|Year : 2017 | Volume
| Issue : 6 | Page : 180-184
Scleroderma mimicker – Eosinophilic fasciitis
Debanjali Sinha, Alakendu Ghosh
Department of Rheumatology, IPGME and R and SSKM Hospital, Kolkata, West Bengal, India
|Date of Web Publication||23-Nov-2017|
Department of Rheumatology, IPGME and R and SSKM Hospital, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Eosinophilic fasciitis is an uncommon connective tissue disorder characterized by thickening of the deep fascia and overlying skin and subcutaneous tissue. It may mimic scleroderma and other scleroderma-like conditions. It may be a manifestation of paraneoplastic disorders or may be associated with hematological disorders including lymphomas. Definitive diagnosis is made on histological examination of a deep skin biopsy revealing thickened deep fascia and infiltration by lymphocytes and eosinophils. Enhancement of deep fascia on Gadolinium contrast-enhanced magnetic resonance imaging may be used as a substitute for skin biopsy. Ultrasound imaging is an evolving imaging tool for diagnosing it. Glucocorticoids with or without immunosuppressive agents remains the mainstay of therapy with good response, generally. A younger age of onset, morphea like lesions and dermal fibrosclerosis is more likely to be associated with the refractory disease. Early diagnosis and appropriate treatment may result in better outcomes in terms of morbidity and quality of life of the patients.
Keywords: Deep fascia, dermal fibrosis, eosinophils, fasciitis, myositis, paraneoplastic, scleroderma mimic
|How to cite this article:|
Sinha D, Ghosh A. Scleroderma mimicker – Eosinophilic fasciitis. Indian J Rheumatol 2017;12, Suppl S1:180-4
| Introduction|| |
Cutaneous fibrosing disorders encompass a wide spectrum of diseases which are united by the presence of varying degrees of skin fibrosis. The nature and distribution of skin involvement, presence or absence of systemic complications, and unique associated laboratory abnormalities help to distinguish between these diseases. It is thus necessary that an effort is made to accurately differentiate between these fibrosing disorders, to guide appropriate long-term management.
| Scleroderma|| |
The French physician Elie Gintrac  has been credited with coining the term scleroderma (which literally means “hard skin”) in 1847 although it had already been used a decade earlier, in 1836, by Giambattista Fantonetti of Pavia. In scleroderma, there is involvement of the fingers, hands, forearms, distal legs, feet, and the face more commonly and more severely than the proximal limbs and anterior trunk. The mid-back is typically spared. There are three phases of skin involvement in scleroderma:
- Edematous phase characterized by nonpitting edema of the affected body areas
- Fibrotic phase: Skin induration with loss of body hair and decline in sweating capacity
- Regression phase: Skin regression characteristically occurs in order that is reverse of initial involvement, with softening on the trunks followed by proximal and then distal extremities.
The presence of Raynaud's phenomenon distinguishes it from the other causes of skin tightening.
The 2013 Classification Criteria for Systemic Sclerosis incorporate disease manifestations of the three hallmarks of SSc: Fibrosis of the skin and/or internal organs, production of specific autoantibodies, and evidence of vasculopathy. The sensitivity and specificity for the 2013 criteria were 0.91 and 0.92, respectively.
- Localized scleroderma
- Scleroderma variants:
- Eosinophilic syndromes:
- Eosinophilic fasciitis (EF)
- Eosinophilia-myalgia syndrome – contaminant of the dietary supplement L-tryptophan used principally to treat insomnia
- Toxic oil syndrome – adulterated rapeseed oil
- Scleredema adultorum of buschke
- Scleredema diabeticorum
- Scleredema neonatorum
- Nephrogenic systemic fibrosis
- Chronic graft versus host disease
- Metabolic diseases:
- Porphyria cutanea tarda
- Werner syndrome
- Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome
- Stiff skin syndrome
- Reflex sympathetic dystrophy
- Diabetic cheiroarthropathy
- Drugs: Bisoprolol, bleomycin, bromocriptine, carbidopa, d-penicillamine, pentazocine
- Occupational exposure – epoxy resins, organic solvents, polyvinyl chloride, silica
- Chemicals and pesticides – benzene, malathion, naphthalene, toluene, trichloroethylene, vinyl chloride monomers. A schematic way of approaching a patient with scleroderma like skin changes has been shown in [Table 1] below.
