Imatinib as a potentially effective therapeutic alternative in corticosteroid-resistant eosinophilic fasciitis.

Eosinophilic fasciitis (EF) is a rare condition in children that is typically treated with systemic corticosteroids. We present the case of a 9-year-old boy with biopsy-proven EF, refractory to systemic corticosteroids and methotrexate. The tyrosine kinase inhibitor imatinib was added as adjuvant therapy, leading to improvement in joint function and skin laxity. Our case is the first to suggest the anti-fibrotic properties of imatinib may benefit EF patients.

Characteristics of Japanese patients with eosinophilic fasciitis: A brief multicenter study.

Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co-occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20-80 mg/day), methotrexate (6-10 mg/week), cyclosporin (100-150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first-line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis.

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.

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA).

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis, and the chronic fatigue syndrome. The aluminum-containing adjuvants in the hepatitis B vaccine and the human papillomavirus vaccine in particular have been stated to be the major causes of the disorder. Here, we review the specificity of the diagnostic criteria for ASIA. We also examine relevant human data, pertaining to causation, particularly from patients undergoing allergen-specific immunotherapy (IT). Patients undergoing allergen-specific IT receive 100 to 500 times more injected aluminum over 3 to 5 years, compared with hepatitis B and human papillomavirus vaccine recipients. In a large pharmacoepidemiological study, in contrast to case series of ASIA, patients receiving aluminum-containing allergen IT preparations were shown to have a lower incidence of autoimmune disease. In another clinical trial, there were no increases in exacerbations in a cohort of patients with systemic lupus erythematosus immunized with the hepatitis B vaccine. Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations as well as to those undergoing allergen-specific IT.

[Autoimmune/inflammatory syndrome induced by adjuvants. A new clinical entity?] / Síndrome autoinmune/inflamatorio inducido por adyuvantes. ¿Una nueva entidad clínica?

Recently Shoenfeld and Agmon-Levin proposed a new clinical entity called autoimmune/inflammatory syndrome induced by adjuvants (ASIA), which includes four clinical entities called: 1) siliconosis, 2) Gulf War syndrome, 3) macrophage myofasciitis) and 4) post-vaccination phenomenon associated with adjuvants. They all have a common denominator: a prior exposure to immunoadjuvants, and, in addition, they also share several clinical criteria associated to chronic inflammation and autoimmune reactions. This proposal still needs to be validated by the scientific community, but nowadays is a topic of hot discussion in the literature and in various international conferences. In this revision article, we analyze the characteristics of this syndrome, the current mechanisms possibly involved in the pathogenesis, and the more recent reports regarding ASIA associated to vaccine and some foreign substances.

Recientemente Shoenfeld y Agmon-Levin han propuesto una nueva entidad clínica denominada síndrome autoinmune/inflamatorio inducido por adyuvantes (ASIA, por sus siglas en inglés), el cual incluye cuatro entidades denominadas: 1) siliconosis, 2) síndrome de la guerra del Golfo, 3) miofascitis macrofágica y 4) fenómeno posvacunación asociado a adyuvantes. Todos ellos tienen un denominador común: una exposición previa a inmunoadyuvantes y además comparten varios criterios clínicos asociados a inflamación crónica y reacciones autoinmunes. Esta propuesta aún debe ser validada por la comunidad científica, pero hoy en día es un tema de intenso debate en la literatura biomédica y en varias conferencias internacionales. En esta revisión, se analizan las características de este síndrome, los mecanismos actuales posiblemente implicados en la patogénesis y los más recientes informes sobre ASIA asociada a vacunas y a algunas sustancias extrañas.

Morphea and Eosinophilic Fasciitis: An Update.

Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.

Atypical presentations of eosinophilic fasciitis.

Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

Fascitis eosinofílica. A propósito de un caso / Eosinophilic fasciitis. Apropos of a case

La fascitis eosinofílica es un síndrome esclerodermiforme poco frecuente y de etiología desconocida que afecta predominantemente a las extremidades. Se han barajado varias hipótesis sobre su etiología y en algunos casos se ha descrito antecedente traumático. Presentamos un caso de una paciente de 54 años que tras presentar traumatismo sobre las rodillas inicia un cuadro de mialgias, induración cutánea y retracción progresiva de diversas articulaciones iniciado en los miembros inferiores y posteriormente en los miembros superiores y en el tronco. Realizamos el seguimiento de la paciente, mostrando su manejo desde el punto de vista rehabilitador y evolución. La paciente mejoró tanto sus balances articulares como la marcha y el dolor. La fascitis eosinofílica es una enfermedad infrecuente en la que debemos realizar el diagnóstico diferencial con otros síndromes esclerodermiformes. La rehabilitación puede ayudar a reducir y evitar el progreso de las contracturas (AU)

Eosinophilic fasciitis is a rare scleroderma syndrome of unknown cause that predominantly affects the extremities. Several hypotheses have been proposed to explain its etiology and there have been reports of some patients with a history of trauma. We present the case of a 54-year-old woman who, after a knee injury, developed myalgia, progressive skin induration and retraction of various joints, starting in the lower limbs and spreading to the upper limbs and trunk. We describe the rehabilitation management and outcome of this patient. The patient showed improvement in both balance, joint pain, and gait. Eosinophilic fasciitis is a rare disease that requires a differential diagnosis with other scleroderma syndromes. Rehabilitation can help reduce and prevent progression of contractures (AU)

Morphological clues in the diagnosis of sclerodermiform dermatitis.

In this report, we review 5 sclerodermiform cutaneous conditions: eosinophilic fasciitis, systemic nephrogenic fibrosis, scleredema, scleromyxedema, and toxic oil syndrome. We emphasize the morphological differences between the conditions and some morphological clues that are important to differential diagnosis.

Myofascial pain syndromes and their evaluation.

Myofascial pain refers to a specific form of soft-tissue rheumatism that results from irritable foci (trigger points) within skeletal muscles and their ligamentous junctions. It must be distinguished from bursitis, tendonitis, hypermobility syndromes, fibromyalgia and fasciitis. On the other hand it often exists as part of a clinical complex that includes these other soft-tissue conditions, i.e., it is not a diagnosis of exclusion. The clinical science of trigger points can be traced to the pioneering work of Kellgren in the 1930s, with his mapping of myotomal referral patterns of pain resulting from the injection of hypertonic saline into muscle and ligaments. Most muscles have characteristic myotomal patterns of referred pain; this feature forms the basis of the clinical recognition of myofascial trigger points in the form of a tender locus within a taut band of muscle which restricts the full range of motion and refers pain centrifugally when stimulated. Although myofascial pain syndromes have been described in the medical literature for about the last 100 years, it is only recently that scientific studies have revealed objective abnormalities.

Blood oxidative stress status in patients with macrophagic myofasciitis.

The study aimed at determining the presence of an oxidative stress in patients with macrophagic myofasciitis (MMF), a new inflammatory myopathy with suspected toxic etiology related to aluminium hydroxide-containing vaccines. A total of 30 MMF patients (nine males, 21 females; aged 42+/-14 years), whose diagnosis was confirmed by deltoid biopsy, have been included and compared to 38 sex- and age-matched healthy control subjects (10 males, 28 females; aged 43+/-8 years). The blood oxidative stress status has been evaluated by assaying six parameters: plasma lipid peroxidation products (thiobarbituric acid-reactive substances: TBARS) and antioxidant defense systems: plasma vitamin E and glutathione peroxidase (GSH-Px) activity, erythrocyte GSH-Px and Cu,Zn-superoxide dismutase (SOD) activities. Plasma selenium was also determined as a trace element essential to the activity of GSH-Px. Statistical significance was evaluated by the Mann-Whitney test. Plasma GSH-Px activity, selenium and vitamin E concentration were significantly lower in MMF group than in controls (P=0.004, P=0.003 and P=0.009, respectively), with a positive correlation in MMF patients between plasma GSH-Px activity and selenium concentration (rho=0.0001). The other parameters of oxidative stress did not significantly differ between both groups. A macrophage activation could occur in MMF, consequently to chronic stimulation by aluminium-containing vaccines, and could participate to the lower values of selenium and vitamin E observed in comparison with controls. Nevertheless, since no deficiency in these elements has been observed, no supplementation is to be considered.

