Eosinophilic fasciitis

What is eosinophilic fasciitis?

Eosinophilic fasciitis is a rare fibrosing disorder characterised by oedema and subsequent induration of the skin and subcutaneous tissues. It is typically associated with peripheral eosinophilia.

Eosinophilic fasciitis, also known as diffuse fasciitis or Shulman syndrome, may exhibit overlapping clinical and/or histopathologic features with morphoea. This leads to uncertainty as to whether the two are distinct entities or fall along the same disease spectrum.

Indurated skin thickening causing limited joint mobility due to eosinophilic fasciitis 

Who gets eosinophilic fasciitis?

The epidemiology of eosinophilic fasciitis has yet to be well described. Several case series have reported a mean age at diagnosis to be in the sixth decade. However, reported cases have ranged in age from childhood to the elderly. Eosinophilic fasciitis affects both males and females.

What causes eosinophilic fasciitis?

The aetiology and pathogenesis of eosinophilic fasciitis are unknown, although an immune-mediated mechanism is suspected.

While the majority of cases are idiopathic, reported triggers or associated factors include:

• Strenuous physical activity: precedes clinical findings in ~30% of cases (may provoke an autoimmune response targeting damaged fascia)
• Radiation therapy or burns
• Infections eg, Mycoplasma arginini, Borrelia burgdorferi
• Medications, including statins, heparin, phenytoin, carbidopa, and immune checkpoint inhibitors (eg, pembrolizumab, nivolumab)
• Autoimmune diseases, including thyroid disease, systemic lupus erythematosus, Sjögren syndrome, primary biliary cirrhosis, and inflammatory bowel disease
• Haematologic disorders or malignancies
• Chronic graft-versus-host disease
• Initiation of haemodialysis.

What are the clinical features of eosinophilic fasciitis?

Eosinophilic fasciitis is typically acute in onset, with cutaneous findings evolving over time. The extremities, trunk, and neck are most commonly involved and most patients have bilateral skin changes, which may include:

• Initially, non-pitting oedema with associated erythema and pain
• With disease progression, symmetrical woody induration and puckering of the skin, resulting in an orange-peel texture (‘peau d'orange’)
• “Groove sign”– a linear depression following the path of superficial veins in the affected area, best appreciated with elevation of the limb and tangential lighting.

Extension of skin changes to the distal digits is characteristically absent, which can be a helpful finding to distinguish eosinophilic fasciitis from systemic sclerosis.

Extra-cutaneous features include:

• Constitutional symptoms, such as fatigue, fever, or weight loss
• Joint contractures (seen in 50 to 67% of patients)
• Inflammatory arthritis (seen in up to 50% of patients)
• Myalgia, myositis
• Haematologic disorders (eg, aplastic anaemia, monoclonal gammopathy, lymphoma, myeloproliferative disorders, myelodysplastic syndromes) may be seen in up to 10% of patients
• Rarely, visceral involvement (eg, pleural effusion, pericarditis, renal involvement).

Induration of the skin and the” groove sign” - an indentation along the course of a superficial vein  

“Orange skin” thickening and a “groove sign” 

What are the complications of eosinophilic fasciitis?

• Restricted range of movement and mobility due to joint contractures and arthritis
• Carpal tunnel syndrome due to local compression of the median nerve
• Restrictive lung disease due to truncal involvement
• Rare visceral involvement

How is eosinophilic fasciitis diagnosed?

Eosinophilic fasciitis should be suspected based on typical clinical findings and confirmed on deep skin-to-muscle incisional biopsy.

Histological features of eosinophilic fasciitis include:

• Thickening of the deep fascia
• Patchy infiltrates of lymphocytes, plasma cells, histiocytes, and eosinophils within the fascia and subfascial muscle
• Dermal fibrosis.

An inflammatory infiltrate with scattered eosinophils in the perimuscular fascia 

Magnetic resonance imaging (MRI) can be useful to highlight areas of fascial inflammation, as demonstrated by increased T2 signal in the subcutaneous and deep fascia.

The following blood test abnormalities may be observed:

• Transient peripheral eosinophilia (does not correlate with disease severity)
• Elevated acute phase reactants (eg, CRP, ESR)
• Polyclonal hypergammaglobulinaemia
• Elevated serum aldolase (correlates with disease severity)
• Elevated serum type III procollagen peptide (PIIIP) (correlates with disease severity)

What is the differential diagnosis for eosinophilic fasciitis?

• Other sclerosing skin disorders such as:
  • Morphoea
  • Systemic sclerosis
  • Nephrogenic systemic fibrosis
  • Scleromyxoedema
  • Scleroedema
  • Eosinophilia-myalgia syndrome (associated with ingestion of L-tryptophan supplements)
  • Chronic graft-versus-host disease with sclerotic manifestations
• Inflammatory disorders with peripheral eosinophilia:
  • Hypereosinophilic syndrome
  • Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome)

What is the treatment for eosinophilic fasciitis?

General measures

Physical and occupational therapy are important for maintaining joint mobility and preventing contractures.

Specific measures

Treatment should be initiated as soon as possible after the diagnosis is made.

First-line: Systemic steroids (eg, oral prednisone or pulse intravenous methylprednisolone). A starting dose equivalent to 1 mg/kg of prednisone per day is suggested, which is tapered over 6–24 months as tolerated.

Second-line agents (eg, DMARDs) may be added to improve therapeutic response and/or to spare the use of steroids and these include:

• Methotrexate (generally regarded as second-line)
• Mycophenolate mofetil
• Hydroxychloroquine

Once remission is achieved, therapy is maintained for several months before an attempt at discontinuation.

For refractory disease, various other treatments have been reported, including:

• Cyclosporin
• Azathioprine
• Tocilizumab
• Infliximab
• Rituximab
• Dapsone
• JAK inhibitors
• Imatinib
• Psoralen + ultraviolet A (PUVA phototherapy), ultraviolet A1 (UVA1 phototherapy)
• Intravenous immunoglobulin
• Mepolizumab.

What is the outcome for eosinophilic fasciitis?

Eosinophilic fasciitis typically responds to treatment within the first few weeks, with clinical improvement seen over many months. The reported rate of complete response is 60–69%.

Diagnostic delay has been associated with a lower likelihood of response to treatment. Patients with incomplete response may develop chronic thickening of the skin and contractures.

Some patients with eosinophilic fasciitis may improve spontaneously without treatment.