Eosinophilic fasciitis (EF) or Shulman syndrome, is a scleroderma-like syndrome with an early phase characterized by erythema and edema distributed over the limbs or trunk and a later phase, dominated by collagenous thickening of the subcutaneous fascia. It is a rare connective tissue disorder presenting variable clinical manifestations: acute onset with painful and swollen extremities and progression to disabling cutaneous fibrosis, joint contractures, arthritis, neuropathy, and myositis.¹ EF mainly affects adults with ages 40 and 50 years old, with no apparent gender predilection, but it appears to affect men earlier.²

The majority of patients with EF (61-83%) have peripheral blood eosinophilia.³ Peripheral eosinophilia is transient and it is not correlated with disease severity. Over 50 percent of patients have an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as a polyclonal hypergammaglobulinemia.¹

Up to 10 percent of patients associate hematologic abnormalities (aplastic anemia, lymphoma, acquired amegakaryocytic thrombocytopenia, myeloproliferative disorders, myelodysplastic syndromes, lymphocytic and eosinophilic leukemia) and EF can be the presenting manifestation.¹

Case report

We report the case of a 75-year-old man with sclero-indurative skin evolving for almost 8 months. Clinical examination revealed alopecic, shiny skin affecting almost the entire body (Figure 1), with the exception of hands, face, feet, perigenital area, furrows along the course of the superficial veins, the "groove sign” at the upper extremities, impaired mobility of ankles, knees and elbows. In addition, on both thighs a persistent, blotchy, purple, net-like pattern was noticed, suggestive for livedo reticularis (Figure 2). The patient had no relevant personal and family medical history, he was not taking any medication, not smoking, denied excessive alcohol consumption and worked as a farmer.

Figure 1. Infiltration and sclerosis of the skin of the trunk

Figure 2. Sclero-indurative, shiny and alopecic skin and livedo reticularis in the lower legs

Laboratory studies showed eosinophilia (9.01%, reference range 0.00-0.20%), elevated ESR (30 mm/1h, reference range 1-10 mm/1h), CRP (6.70 mg/L, reference range 0-5 mg/L). Further investigations for the underlying mechanism of livedo reticularis showed mutated factor V of coagulation (also known as Factor V Leiden).

We took into consideration for differential diagnosis several scleroderma-like disorders: eosinophilic fasciitis, localized and systemic sclerosis, nephrogenic systemic fibrosis, scleromyxedema, scleredema and eosinophilia myalgia syndrome. A full-thickness incisional biopsy of skin and subcutaneous tissues down to the muscle surface showed thickening and sclerosis of the fascia and diffuse inflammation with lymphocytes, monocytes, plasmocytes (Figure 3), and eosinophils (insert). Imaging studies excluded an association with internal malignancies. Based on the clinical aspect of the lesions, the biopsy and laboratory results, the diagnosis of EF was established. We considered that eosinophilia was associated with the connective tissue disease and, as it normalized after starting the treatment, we did not consider it necessary to perform bone marrow biopsy.

Systemic treatment with corticosteroids (0.5 mg/kg/bw) in decreasing dose, in association with hydroxychloroquine (400 mg/day), colchicine (1 mg/day) and pentoxifylline (400 mg/day) induced good clinical response and normalizing of the elevated parameters after 6 months (eosinophils 0.92%, ESR 5 mm/h and CRP 0.6 mg/L) and it was continued for almost 18 months.

Figure 3. Inflammation, eosinophils (insert), thickening and sclerosis of the fascia (hematoxylin and eosin stain, 40×)

EF is considered a rare disorder. The etiology still remains unclear and up to this date its pathogenesis is poorly understood.

Clinically, lifting the affected limb lowers the venous pressure, the effect is a visible indentation that marks the place of a superficial vein, known as the "groove sign”. The pathogenesis behind the appearance of this sign resides in the reduction of the superficial dermis and epidermis together with the immobility of the connective tissue surrounding the superficial veins. Arthritis occurs in few cases of EF and it usually affects the joints nearer to the fasciitis.^4,5

The differential diagnosis can be sometimes challenging both clinically and on pathological examination, especially when eosinophils are not present. The absence of eosinophils does not indicate that we can exclude the diagnosis.^6,7

The presence of livedo reticularis required thorough investigations of the underlying mechanism that led to the identification of mutated factor V of coagulation. Although EF may associate hematological abnormalities, to our knowledge, the co-existence of EF and Factor V Leiden has not been reported before. It is important to keep in mind that EF can appear before the onset of the other disorders and early signs should be checked during the follow-up.

Systemic corticosteroids in progressively decreasing dosage, combined with hydroxychloroquine, colchicine and pentoxifylline led to significant clinical improvement after one and a half year.

We have reported a case of eosinophilic fasciitis with livedo reticularis caused by factor V Leiden. This coagulation abnormality associated with EF has never been reported before and was considered to be a random association.

Early diagnosis of this rare disease can influence the treatment, prognosis, morbidity and the patient’s quality of life and can enable early detection of associated serious hematologic disorders and prevent long lasting sequelae.

1. Helfgott S, Varga J. Eosinophilic fasciitis. In: Post TW (ed). UpToDate. Waltham, MA: UpToDate Inc; 2018. Accessed on: 02 May 2018. Available at: https://www.uptodate.com.

2. Lamback EB, Resende FS, Lenzi TC. Eosinophilic fasciitis. An Bras Dermatol 2016;91:57-9. [Crossref]

3. Falanga V, Medsger TA Jr. Frequency, levels, and significance of blood eosinophilia in systemic sclerosis, localized scleroderma, and eosinophilic fasciitis.J Am Acad Dermatol 1987;17:648-56. [Crossref]

4. Heidary N, Cheung W, Wang N, Kamino H, Franks AG Jr. Eosinophilic fasciitis/generalized morphea overlap. Dermatology Online Journal 2009;15:2.

5. Ortega-Loayza AG, Merritt BG, Groben PA, Morrell DS. Eosinophilic fasciitis in a female child. J Am Acad Dermatol 2008;58:S72-4. [Crossref]

6. Smith LC, Cox NH. Dapsone treatment for eosinophilic fasciitis Arch Dermatol 2008;144:845-7. [Crossref]

7. Bielsa I, Ariza A. Deep morphea. Semin Cutan Med Surg 2007;26:90-5. [Crossref]