Eosinophilic Fasciitis  

Eosinophilic Fasciitis – Introduction

• Eosinophilic fasciitis (EF) is a rare inflammatory disease of the fascia characterized by involvement of the skin and soft tissues associated with hematologic abnormalities that was first described by Lawrence Shulman in 1974. ¹ 
• This condition initially presents with acute onset of symmetrical erythema, edema, and induration of the extremities and/or trunk.
• Later it may progress to sclerosis of the dermis and subcutaneous fascia leading to contractures, which cause significant morbidity.

Synonyms

• Shulman syndrome
• Diffuse fasciitis with eosinophilia

ICD-10CM CODE
M35.4	Diffuse (eosinophilic) fasciitis

Epidemiology & Demographics ¹

• •Exact incidence of EF is unknown.
• •Women are 1.3 to 2.1 times as likely as men to be affected.
• •Age of onset: 20 to 60 yr.

Physical Findings & Clinical Presentation

• •Cutaneous: Painful and erythematous edema in the involved extremities, mostly symmetrical but can be unilateral. Peau d’orange or pseudocellulite, Groove sign (visible indentation of superficial vein;). Face, hands, and feet are typically spared
• •Musculoskeletal: Limited joint mobility (joint contractures in 50% to 60% of patients), prayer sign, significant fascia fibrosis.
• •Neuropathies: Cranial and peripheral neuropathies (carpal tunnel syndrome, mononeuritis multiplex).
• •Constitutional: Myalgia, muscle weakness, fatigue, weight loss.
• •Hematologic: Up to 10% of EF cases have been associated with hematologic disorders such as aplastic anemia, myeloproliferative disorders, lymphoma, leukemia, and multiple myeloma.
• •Pulmonary: Restrictive lung disease due to extensive fibrosis in the trunk.
• •Patients with EF often lack visceral involvement or history of Raynaud phenomenon.

Etiology ¹

Most cases are considered idiopathic. A proposed mechanism of disease is a nonspecific immune-mediated inflammation of the fascia triggered by muscle stress (exercise or trauma, 28% to 46% of patients), medications (statins, subcutaneous heparin, phenytoin, checkpoint inhibitors), exposures (radiation therapy, burns), infection (Borrelia burgdorferi, Mycoplasma arginini), autoimmune disease (lupus, thyroid disease), hematologic disorder (<10%), solid neoplasms (rare). ²

Diagnosis

Differential Diagnosis ^2 , 3

• •Localized scleroderma: Morphea, linear
• •Systemic scleroderma
• •Scleroderma-like disorders: Nephrogenic systemic fibrosis, scleromyxedema, scleroderma
• •Hypereosinophilic syndrome
• •Deep vein thrombosis
• •Cellulitis
• •Sclerodermoid graft-versus-host disease

Workup

• •Diagnosis by histopathology from a full-thickness biopsy of fascia is considered the gold standard. Findings include lymphocytic infiltrate, fascial thickening, and fibrosis. ³
• •Universally accepted, validated diagnostic criteria are lacking.
• •Proposed diagnostic criteria (two major or one major and two minor). ⁴
  • 1.Major:
    • a.Swelling, induration, and thickening of the skin and subcutaneous tissue that is symmetric or nonsymmetric, diffuse (extremities, trunk, and abdomen), or localized (extremities)
    • b.Fascial thickening with accumulation of lymphocytes and macrophages with or without eosinophilic infiltration (determined by full-thickness wedge biopsy of clinically affected skin)
  • 1.Minor:
    • a.Eosinophilia >0.5 × 10 ⁹ /L
    • b.Hypergammaglobulinemia >1.5 g/L
    • c.Muscle weakness and/or elevated aldolase levels
    • d.Groove sign and/or peau d’orange
    • e.Hyperintense fascia on MRI T2-weighted images
• •Exclusion criteria: Diagnosis of systemic sclerosis

Laboratory Tests ³

• •Peripheral eosinophilia in 64% to 86% of cases in early stage
• •Elevated erythrocyte sedimentation rate and/or elevated aldolase usually correlates with disease activity
• •Creatinine kinase usually normal
• •Hypergammaglobulinemia (35%)
• •Monoclonal gammopathy (16%)

Imaging Studies

• •MRI during initial workup ³ : Identifies presence of fascia edema and inflammation. Can guide appropriate site for biopsy or be used if biopsy nondiagnostic
• •PET-computed tomography (though limited data based on case reports). Alternative if MRI is contraindicated or not available
• •Ultrasound: Decreased subcutaneous compressibility, increased muscle fascial thickness. May be used for monitoring of treatment.

Treatment

Acute General Treatment

• •Given the rarity of EF, no randomized controlled trials have been performed to date.
• •Corticosteroids (prednisone 0.5 to 1 mg/kg/day) are considered mainstay of treatment. ^2 , 3
• •Based on a recent retrospective review from 2016 of the largest cohort of EF patients to date, complete response is more likely with combination of corticosteroids and methotrexate compared to other treatment combinations, corticosteroid therapy alone, or treatment without corticosteroids. ¹²³
• •Other potential agents based on case reports include mycophenolate mofetil (MMF), intravenous immunoglobulin (IVIG), cyclosporine, azathioprine, infliximab, rituximab, and sirolimus as well as ultraviolet A phototherapy or extracorporeal photochemotherapy.

Chronic Treatment

• •Treatment duration is variable. Patients are monitored for clinical response, and medications are decreased/discontinued accordingly.
• •Patients with incomplete response may require increased doses of corticosteroids.

Disposition

• •Improved outcomes with early treatment.
• •Long-term prognosis is unknown but is generally good.
• •Relapse can occur after cessation of steroids.

Referral

Dermatology for full skin-to-muscle biopsy. Rheumatology to guide diagnosis and management. Surgical evaluation to reduce contracture and maintain function.

Pearls & Considerations

Comments

• •Physical therapy is a crucial, but often overlooked, part of managing EF.
• •Patients should be started on prophylaxis for opportunistic infections when treated with long-term corticosteroids or immunosuppression.

References

1.Mazori D.R., et al.: Eosinophilic fasciitis: an updated review on diagnosis ands treatment . Curr Rheumatolog Rep 2017; 19: pp. 74.

2.Wright N.A., et al.: Epidemiology and treatment of eosinophilic fasciitis: an analysis of 63 patients from 3 tertiary care centers . JAMA Dermatol 2016; 152: pp. 97-99.

3.Fett N., et al.: Eosinophilic fasciitis: current concepts . Clin Dermatol 2018; 36: pp. 487-497.

4.Pinal-Fernandez I., et al.: Diagnosis and classification of eosinophilic fasciitis . Autoimmun Rev 2014; 13: pp. 379-382.

Suggested Readings

• Au Eong D.T.M., et al.: Ultrasound in the diagnosis and monitoring of eosinophilic fasciitis . Rheumatology (Oxford) 2021; 60 (3): pp. e107-e108.
• Chan K.K., et al.: Eosinophilic fasciitis following checkpoint inhibitor therapy: four cases and a review of literature . Oncologist 2019; 25 (2): pp. 140-149.