EF (also called Shulman syndrome) is an uncommon disorder of unknown etiology and poorly understood pathogenesis.
The following have been suggested as possible triggers or factors associated with EF:
- Strenuous exercise 
- Initiation of hemodialysis 
- Infection with Borrelia burgdorferi;, Mycoplasma arginini ection 
- Physical factors such as radiation therapy and burns 
- Graft-versus-host disease 
- Autoimmune diseases including thyroid disease,, primary biliary cirrhosis, systemic lupus erythematosus, and Sjögren's syndrome
- Hematologic disorders-hematologic disorders can be associated with EF in up to 10 percent of patients and can be the presenting manifestation 
- Aplastic anemia 
- Acquired amegakaryocytic thrombocytopenia 
- Myelodysplastic syndromes 
- Myeloproliferative disorders 
- Lymphoma, especially peripheral T cell lymphoma ,
- Lymphocytic and eosinophilic leukemia 
- Multiple myeloma 
- Paroxysmal nocturnal hemoglobinuria 
- Exposure to certain medications including statins, phenytoin, ramipril, and subcutaneous heparin, influenza vaccination and natalizumab (humanized monoclonal antibody against the cell adhesion molecule α4-integrin),
- Idiopathic – majority.
| Clinical Manifestations|| |
Skin involvement typically starts with acute onset symmetric nonpitting edema of arms and limbs sparing hands and feet. It is followed by induration with puckering giving the appearance of peau d'orange and the formation of groove sign. Characteristic “Groove sign” is a dimpled appearance along the medial aspect of both arms especially upon elevation when the brachial and other superficial veins collapse [Figure 1]. Apart from this, inflammatory arthritis can occur in 40% of the patients and flexion contractures of the joints in about 56%. There may be myalgia and muscle weakness, but inflammatory myositis is uncommon. Cranial and peripheral neuropathies are not uncommon. Carpal tunnel syndrome has been a commonly described peripheral neuropathy (23%). Visceral involvement is absent in almost all patients with EF [Figure 1]a.
|Figure 1: (a) Eosinophilic fasciitis – groove sign. (b) T1 postcontrast magnetic resonance image of the patient's leg, showing thickening and contrast enhancement of the fascial plane (arrows showing thickened fascia). (c) Ultrasonography of legs (picture on left is from right leg and picture on right is from left leg) showing thickened fascia of the patient (the double-headed arrow shows the thickness of the fascia with measurements embedded). (d) Ultrasonography of leg of a normal person (the double-headed arrow shows the normal thickness of fascia with measurements)|
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| Investigations|| |
Peripheral eosinophilia is present in the majority of patients, about 80%. Peripheral blood eosinophil counts do not correlate with disease severity and is not useful for evaluation of treatment response or follow-up. Erythrocyte sedimentation rate and C-reactive protein may be raised and polyclonal hypergammaglobulinemia may be present in 30%–40%. Low titers of antinuclear antibodies without detectable anti-extractable nuclear antigen (anti-ENA) antibodies may be present.
Skin biopsy for EF requires an elliptical full thickness incisional biopsy of skin and subcutaneous tissues down to the muscle surface. Early in the course of the disease, the deep fascia and lower subcutis are edematous with inflammatory infiltrates mainly composed of lymphocytes and/or eosinophils. The infiltrates in the fascia are mainly composed of macrophages and CD8 + T lymphocytes. Eosinophil infiltrates are present in the majority of patients but not all, and can become absent in a chronic phase of the disease or after corticosteroid treatment. Eosinophils may also be the predominant infiltrating cells in some, 5/52 patients in one study. The epidermis and dermis are usually unaltered or mildly affected. These structures become thickened and sclerotic as the illness progresses, with the disappearance of inflammatory cell infiltrates.
Magnetic resonance imaging
The increased T2 signal in the subcutaneous and deep fascia and enhancement of these structures on fat-suppressed T1 images after gadolinium administration have been noted [Figure 1]b.
Ultrasonography – Ultrasonography findings in EF have been reported to show a possible correlation with magnetic resonance imaging (MRI), and thus can be considered as an alternative imaging evaluation modality [Figure 1]c and [Figure 1]d.
