Abstract
Eosinophilic fasciitis (EF) is a rare fibrosing disorder caused by an autoimmune response to an unknown trigger. Many possible triggers have been suggested including strenuous exercise, drug or chemical exposure, and preceding infection. We present a case of a female patient, age 69 years, who developed EF following SARS-CoV-2 infection. There have been several advances in the diagnosis and management of EF since it was first described 50 years ago. EF is a mimic of scleroderma, but key clinical features can be used to differentiate between the two diagnoses. Laboratory abnormalities include eosinophilia, elevated inflammatory markers, and hypergammaglobulinemia. A full thickness biopsy of the skin including muscle and fascia is recommended to confirm the diagnosis. Imaging modalities such as ultrasound and magnetic resonance imaging have been increasingly used in the diagnosis and follow-up of EF. Corticosteroids remain the first line in treatment of EF. Combination of steroids and methotrexate have shown the best possible outcome. Early diagnosis is important for better treatment response.
Eosinophilic fasciitis (EF) is a rare fibrosing disorder caused by an autoimmune response to an unknown trigger. Many possible triggers have been suggested including strenuous exercise, drug or chemical exposure, and preceding infection. We present a case of a female patient, age 69 years, who developed EF following SARS-CoV 2 infection. There have been several advances in the diagnosis and management of EF since it was first described 50 years ago. EF is a mimic of scleroderma, but key clinical features can be used to differentiate between the two diagnoses (Table 1). Laboratory abnormalities include eosinophilia, elevated inflammatory markers and hypergammaglobulinemia. A full thickness biopsy of the skin including muscle and fascia is recommended to confirm the diagnosis. Imaging modalities such as ultrasound and magnetic resonance imaging have been increasingly used in the diagnosis and follow up of EF. Corticosteroids remain the first line in treatment of EF. Combination of steroids and methotrexate have shown the best possible outcome. Early diagnosis is important for better treatment response.
Differences between eosinophilic fasciitis and systemic sclerosis
Case Presentation
A female patient, age 69 years, with a past medical history of osteoarthritis, osteoporosis, fibromyalgia, and hypothyroidism presented with concern about skin thickening and stiffness in the upper arms, chest, and neck. She stated that her skin was hard and bumpy and spreading down the arm. She had COVID infection about a month before her symptoms started. She denied night sweats or fever. She denied any sick contacts, travelling, cough, sputum production, photosensitivity, ulcers in the mouth or nose, no discoloration of digits with exposure to cold, digital ulcer, or dysphagia. She denied history of tick bite. She denied history of significant exercise.
She had tightness of the skin with firm induration of the skin of upper chest, neck, and bilateral medial upper arms (Figure 1). There was no erythema or warmth of the skin. No sclerodactyly or telangiectasia was noted of the hands or face. Joint examination was normal. Physical examination was otherwise unremarkable.
Right upper arm with peau d’orange appearance and Groove sign.
Her complete blood cell count showed hemoglobin of 7.57 mmol/L, white cell count 6.5 × 109/L, and platelet count of 267 × 109/L. She had peripheral eosinophilia at 11% with absolute eosinophil count 0.7 × 109/L. The sedimentation rate was elevated at 32 mm/hour. Gamma globulin was normal (13.5 g/L), and IgA was normal (16.01micromol/L). Her C3 was elevated at 1.63 g/L, and C4 was normal at 0.28 g/L. She was noted to have minimally elevated ANA 1:80 speckled pattern. The ENA, including Scl70 and anti-RNP antibodies, were negative. Rheumatoid factor and anti-CCP antibodies were negative. Thyroid function tests were normal. Chest radiograph was normal. Mammogram did not reveal any evidence of adenopathy or breast cancer, and colonoscopy was also unremarkable. She has a history of esophageal stricture, which required dilatation.
Skin biopsy showed a preserved dermis and epidermis with predominant involvement of the deep subcutis and fascia (Figure 2) with chronic inflammatory cells, including lymphocytes, histiocytes, and focal area of predominant eosinophils (Figure 3). There were prominent sclerotic changes involving the subcutaneous tissue and fascia (Figure 4). These findings were consistent with eosinophilic fasciitis.
