Revisiting idiopathic eosinophilic myositis: towards a clinical-pathological continuum from the muscle to the fascia and skin.

OBJECTIVES: Idiopathic inflammatory myopathies are mainly defined by inflammatory infiltrates within the muscle (lymphocytes and macrophages). Eosinophil muscle infiltration has been described in idiopathic eosinophilic myositis (IEM) and rarely in EF. This study aimed to further delineate the nosological frame of idiopathic eosinophil muscle infiltration through the exhaustive analysis of IEM and EF patients. METHODS: This multicentre retrospective case series included IEM patients diagnosed between 2000 and 2022. IEM inclusion criteria were eosinophilic muscle infiltration with myositis pathological features, after the exclusion of differential diagnoses. An additional group of EF patients diagnosed between 2016 and 2022 was constituted. Inclusion criteria were an EF diagnosis and fascia thickening with inflammatory infiltrate. RESULTS: A total of 20 IEM cases and 10 EF cases were included. The median (interquartile range) age at diagnosis was 65 (49-70) years; there were 18 males. Data analysis delineated four subgroups: focal EM (FEM, n = 3), diffuse EM (DEM, n = 6), eosinophilic myofasciitis (EMF, n = 11) and EF (n = 10). FEM represented a limited and benign form of myositis. DEM cases presented objective muscle impairment with eosinophilic muscle infiltration. EMF patients presented subjective muscle impairment (myalgia, 55%), fasciitis (on histology and/or imaging), eosinophilic muscle infiltration and frequent hypereosinophilia (55%). EF patients presented myalgia (50%), muscle lesions on histology with fascia-restricted inflammatory infiltrates with (60%) or without (40%) eosinophils. CONCLUSIONS: The analysis of IEM and EF patient characteristics delineates four subgroups (FEM, DEM, EMF and EF) in terms of clinical, laboratory, imaging, pathological and outcome specificities, and proposes an adapted diagnostic and care management approach.

Eosinophilic Fasciitis: Current and Remaining Challenges.

Eosinophilic fasciitis (EF), defined as diffuse fasciitis with eosinophilia by Shulman in 1974, is a disease with unknown etiology and whose pathogenesis is still being researched. The diagnosis is based on the clinical aspects (skin induration with an "orange peel" appearance), the lab results (eosinophilia, increased inflammatory markers), the skin biopsy with the pathognomonic histopathological result, as well as the typical MRI changes. The treatment includes glucocorticoids and immunosuppressive drugs. Due to severe refractory cases, the treatment remains a challenge. EF is still a disease with potential for further research.

[Imaging of eosinophilic fasciitis in ultrasound and MRI (magnetic resonance imaging): a case report]. / Darstellung der eosinophilen Fasziitis in Ultraschall und MRT (Magnetresonanztomographie): ein Fallbericht.

Eosinophilic fasciitis (EF, also known as Shulman syndrome) is an uncommon connective tissue disease characterized by inflammatory thickening of the fasciae as well as swelling and hardening of the skin. It mostly affects the lower extremities. Swollen and indurated skin, together with the groove sign, are typical clinical signs. So far, biopsy evidence of inflammation and thickening of the fascia has been the gold standard for diagnosis. Magnetic resonance imaging (MRI) is mentioned in the literature as an alternative method for confirming the diagnosis. We present a case of asymmetric EF in a 54-year-old German male. He came with painful induration of the right forearm, with a characteristic groove sign and limitation of motion of the right hand. The blood count revealed eosinophilia with 0.57 G/l or 9.6% (normal: 0.05-0.5 G/l and 0.5-5.5%), ANA and ENA were negative. The diagnosis was confirmed histologically and we were able to detect a thickened fascia in MRI and ultrasound imaging. The EF also appeared in the left lateral malleolus during the course of the illness. Treatment was carried out with prednisolone and methotrexate.

An unusual case of eosinophilia, myalgia and skin contractures: Shulman's disease revisited.

Shulman's disease (eosinophilic fasciitis) is a very rare autoimmune disorder with an unknown etiopathogenesis. During the initial period of disease, it usually causes limb and trunk edema followed by collagenous thickening of the subcutaneous fascia. Eosinophilia is a predominant laboratory finding during the initial phase of the disease and less prominent in the later phases. Patients may also present with arthritis, myositis, peripheral neuropathy, and rarely pleuropericarditis. Here, we are reporting a case of eosinophilic fasciitis presenting with vague constitutional symptoms, fever, and peripheral blood eosinophilia followed by rapidly evolving skin tightening with joint contractures and muscle stiffness, which misled the treating team toward Scleroderma and its overlap syndromes. The diagnosis was finally clinched by a full-thickness skin biopsy along with underlying fascia and muscle tissue from an effected area, with a gratifying treatment response to standard immune suppression.

