurgery.

The Non-medical Approach for Erythromelalgia

• Hypnosis.

• Biofeedback.

• Acupuncture.

Triggers can be avoided by following methods.

• Remain in a cool environment.

• Decreased physical activity.

• Limp elevation.

• Avoiding excess clothing.

• Portable fans and cool water immersion give relief.

What Is the Differential Diagnosis of Erythromelalgia?

• Acrocyanosis.

• Polyneuropathy.

• Peripheral vascular diseases.

• Raynaud phenomenon.

• Gout.

• Cellulitis.

• Lipodermatosclerosis.

• Vasculitis.

• Fabry disease.

• Neoplasms:angikeratomas.

• Complex regional pain syndrome(CRPS).

What Are the Complications of Erythromelalgia?

To alleviate pain, patients will attempt to cool the affected areas. Sometimes cooling methods cause skin maceration and lead to further complications.

• Blistering.

• Ulceration.

• Cyanosis.

• Gangrene.

• Secondary infection.

• Amputation in chronic gangrene cases.

• Malnutrition.

• Hypothermia.

• Chronic depression.

Conclusion:

Erythromelalgia is a rare disease with redness, warmth, and pain in the extremities. Symptoms are provoked by increased temperature and reduced by cooling the body temperature. Proper history taking and physical examination is done to avoid misdiagnosis. Patient education and rehabilitation programs help improve the awareness of erythromelalgia. It is better to avoid the triggers for erythromelalgia to reduce the flare-ups.