[Eosinophilic fasciitis: From pathophysiology to therapeutics]. / Fasciite à éosinophiles : actualités physiopathologiques et nouvelles voies thérapeutiques.

Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized by painful edema and induration of the limbs and trunk, likely associated with hypereosinophilia and hypergammaglobulinemia. EF causes arthralgia and range of motion limitation, leading to significant functional impairment and poor quality of life. Since its description by Shulman in 1974, over 300 cases have been reported. We present here a review of the latest diagnostic, pathophysiological and therapeutic developments in this disease. Magnetic resonance imaging appears useful to guide diagnosis and biopsy. Diagnosis is based on a deep skin biopsy involving the fascia, which will reveal edema, sclerofibrosis of the muscular fascia and subcutaneous tissue, and an inflammatory infiltrate sometimes composed of eosinophilic polynuclear cells. EF may occur in patients treated with immune checkpoint inhibitors and the diagnosis should be raised in case of cutaneous sclerosis in these patients. The pathophysiology of the disease remains poorly understood, and its management lacks randomized, controlled, blinded trials. First-line treatment consists in oral corticosteroid therapy, sometimes combined with an immunosuppressant, mainly methotrexate. A better understanding of the pathophysiology has opened new therapeutic perspectives and clarified the role of targeted therapies in the management of EF, such as interleukin-6 inhibitors, whose efficacy has been reported in several cases.

[Enteroviral infections in adults treated with rituximab: A new case of chronic meningitis and myofasciitis and literature review]. / Infections à entérovirus de l'adulte traité par rituximab : un nouveau cas de méningite et myofasciite chronique et revue de la littérature.

INTRODUCTION: Chronic enterovirus infections can occur in primary immunodeficiency with hypogammaglobulinemia. They usually associate meningitis and myofasciitis. Such infections have also been described in adults with rituximab-induced hypogammaglobulinemia. CASE REPORT: We report the case of a 33-year-old woman who was given rituximab for immune thrombocytopenia and developed rituximab-induced hypogammaglobulinemia (IgG 4.4g/L). One year after the last rituximab infusion, she developed lower limbs myofasciitis, followed two months later by a chronic lymphocytic meningitis. PCR in the serum and the cerebrospinal fluid at the time of the meningitis and the myofasciitis were positive to the same enterovirus (echovirus 11) while it was negative in the fascia biopsy. Under treatment with intravenous immunoglobulins, all symptoms and laboratory abnormalities improved and enterovirus PCR became negative. CONCLUSION: We report a case of chronic enterovirus infection associating meningitis and myofasciitis in an adult with rituximab-induced hypogammaglobulinemia. Outcome was favorable under treatment with intravenous immunoglobulins.

Eosinophilic fasciitis: From pathophysiology to treatment.

Eosinophilic fasciitis is a disease originally proposed as "diffuse fasciitis with eosinophilia" by Shulman in 1974. The patients with this disease often have history of strenuous exercise or labor a few days to 1-2 weeks before the onset. The chief symptoms are symmetrical, full-circumference swelling and plate-like hardness of the distal limbs. This is accompanied by redness and pain in the early stages, with many cases exhibiting systemic symptoms such as fever or generalized fatigue. The lesions have been observed extending to the proximal limbs, though never on the face or fingers. En bloc biopsies from the skin to the fascia show marked fascial thickening and inflammatory cell infiltration by the lymphocytes and plasma cells. Eosinophilic infiltration is useful for the diagnosis but is only seen in the early stages of the disease. Recently, "Diagnostic criteria, severity classification, and clinical guidelines for eosinophilic fasciitis" were published. This review article discusses about eosinophilic faciitis in detail, from its pathophysiology to the treatment.

[Paraneoplastic syndromes in rheumatology]. / Paraneoplastische Syndrome in der Rheumatologie.

Malignancies can present as inflammatory rheumatic diseases. These rheumatic paraneoplastic syndromes are rare, but characteristic in their pattern. This article focuses on epidemiology, clinical and diagnostic features as well as treatment of paraneoplasic rheumatic diseases such as paraneoplastic arthritides, vasculitides, myositis and hypertrophic osteoarthropathy. The knowledge of their clinical patterns is of utmost importance for early diagnosis and prognosis of yet undiagnosed malignancies.