The effects of thermal and mechanical material properties on tumorous tissue during hyperthermia treatment.

Although there have been numerous reports in several articles about the viscoelastic properties of biological tissues, no effort has been made to investigate the combined thermal and mechanical behavior of the viscoelastic tissue. At present, the model of thermo-viscoelasticity theory with variable thermal conductivity and rheological properties of the volume is considered to investigate bio-thermo-mechanics behavior in living tissue within the context of the Lord-Shulman theory. The model is applied to a limited thickness, cancerous layer problem. The problem was solved analytically in the transformed domain using Laplace transform as a tool. The exact solution is obtained in the context of transformation Laplace. Numerical results are given and illustrated graphically for the distributions of temperature, displacement, and stress. Some correlations are produced with the results obtained for the absence of the thermal relaxation parameter. The effects of variable thermal and volume materials properties, blood perfusion rate on the behavior of various fields are examined.

Eosinophilic fasciitis (Shulman's disease): review and comparative evaluation of seven patients.

OBJECTIVES: Eosinophilic fasciitis (EF) was described in 1974 by Shulman as a rare fibrosing connective tissue disease of unknown etiology. An undetermined trigger is thought to lead to the degranulation of eosinophils that interact with fibroblasts and express fibrogenic cytokines including the transforming factor of tumor growth a and b and interleukins 1 and 6. The purpose of this study was to summarize seven cases of EF in a central hospital. MATERIAL AND METHODS: This was a retrospective and descriptive study of a population with EF of a central hospital. All patients diagnosed with EF in a hospital unit were admitted to the study between January 1, 2005, and April 30, 2018. RESULTS: A total of seven patients diagnosed with EF were analyzed. The median age of the population at the time of diagnosis was 56 years, and 57% of the patients were women. All patients had elevated peripheral eosinophilia and sedimentation rate, and only one patient had hypergammaglobulinemia. All patients had edema and cutaneous thickening of the limbs, 57% had constitutional symptoms, and 57% had inflammatory arthritis with joint contracture. Prednisolone (PDN) therapy was initiated in all patients, and only in two was the association of PDN with methotrexate (MTX) initially performed. In one patient triple therapy of PDN, MTX, and cyclosporine was required. At the time of this publication, only one patient maintains active disease, and tocilizumab has been initiated. CONCLUSIONS: Recent studies show a more favorable response from the combination of PDN and MTX than from PDN alone. Considering the rarity of the disease, more long-term studies are needed regarding the etiopathogenetics, progression, recurrence of EF, and new effective therapies.

[Sarcoid-like granulomatosis associated with eosinophilic fasciitis]. / Fasciite de Shulman associée à un infiltrat granulomateux sarcoïdosique.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare condition characterized by swelling of the extremities, sclerodermatous evolution and frequent hypereosinophilia. Hematological disorders, including aplastic anemia, solid tumors and autoimmune diseases, may be associated with EF. EF is usually not associated with granulomatous diseases. CASE REPORT: Herein we describe the case of an 80-year-old man with symmetrical swelling and sclerosis of the legs, typical of EF, associated with skin and lymph node granulomas. Oral prednisone treatment resulted in complete clinical remission. DISCUSSION: Association of EF and granulomatous disease is uncommon. Our case highlights the possible association of EF with sarcoidosis-like reactions.

Eosinophilic Fasciitis: an Updated Review on Diagnosis and Treatment.

PURPOSE OF REVIEW: First recognized in 1974, eosinophilic fasciitis (EF) is a fibrosing disorder of the fascia with characteristic cutaneous and hematologic manifestations. This review discusses recent trends in the diagnosis and treatment of EF. RECENT FINDINGS: Although fascial biopsy has classically been considered the gold standard for making a diagnosis of EF, radiologic imaging, particularly magnetic resonance imaging, has been increasingly used for both diagnosis and monitoring of treatment response. Systemic corticosteroids remain the first-line treatment for EF; however, their often prolonged use in the treatment of EF has prompted a search for adjunctive therapies. Methotrexate has emerged as the leading corticosteroid-sparing agent for EF. Since EF was initially described over 40 years ago, important diagnostic and therapeutic progress has been made. Future efforts should be directed at the pursuit of prospective studies including clinical trials and evidence-based guidelines.

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.

Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research.

The American Society for Apheresis (ASFA) conducted a 1 day consensus conference on Thrombotic Thrombocytopenic Purpura (TTP) during its annual meeting in Atlanta, GA, on April 10, 2012. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to definitions, classification, pathophysiology, diagnosis, management, and future research in TTP. These questions were provided to the seven invited speakers who are the experts in the field of TTP. Two moderators conducted the proceedings of the conference which was attended by more than 100 participants. After each presentation, there was an open discussion that included moderator-selected written questions submitted by the audience. A medical writer-generated transcript of the proceedings as well as each presentation was made available to the authors. Each summary was reviewed and approved by the respective speaker before submission of this article. The subcommittee also developed seven key questions for blinded, electronic polling conducted by the moderators to generate a consensus amongst the speakers. This article includes these presentation summaries as well as results of the electronic poll.

