CASO CLÍNICO Delayed diagnosis of eosinophilic fasciitis: a case report and review of the literature Aydin E 1, Turan Y 1, Yildirim C 1, Tataro ğlu C 1, Çullu E 1, Sendur OF 1 ACTA REUMATOL PORT. 2015;40: 179-184 AbstrAct have a pathogenic role 2-9 . The onset of the symptoms usually present with acute edema and pain in the limbs, Eosinophilic fasciitis (EF) is an uncommon entity cha - followed by thickening of the dermis or subcutaneous racterized by edema, skin thickening and hyperpig - fascia and hyperpigmentation. Skin tightness may pre - mentation of extremities. Laboratory findings are vari - sent with woody induration, “peau d’orange” appear - able and may include peripheral eosinophilia, hyper - ance, and groove sign. Laboratory analysis reveals in - gammaglobulemia, and elevated acute phase reactants. creased eosinophilia, hypergammaglobulinemia and el - A full-thickness skin/fascia/muscle biopsy is the gold evated acute phase reactants in peripheral blood sam - standart for diagnosis. Since EF is an uncommon dis - ples. The definitive diagnosis is based on the presence order and the clinic presentation mimics scleroderma, of inflammatory cell infiltration in the fibrotic fascia, as it takes a long time to make definitive diagnosis. We assessed by a full-thickness skin/fascia/muscle biopsy. present a case diagnosed two years after its onset and Morphea, systemic sclerosis and eosinophilia-myalgia responded well to the treatment. We also include here - syndrome should be consi dered in the differential di - in the results of our literature survey regarding delayed agnosis. The clinical manifestations of EF may suggest diagnosis of Eosinophilic fasciitis. systemic sclerosis although patients with systemic scle - rosis have sclerodactyly, visceral organ involvement or Keywords: Case report; Delayed diagnosis; Eosino - Raynaud’s phenomenon. Today, the first line treatment philic fasciitis; Peripheral eosinophilia. is with high-dose steroids and these are effective in most of the cases. Immunosuppressant drugs and methotrex - ate (MTX) can be added in refractory cases. IntroductIon As the clinical manifestations of EF mimic systemic sclerosis, the biopsy is often neglected, resulting in dif - Eosinophilic fasciitis (EF) is a rare rheumatic disorder ficult or delayed diagnosis. In this article, we present a of unknown etiology 1. It is characterized by an inflam - case with EF who was diagnosed two years after the on - matory edema, scleroderma-like skin changes and hy - set of the symptoms and responded to the treatment perpigmentation in involved limbs 2. The disease is well. more common in females than males and diagnosed more frequently in middle age 2. Although the pathophysiology of the disease is still cAse report unknown, severe physical activity, infections ( Borrelia burgdorferi , Mycoplasma arginini ), toxicity (trichloro - A-65-year-old female patient, who had a history of two- ethylene, denatured fats, L-tryptophan), medications month-pain in her left arm, was admitted to our out - (statins, lansoprazole, phenytoin), hematological di - patient clinic. She had complained about a painless seases (lymphoma, leukemia, multiple myeloma, aplas - swelling and stiffness in her left fo rearm for two years, tic anemia, pernicious anemia) have been suggested to accompanied by subsequent pain. The patient visited our outpatient clinic with the complaint of increasing pain lasting for two months. The history of the patient 1. Department of Physical and Rehabilitation, Adnan Menderes revealed hypertension. Physical examination showed University Hospital non pitting edema and stiffness beginning from the left ÓRgÃO OfICIAL DA SOCIEDADE PORTUgUESA DE REUMATOLOgIA 179 DelayeD Diagnosis of eosinophilic fasciitis: a case report anD review of the literature A FIGure 1. Non pitting edema and stiffness beginning from the left elbow to the wrist elbow to the wrist (Figure 1). There was a groove sign b between muscle groups. Dorsiflexion and palmar flex - ion of the left wrist was slightly limited and painful. Neurological examination was normal. The visual ana - logue scale (VAS) score for pain was 9 cm. Laboratory analysis showed an erythrocyte sedimentation rate (ESR) of 31 mm/h, C-reactive protein (CRP) of 5.23 mg/L, rheumatoid factor (RF) (-), anti-nuclear anti - body (ANA) (-), anti-smooth muscle antibody (ASMA) (-), anti-mitochondrial antibody (AMA) (-), and nor - mal complete blood count (CBC), routine biochemi - cal tests, and hepatic biomarkers. Serum IgE level was slightly over the borderline. Abdo minal ultrasound and echocardiography demonstra ted normal findings. FIGure 2. Fibrocollagenous inflammatory cells consisting of Magnetic resonance imaging (MRI) of the left forearm lymphocytes in connective tissue