Diagnostic criteria, severity classification and guidelines of eosinophilic fasciitis.

We established diagnostic criteria and severity classification of eosinophilic fasciitis because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for eosinophilic fasciitis, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of eosinophilic fasciitis.

Long-term outcome of eosinophilic fasciitis: A cross-sectional evaluation of 35 patients.

BACKGROUND: Eosinophilic fasciitis (EF) is a connective tissue disease with an unknown long-term course. OBJECTIVE: To evaluate presence and determinants of residual disease damage in patients with EF after long-term follow-up. METHODS: Patients with biopsy-proven EF were included for this cross-sectional study. Outcome measures included the Physician's Global Assessment of Disease Activity, Physician's Global Assessment of Damage (PhysGA-D), skin pliability scores, passive range of motion, and health-related quality of Life (HRQoL) questionnaires. RESULTS: In total, 35 patients (24 of whom were female [68.6%]) with a median age of 60 years participated. All patients had detectable residual damage. Impairment of HRQoL, assessed by the Dermatology Quality of Life Index and the 36-Item Short-Form Survey, correlated to the extent of residual damage. The PhysGA-D score at participation correlated to signs of severe disease at presentation, such as increased C-reactive protein level (Spearman's rho [rs ] = 0.486, P = .006), involvement of the neck (rs = 0.528, P = .001) and trunk (rs = 0.483, P = .003), prolonged time to disease remission (rs = 0.575, P = .003), and presence of concomitant morphea (rs = 0.349, P = .040). Lastly, maximum methotrexate dose correlated negatively to PhysGA-D score at study participation (rs = -0.393, P = .022). LIMITATIONS: Sample size. CONCLUSION: All patients with EF had detectable residual damage. Impairment of HRQoL correlated to the extent of residual damage. Advanced age and signs of severe disease at presentation were associated with the severity of residual damage.

Eosinophilia in Rheumatologic/Vascular Disorders.

Peripheral and tissue eosinophilia can be a prominent feature of several unique rheumatologic and vascular diseases. These diseases span a wide range of clinical features, histologic findings, therapeutic approaches, and outcomes. Despite the rare nature of these entities--which makes large-scale studies challenging--knowledge has continued to grow regarding their epidemiology, pathophysiology, and management. This review compares and contrasts 5 rheumatologic and vascular conditions in which eosinophilia can be seen: eosinophilic granulomatosis with polyangiitis (Churg-Strauss), immunoglobulin G4-related disease, diffuse fasciitis with eosinophilia, eosinophilia-myalgia syndrome, and eosinophilic myositis.

Clinical, neuropathological and radiological evidence for a rare complication of rituximab therapy.

We report a rare case of myofasciitis and meningitis with deafness caused by systemic enterovirus infection in the setting of hypogammaglobulinaemia induced by rituximab. Whilst effective and generally safe, anti- CD 20 antibody therapy is increasingly recognised to result in unusual infectious complications to be considered in a treated patient presenting with neurological symptoms. These cases may pose diagnostic difficulties and can have atypical presentations. We present this rare complication of rituximab therapy, with histopathological confirmation of myofasciitis. In the older literature, enterovirus associated myofasciitis may have erroneously been termed dermatomyositis and we review the literature to demonstrate this important nosological point.

Extracorporeal photopheresis for the treatment of autoimmune diseases.

The immune system is tasked with the unique challenge of recognizing foreign pathogens and damaged cells while at the same time preserving and protecting the integrity of "self". When this process fails, severe consequences including cancer and autoimmunity are the end result. Current therapies aimed at treating autoimmune disorders result in generalized immunosuppression and place the patient at increased risk for infection and malignancy. ECP is a potential therapeutic intervention that recapitulates natural physiologic processes of tolerance induction to restore immune homeostasis. Several clinical trials suggest that ECP may be used to treat a broad spectrum of autoimmune diseases.

