Acrodermatitis Chronica Atrophicans (ACA)

Introduction:

Acrodermatitis chronica atrophicans (ACA) is the late or third stage of European Lyme borreliosis, caused by an ongoing infection with ‘Borrelia afzelii’ . Initially identified in 1883 and described in 1902, ACA is a progressive skin condition characterized by fibrosis and tissue atrophy, resembling tissue paper in its appearance.

Pathophysiology and Etiology of Acrodermatitis Chronica Atrophicans (ACA)

Causative Agents:

Acrodermatitis chronica atrophicans (ACA) is primarily caused by Borrelia afzelii , though Borrelia garinii , another genospecies from the Borrelia burgdorferi sensu lato complex, has also been implicated. These spirochetes are transmitted to humans via tick bites and are the underlying cause of Lyme borreliosis.

Borrelia afzelii

Pathophysiology:

Unlike other forms of Lyme disease, ACA does not resolve spontaneously, suggesting a unique pathogenic mechanism. The exact process through which ACA develops is not fully understood, but several factors contribute to the persistence of Borrelia in the skin:

1. Spirochete Persistence: Despite strong immune responses, the Borrelia spirochetes persist in the skin. This persistence might be due to:

Resistance to the complement system: This allows the bacteria to evade destruction by immune responses.
Immune evasion: The spirochetes can escape into immunologically protected sites, such as endothelial cells and fibroblasts, making it difficult for the immune system to target and eliminate them.
Antigenic variation: The pathogen may change its surface antigens, causing the immune system to fail in mounting an effective or appropriate response.

2. Immune Dysfunction:

Inadequate antibody response: Patients with ACA exhibit a narrow spectrum of antibodies and lack sufficient protective antibodies. The immune system’s response, particularly cellular immunity, may be weakened.
Downregulation of MHC Class II molecules: Reduced expression of these molecules on Langerhans cells (immune cells in the skin) impairs the activation of T-cells, crucial for an effective immune response.
Cytokine expression: ACA is associated with a restricted cytokine profile, including the absence of interferon-gamma, which may prevent the immune system from clearing the infection effectively.

3. Autoimmune Considerations: Cross-reactive antibodies may contribute to tissue damage, though the role of autoimmunity in ACA remains unclear. The chronicity of the condition may involve an immune response that inadvertently harms the host tissues.

Pathogenesis of Atrophic Skin Changes:

The exact mechanism behind the characteristic skin atrophy in ACA is not well understood. However, it is hypothesized that:
Periarticular sites may be particularly affected due to lower skin temperatures or reduced oxygenation in these areas, which could create a favorable environment for the persistence of Borrelia spirochetes.
Influence of Untreated Lyme Borreliosis: Failure to treat early-stage Lyme borreliosis adequately allows the infection to progress to ACA. This underscores the importance of early detection and treatment to prevent the chronic, progressive skin damage associated with ACA.

Clinical Presentation:

ACA usually manifests on the extremities, especially on the extensor surfaces, and follows two distinct phases:

1. Inflammatory Phase:

Involves bluish-red discoloration and swelling of the skin.
Patients may develop soft, painless, poorly demarcated plaques that can coalesce.
The condition typically starts on the distal extremities and spreads proximally.

2. Atrophic Phase:

Occurs months or years later, characterized by dark red or brown discoloration.
The skin becomes thin, translucent, and wrinkled, resembling cigarette paper.
Skin atrophy is associated with prominent blood vessels, loss of hair, and absence of sebaceous or sweat glands.
Telangiectasia and focal hyperpigmentation may be present.

Associated Symptoms:

Fibrotic nodules can form, usually on the extensor surfaces of the elbows, knees, and adjacent joints.
Skin may ulcerate, and malignant lesions can develop.
ACA can also cause deformities in the fingers and toes if untreated.

Systemic Involvement:

Neurological involvement is common in ACA, often presenting as sensory polyneuropathy. Symptoms such as pain, paresthesia, and even paresis (partial paralysis) can occur, and patients may exhibit abnormal vibratory thresholds. While cerebrospinal fluid abnormalities are rare, localized neuropathy often correlates with visible ACA lesions on the extremities.