Low power image showing normal epidermis and dermis with increased widening/thickening of deep subcutaneous septa (Hematoxylin and Eosin, 2×).
High power image showing a mixture of inflammatory cells, including eosinophils, lymphocytes, neutrophils. There is prominent degranulation of eosinophils with “flame figures” along the base of the biopsy, likely indicating dense eosinophilic inflammation of fascia. (Hematoxylin and Eosin, 40×).
Deep subcutaneous inflammation and hyalinized collagen of septa along the base of the deep excisional biopsy. (Hematoxylin and Eosin, 10×).
The patient was treated with a tapering dose of prednisone starting at 60 mg daily and sulfamethoxazole–trimethoprim for pneumocystis pneumonia prophylaxis. She was started on methotrexate 15 mg oral weekly and folic acid daily.
Her methotrexate was on hold for few weeks when she developed herpes zoster ophthalmicus. She was started on hydroxychloroquine 5 mg/kg daily while the methotrexate was on hold. She was restarted on methotrexate when her eye infection resolved. During a follow-up visit about 2 years after initial presentation, the induration in the upper arms and chest had completely resolved. Inflammatory markers and eosinophil count normalized.
Discussion
Eosinophilic fasciitis is a rare connective tissue disorder that was first described by Dr. Lawrence Shulman in 1974.1 Eosinophilic fasciitis causes pseudo cellulite, or peau d’orange, appearance of the skin.2 The exact cause of eosinophilic fasciitis is unknown, although it is presumed to be an autoimmune process.3 Many possible triggers have been suggested. The most commonly described trigger is a history of strenuous exercise or physical labor4 or a history of traumatic injury, such as bruising shortly prior to the onset of the disease. Additionally, several studies have described eosinophilic fasciitis associated with the use of various drugs, including some statins, phenytoin, ramipril, natalizumab, subcutaneous heparin and influenza vaccination, or following exposure to chemicals such as trichloroethylene and trichloroethane.5,6 It has also been suggested that some cases may be related to infection with Borrelia burgdorferi or mycoplasma. Other cases have occurred following hemodialysis or radiotherapy.6 Certain chemicals such as tryptophan could act as a trigger for the development of eosinophilic fasciitis. There have been several case reports that have shown an association with checkpoint inhibitors.7,8 Eosinophilic fasciitis has been described after COVID vaccination.9 There have been very few recent case reports with eosinophilic fasciitis following COVID infection.10,11
The disease process is characterized by changes that promote proliferation of fibrous tissue and prevents its breakdown. Dermal fibroblasts in EF demonstrate increased expression of type I collagen and fibronectin. There is also increased expression of connective tissue growth factor genes and fibrosis-related cytokines like transforming growth factor beta 1 (TGF-β1). Increased production of tissue inhibitor of metalloproteinase-1 (TIMP-1) decreases activity of enzymes which break down collagen.3,4
The distal limbs can be affected by EF, presenting initially with swelling, redness, and pain, followed by progressive fibrosis that develops into plate-like hardness. Involvement of the limbs is typically symmetrical and circumferential. The skin of the affected limbs takes on a peau d’orange (orange peel) appearance.4,5 Systemic symptoms of fever and generalized fatigue are also often seen. As the disease progresses, fibrosis in the limbs may result in joint contractures and nerve entrapment. For example, flexion contracture of the fingers and carpal tunnel syndrome can be seen with fibrosis of the forearms.4 A classic physical examination finding of eosinophilic fasciitis is the Groove sign,12,13 in which depressions can be seen along the course of superficial veins. Fibrosis affects the muscular fascia and subcutaneous connective tissue but spares the dermis and epidermis. When an affected limb is elevated, the superficial skin layers are pulled inward as venous pressure drops, causing the groove sign to become more prominent.
A full thickness biopsy of the skin containing muscle and fascia is recommended for diagnosis. Histologic examination demonstrates fibrotic changes to the subcutaneous fat and connective tissue. The characteristic finding is marked hypertrophy of the fascia with infiltration of inflammatory cells, predominantly lymphocytes and plasma cells.3 Eosinophilic infiltration of the fascia is seen only in the early acute stage of the disease and is not necessary for diagnosis.6
Laboratory abnormalities include peripheral eosinophilia, elevated inflammatory markers including sedimentation rate and C reactive protein, and hypergammaglobulinemia. Eosinophilia is the most typical feature, but it is not necessary for diagnosis. Eosinophilia is present during initial stages of the illness and responds well to corticosteroid therapy.
