Eosinophilic fasciitis (EF) is a rare connective tissue disease which closely resembles other scleroderma-like diseases. EF presents with painful swelling and hardening of the distal limbs and is often preceded by a history of strenuous exercise. The marked fascial fibrosis in EF can lead to joint contractures and causes significant morbidity in affected individuals. The authors present a rare case of EF presenting as an ichthyosiform eruption of the bilateral ankles with gradual improvement after the implementation of oral prednisone, hydroxychloroquine, and methotrexate.

© 2023 The Author(s). Published by S. Karger AG, Basel

Eosinophilic fasciitis (EF) is a rare connective tissue disease which closely resembles other scleroderma-like diseases. EF presents with painful swelling and hardening of the distal limbs and is often preceded by a history of strenuous exercise. The marked fascial fibrosis in EF can lead to joint contractures and causes significant morbidity in affected individuals. The authors present a rare case of EF presenting as an ichthyosiform eruption of the bilateral ankles with gradual improvement after the implementation of oral prednisone, hydroxychloroquine, and methotrexate (MTX). The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000529477).

The patient is a 54-year-old female with no significant past medical history who presented to the dermatology clinic complaining of worsening tightness to her bilateral hands and feet with predominant scaling to the dorsal ankles. On physical examination, she had symmetrically distributed erythematous to red-brown, shiny plaques with woody induration to the distal dorsal forearms extending to the dorsal hands and distal lower legs extending to the dorsal feet with thickened scale to the dorsal ankles (Fig. 1, 2). There was a significant decrease in the range of motion (ROM) of her hands, wrists, and ankles. Review of systems was negative for joint pain, morning stiffness, dysphagia, Raynaud’s phenomenon, chest pain, cough, headaches, recent weight loss, or dry mouth/eyes. She denied daily medications outside of over-the-counter vitamins or recent strenuous activity. There was no family history of autoimmune disease. She was previously evaluated by podiatry who started her on topical clotrimazole/betamethasone cream without improvement. A 4-mm punch biopsy was taken from the right forearm with the differential diagnosis including systemic sclerosis versus diffuse/inflammatory morphea versus EF. Initial biopsy results demonstrated sclerosing changes but were otherwise inconclusive. Thus, an incisional biopsy from the left forearm was performed. Histopathologic examination demonstrated a relatively normal appearance in the superficial dermis and sclerosis of the reticular dermis and the septum of the subcutaneous fat and fascia. A dense mixed inflammatory cell infiltrate is seen in the sclerotic fascia containing lymphocytes, numerous plasma cells, along with focal scattered eosinophils (Fig. 3). Inflammatory markers including ESR and CRP were elevated. Complements C3/C4, anti-CCP, anti-RNP, anti-Smith, anti-SCL-70, anti-SSA, anti-SSB, and RF were negative. CBC, CMP, SPEP, and UPEP were unremarkable. The patient was initially started on 40 mg of prednisone with calcium and vitamin D supplementation, followed by 200 mg of hydroxychloroquine QD 2 weeks later. After baseline examination by an ophthalmologist 6 weeks later, her hydroxychloroquine was increased to 200 mg BID. After 4 months of therapy with prednisone and hydroxychloroquine, tapering doses of prednisone led to evidence of relapse including fibrotic changes extending to the proximal forearms. Consequently, MTX was initiated at 15 mg once weekly with 1 mg of folic acid given on days not taking MTX. After 2 months, her MTX was increased to 20 mg followed by 25 mg 1 month later. Her ROM of her hands and feet gradually improved while on therapy. However, the patient had experienced side effects after 3 months of therapy with 25 mg of MTX, so her dose was decreased back to 20 mg. Her alopecia resolved at the lower dose and the patient’s prednisone was successfully tapered off, 11 months after initiating prednisone therapy. The patient regained full ROM of her hands with softening of the tissues of the upper extremities. The ROM of the patient’s ankles/feet has improved, but not to the extent of her hands, and the patient still has reduced ROM with some fibrotic changes on the dorsal feet. Additionally, minimal scale can be appreciated inferior to the medial and lateral malleolus. To date, the patient continues taking 200 mg hydroxychloroquine BID and 20 mg MTX once weekly without prednisone over the past 9 months. The authors plan to slowly taper the MTX and monitor for disease relapse.

Clinical images. a Symmetrically distributed erythematous to red-brown, shiny plaques with woody induration to the distal forearms extending to the dorsal hands. b Reduced range of motion when attempting to make a fist.

Clinical image. Symmetrically distributed erythematous to red-brown, shiny plaques with woody induration to the distal lower legs extending to the dorsal feet with thickened overlying scale.

Eosinophilic fasciitis (H&E stain, ×10 magnification). Dense mixed inflammatory cell infiltrate is seen in the sclerotic fascia containing lymphocytes, numerous plasma cells, along with focal scattered eosinophils.