Rehabilitación y tratamiento ortopodológico en rotura de la fascia plantar. Caso clínico

Presentamos en este trabajo un caso clínico en el que una excesiva terapia con infiltraciones de corticoides y un tratamiento ortopodológico no satisfactorio, unido a práctica deportiva excesiva, provocan que una fascitis plantar recurrente desemboque en la rotura parcial de la misma con la consecuente impotencia funcional. Planteamos así, después de un exhaustivo estudio biomecánico, un tratamiento ortopodológico personalizado junto con electroterapia como elemento coadyuvante, y siempre en coordinación con el trabajo del fisioterapeuta en aquellas alteraciones músculo-tendinosas que sin duda tienden a cronificar la patología. (AU)

Scleroderma-like cutaneous syndromes.

Several distinct entities associated with dermal fibrosis can mimic scleroderma/systemic sclerosis. The list of scleroderma-like conditions or scleroderma variants includes eosinophilic fasciitis, localized forms of scleroderma, scleredema and scleromyxedema, keloids, and environmental exposure-associated conditions including eosinophilia-myalgia syndrome and pseudosclerodermas induced by various drugs. Although these conditions are relatively uncommon, their accurate recognition is essential to avoid misdiagnosis and inappropriate therapy. The pathogenesis of these scleroderma variants appears to share similarities with each other and with that of scleroderma. Better understanding of scleroderma-like disorders is emerging through epidemiologic investigations, and in vivo and in vitro experimental research. Activation of eosinophils and disordered regulation of fibroblast collagen synthesis, apoptosis, and proliferation are recurrent findings in these disorders. The etiologic role of infection with Borrelia species or other microorganisms remains controversial. Cytokines such as transforming growth factor-beta, interleukin-4, interleukin-13, and connective tissue growth factor contribute to fibrosis in these disorders by inducing an accentuated and persistent fibrogenic response to tissue injury. The role of genetic factors in susceptibility and clinical expression of scleroderma-like conditions remains to be systematically addressed. Because of the relative rarity of these conditions, few well-controlled clinical treatment trials have been performed. In addition, there is no consensus on optimal management. Much anecdotal information and small clinical series indicate that phototherapy may have a role in the treatment of scleroderma-like conditions.

Atypical presentation of plantar fasciitis secondary to soft-tissue mass infiltration.

This article describes a patient with plantar fascial pain who presented to the office of one of the authors. Physical examination and the patient's description of the history of symptoms revealed classic signs and symptoms of plantar fasciitis. The patient was treated with numerous conservative modalities, including ultrasound, nonsteroidal anti-inflammatory medications, trigger-point injections, over-the-counter orthoses, and stretching exercises. When the pain was not relieved by these conservative measures, magnetic resonance imaging of the area was performed. Visualization of the insertional area of the plantar fascia revealed a mass inferior to, as well as infiltrated into, the plantar fascia. Surgical excision of the lesion resulted in complete elimination of the patient's pain.

[Cervical necrotizing fasciitis].

Necrotizing fasciitis of the head and neck is a rare infection caused by a mixed bacterial flora with anaerobic predominance. Mortality is due to misdiagnosis which results in late and inadequate treatment. The natural course of this serious infection involves spreading necrosis of the soft tissues of the neck with erosion of major blood vessels. A 33-year-old man and a 66-year-old woman are presented to demonstrate the usual etiological factors of cervical necrotizing fasciitis, mainly dental and pharyngeal infections. Diagnosis is by bacteriological culture and CT-scan; a high degree of clinical suspicion is necessary. Treatment included aggressive surgery, appropriate antibiotic coverage and hyperbaric oxygen, and resulted in successful outcomes in our 2 cases.

Early recognition of neonatal abdominal wall necrotizing fasciitis.