[Eosinophilic fasciitis, morphea and vitiligo in a single patient]. / Association fasciite avec éosinophilie, morphées et vitiligo.

BACKGROUND: Fasciitis with eosinophilia (FE), or Shulman syndrome, is a rare disease of unknown origin for which the nosological profile has not been clearly defined. It is clinically characterised by oedema and induration of the limbs with hypereosinophilia. It may be associated with morphea, in which case it carries a poor prognosis, or other diseases, particularly autoimmune conditions. Herein, we report a case of fasciitis associated with eosinophilia, morphea and vitiligo. PATIENT AND METHODS: A 45-year-old male patient followed up for vitiligo for 20 years had been presenting swelling and induration of the skin on all 4 limbs for the previous 7 months associated with morphea on the trunk. Treatment consisting of systemic corticosteroids and methotrexate was initiated and displayed a certain degree of efficacy. DISCUSSION: The association of morphea/fasciitis with eosinophilia is a classical finding; the presence of vitiligo raises the question of possible association between these different disorders.

A difficult diagnosis of eosinophilic fasciitis: A case report.

Eosinophilic fasciitis can be a debilitating diagnosis and is often delayed given its similarities to other sclerotic conditions including morphea, such as bound-down indurated skin and inflammation and sclerotic thickening of tissue layers on histopathology. Delaying treatment can lead to joint contracture and residual hardness in skin which has both cosmetic and functional implications. Therefore, finding the definitive diagnosis and differentiating from other sclerotic diseases is important early in the disease course. We present a case of a 77-year-old female with a generalized rash on her back and extremities, and progressive symptoms of pain, joint contractures, and limited movement, which highlights the challenges in diagnosis and management given clinical and histological parallels between eosinophilic fasciitis and morphea.

Tocilizumab in the Treatment of Eosinophilic Fasciitis: A Case Study and Review of Literature.

Eosinophilic fasciitis (EF) is a rare connective-tissue disorder that is characterised by subacute onset of erythema, oedema, and induration of the skin and soft tissues of the limbs and trunk. Although several triggers have been hypothesised to be associated with EF, the aetiology of eosinophilic fasciitis (EF) is still unclear, and several treatment regimens have been proposed to treat this disease. In this article, we report a case of a 72-year-old gentleman with multiple comorbidities who presented to the clinic for diffuse skin thickening present on his forearms, thighs, legs bilaterally, and over the pelvis. The patient was diagnosed with EF and failed multiple treatment regimens including prednisone, methotrexate, rituximab, but finally responded and was maintained on tocilizumab. In this article, we will review the current understanding of EF, diagnostic approach, popular treatments and review other cases of EF in which tocilizumab was used.

The first case of SARS-CoV-2-induced eosinophilic fasciitis.

Eosinophilic fasciitis (EF), also known as Shulman syndrome, is a rare auto-immune fibrosing disorder of the fascia. Etiopathogeny of EF is still unclear. Nowadays, it is widely known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce hyper-stimulation of the immune system. Several cases with fasciitis and rhabdomyolysis induced by coronavirus disease 2019 vaccines have been reported in the literature. Herein, we report the first case of EF possibly triggered by SARS-CoV-2 infection. A 45-year-old Tunisian woman, with no medical history, presented to our department with severe widespread muscle pain noticed one month after a SARS-CoV-2 infection. Physical examination showed an induration of the skin and subcutaneous tissue of the arms, forearms and legs with a restricted joint mobility. The level of eosinophils was 430 E/mm3 (6.1%) [1-4%]. Electromyography and creatine kinase levels were normal. Myositis-related antibodies were negative. Magnetic resonance imaging of the left arm showed high-intensity signal and thickness of the fascia without evidence of muscle or bone involvement. A muscular biopsy from the right deltoid showed thickening and inflammation of the fascia. The patient received intraveinous injections of 1000 mg of methylprednisolone for 3 days with an oral relay of 1 mg/kg per day of prednisone equivalent during 4 weeks. At one-month follow-up, a significant improvement of the skin induration and myalgia was observed, with a disappearance of the biological inflammatory syndrome. This brief report suggests a potential link between SARS-CoV-2 infection and new-onset of auto-immune fasciitis.

Eosinophilic Fasciitis Presenting as an Ichthyosiform Eruption of the Bilateral Ankles.

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.

Diagnostic Utility of Magnetic Resonance Imaging in Eosinophilic Fasciitis: A Case Report and Review of Literature.