Imatinib mesylate for the treatment of steroid-refractory sclerotic-type cutaneous chronic graft-versus-host disease.

Sclerotic skin manifestations of chronic graft-versus-host disease (ScGVHD) lead to significant morbidity, including functional disability from joint range of motion (ROM) restriction. No superior second-line therapy has been established for steroid-refractory disease. Imatinib mesylate is a multikinase inhibitor of several signaling pathways implicated in skin fibrosis with in vitro antifibrotic activity. We performed an open-label pilot phase II trial of imatinib in children and adults with corticosteroid-refractory ScGVHD. Twenty patients were enrolled in a 6-month trial. Eight received a standard dose (adult, 400 mg daily; children, 260 mg/m(2) daily). Because of poor tolerability, 12 additional patients underwent a dose escalation regimen (adult, 100 mg daily initial dose up to 200 mg daily maximum; children, initial dose 65 mg/m(2) daily up to 130 mg/m(2) daily). Fourteen patients were assessable for primary response, improvement in joint ROM deficit, at 6 months. Primary outcome criteria for partial response was met in 5 of 14 (36%), stable disease in 7 of 14 (50%), and progressive disease in 2 of 14 (14%) patients. Eleven patients (79%), including 5 with partial response and 6 with stable disease, demonstrated a positive gain in ROM (range of 3% to 94% improvement in deficit). Of 13 patients with measurable changes at 6 months, the average improvement in ROM deficit was 24.2% (interquartile range, 15.5% to 30.5%; P = .011). This trial is registered at http://clinicaltrials.gov as NCT007020689.

Chronic graft-versus-host disease presenting as eosinophilic fasciitis: therapeutic challenges and an additional case.

Chronic graft-versus-host disease (cGVHD) is one of the main late complications of allogeneic hematopoietic stem cell transplant and a major contributor to the mortality and morbidity in surviving recipients. Skin is the most common involved organ in cGVHD and may mimic a wide spectrum of dermatological conditions in its clinical and histopathologic manifestations. Some of the commonly simulated diseases are scleroderma, morphea, and lichen sclerosus. Chronic GVHD simulating eosinophilic fasciitis (EF) is relatively rare, frequently presenting with skin induration, a typical "peau d'orange" appearance, peripheral blood eosinophilia, myalgia, arthralgia, and arthritis leading to joint contractures in severe cases.Diagnosis is based on clinical manifestations and histopathology. Treatment is challenging because most cases are refractory to first-line therapy of glucocorticoids and calcineurin inhibitors (CNIs), and there is no standard second-line therapy.We report a comprehensive review of literature on all reported cases of CGVHD presenting as EF. We also describe an additional interesting case of cGVHD presenting as EF that was resistant to traditional therapy of high-dose glucocorticoids and cyclosporin A, but showed complete resolution of skin manifestations after addition of imatinib.Chronic GVHD presenting as EF is a rare variant of sclerodermatous cGVHD. Diagnosis is difficult, and treatment of cGVHD mimicking EF remains a therapeutic challenge because of obscure pathogenesis and poor response to traditional immunosuppressive medications. Emerging insights into the pathogenesis of cGVHD have resulted in the development of novel targeted therapies, which may improve outcomes and should be attempted in this subset of the disease. Larger studies are warranted to substantiate these preliminary findings.

Fascitis eosinofílica: a propósito de un caso / Eosinophilic fasciitis: an account of a case

Eosinophilic fasciitis is a rare entity characterized by induration of skin and peripheral eosinophilia. The pathogenesis is still not well known, but is known association with hematological, autoimmune or neoplastic diseases. The complex and not well standardized treatment. For a patient of 66 years presented with a history of morphea...

La Fascitis Eosinofílica (FE) es una entidad muy infrecuente, caracterizada por induración de piel y eosinofilia periférica. La patogenia aún no es bien conocida, pero es sabida la asociación con enfermedades hematológicas, autoinmunes o neoplásicas. El tratamiento es complejo y no bien estandarizado. Se presenta el caso de una paciente de 66 años, con antecedentes de morfea...

Paraneoplastic syndromes in rheumatology.