and fat tissue. (H-F, x200) showed increased heterogeneous T2 signal indicating edema and inflammation in the fascial planes involv - ing extensor and partially flexor carpi ulnaris muscle VAS score for pain was found to be 1 cm with de - and tendon. The examination of the skin/fascia/mus - creased swelling and stiffness in the left upper ex - cle biopsy samples taken from the left forearm revealed tremity. Methotrexate was maintained while corticos - perilobular mononuclear cell infiltration in the sub - teroid treatment was discontinued, with a gradually cutaneous adipose tissue. There was an increased acel - reduction after one year of treatment, in which the pain lular collagen matrix, capillary endothelial swelling and swelling was fully recovered. and perivascular mononuclear cell infiltration in the fascia and lymphocytic cell infiltration in the adjacent adipose tissue (Figure 2). The patient was diagnosed dIscussIon as EF based on the clinical signs and histopathological fin dings. A treatment of fluocortolone 40 mg/day and Eosinophilic fasciitis was first described by Shulman as MTX 20 mg/week was initiated. A prophylactic treat - a variant of scleroderma and it was defined as “eosi - ment for preventing osteoporosis was also added. The nophilic fasciitis” by Rodnan in 1975 1,10 . Most patients patient was administered physical therapy for 10 ses - are in their third to sixth decades, however pediatric sions including transcutaneous electrical nerve stimu - cases also have been reported 11,12 . Although the lation (TENS) (30 min/day) and cold pack (4 x 10 etiopathogenesis of the disease is still unknown, there min/day) on her left wrist and exercises for range of are some reports showing EF accompanied by hema - joint motion and stretching. At the first month, the tological diseases including aplastic anemia, hemoly - ÓRgÃO OfICIAL DA SOCIEDADE PORTUgUESA DE REUMATOLOgIA 180 ayDin e et al tic anemia, leukemia, and lymphoma, other malignan - differential diagnosis of EF and myositis. In addition, cies and autoimmune diseases including Hashimoto’s MRI is a useful imaging technique in the selection of thyroiditis, systemic sclerosis and Sjogren’s syn - biopsy site and monitorization of the treatment pro - drome 5,6,13-15 . The onset of the disease is triggered by cess 24,25 . In consistency with the literature data, in our severe phy sical activity in more than half of the patients case MRI of the upper extremity showed increased and there are also some case reports showing EF asso - hete rogeneous T2 signal indicating edema and inflam - ciated with trauma, hemodialysis, insect bite, pheny - mation in the fascial planes involving extensor and par - toin use, tially flexor carpi ulnaris muscle and tendon, reduced exposure to trichloroethylene, and Borrelia burgdor - adipose tissue, and signal loss in T1-weighted series. In feri 3,7-9,16,17 . A study investigating the cytokine profile in these adjacent regions, increased subcutaneous adipose EF demonstrated increased cytokine abnormalities and tissue was observed. However, there is a limited data on transforming growth factor b-1 levels similar to patients the sensitivity and specificity of MRI in the diagnosis of with atopic diseases, suggesting that autoimmune EF. mechanisms may also play a role in the pathogenesis of The definitive diagnosis is based on the full-thick - EF 18 . The major symptoms include usually symmetri - ness skin/fascia/muscle biopsy. The biopsy findings cal acute or subacute pain and edema in the limbs, limi - often show normal but rarely atrophic epidermis. Al - ted range of joint motion and thickened skin. Review though half of the patients had sclerosis in the dermis, of literature revealed case reports with unilateral pre - there are cases without sclerosis. Sclerosis is accompa - sentation similar to our case 19-21 . The disease is nied by lymphocyte, eosinophilia, plasma cells and his - characteri zed by “peau d’orange” appearance and tiocytic infiltration. The fascia beyond dermis is woody induration, as well as edema and erythema 2. thicken ed by 2-15 folds. Eosinophilic infiltration Face and hands are rarely involved. A groove sign due which is disease-specific in fascia is rarely seen. Mus - to skin indurations on superficial veins is a specific cular bio psy results usually show lymphocyte, plasma characte ristic of the disease. In our case, symptoms cell and histiocytic infiltration 22 . The pathological find - were unilateral and the groove sign was also present. ings of skin/fascia/muscle biopsy in consistent with all We could not find any triggering factor, as no detailed these findings suggested definitive diagnosis of EF in information was obtained from the patient since the our case. complaints started two years