Eosinophilic fasciitis (EF), also known as Shulman syndrome, is a rare scleroderma-like disorder that is characterized by an acute onset of induration, swelling, erythema, and tenderness of the skin and deep fascia, often affecting all four limbs. We report a case of eosinophilic fasciitis in a 51-year-old female patient, whose diagnosis of EF was made based on the findings from clinical evaluation and magnetic resonance imaging (MRI) but without skin biopsy. She was treated with a combination therapy of prednisolone and methotrexate, and her response to therapy was assessed via clinical assessment and MRI. MRI may be a useful non-invasive diagnostic tool for not only supporting but also confirming the clinical diagnosis of EF when a skin-to-muscle biopsy is not available or cannot be performed, as well as for monitoring disease activity and response to therapy. Further prospective studies should be conducted to evaluate the precise sensitivity and specificity of MRI in diagnosing EF and also to create more structured protocols to guide the diagnosis and management of EF.

Eosinophilic Fasciitis and Smoldering Multiple Myeloma: An Exceptional Association in Young Adults.

Eosinophilic fasciitis (EF) or Shulman's fasciitis is a rare condition characterized by subcutaneous edematous induration sparing the face and distal extremities and progressing to skin sclerosis. Its association with other pathologies, notably hemopathies, is described in the literature, but its association with smoldering multiple myeloma remains very rare, especially in a younger subject.

Mycophenolate mofetil and mycophenolic acid for the treatment of eosinophilic fasciitis: report of two cases and literature review.

Eosinophilic fasciitis (EF) is an uncommon autoimmune connective tissue disorder characterized by edema, erythema, and subsequent induration of the extremities. It is commonly treated with corticosteroids but there is no treatment ladder for immunosuppressants or steroid-sparing agents. We report two EF cases treated effectively with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and present a literature review. We performed a MEDLINE search using the keywords 'eosinophilic fasciitis', 'Shulman syndrome', 'mycophenolic acid', or 'mofetil mycophenolate', and found 8 articles with 27 cases in which MMF or MPA was used. Twenty-nine cases were reviewed (2 reported herein and 27 from the literature search); all patients received a combination of systemic corticosteroids and MMF. MMF/MPA were given as a steroid-sparing agent in 27 (93.1%), in 1 (3.4%) as adjunctive therapy with other immunosuppressants, and in one, as monotherapy 1 (3.4%). Nineteen had a complete response, 6, a partial response, and 2 were unresponsive to diverse immunomodulators; in 2 cases, the outcome was not reported. MMF and MPA show promising therapeutic results and could be a treatment option to reduce corticosteroid related side effects.

A Modified Two-Relaxation Thermoelastic Model for a Thermal Shock of Rotating Infinite Medium.

A unified form of thermoelasticity theory that contains three familiar generalized thermoelasticity. The Lord-Shulman theory, Green-Lindsay theory, and the classical one can be outlined in this form. The field quantities of a rotating/non-rotating half-space with and without the effect of the decay parameter can be obtained due to the unified thermoelasticity theory. The present medium is subjected to a time-dependent thermal shock taking into account that the magnitude of the thermal shock wave is not totally fixed but decaying over time. A special case of a thermal shock waveform with constant magnitude may be considered. The field quantities such as temperature, displacements, and stresses of the present problem are analytically obtained. Some plots of these field variables are presented in two- and three-dimensional illustrations in the context of refined theories.

Response of recalcitrant generalized morphea to intravenous immunoglobulins (IVIg): three cases and a review of the literature.

BACKGROUND: Generalized morphea and eosinophilic fasciitis are difficult-to-treat inflammatory and sclerosing skin diseases. Few cases have been reported in which intravenous immunoglobulins were of benefit, possibly owing to their immunomodulatory and antifibrotic properties. OBJECTIVES: We present three new patients with generalized morphea treated with intravenous immunoglobulins as well as a review of the literature. MATERIALS & METHODS: Three hospitalized patients (two men, age 66 and 65 years, respectively, and a 67-year-old woman) with generalized morphea who received therapy for the first time are described. RESULTS: The three patients were treated with intravenous immunoglobulins (1.5-2 g/kg body weight over three to four consecutive days every four weeks). This was combined with corticosteroid pulse therapy in all patients, methotrexate in two patients and mycophenolate mofetil in one patient, respectively. Marked and steady improvement of skin sclerosis was evident in all patients, one to five months after treatment initiation. No adverse events were observed. To date, there are 12 reports of 16 patients with generalized morphea or eosinophilic fasciitis treated with intravenous immunoglobulins. The treatment was highly effective in the majority of patients (9/16) and yielded a favourable risk profile. CONCLUSION: Our cases add to the hitherto limited evidence that the administration of intravenous immunoglobulins in combination with glucocorticoids and conventional immunosuppressive agents is a safe and effective therapy against morphea. It seems appropriate to verify these results in future high-quality studies.