Atypical Presentation of Eosinophilic Fasciitis with Pitting Edema

Abstract

Eosinophilic fasciitis (EF) is a rare condition involving inflammation of the fascia and peripheral eosinophilia of unknown etiology leading to tissue fibrosis. Clinical presentation includes peripheral eosinophilia, symmetrical skin thickening with subcutaneous tissue induration of the extremities and rashes developing acutely over a period of days to weeks. An unusual feature of EF is the presence of symmetric pitting edema presumed to be secondary to vascular leakage. This is a case of eosinophilic fasciitis presenting in atypical fashion with pitting peripheral edema in addition to the classic symptoms.

Introduction

Eosinophilic fasciitis (EF) is a rare condition involving inflammation of the fascia and peripheral eosinophilia of unknown etiology leading to tissue fibrosis.^1–3 As of 2007, there are approximately 250 cases reported in the medical literature.⁴ Clinical presentation includes peripheral eosinophilia, symmetrical skin thickening with subcutaneous tissue induration of the extremities and rashes developing acutely over a period of days to weeks.^5–7 The absence of Raynaud's phenomenon and internal organ involvement distinguishes this condition from collagen vascular disease such as scleroderma.^1,8–11 An unusual feature of EF is the presence of symmetric pitting edema presumed to be secondary to vascular leakage.^3,6,8 Full-thickness skin biopsy showing perivascular inflammation composed of lymphocytes, plasma cells, and eosinophils in the subcutis and fascia or characteristic MRI findings are required to confirm the diagnosis.^8,12,13 This is a case of an atypical presentation of eosinophilic fasciitis with symmetric pitting edema.

Case Report

DM is a 64-year-old man with a chief complaint of generalized arthralgia and stiffness, and numbness, with symmetric pitting edema of all of his extremities. He denied fever, GI symptoms, unexplained weight loss, rash, hives, angioedema, adenopathy, and had had no history of atopic disease. PMHx included Hx of skin cancer and paroxysmal atrial fibrillation controlled on Diltiazem. He was not taking any herbal medicine. The general physical examination was remarkable for 2+ pitting edema of bilateral lower extremities (Figure 1), and mild edema of the bilateral forearms. There was no jugular venous congestion, hepatomegaly, or pre-sacral edema. Musculoskeletal and cardiopulmonary examinations were normal.

Figure 1.

Patient's right lower extremity demonstrates 2+ pitting edema.

Initial laboratory values included a complete blood count remarkable for 69% eosinophilia (9,900 Eosinophil count), normal serum levels of electrolytes, creatinine, alkaline phosphatase, and aminotransferases. The serum albumin level was decreased at 3.6 gm/dl without proteinuria on UA. ESR, RF, ANA, ANCA, and IgE were unremarkable. Parasitic infection studies were negative. Bone marrow biopsy showed no evidence of malignancy. Analysis of a full-thickness skin biopsy while on systemic steroids revealed chronic inflammation of the fascia with scattered eosinophils consistent with partially treated Eosinophilic fasciitis (Figure 2, Figure 3).

Figure 2.

A full thickness biopsy specimen from the patient in low power of magnification revealed chronic inflammation of the fascia with marked cellular inflammation.

Figure 3.

A full thickness biopsy specimen from the patient in high power of magnification revealed chronic inflammation of the fascia involving lymphocytic infiltration and scattered eosinophils consistent with partially treated Eosinophilic fasciitis.

After initiating therapy with oral prednisone, the patient reported marked decrease in peripheral edema, joint stiffness and labs indicated normalization of peripheral eosinophil counts. He remained clinically improved with complete remission of pitting edema and joint stiffness on tapering daily doses of prednisone to 15 mg, below which symptoms returned. The patient remains clinically stable and is currently on titrating dose of cyclosporine and prednisone of 3.5 mg/day.

Discussion

The etiology of EF is unknown. Most cases are idiopathic. Some cases are associated with strenuous exercise, trauma, initiation of hemodialysis, infection with Borrelia burgdorferi, radiation therapy, hematologic disorders, and Graft-versus-host disease.^{1,3,8,9,14–17} Some drugs including simvastatin, atorvastatin, and phenytoin have been implicated.^18–20

The pathophysiology of EF is unclear but it is postulated to involve a proinflammatory and fibrogenic cytokine response including IL-5, IFN-gamma, and TGF-beta resulting in an inflammatory cell infiltration that dysregulates production of extracellular matrix proteins and increases collagen production by fibroblasts, which ultimately leads to progressive fibrosis of affected tissues.^21–25

The differential diagnosis of symmetric pitting edema includes conditions associated with low oncotic pressure or venous insufficiency and congestive heart failure.⁸ Other differential diagnoses to consider with similar presentation accompanied by peripheral eosinophilia include eosinophilia-myalgia syndrome, localized fibrosing disorders, scleroderma, and systemic sclerosis.

Full-thickness biopsy including skin, subcutaneous fat, fascia and muscle of the affected area is the essential study for diagnosing eosinophilic fasciitis especially in an atypical presentation.²⁶ In EF, perivascular eosinophilic inflammation is predominantly in the subcutis and deep fascia.⁸ In contrast, scleroderma shows signs of inflammation, collagen deposition, and fibrosis more in the superficial dermis.⁸

In our patient, bone marrow biopsy results indicated no leukemic etiology and further workup showed no evidence of nephrotic syndrome, parasitic infection, or collagen vascular disease. Skin biopsy confirmed the presence of chronic fascial inflammation with scattered eosinophils consistent with the patient being partially treated on systemic corticosteroids.

Therapy using corticosteroids at 1mg/kg/day is considered first line therapy based on consensus.^3,9,27 Since relapses can occur, and many patients do not respond to corticosteroids, other immunosuppressive or immunomodulatory agents are required for some patients to obtain a therapeutic response and/or used as steroid-sparing agents.^3,10 Alternative agents including cyclosporine, dapsone, hydroxychloroquine, azathioprine, and methotrexate have been used as steroid sparing or disease modifying therapy.^{8,10,28,29,30}

Conclusion

This is a case of Eosinophilic fasciitis presenting in atypical fashion with pitting peripheral edema in addition to the classic symptoms of joint stiffness and peripheral eosinophilia on CBC. Bone marrow biopsy results indicated no leukemic etiology and further workup showed no evidence of nephrotic syndrome, parasitic infection, or collagen vascular disease. Skin biopsy confirmed the presence of chronic fascial inflammation with scattered eosinophils consistent with the patient being partially treated on systemic corticosteroids. Therapy using corticosteroids at 1mg/kg per day is considered first line therapy based on consensus.^3,9,27 Alternative agents including cyclosporine, dapsone, hydroxychloroquine, azathioprine, and methotrexate have been used as steroid sparing or disease modifying therapy though EF often regresses spontaneously.^{8,10,28,29,30} To date the patient remains on oral prednisone and cyclosporine with improved symptom control and normalized peripheral eosinophil counts.

Conflict of Interest

None of the authors identify any conflict of interest.