Eosinophilic Fasciitis: Symptoms, Types, Causes and Treatment

Eosinophilic fasciitis (EF), also known as Shulman’s disease, is a rare and intriguing connective tissue disorder. Often described as a scleroderma-like syndrome, EF is distinct in its clinical features, causes, and management. While the disease remains somewhat mysterious due to its rarity and evolving diagnostic criteria, recent advances have shed light on its presentation, underlying mechanisms, and therapeutic strategies. This article comprehensively explores the symptoms, types, causes, and treatment options for eosinophilic fasciitis, drawing on the latest research and clinical guidelines.

Symptoms of Eosinophilic Fasciitis

Eosinophilic fasciitis often begins subtly, but its symptoms can quickly become both physically and emotionally challenging for those affected. Recognizing the hallmarks of this disease early is crucial for timely diagnosis and management. Let’s explore the key symptoms that define EF.

Symptom	Description	Frequency/Note	Sources
Swelling	Symmetrical, often affects limbs	Early symptom	1 3 5 8
Skin Induration	Thickening and hardening of skin and subcutaneous tissue	Progresses after initial swelling	1 3 4 5 8
Pain	Aching or tenderness in affected areas	Common in early stages	3 5 8
Joint Contracture	Limited mobility, especially in hands and feet	Can cause long-term disability	4 5 7
Peripheral Eosinophilia	Elevated eosinophil count in blood	Not always present, but frequent	1 5 8
Constitutional Symptoms	Fatigue, fever, malaise	Present in some cases	3 5
Absence of Raynaud’s	No color changes in fingers/toes	Distinguishes EF from scleroderma	2 7 8

Table 1: Key Symptoms of Eosinophilic Fasciitis

Early and Classical Symptoms

The initial presentation of EF often includes symmetrical swelling and redness of the limbs, particularly the forearms and legs. Patients may describe a sensation of tightness or discomfort, soon followed by the development of plate-like induration—an unmistakable hardening and thickening of the skin and underlying soft tissues. This induration can restrict movement and lead to joint stiffness.

• Skin Changes: The skin over affected areas becomes thickened and woody. In some cases, the skin may appear shiny or develop a "peau d’orange" (orange peel) texture.
• Pain and Tenderness: Aching pain and tenderness are common, especially during the early inflammatory phase. This can interfere with daily activities.

Systemic and Laboratory Findings

While EF is primarily a localized disease, some patients experience systemic symptoms such as low-grade fever, fatigue, or malaise, especially in the active phase of the disease 3 5. A notable laboratory hallmark is peripheral eosinophilia—an elevated number of eosinophils in the blood. However, this finding is not universal and may be absent, especially in chronic or late-stage disease 1 8.

Other laboratory abnormalities can include:

• Hypergammaglobulinemia: Increased gamma globulin levels in the blood, reflecting immune activation 1 2 5.
• Elevated ESR (Erythrocyte Sedimentation Rate): Indicates ongoing inflammation 1 5.

Musculoskeletal Manifestations

EF frequently leads to joint contractures, which are limitations in the normal range of motion, most often affecting the hands, wrists, and ankles. This can be disabling and may persist even after the inflammation subsides if not addressed early 4 5 7. Some patients may also develop carpal tunnel syndrome due to thickening around the wrist.

Distinguishing Features

A key distinguishing feature of EF is the absence of Raynaud’s phenomenon (color changes in the fingers/toes in response to cold), which helps differentiate it from systemic sclerosis and related conditions 2 7 8. Additionally, internal organ involvement is rare in EF, setting it apart from other connective tissue diseases.

Types of Eosinophilic Fasciitis

Eosinophilic fasciitis is not a uniform disease; its presentation can vary widely. Understanding the different types or variants is vital for accurate diagnosis and tailored management.

Type/Variant	Description	Key Features	Sources
Classic EF	Symmetrical limb involvement	No face/finger involvement	3 6 8
Morphea-like EF	Overlaps with localized scleroderma (morphea)	Plaque-like skin lesions	1 8 13
Atypical EF	Unusual presentations, e.g., with Raynaud’s	Rare, overlaps other syndromes	2 7
Drug-induced EF	Triggered by medications (e.g., checkpoint inhibitors)	Linked to immunotherapy	10

Table 2: Variants of Eosinophilic Fasciitis

Classic Eosinophilic Fasciitis

Classic EF typically presents with symmetrical swelling and induration of the limbs, specifically sparing the fingers, toes, and face. The trunk may be affected, but internal organs are usually not involved. This type is what most clinicians refer to when describing EF 3 6 8.

Morphea-like Variant

Some patients develop plaque-like, localized skin lesions resembling morphea (localized scleroderma). This overlap can sometimes make diagnosis challenging, as morphea and EF may coexist or transition from one to the other 1 8 13. These cases may require a different therapeutic approach.

Atypical and Overlap Syndromes

Rare cases with atypical features, such as the presence of Raynaud’s phenomenon or internal organ involvement, have been reported 2 7. These atypical forms blur the lines between EF and other connective tissue diseases, underlining the importance of thorough diagnostic evaluation.

Drug-Induced EF

Recent reports have identified immune checkpoint inhibitors—used in cancer therapy—as potential triggers for EF. This drug-induced EF often presents similarly to classic EF but requires the added step of discontinuing the offending medication 10. Drug-induced forms highlight the importance of a thorough medication history in patients with new-onset EF.

Causes of Eosinophilic Fasciitis

The precise cause of eosinophilic fasciitis remains elusive, but research suggests a complex interplay of immune, environmental, and possibly genetic factors. Understanding what triggers the disease is crucial for both prevention and management.