Initial treatment is with systemic glucocorticoids, usually starting at doses equivalent to prednisone 1 mg/kg/day. Doses are reduced as the affected skin softens, which can take from weeks to months. In patients with no evidence of a response to prednisone at doses of up to 1.5 mg/kg/day given for 3 months, low dose methotrexate (15–25 mg) may be used as a second-line therapy. Lebeaux et al. did a study on the therapeutic response in 32 patients of EF. All patients were treated with corticosteroids as a first-line therapy. Fifteen patients (47%) received methylprednisolone pulses at treatment initiation and 14 patients (44%) received an immunosuppressive drug, usually Methotrexate (86%), as a second-line therapy. Complete remission was achieved in 69% of patients; in 17 (94%) of the 18 patients who received steroids alone and in 5 (36%) of the 14 patients who received an immunosuppressive drug. Remission with disability occurred in 19% and failure with the persistent active disease in 12%. A poor outcome was associated with a diagnosis time delay of >6 months (odds ratio [OR] = 14.7) and the lack of 1-methyl-4-phenylpyridiniums (OR = 12.9). Alternatives to methotrexate include hydroxychloroquine and mycophenolate. Some of the other medical interventions include sulfasalazine, azathioprine, infliximab, rituximab, intravenous immune globulin, dapsone, cyclosporine A, D-penicillamine, psoralen plus ultraviolet A photochemotherapy, and antithymocyte globulin.,,,,,
Patients with morphea-like skin lesions were 1.9 times more likely to develop persistent fibrosis than patients without these lesions. Younger age (under 12 years) at onset was associated with 1.6 times greater risk, trunk involvement 1.4 times and the presence of dermal fibrosclerosis was associated with 1.4 times greater risk of refractory fibrosis.
Surgical intervention – Surgical options after failure of immunosuppressives are release of joint contractures, release of carpal tunnel syndrome and fasciectomy.
| Conclusion|| |
EF or Shulman syndrome is a rare, localized cutaneous fibrosing disorder. It is a close mimicker of scleroderma, but unlike scleroderma, it affects the fascia, not the skin (dermis). Early diagnosis and prompt treatment of EF may have a positive impact on the patient's morbidity, quality of life, and even on the disease remission.
We would like to acknowledge the contribution of Dr. Sumantro Mondal, Post-Doctoral Resident, Department of Rheumatology, IPGME and R, Kolkata for providing the pictures on imaging.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gintrac E. Note Scleroderma. Rev Med Chir (Paris) 1847;2:263.
Fantonetti GB. Forget's chorionitis or sclerosing skin. Giorn Progr Patol Terap Venice 1847;602.
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al
. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737-47.
Shulman LE. Diffuse fasciitis with eosinophilia: A new syndrome? Trans Assoc Am Physicians 1975;88:70-86.
Florell SR, Egan CA, Gregory MC, Zone JJ, Petersen MJ. Eosinophilic fasciitis occurring four weeks after the onset of dialysis in a renal failure patient. J Cutan Med Surg 2001;5:33-6.
Hashimoto Y, Takahashi H, Matsuo S, Hirai K, Takemori N, Nakao M, et al.
Polymerase chain reaction of Borrelia burgdorferi
flagellin gene in Shulman syndrome. Dermatology 1996;192:136-9.
Mosconi S, Streit M, Brönimann M, Braathen L. Eosinophilic fasciitis (Shulman syndrome). Dermatology 2002;205:204-6.
Silló P, Pintér D, Ostorházi E, Mazán M, Wikonkál N, Pónyai K, et al.
Eosinophilic fasciitis associated with Mycoplasma arginini
infection. J Clin Microbiol 2012;50:1113-7.
Sherber NS, Wigley FM, Paget SA. Diffuse fasciitis with eosinophilia developing after local irradiation for breast cancer. Clin Rheumatol 2009;28:729-32.
Ganta CC, Chatterjee S, Pohlman B, Hojjati M. Chronic graft-versus-host disease presenting as eosinophilic fasciitis: Therapeutic challenges and an additional case. J Clin Rheumatol 2015;21:86-94.
Imren S, Tüzüner N, Yazici H. Eosinophilic fasciitis with thyroid disease. Clin Exp Rheumatol 1988;6:96-7.
Hur JW, Lee HS, Uhm WS, Jun JB, Bae SC, Park CK, et al.
Eosinophilic fasciitis associated with autoimmune thyroiditis. Korean J Intern Med 2005;20:180-2.