Diagnosis:

Diagnosis relies on a detailed clinical history, epidemiologic data, and confirmation via histopathology and serologic testing. ELISA, indirect immunofluorescence, and Western blot assays are commonly used to detect Borrelia burgdorferi antibodies.

Management of Acrodermatitis Chronica Atrophicans (ACA)

The treatment of ACA, the late-stage manifestation of Lyme borreliosis, focuses on eradicating the infection and addressing any complications related to the disease. The choice of therapy depends on the presence of other signs of Lyme disease, the stage of ACA, and the results of serologic testing.

Approach to Treatment:

1. Antibiotic therapy:

Oral antibiotics are typically the first-line treatment in ACA, especially in the absence of systemic Lyme disease manifestations. Common options include:
Doxycycline (100 mg twice daily for 3-4 weeks).
Amoxicillin (500 mg three times daily for 3-4 weeks), especially in children or those allergic to doxycycline.
For patients with more advanced or systemic Lyme disease or those with high levels of antibodies, intravenous antibiotics are preferred. These include:
Ceftriaxone (2 g daily for 21-28 days).
Cefotaxime or Penicillin G are also used in some cases.

Studies suggest that many patients, even in the chronic stage of ACA, can benefit from antibiotic treatment. In some patients, symptoms completely resolve after a 3-4 week course of IV ceftriaxone.

2. Early vs. Late Stage Treatment:

In the early inflammatory stage of ACA, prompt antibiotic treatment can lead to full recovery and prevent further skin and tissue damage.

In the chronic atrophic phase , while antibiotics can stop the progression of the disease, many of the skin changes (like atrophy and fibrosis) may be irreversible . Patients should be informed that improvement may be partial.

3. Management of Complications:

Fibrotic nodules and joint deformities can occur if ACA progresses untreated. In these cases, physical therapy may help improve joint mobility and prevent further deformity.

Ulcerations on atrophic skin are common and can be challenging to treat. Proper wound care is essential, and in some cases, dermatologic consultation may be required for managing these lesions.

4. Consultations for Systemic Involvement:

If extracutaneous signs of Lyme disease are present (neurologic, rheumatologic, or cardiac), appropriate consultations with specialists (neurologist, rheumatologist, cardiologist) should be made.

Neurologic symptoms , such as sensory polyneuropathy, may require further evaluation with neurophysiologic tests and long-term monitoring.

5. Coinfections and Differential Diagnosis:

ACA patients may also have co-infections like babesiosis or ehrlichiosis, which are transmitted by the same tick vector. In regions where these infections are prevalent, testing for these conditions should be considered, especially if symptoms persist despite appropriate Lyme treatment.

Coinfections require additional treatments, for example, atovaquone and azithromycin for babesiosis or doxycycline for ehrlichiosis.

6. Vaccination:

While the US FDA approved a vaccine for Lyme disease in 1999, it is no longer available. A new recombined vaccine targeting B. afzelii and B. garinii , the prevalent strains in Europe, is being developed but is not yet in widespread use.

Long-Term Monitoring:

Patients should be followed up to monitor the progression of the disease and the effectiveness of treatment. In the atrophic phase, even though antibiotics may halt progression, skin changes may persist.

Regular skin checks are recommended to monitor for any complications such as ulcers or skin cancers, as there is a small but present risk of malignancy in long-standing ACA cases.

Patient Education:

Patients should be informed that ACA may take several weeks or months to improve after the start of treatment. Improvement in symptoms may be gradual.

Early diagnosis and treatment of Lyme borreliosis are crucial to prevent the development of ACA, especially in endemic regions.

Prognosis:

Early treatment can result in complete resolution, though the atrophic phase symptoms may only partially reverse. Patients in the inflammatory phase should expect gradual symptom relief over several weeks or months following treatment.

Conclusion:

ACA is a rare but significant manifestation of Lyme borreliosis, requiring timely diagnosis and appropriate treatment to prevent long-term complications. While antibiotic therapy is effective, early intervention is key to preventing irreversible skin and nerve damage.