Necrotizing fasciitis (NF) of the abdominal wall occurring in newborns is associated with a 50% mortality rate. Improved survival requires early diagnosis followed by aggressive surgical débridement. During a 10-year period, we treated 7 infants who developed NF. During the same period, 32 infants were admitted with omphalitis that did not progress to NF. The patients with omphalitis and those with NF were compared. Tachycardia, abnormal white blood cell counts, induration, and violaceous skin discoloration were seen exclusively in the NF patients. Polymicrobial infections were documented in 28% of the omphalitis patients and 86% of the NF patients. All omphalitis patients survived, whereas 5 of 7 (71%) NF patients died. Adjuvant hyperbaric oxygen therapy was used for 4 infants with NF, 2 of whom survived (50%). NF is a highly morbid disease, that can be distinguished from other infant abdominal wall infections by the skin changes, white blood cell counts, heart rate, and microbiologic results. Prompt diagnosis of NF improves survival when combined with aggressive surgical débridement.

Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis. A clinical and experimental study.

Between 1971 and 1987, 32 patients with clostridial gas gangrene were treated in the Department of Surgery, University of Turku. A presumptive diagnosis of gas gangrene was made on the basis of the clinical appearance of the patient and a predominance of Gram positive rods on stain. Between 1973 and 1989, 11 patients with perineal necrotizing fasciitis (Fournier's gangrene) were treated. The diagnosis was based on fulminating progression of perineal gangrene and on the presence of multiple pathogenic organisms in the primary Gram stain or culture. All patients in both series underwent surgical debridement, antibiotic therapy, and intensive care. In addition, the patients were exposed to pure oxygen at 2.5 atmospheres absolute pressure (ATA) for 120 minutes. Three such treatments were given during the first 24 hours after admission after which the treatment was repeated twice daily. Seventeen patients with clostridial gas gangrene had diffusely spreading myonecrosis; 6 died. Fifteen patients developed clostridial cellulitis with toxicity; 3 died. Thus, the overall mortality in gas gangrene was 28%. All the 9 patients who died had been transferred from other hospitals in Finland and were moribund on arrival. The infection in 8 of these patients developed postoperatively. None of the patients with a posttraumatic infection died. Each of the patients with Fournier's gangrene had had nonspecific symptoms before the gangrene became evident. The infection originated from the anorectal area in 5 patients, 1 patient had sustained a scrotal trauma and in 5 patients the underlying condition was unknown. One patient died 2 days after admission. Six patients required a colostomy. To evaluate the therapeutic value of hyperbaric oxygen (HBO) treatment, two experimental models of clostridial gas gangrene, mono- and multimicrobial, were developed in rats. In the monomicrobial infection model, 10(7) colony forming units (cfu) of Clostridium perfringens were injected intramuscularly into the left hind limb of the rat. The mortality of untreated rats was 100%. The mortality of the rats treated with surgery alone was 38% compared to 13% when surgery was used in combination with HBO (p < 0.01; chi 2 test). In the group treated with HBO and surgery, 94% of the survivors healed completely and were able to walk normally, whereas the corresponding figure in the rats treated with surgery alone was 20% (p < 0.001; chi 2-test). In the multimicrobial gas gangrene model the infection was induced by an intramuscular injection of a mixture containing approximately 10(7) cfu of each of the following bacteria: Clostridium perfringens, Bacteroides fragilis, Escherichia coli and Streptococcus faecalis.(ABSTRACT TRUNCATED AT 400 WORDS)

Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with eosinophilia.

The eosinophilia-myalgia syndrome, which is associated with the ingestion of L-tryptophan that contained products, occurred as an epidemic in the United States in 1989. Eosinophilia-myalgia syndrome is similar in many ways to the toxic-oil syndrome, which occurred in Spain in 1981, and to diffuse fasciitis with eosinophilia, which has been noted since 1974 to occur sporadically. Recent studies have clarified the epidemiology, histopathology, and clinical features of eosinophilia-myalgia syndrome. These studies are reviewed, and comparisons to the related syndromes, toxic-oil syndrome and diffuse fasciitis with eosinophilia, are made.