Cause/Trigger	Mechanism/Description	Notable Details	Sources
Strenuous Exercise	Physical exertion preceding onset	Reported in many cases	3 5 12
Immune Dysregulation	Abnormal activation of immune system	Involvement of eosinophils, T-cells, cytokines	1 9 11 12
Drug-Induced	Medications, esp. immune checkpoint inhibitors	Emerging cause	10
Unknown Factors	No clear trigger in many cases	Idiopathic	1 5 11

Table 3: Proposed Causes and Triggers of Eosinophilic Fasciitis

Physical Triggers: Exercise and Trauma

A significant number of EF cases are reported after recent strenuous physical activity, such as heavy labor, intense exercise, or even repetitive movements (e.g., drumming) 3 5 12. It is thought that mechanical stress on the fascia may trigger an abnormal immune response in susceptible individuals.

Immune System Dysregulation

EF is considered an immune-allergic disorder, with evidence pointing to dysregulation of the immune system. The disease is characterized by:

• Eosinophil Activation: Eosinophils, a type of white blood cell involved in allergic responses, infiltrate the fascia and release fibrogenic cytokines, leading to tissue thickening 1 5 9.
• Cytokine Mediation: Interleukins (IL-4, IL-5, IL-6, IL-33) and transforming growth factors are implicated in driving the fibrotic process 5 9 12.
• T-cell Involvement: Abnormal T-cell clones and increased interleukin production have been observed in some patients, supporting an autoimmune component 9 11.

Drug-Induced and Paraneoplastic Forms

Certain medications, notably immune checkpoint inhibitors used for cancer therapy, have been linked to the development of EF. These cases may be reversible upon discontinuation of the offending drug and initiation of immunosuppressive therapy 10.

There are also rare associations of EF with hematologic malignancies, such as leukemia and myeloproliferative disorders, although a causal relationship is not well established 7 9.

Idiopathic Cases

Despite extensive investigation, many patients with EF have no identifiable trigger or underlying risk factor. This idiopathic nature underscores the complexity of EF and the need for further research 1 5 11.

Treatment of Eosinophilic Fasciitis

Managing EF requires a patient-centered and often multidisciplinary approach. While some patients may experience spontaneous remission, most benefit from prompt medical therapy to prevent long-term disability.

Treatment	Role/Indication	Effectiveness/Notes	Sources
Corticosteroids	First-line; reduces inflammation	Mainstay, induces remission	1 5 8 13 14 16
Methotrexate	Steroid-sparing, 2nd-line or adjunct	Useful in resistant cases	5 8 13 14 16
Other Immunosuppressants	For refractory cases	Mycophenolate, azathioprine, cyclosporine, tocilizumab	5 8 13 16
Physical Therapy	Prevents/treats joint contractures	Essential adjunct	10 16
Spontaneous Remission	May occur in some patients	Unpredictable, not reliable	1 7

Table 4: Treatment Approaches for Eosinophilic Fasciitis

First-Line Therapy: Corticosteroids

Systemic corticosteroids, such as prednisone, are the cornerstone of EF treatment. They rapidly reduce inflammation and can induce remission in most patients. High-dose intravenous methylprednisolone pulses may offer advantages in severe cases or when rapid control is needed 1 5 8 13 14 16. Early initiation of steroids is associated with better outcomes and reduced risk of long-term disability 13.

Steroid-Sparing Agents and Combination Therapy

Due to the potential side effects of long-term steroid use, adjunctive immunosuppressive therapy is often employed. Methotrexate is the most widely used steroid-sparing agent and has shown efficacy in both inducing and maintaining remission, especially in patients with morphea-like lesions or those unresponsive to steroids alone 5 8 13 14 16.

Other agents, such as mycophenolate mofetil, azathioprine, cyclosporine, and biologics like tocilizumab, may be considered in refractory or relapsing cases 5 8 13 16. Treatment regimens are frequently individualized based on disease severity, comorbidities, and patient response.

Physical and Supportive Therapy

Physical therapy is a critical component of EF management, aiming to maintain joint mobility, prevent contractures, and optimize functional outcomes 10 16. Early and ongoing physiotherapy should be integrated into every patient’s care plan.

Monitoring and Prognosis

Regular monitoring of clinical symptoms, laboratory markers (eosinophil count, ESR), and, in some cases, imaging (e.g., MRI) is essential to guide therapy and detect relapses or complications 8 14. The majority of patients respond well to treatment, but delayed diagnosis or inadequate therapy can lead to persistent disability.

Spontaneous Remission and Relapse

Some patients may experience spontaneous improvement; however, this is unpredictable and not a basis for withholding therapy, especially in those with significant symptoms or risk of contracture 1 7. Relapses can occur and may require renewed immunosuppressive treatment.

Conclusion

Eosinophilic fasciitis is a rare but distinct connective tissue disease with unique clinical, laboratory, and pathological features. Early recognition and intervention are key to minimizing long-term complications and maximizing quality of life for patients.

Key takeaways:

• Symptoms include symmetrical limb swelling, skin induration, pain, joint contracture, and peripheral eosinophilia, but lack Raynaud’s phenomenon and internal organ involvement.
• Types range from classic symmetrical EF to morphea-like and drug-induced variants.
• Causes are multifactorial, involving immune dysregulation, physical triggers like exercise, medications, and, in some cases, idiopathic origins.
• Treatment is centered on corticosteroids, often combined with steroid-sparing agents like methotrexate, with physical therapy playing a crucial supportive role.

Understanding EF’s nuances empowers clinicians, patients, and families to recognize symptoms early and collaborate on effective, individualized treatment plans.