Clinical And Pathological Research For Eosinophilic Fasciitis

Background and objectivesEosinophilic fasciitis (EF) is a rare immune-allergic disorder characterized by scleroderma-like lesions of deep fascia and skin of the upper and lower extremities. The detailed mechanisms underlying the etiology and pathogenesis of EF remain to be clearly illuminated. Peripheral blood eosinophilia, hypergammaglobulinemia and elevated erythrocyte sedimentation rate (ESR) are principle findings of laboratory investigation with clinical implications. Typical pathological evidence showing deep fascia inflammatory infiltration and thickening by muscle and fascia biopsy is crucial in establishing the diagnosis. Magnetic Resonance Imaging (MRI) is currently applied as the optimal imaging modality for non-invasive diagnostic purpose and evidence of affected fascia of hyper-intense signal strength on T2-weighted images facilitates the confirmation of EF and decision of accurate muscle biopsy sites. Since the first delineation in 1974 by Shulman, there has been no consensus regarding the diagnostic criterion for EF to date. The definitive diagnosis needs to be confirmed by muscle biopsy with the aid of a comprehensive analysis of clinical, laboratory and imaging evidence. EF is easily misdiagnosed as other diseases due to its clinical rarity and diverse manifestations and atypical examination findings. Specifically, systemic scleroderma (SSc) is to a large extent akin to EF in regards to clinical manifestations and laboratory and imaging findings and it should be therefore distinguished and excluded with caution from EF.In the report, we described three cases of EF and one case of early SSc in details and aimed to further summarize and discuss the clinical features, pathological changes and treatment strategies of EF, with an emphasis on the differential diagnosis with SSc.Materials and methodsBetween September 2013 and December 2014, three patients with EF admitted to the Department of Neurology, Qilu Hospital affiliated to Shandong University were consecutively recruited and underwent detailed history taking, comprehensive physical examination of nervous system, corresponding laboratory and imaging investigation (chest computed tomography [CT], echocardiography and muscle magnetic resonance imaging [MRI]), electromyography (EMG) and muscle and fascia biopsy. The definite diagnosis refers to the criterion proposed by Fernandez and his colleagues. After confirmation, all the three cases underwent systematic treatment and were followed up regularly on purpose of status monitoring, repetitive examinations and therapeutic regimen adjustment. All the three cases received a clinical follow-up for at least half a year. Meanwhile, the report enrolled one case with SSc for further discussion on differential diagnosis.Results(1) The three patients were all male with a mean age of 24 at onset. A history of excessive physical activity was traced in two cases and trauma and bone fracture history was traced in one case. In all the three patients, the symptoms began from their legs and were manifested as symmetrical swelling of the legs and pressing or motion myalgia of the affected muscles. The swelling then vanished and developed into induration of bilateral calf muscles and the disease gradually extended to upper limbs and caused induration of muscle and skin of bilateral forearms. Movement limitations of the affected joints mostly involved carpal, metacarpophalangeal and knee joints. Physical examination of nervous system revealed the pray sign in all the three patients and groove sign in one patient and peau d’orange was not observed. In one case muscle strength 5- grade was found in the affected muscles and in all the three patients symmetrical weakened or disappeared tendinous reflexes were detected. The rest examinations were normal.(2) Laboratory examinations demonstrated peripheral blood eosinophilia and elevated ESR, C reactive protein (CRP) and Immunoglobulin E (IgE) in all the three patients. Antinuclear antibodies were tested positive in low titer in one case. The rest examinations were normal.(3) All the cases received the scanning of chest CT which showed no abnormal changes. One case was scanned with MRI on calf muscles which demonstrated bilateral abnormal signal intensity underneath skin and fat layer.(4) Fascia and muscle biopsy showed fascial thickening and chronic infiltration by inflammatory cells composed of lymphocytes, histiocytes, plasma cells and eosinophils in fascia and muscular interstitial in the three cases. Muscle fibers were consistently inflamed in two cases in which regenerative and necrotic fibers were frequently observed. Immunohistochemical staining for MHC-I showed markedly enhanced staining of affected fascial and myolemma compared to normal controls.(5) In consistent with the results of fascia and muscle biopsy, EMG presented the evidence of myogenic changes in the two cases with concomitant myositis and another case was tested normal.(6) All the three patients underwent combined therapy of glucocorticoid and immunosuppressive agents. Glucocorticoid alone might normalize all the laboratory indexes but fail to relieve the symptoms or prevent the disease development. Adding immunosuppressive agents which accumulates to certain total doses led to an obvious clinical remission in all the patients. Additionally, EF patients with concomitant myositis demonstrated slower improvement and longer treatment course than the case with isolated EF.(7) Differential diagnosis of EF with early SSc:the two diseases are to a large extent similar in regards to clinical manifestations and laboratory findings. SSc should be taken into consideration if Raynaud’s phenomena, finger swelling, positive antinuclear antibodies with a high titer and multiple organ involvement are present.Conclusions(1) EF is a rare immune-allergic disorder and excessive physical activities and trauma are among the most common triggering factors. The typical clinical manifestations include symmetrical induration of skin and muscle and movement limitations of affected joints of upper and lower extremities. Besides, it is of importance to notice the Raynaud’s phenomenon,acrosclerosisand involvement of other organs and systems.(2) Except for peripheral blood eosinophilia, elevated ESR, CRP and IgE (manifested as inflammatory syndrome) are principle findings of laboratory investigation with clinical implications. MRI is currently applied as the optimal imaging modality for non-invasive diagnostic purpose, which depicts strongly enhanced signal intensity within the involved fascia on T2-weighted images. Muscle and fascia biopsy of affected skin is indispensable for a confirmed diagnosis and characteristic pathological features comprise a fascial thickening with chronic infiltration of inflammatory cells, occasionally eosnophils.(3) Muscle biopsy and EMG can be applied to confirm the EF cases with combined myositis. The clinical manifestations of EF cases with concomitant myositis are similar with those of isolated EF cases. Physical examination reveals no obvious decreased muscle strength and serum muscle enzymes are tested normal. However, EF patients with concomitant myositis showed slower improvement and longer treatment course than the case with isolated EF.(4) Glucocorticoid is the cornerstone of therapy for EF and combination therapy of glucocorticoid and immunosuppressive agents is recommended if the efficacy of glucocorticoid alone is unsatisfactory.