Erythema Elevatum Diutinum (EED): Etiology, Clinical Features, Diagnosis, and Treatment

What Is Erythema Elevatum Diutinum?

Erythema elevatum diutinum is a rare and long-lasting skin condition that causes red or purple bumps and patches on certain parts of the body. These skin issues often do not hurt, but some people might feel pain or a burning feeling. Besides skin issues, it can also lead to problems like joint pain and fever. This condition can happen because of infections, blood problems, autoimmune diseases, or other health concerns. The good news is that it often gets better by itself after 5 to 10 years. EED can happen at any age, although it usually affects people between 30 and 60 years old. It occurs at the same rate in both men and women.

What Is the Etiology Behind Erythema Elevatum Diutinum?

The exact reason behind erythema elevatum diutinum is not well known, but it is believed to happen because of immune system issues in the small blood vessels under the skin. This leads to inflammation and other problems. The skin changes seen in EED are due to immune system issues causing damage to the vessels and possibly also through the involvement of certain antibodies. There might be chemicals called cytokines, particularly interleukin-8, that play a role in starting this process by attracting certain types of white blood cells to the vessels. Over time, this can cause damage and result in skin changes that might become more severe. This condition is associated with various factors, including underlying health conditions, as mentioned below:

1. Autoimmune Disorders: One prominent association with EED is autoimmune diseases. Many individuals diagnosed with this disorder also have underlying autoimmune disorders such as rheumatoid arthritis, lupus, or celiac disease. It is theorized that EED may represent an immune system response triggered by these autoimmune conditions.

2. Infectious Triggers: There is evidence to suggest a possible connection between EED and certain infections. In particular, streptococcal infections have been linked to the development of erythema elevatum diutinum. Infections caused by viruses, such as hepatitis B and HIV (human immunodeficiency virus), also contribute to this condition.

3. Genetic Factors: While not a direct cause, genetic factors may play a role in predisposing some individuals to develop erythema elevatum diutinum. Research has suggested that certain genetic markers may increase susceptibility to the condition.

4. Other Causes: In some cases, EED may be associated with other conditions or factors, such as malignancies, inflammatory disorders, or medications. These associations are less common and often occur alongside other underlying health issues.

However, the exact mechanisms underlying this relationship require further investigation.

What Are the Clinical Features of Erythema Elevatum Diutinum?

• Initially, erythema elevatum diutinum (EED) lesions begin as papules or nodules found on the backs of the hands.

• EED can affect various extensor surfaces of the body, including the knees, elbows, wrists, ankles, fingers, toes, buttocks, trunks, forearms, legs, palms, and soles.

• When EED lesions appear on the face, they closely resemble those of granuloma faciale (a skin condition characterized by reddish-brown patches or plaques on the face).

• EED lesions tend to emerge symmetrically.

• Over time, the color of these lesions evolves, transitioning from yellow or pinkish to shades of red, purple, or brown.

• The size of EED lesions can fluctuate during the day, returning to their original size overnight.

• These lesions may develop into blisters or ulcers in rare cases.

• When touched, these lesions usually feel firm and can move slightly over the underlying tissue.

• EED can manifest with varying symptoms; it may be asymptomatic and cause pain, itching, or a burning sensation.

• Symptoms can worsen when exposed to cold conditions.

• Some individuals with EED may also experience joint pain, known as arthralgia.

How Can Erythema Elevatum Diutinum Be Diagnosed?

During the time of physical examination, different characteristics of the lesion are assessed, which include the following:

• Lesion Appearance: EED manifests as papules, plaques, or nodules that can be colored in shades of red-brown, yellowish, or violaceous.

• Distribution: These lesions tend to appear symmetrically and are commonly found on acral and periarticular sites, including the extensor surfaces of the elbows, knees, ankles, hands, and fingers. Additional areas affected may include the face, retro-auricular area, axillae, buttocks, and genitalia. The trunk is often spared from EED lesions.

• Texture: In most cases, EED lesions feel firm and are mobile over the underlying tissue, except when they occur on the palms and soles.

• Progression: Initially, EED lesions are erythematous and soft, but with time, they can transition to red-brown or violaceous in color and become firm due to fibrosis. Over the course of the disease, these lesions can change in color, increase in size, and multiply.

• Symptoms Assessment: EED lesions are asymptomatic, but some patients may experience pruritus (itching), or burning or tingling sensations, particularly in the early stages.

  1. In cases related to HIV infection, nodular lesions on the palms and soles that evolve into bulky masses are characteristic.

  2. In some instances, individuals with EED may develop joint pain, known as arthralgias. However, involvement of areas beyond the skin is exceedingly rare, with exceptions including ocular abnormalities such as scleritis, uveitis, autoimmune keratolysis, and peripheral keratitis.

The different diagnosis methods and their peculiar findings include:

1. To diagnose EED, a skin biopsy is the primary and most valuable diagnostic tool.

2. While electron microscopy can reveal features of leukocytoclastic vasculitis (a condition involving inflammation and damage to small blood vessels), it is not routinely necessary for diagnosis.

3. Patients with EED frequently exhibit an elevated erythrocyte sedimentation rate (ESR).

4. Diagnostic markers, such as IgA (immunoglobulin A) antineutrophil cytoplasmic antibodies and immunoelectrophoresis, can aid in confirming the diagnosis and identifying potential gammopathies.

What Are the Treatments for Erythema Elevatum Diutinum?

Treating EED poses challenges due to its chronic and recurring nature. There are different therapeutic strategies to try to help with the condition, but making it better usually means dealing with the things that caused it in the first place.

1. Dapsone: A sulfonamide antibiotic, is a primary treatment due to its ability to hinder neutrophil chemotaxis and function. Despite its effectiveness, relapse is frequent upon discontinuation, and it may not be effective for nodular lesions due to fibrosis.

2. Additional Therapies:

• NSAIDs (nonsteroidal anti-inflammatory drugs), Niacinamide, Tetracyclines, Hydroxychloroquine, Colchicine, and plasmapheresis are among the therapeutic options available.

• Niacinamide, an inhibitor of cyclic AMP (adenosine monophosphate), can help suppress antigen-induced lymphocyte transformation. It has fewer side effects compared to Dapsone.

• For mild cases, topical and intralesional corticosteroids can provide relief. However, systemic corticosteroids are rarely recommended.

• Antimicrobials, like Tetracyclines, are believed to modify neutrophil behavior, dampening chemotaxis and phagocytosis.

3. Local Surgical Excision: In cases of localized fibrotic nodules, surgical excision can be beneficial.

4. Recurrence Prevention: Recurrence rates of EED are high. No matter which treatment is used, EED often comes back if the things that caused it in the first place are not managed.

Conclusion:

Erythema elevatum diutinum is a rare and confusing skin problem. It causes reddish-purple bumps on the skin that can be painful and impact daily life. The exact cause is uncertain, but it is often associated with underlying autoimmune disorders and infections. This highlights the importance of a thorough evaluation and treatment of any linked conditions by healthcare professionals, including dermatologists and rheumatologists. Early diagnosis and appropriate management can assist individuals with EED in leading more comfortable lives and reducing the impact of this challenging condition on daily activities.