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M35.4 for clinicians

A reference for GPs and specialists — differential diagnosis, diagnostic criteria, and therapeutic approach in eosinophilic fasciitis.

M35.4 ICD-10 code

1974 First described (Shulman)

> 6 mo Delay linked to worse outcome

/ 01

When to suspect it

EF is easy to mistake for scleroderma. The pattern that should raise it: rapidly progressive, symmetrical limb induration that spares the fingers and toes, often after a bout of unaccustomed exertion, with blood eosinophilia.

SKIN

Symmetrical limb induration

Firm, woody swelling of the forearms and legs that spares the fingers, toes and face — unlike scleroderma.

GROOVE

Groove sign

Superficial veins sink into the indurated tissue, leaving a linear furrow — most visible when the limb is elevated.

PEAU

Peau d'orange

Dimpled, orange-peel skin texture over affected areas as the fascia tethers the overlying skin.

ROM

Contractures & prayer sign

Early loss of joint range; inability to fully appose the palms signals fascial tightening.

TRIG

Exertional onset

Up to half of cases follow unusually strenuous physical activity in the preceding weeks.

EOS

Peripheral eosinophilia

Blood eosinophilia is common at presentation but may be transient and is not required for diagnosis.

/ 02

Diagnostic criteria

The most cited framework is the Pinal-Fernández 2014 set — two major and five minor criteria. Definitive diagnosis still rests on a full-thickness biopsy.

/ required findings

Two major criteria

Swelling, induration and thickening of the skin and subcutaneous tissue — symmetrical or not, diffuse or localised to the limbs.
Fascial thickening with an infiltrate of lymphocytes and macrophages, with or without eosinophils, on full-thickness wedge biopsy.

/ supportive findings

Five minor criteria

Peripheral eosinophilia > 0.5 × 10⁹/L.
Hypergammaglobulinaemia > 1.5 g/L.
Muscle weakness and/or raised serum aldolase.
Groove sign and/or peau d'orange.
Hyperintense fascia on T2-weighted MRI.

/ Pinal-Fernández 2014

Diagnosis is supported by two major criteria, or one major plus two minor. A full-thickness skin-to-muscle biopsy remains the reference standard; MRI can target the biopsy site and reduce sampling error.

/ 03

Differential diagnosis

The central distinction is from systemic sclerosis. EF spares the fingers and lacks Raynaud's, sclerodactyly, telangiectasia and nailfold capillary changes — and adds the groove sign and peau d'orange that scleroderma does not show.

SSc

Systemic sclerosis

Sclerodactyly, Raynaud's, nailfold capillary loops and ANA positivity point away from EF, which spares the digits.

MORPH

Morphoea

Shares deep-tissue fibrosis and can coexist with EF; morphoea is plaque-like and dermal, EF is deeper and fascial.

NSF

Nephrogenic systemic fibrosis

Consider with renal failure and prior gadolinium exposure; distribution and history differ.

EMS

Eosinophilia-myalgia syndrome

Toxin-linked (historically L-tryptophan); prominent myalgia, neuropathy and systemic features.

SMX

Scleromyxoedema

Mucin deposition with waxy papules and a monoclonal gammopathy; biopsy distinguishes it.

HES

Hypereosinophilic syndrome / EGPA

Marked, sustained eosinophilia with multi-organ involvement rather than localised fascial disease.

/ 04

Workup

Confirm the tissue diagnosis, map disease extent, and screen for the haematological associations that change management.

Full-thickness biopsy

Incisional skin-to-muscle wedge including fascia — the reference standard for diagnosis.

MRI

MRI of the affected limb

Fascial T2 hyperintensity and post-contrast enhancement support the diagnosis, guide the biopsy and track activity.

LAB

Bloods

Full blood count with eosinophils, serum aldolase, gammaglobulins / electrophoresis, ESR and CRP; ANA is usually negative.

HEME

Haematological surveillance

Screen for cytopenias and lymphoproliferative or myelodysplastic associations at diagnosis and on follow-up.

/ 05

Treatment & escalation

There is no randomised-trial standard. Practice converges on early systemic corticosteroids, with methotrexate added as the steroid-sparing partner and pulses reserved for severe disease.

Step 01 · confirm

Secure the diagnosis

Biopsy ± MRI before committing to long-term steroids; document baseline range of motion and eosinophil count.

Step 02 · first line

Systemic corticosteroids

Prednisone around 0.5–1 mg/kg/day is the usual starting point; most patients improve within weeks.

Step 03 · severe disease

Pulse methylprednisolone

IV pulses are used for extensive or rapidly progressive disease and have been linked to better response.

Step 04 · steroid-sparing

Add methotrexate

Combination with methotrexate outperforms steroids alone for complete remission and allows steroid tapering.

Step 05 · taper

Taper slowly over months

Guide the taper by skin softening, range of motion and MRI activity rather than the calendar.

Step 06 · monitor

Watch for relapse

Around a quarter of responders relapse; keep monitoring blood counts and function long-term.