Eosinophilic fasciitis

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation and thickening of the fascia, the connective tissue surrounding muscles, blood vessels, and nerves. It often presents with skin changes, joint stiffness, and peripheral eosinophilia. Early recognition is crucial to prevent complications such as joint contractures and functional impairment.

Etiology and Risk Factors

Causes

The exact cause of eosinophilic fasciitis is not fully understood, and most cases are considered idiopathic. However, several triggers have been associated with the development of the disease:

• Strenuous exercise: Intense physical activity may precede the onset in some patients, suggesting a role for mechanical stress.
• Infections: Certain viral and bacterial infections have been reported as potential initiating factors.
• Medications: Drugs such as statins, phenytoin, and certain monoclonal antibodies have been occasionally linked to disease onset.

Risk Factors

While eosinophilic fasciitis can occur in any individual, some factors may increase susceptibility:

• Age and gender: Most cases occur in adults between 30 and 60 years, with a slight male predominance.
• Genetic and environmental influences: Although rare, familial cases suggest a possible genetic predisposition. Environmental exposures may also play a role in disease development.

Pathophysiology

Eosinophilic fasciitis involves inflammation and fibrosis of the fascia, leading to skin thickening and restricted movement. Eosinophils and other immune cells infiltrate the affected tissue, releasing cytokines and growth factors that stimulate fibroblast activity. This results in excessive collagen deposition and fascial fibrosis. The molecular pathways implicated include the activation of T cells, increased interleukin levels, and abnormal extracellular matrix remodeling. The disease primarily affects the limbs but may occasionally involve the trunk and other regions.

Clinical Features

Skin Manifestations

Skin involvement is often the earliest and most noticeable feature of eosinophilic fasciitis. Patients may present with:

• Edema and swelling: Initial swelling of the limbs, often symmetrical, is common.
• Induration: The skin becomes firm and thickened, sometimes described as having a peau d’orange appearance.
• Hyperpigmentation: Darkening of the skin may occur over affected areas, especially after prolonged inflammation.

Musculoskeletal Manifestations

• Joint stiffness and contractures: Reduced range of motion may develop due to fascial thickening and fibrosis.
• Muscle weakness and pain: Patients often report discomfort and difficulty performing daily activities.

Systemic Symptoms

• Fever and malaise: Mild systemic symptoms may accompany active disease.
• Peripheral eosinophilia and laboratory abnormalities: Elevated eosinophil counts, increased ESR, and elevated CRP are frequently observed.

Diagnosis

Clinical Evaluation

Diagnosis begins with a thorough history and physical examination. Physicians assess the pattern of skin thickening, joint involvement, and presence of systemic symptoms. Differentiating eosinophilic fasciitis from scleroderma and other connective tissue disorders is critical, as treatment strategies differ significantly.

Laboratory Investigations

• Complete blood count: Eosinophilia is a hallmark finding in many patients.
• Inflammatory markers: ESR and CRP may be elevated, indicating active inflammation.
• Autoantibodies: Typically negative, helping to distinguish from autoimmune connective tissue diseases.

Imaging Studies

• MRI: Useful for detecting fascial thickening, edema, and the extent of tissue involvement.
• Ultrasound: Can visualize subcutaneous and fascial changes and guide biopsy procedures.

Histopathology

Definitive diagnosis often requires a full-thickness skin and fascia biopsy. Histopathologic findings include inflammatory cell infiltrates dominated by eosinophils, lymphocytes, and plasma cells, along with thickened fascia and collagen deposition. Biopsy results help confirm the diagnosis and exclude other fibrosing conditions.

Treatment

Pharmacological Therapy

Systemic corticosteroids are the mainstay of treatment for eosinophilic fasciitis, helping to reduce inflammation and prevent progression of fibrosis. In patients with inadequate response or steroid dependence, immunosuppressive agents such as methotrexate or azathioprine may be used. Biologic therapies targeting specific immune pathways are considered in refractory cases or when conventional therapies are contraindicated.

Non-Pharmacological Management

• Physical therapy: Regular range-of-motion exercises help prevent joint stiffness and contractures, maintaining mobility and functional capacity.
• Supportive care: Skin care, adequate nutrition, and monitoring for secondary complications improve overall patient outcomes and quality of life.

Prognosis and Complications

The prognosis of eosinophilic fasciitis varies depending on the severity of the disease and the timeliness of treatment. Many patients respond well to corticosteroids, achieving partial or complete remission. Early intervention is crucial to prevent permanent joint contractures and functional disability.

Potential complications include persistent skin thickening, chronic joint stiffness, and muscle weakness. Rarely, severe cases may involve systemic manifestations such as hematologic abnormalities or organ involvement. Regular follow-up and monitoring are essential to manage disease activity and minimize long-term sequelae.

Research and Future Directions

Ongoing research in eosinophilic fasciitis is focused on better understanding its pathogenesis and developing targeted therapies. Studies are investigating the role of cytokines, eosinophil activation, and genetic factors in driving fascial inflammation and fibrosis. Advances in imaging techniques, including high-resolution MRI and elastography, are improving early detection and monitoring of disease progression.

Emerging treatments include biologic agents that target specific immune pathways and novel immunomodulatory therapies. Clinical trials are evaluating the efficacy of these interventions in patients with refractory or severe disease. Additionally, research on biomarkers aims to provide tools for early diagnosis, predicting treatment response, and monitoring disease activity.

References

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