Magnetic resonance imaging and ultrasound could be helpful in localizing the site of the biopsy.14 Magnetic resonance imaging shows hyperintense fascia on T2 weighted images.4 Skin ultrasound is a useful modality for evaluation and monitoring eosinophilic fasciitis.7,15 Tissue compressibility measured with ultrasound was lower in EF compared to other fibrosing disorders.16
There have been no established treatment guidelines due to the rarity of the disease and lack of randomized control trials. Corticosteroids are the first line of therapy.17 Prompt treatment is important for the best possible outcome. A combination of corticosteroids with methotrexate has shown the best possible outcome.7,17,18 Mycophenolate has been shown to be effective as a steroid sparing agent.2,19 Hydroxychloroquine may be beneficial in the treatment of eosinophilic fasciitis.20 Rituximab9,21 and intravenous immunoglobulins have been used for treatment of resistant cases of eosinophilic fasciitis. Physical therapy is important for patients who develop joint contractures.
There are no universally accepted criteria for the diagnosis of eosinophilic fasciitis, since the disease is exceedingly rare. Eosinophilic fasciitis is a scleroderma mimic. The main clinical features that distinguish eosinophilic fasciitis from scleroderma are listed in Table 1.
Cellulitis was excluded in our patient due to bilateral symmetrical involvement of both upper extremities and absence of signs and symptoms of infection. Other differential diagnoses considered were morphea and scleroderma. The presence of eosinophilia and biopsy evidence of eosinophilic infiltration confirmed the diagnosis of eosinophilic fasciitis. Scleroderma causes hardening of the skin due to excessive mucin deposition in the dermis. Our patient had an intact dermis with no mucin deposition, which ruled out scleroderma.
Our patient developed symptoms about 1 month after she developed a COVID infection. It is possible that the COVID infection triggered an autoimmune response. There has been a previously reported case of eosinophilic fasciitis induced by COVID, which the authors claim to be the first case.10 More recently, a case series of three cases of eosinophilic fasciitis secondary to COVID-19 has been published (Table 2).11
Previous case reports on eosinophilic fasciitis after COVID infection
Footnotes
Disclosures: The authors have not reported financial support or conflicts of interest related to this work.
- Received January 28, 2024.
- Revision received May 2, 2025.
- Accepted May 6, 2025.
References
- 1.↵Shulman LE. Diffuse fasciitis with hypergammaglobulinemia and eosinophilia: a new syndrome?. J Rheumatol. 1984;11(5):569-570.
- 2.↵Shaw KS, Vleugels RA. Eosinophilic Fasciitis. N Engl J Med. 2023;388(19):e65. doi:10.1056/NEJMicm2212023
- 3.↵Fett N, Arthur M. Eosinophilic fasciitis: Current concepts. Clin Dermatol. 2018;36(4):487-497. doi:10.1016/j.clindermatol.2018.04.006
- 4.↵Mazori DR, Femia AN, Vleugels RA. Eosinophilic Fasciitis: an Updated Review on Diagnosis and Treatment. Curr Rheumatol Rep. 2017;19(12):74. Published 2017 Nov 4. doi:10.1007/s11926-017-0700-6.