For patients that present with musculoskeletal symptoms, diagnostic procedures carried out by physicians and rheumatologists are primarily aimed at confirming or excluding the occurrence of primary rheumatic diseases. Another important trigger for musculoskeletal disease, however, is the presence of a tumour. Careful clinical investigation and knowledge of the gestalt of musculoskeletal syndromes related to respective tumour entities is of utmost importance for the diagnosis of paraneoplastic rheumatic diseases such as hypertrophic osteoarthropathy, paraneoplastic polyarthritis, RS3PE syndrome, palmar fasciitis and polyarthritis, cancer-associated myositis and tumour-induced osteomalacia. This places great responsibility on rheumatologists in diagnosing malignancies and referring the patient for effective treatment. The selective influence of tumours on musculoskeletal tissue is surprising and indicates that tumours alter tissues such as the periosteum, synovial membrane, subcutaneous connective tissue, fascia, muscles and bones by specific molecular processes. Some of the underlying mechanisms have been unravelled, providing valuable information on the physiologic and pathophysiologic roles of mediators such as vascular endothelial growth factor and fibroblast growth factor 23.

Clinical evaluation and management of benign soft tissue tumors of the extremities.

Benign lesions comprise a majority of soft tissue tumors. It has been estimated that their incidence outnumbers that of malignant tumors by a factor of at least 100 [1]. While history and physical examination can start the diagnostic process, imaging including the use of magnetic resonance imaging can be more helpful. Biopsy of these tumors is sometimes necessary and can be performed in a number of ways, often in conjunction with definitive treatment. Specific diagnostic and treatment strategies for a number of the more commonly encountered benign soft tissue tumors including lipomas, pigmented villonodular synovitis and hemangiomas are reviewed. An algorithm for the management of benign soft tissue tumors is discussed.

Diagnosis and classification of eosinophilic fasciitis.

Eosinophilic fasciitis (EF) is a rare scleroderma-like syndrome with an unknown etiology and pathogenesis that should be considered an immune-allergic disorder. Painful swelling with progressive induration and thickening of the skin and soft tissues of the limbs and trunk are the clinical hallmarks of the disease. Peripheral blood eosinophilia, hypergammaglobulinemia, and elevated erythrocyte sedimentation rate are the main laboratory findings. Full-thickness wedge biopsy of the clinically affected skin showing inflammation and thickening of deep fascia is essential to establish the diagnosis. The differential diagnosis includes systemic sclerosis and other scleroderma subsets such as morphea, and epidemic fasciitis syndromes caused by toxic agents such as the myalgia-eosinophilia syndrome and toxic oil syndrome. Peripheral T cell lymphomas should also be ruled out. The diagnosis of EF can be established by clinical, laboratory and histological findings, but universally accepted international diagnostic criteria are lacking. Corticosteroids are efficacious and remain the standard therapy for EF, although some patients may improve spontaneously.

Bacillus cereus fasciitis: a unique pathogen and clinically challenging sequela of inoculation.

Bacillus cereus is an aerobic, spore-forming, gram-positive rod. It has historically been associated with "fried rice syndrome," a foodborne diarrheal and emetic illness resulting from eating fried rice dishes that have been sitting at room temperature for hours. We report the case of a 9-year-old boy who developed culture-positive B cereus fasciitis of the right lower extremity after being impaled on a tree branch. This case report further elucidates and emphasizes the importance of recognizing B cereus as a possible cause of severe soft-tissue infection. It must be included in the differential diagnosis of gas gangrene and necrotizing fasciitis.

Nodular fasciitis presenting in an adult woman.

The authors report a 30-year-old Caucasian woman with nodular fasciitis presenting as a nontender lesion to right temporal area. The lesion was removed by en bloc excision and the base was cauterized. Six months later, the patient returned to the clinic for possible recurrence of lesion or for residual lesion; the patient was then injected with a total of 1 cc of kenalog at 20 mg/kg. Two weeks later, the lesion had greatly subsided and the patient was satisfied with the esthetic appearance. Nodular fasciitis is a rare reactive growth with even fewer cases of recurrence. In young patients, steroid injection is an alternative to repeat resection.