In 1974, Lawrence Shulman published “diffuse fasciitis with hypergammaglobulinemia and eosinophilia,” in which he described 2 patients with a scleroderma-like hardening of the distal limbs after a history of strenuous exercise 1–2 weeks prior to onset of symptoms [1]. The term EF has since been used to describe this rare connective tissue disorder characterized by painful swelling and hardening of the skin [2], leading to joint contracture and significant morbidity [3]. In the early stages of EF, symptoms present as a subacute onset of symmetrical edema and erythema in the distal extremities [4]. These lesions may spread to the proximal extremities and trunk, but never involve the face or distal fingers [5, 6]. As the disease progresses, edema is replaced by fascial fibrosis in the mid to deep dermis and subcutaneous tissue [3, 6]. Clinical evidence of the “groove sign” appears as the deep fascia becomes tethered to the underlying fascia and muscle, creating a linear depression which closely parallels the underlying superficial veins [5]. Hair follicles become prominent as depression occurs, leading to a peau d’orange “cobblestone” appearance [3, 5]. Tightening of the forearm tendons may also lead to the nonspecific “prayer sign” [6]. In 50–67% of cases, joint contracture leads to decreased ROM and neuropathies such as carpal tunnel syndrome that may be present in 25% of patients [6, 7]. Patients often also experience systemic symptoms such as fever and malaise [5].

The etiology of EF remains unclear. A history of strenuous exercise, trauma, or intense physical exertion days to 1–2 weeks prior to the onset of symptoms was reported in 28–46% of patients [8]. Other inciting factors include autoimmune diseases (Sjogren’s syndrome, systemic lupus erythematosus, Hashimoto and Graves’ disease, primary biliary cirrhosis, and hemolytic anemia [2]) and pharmaceuticals (ramipril, phenytoin, subcutaneous heparin, statins), although the majority of cases are considered idiopathic [3]. Half of patients experience sudden onset, while others progress more gradually over time [5].

Clinical, imaging, histological, and laboratory findings are relied on for diagnosis of EF. The gold standard of diagnosis is a full-thickness skin biopsy, which includes muscle and fascia [6]. Elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and C-reactive protein are often present [9]. Biopsy results show hyalinized fascial layers [9], increased 2–15 times in thickness, firmly adhered to the underlying skeletal muscle [2]. Additional findings of plasma cell, lymphocyte, and eosinophilic infiltrate are often seen; however, eosinophils are only present in 63–93% of patients, do not correlate disease severity, and are not required for diagnosis [7, 9]. Magnetic resonance imaging has also become increasingly utilized to augment diagnostic capabilities [6]; however, no definitive diagnostic criteria currently exist [2].

EF closely resembles other scleroderma-like diseases and may be difficult to differentiate from other conditions such as systemic and localized scleroderma [6]. Histologically, localized scleroderma exhibits dermal fibrosis, whereas EF displays marked fascial fibrosis [5]. These findings may be complicated by disease progression, however, as localized scleroderma can evolve to include the fascia, and EF can involve the dermis. Additionally, skin biopsies of scleroderma indicate no inflammation [3, 5]. Diagnosis based on histological findings is often inconclusive; therefore, clinical features are relied on for differentiation [5]. Unlike EF, systemic scleroderma may show involvement of distal fingers, nailfold capillary changes, digital ulcers, and/or Raynaud’s phenomenon [3]. Localized scleroderma is slowly progressive and not associated with significant eosinophilia [3]; however, eosinophilia is not seen in many cases of EF [5].

Spontaneous remission is possible; however, systemic corticosteroids are considered the mainstay of treatment [3, 6]. Oral prednisone 0.5–1.0 mg/kg/day tapered over the course of weeks to months was shown to lead to partial or complete remission in 70% of patients [10]. For refractory cases, additional immunosuppressive agents such as MTX 15–25 mg once per week may be used and are especially utilized in patients with morphea-like skin lesions [2, 9]. One retrospective case study demonstrated cotreatment with corticosteroids, and MTX led to higher rates of disease resolution when compared to the traditional, stepwise treatment [8]. Alternatively, a recent study showed initial treatment with pulses of IV methylprednisolone for 3 days before beginning oral prednisone treatment was linked to better outcomes and decreased necessity for further MTX treatment. Treatment of EF remains discretionary, as no large-scale randomized control trials have been conducted. Current treatment is based on retrospective case studies and small case series and reports [10]. Improvement of symptoms can take months, and no measurable clinical parameters currently exist to indicate definitive resolution of EF. In 1 study evaluating patient outcomes, all 35 participants experienced long-term sequelae, most commonly decreased ROM in affected joints and residual cutaneous fibrosis [6].

This case report was reviewed and approved by Beaumont Health Research Review Committee on March 15, 2022. Written informed consent was obtained from the participant for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

No funding sources.

Nedyalko N. Ivanov provided substantial contributions to the drafting and revision of the manuscript. Ashley Garvin provided substantial contributions to survey design and drafting and revision of the manuscript. Michael J. Mahon and Sean Stephenson revised the article critically for important intellectual content and gave final approval for the article to be published. All authors agreed to be accountable for all aspects of the work related to the accuracy or integrity of any part of the work appropriately investigated and resolved.

All data reported in this case study are included in this manuscript and its online supplementary material. Further inquiries can be directed to the corresponding author.

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