- 5.↵Ihn H. Eosinophilic fasciitis: From pathophysiology to treatment. Allergol Int. 2019;68(4):437-439. doi:10.1016/j.alit.2019.03.001
- 6.↵Jinnin M, Yamamoto T, Asano Y, Diagnostic criteria, severity classification and guidelines of eosinophilic fasciitis. J Dermatol. 2018;45(8):881-890. doi:10.1111/1346-8138.14160
- 7↵Shinozaki A, Hayashi S, Hongo T, Okamoto M, Ishikawa S, Igawa K. Efficacy of methotrexate for steroid-resistant eosinophilic fasciitis with delayed start of treatment: a case report. Int J Dermatol. 2023;62(2):e67-e68. doi:10.1111/ijd.16299
- 8.↵Chan KK, Magro C, Shoushtari A, Eosinophilic Fasciitis Following Checkpoint Inhibitor Therapy: Four Cases and a Review of Literature. Oncologist. 2020;25(2):140-149. doi:10.1634/theoncologist.2019-0508
- 9.↵Antuña VL, Puchades F, Tapial JM, Ribelles JC, Sanz F, Tamarit JJ. Eosinophilic fasciitis following SARS-CoV-2 vaccination. JAAD Case Rep. 2023;36:11-14. doi:10.1016/j.jdcr.2022.11.038
- 10.↵Boussaa H, Kamoun M, Miladi S, The first case of SARS-CoV-2-induced eosinophilic fasciitis. Mod Rheumatol Case Rep. 2023;8(1):224-228. doi:10.1093/mrcr/rxad063
- 11.↵Li Y, Kong HE, Cheeley J. Eosinophilic fasciitis following COVID-19: A case series of 3 patients. JAAD Case Rep. 2023;44:6-10. Published 2023 Dec 6. doi:10.1016/j.jdcr.2023.11.019
- 12.↵Camard M, Maisonobe T, Flamarion E. The groove sign in eosinophilic fasciitis. Clin Rheumatol. 2022;41(12):3919-3920. doi:10.1007/s10067-022-06311-y
- 13.↵Pinal-Fernandez I, Callejas-Moraga EL, Roade-Tato ML, Simeon-Aznar CP. Groove sign in eosinophilic fasciitis [published correction appears in Lancet. 2014 Nov 15;384(9956):1748]. Lancet. 2014;384(9956):1774. doi:10.1016/S0140-6736(14)60526-2
- 14.↵Daniel A, Eugénio G, Serra S, Malcata A, Salvador MJ. Diagnostic utility of Magnetic Ressonance Imaging in Eosinophilic Fasciitis. Diagnostic utility of Magnetic Ressonance Imaging in Eosinophilic Fasciitis. Acta Reumatol Port. 2017;42(3):271-272.
- 15.↵Pousa-Martínez M, Ginarte M, Suárez-Peñaranda JM, Vázquez-Veiga H. Skin ultrasound is a useful tool for evaluating and monitoring eosinophilic fasciitis. Int J Dermatol. 2018;57(6):743-745. doi:10.1111/ijd.13986
- 16.↵Kissin EY, Garg A, Grayson PC, Ultrasound assessment of subcutaneous compressibility: a potential adjunctive diagnostic tool in eosinophilic fasciitis. J Clin Rheumatol. 2013;19(7):382-385. doi:10.1097/RHU.0000000000000020
- 17.↵Wright NA, Mazori DR, Patel M, Merola JF, Femia AN, Vleugels RA. Epidemiology and Treatment of Eosinophilic Fasciitis: An Analysis of 63 Patients From 3 Tertiary Care Centers. JAMA Dermatol. 2016;152(1):97-99. doi:10.1001/jamadermatol.2015.3648
- 18.↵Pinal-Fernandez I, Selva-O’ Callaghan A, Grau JM. Diagnosis and classification of eosinophilic fasciitis. Autoimmun Rev. 2014;13(4-5):379-382. doi:10.1016/j.autrev.2014.01.019
- 19.↵Loupasakis K, Derk CT. Eosinophilic fasciitis in a pediatric patient. J Clin Rheumatol. 2010;16(3):129-131. doi:10.1097/RHU.0b013e3181d56f73
- 20.↵Fett N, Arthur M. Eosinophilic fasciitis: Current concepts. Clin Dermatol. 2018;36(4):487-497. doi:10.1016/j.clindermatol.2018.04.006
- 21.↵Kougkas N, Bertsias G, Papalopoulos I, Repa A, Sidiropoulos P, Avgoustidis N. Rituximab for refractory eosinophilic fasciitis: a case series with long-term follow-up and literature review. Rheumatol Int. 2021;41(10):1833-1837. doi:10.1007/s00296-021-04887-3
- 22.↵Waters C, Doody O, Ambrose N, Torregiani W. Eosinophilic Fasciitis Following Infection With COVID-19. Ir Med J. 2024;117(9):1032