Lakhanpal S, Ginsburg WW, Michet CJ, Doyle JA, Moore SB. Eosinophilic fasciitis: Clinical spectrum and therapeutic response in 52 cases. Semin Arthritis Rheum 1988;17:221-31.
de Masson A, Bouaziz JD, Peffault de Latour R, Benhamou Y, Moluçon-Chabrot C, Bay JO, et al.
Severe aplastic anemia associated with eosinophilic fasciitis: Report of 4 cases and review of the literature. Medicine (Baltimore) 2013;92:69-81.
Chaudhary UB, Eberwine SF, Hege KM. Acquired amegakaryocytic thrombocytopenia purpura and eosinophilic fasciitis: A long relapsing and remitting course. Am J Hematol 2004;75:146-50.
Haddad H, Sundaram S, Magro C, Gergis U. Eosinophilic fasciitis as a paraneoplastic syndrome, a case report and review of the literature. Hematol Oncol Stem Cell Ther 2014;7:90-2.
Jacob SE, Lodha R, Cohen JJ, Romanelli P, Kirsner RS. Paraneoplastic eosinophilic fasciitis: A case report. Rheumatol Int 2003;23:262-4.
Naschitz JE, Misselevich I, Rosner I, Yeshurun D, Weiner P, Amar M, et al.
Lymph-node-based malignant lymphoma and reactive lymphadenopathy in eosinophilic fasciitis. Am J Med Sci 1999;318:343-9.
Eklund KK, Anttila P, Leirisalo-Repo M. Eosinophilic fasciitis, myositis and arthritis as early manifestations of peripheral T-cell lymphoma. Scand J Rheumatol 2003;32:376-7.
Ferguson JS, Bosworth J, Min T, Mercieca J, Holden CA. Eosinophilic fasciitis associated with hypereosinophilia, abnormal bone-marrow karyotype and inversion of chromosome 5. Clin Exp Dermatol 2014;39:150-3.
Khanna D, Verity A, Grossman JM. Eosinophilic fasciitis with multiple myeloma: A new haematological association. Ann Rheum Dis 2002;61:1111-2.
de Boysson H, Chèze S, Chapon F, Le Mauff B, Auzary C, Geffray L, et al.
Eosinophilic fasciitis with paroxysmal nocturnal hemoglobinuria. Joint Bone Spine 2013;80:208-10.
Long H, Zhang G, Wang L, Lu Q. Eosinophilic skin diseases: A Comprehensive review. Clin Rev Allergy Immunol 2016;50:189-213.
Bujold J, Boivin C, Amin M, Bouchard JP, Soucy J. Eosinophilic fasciitis occurring under treatment with natalizumab for multiple sclerosis. J Cutan Med Surg 2014;18:69-71.
Lebeaux D, Francès C, Barete S, Wechsler B, Dubourg O, Renoux J, et al.
Eosinophilic fasciitis (Shulman disease): New insights into the therapeutic management from a series of 34 patients. Rheumatology (Oxford) 2012;51:557-61.
Jones AC, Doherty M. Eosinophilic fasciitis with late onset arthritis responsive to sulfasalazine. J Rheumatol 1993;20:750-1.
Schiener R, Behrens-Williams SC, Gottlöber P, Pillekamp H, Peter RU, Kerscher M, et al.
Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy. Br J Dermatol 2000;142:804-7.
Pimenta S, Bernardes M, Bernardo A, Brito I, Castro L, Simões-Ventura F, et al.
Intravenous immune globulins to treat eosinophilic fasciitis: A case report. Joint Bone Spine 2009;76:572-4.
Bonnotte B, Chauffert B, Caillot D, Martin F, Lorcerie B. Successful treatment with antithymocyte globulin and cyclosporin A of a severe aplastic anaemia associated with an eosinophilic fasciitis. Br J Rheumatol 1998;37:1358-9.
Khanna D, Agrawal H, Clements PJ. Infliximab may be effective in the treatment of steroid-resistant eosinophilic fasciitis: Report of three cases. Rheumatology (Oxford) 2010;49:1184-8.
Scheinberg M, Hamerschlak N, Kutner JM, Ribeiro AA, Ferreira E, Goldenberg J, et al.
Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004). Clin Exp Rheumatol 2006;24:65-9.
Endo Y, Tamura A, Matsushima Y, Iwasaki T, Hasegawa M, Nagai Y, et al.
Eosinophilic fasciitis: Report of two cases and a systematic review of the literature dealing with clinical variables that predict outcome. Clin Rheumatol 2007;26:1445-51.