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.

Eosinophilic fasciitis (Shulman disease).

The eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by symmetrical and painful swelling with a progressive induration and thickening of the skin and soft tissues. The diagnosis of EF is often based on the association of characteristic skin or subcutaneous abnormalities and a thickened fascia with an inflammatory infiltration, mostly composed of lymphocytes and eosinophils. A peripheral eosinophilia is frequently present, but is not mandatory for the EF diagnosis. The diagnosis might be helped by a muscle magnetic resonance imaging which typically may evidence an increased signal intensity within the fascia and marked fascia enhancement after gadolinium administration at the acute phase of the disease. Differential diagnoses should be ruled out, including eosinophilia-myalgia syndrome (EMS) after L-tryprophane ingestion, hypereosinophilic syndromes (HES), systemic sclerosis, Churg-Strauss syndrome, and/or peripheral T cell lymphomas with cutaneous involvement. Due to the scarcity of the EF disease, there is no consensual therapeutic strategy. However, oral corticosteroids remain the mainstay treatment and may be associated to an immunosuppressive drug such as methotrexate in patients with morphea-like lesions or an unsatisfactory response to corticosteroids alone.

Arteritis de células gigantes: una causa infrecuente de tos crónica / Giant cell arteritis: and uncommon cause of chronic cough

No disponible

Strain-dependent acute lung injury after intra-tracheal administration of a 'refined' aniline-denatured rapeseed oil: a murine model of the toxic oil syndrome?

Most attempts to reproduce the toxic oil syndrome in animals, either with case-related oils or with refined rapeseed oils, have been unsuccessful. An aniline-denatured rapeseed oil that was subsequently refined according to a protocol yielding relevant markers of "toxic oil" (oil RSO160401) had led to possibly relevant lesions following oral administration in mice. Therefore, in the present study, RSO160401 was subjected to a more extended in vivo testing. To try and maximize the response, BALB/c, DBA/2, A/J, and C57BL/6 mice were administered RSO160401 oil by a single intra-tracheal instillation (1ml/kg), with sacrifice 2 or 7 days post-exposure. Intra-tracheal administration led to a strain-dependent acute response: acute pulmonary damage in DBA/2 and A/J mice, and increases in blood eosinophilia in DBA/2 mice (6.5% vs 3.1% in controls). The pulmonary lesions regressed with time after exposure, being more complete in A/J than in DBA/2 mice. The observation of strain-dependent effects suggests that genetic susceptibility is an important factor in disease induction by the RSO160401 oil.

[Diagnostic problems in eosinophilic fasciitis]. / Problemy diagnostyczne zwiazane z eozynofilowym zapaleniem powiezi.

We presented two cases with symptoms of diffuse swelling of subcutaneous tissue, stiffness and tenderness of involved areas, fever, eosinophilia and hypergammaglobulinemia. The inflammatory infiltrates consisting of lymphocytes, plasma cells and eosinophils were yielded in fascia. The difficulties in differentition of the symptoms between eosinophilic fasciitis and "eosinophilia-myalgia syndrome" are discussed.

Eosinofilia: las 215 causas mas frecuentes / Eosinofilia: the 215 more frequent causes

Para la clasificación de la eosinofilia se tienen en cuenta varios parámetros, el más utilizado es el recuento de eosinófilos; la cual la clasifica en leve, moderada y severa, también se ha utilizado para la clasificación el mecanismo de producción, que la divide en clonal y no clonal y el grado de infiltración de tejidos, que la clasifica en tisular, medular y periférica; todas estas han sido realizadas de manera arbitraria. Teniendo en cuenta; las diferentes causas de clasificación, se encuentra la eosinofilia clonal, como una manifestación neoplásica derivada de las células madres CD34, y la eosinofilia no clonal como una manifestación reactiva inducida por mecanismos relacionados a las enfermedades con las cuales se encuentran asociadas; entre estas están, las enfermedades infecciosas; en este grupo sobresalen las infestaciones parasitarias como la causa más frecuente, las enfermedades alérgicas; en particular las reacciones de hipersensibilidad tipo I, las enfermedades inmunológicas no alérgicas; que son divididas en tres grupos; enfermedades autoinmunes órgano-específicas, órgano-inespecíficas y las inmunodeficiencias, encontramos también las asociadas a cáncer; de las cuales se hará mención a las más frecuentes, las alteraciones endocrinas y metabólicas; en donde la insuficiencia suprarrenal en pacientes infectados por el virus de la inmunodeficiencia humana es la que más reporte tiene, las de origen farmacológico y los trastornos idiopáticos; en el que entra el síndrome hipereosinofílico, como un conjunto de trastornos heterogéneos que se definen por un recuento de eosinófilos superior a 1.500 por mm3 por más de seis meses, con compromiso de órganos blancos y exclusión de otras posibles causas de eosinofilia y otros casos de eosinofilia más raros como la eosinofilia familiar y la eosinofilia idiopática adquirida. Es importante recordar que independiente de la causa y del nivel de eosinófilos, el paciente tiene el derecho al diagnóstico y tratamiento...

Panniculitis.

The classification of inflammatory disorders of the subcutaneous tissue has mystified dermatologists for decades. Overlapping clinical and histologic features, and a lack of specific treatments have added to the confusion. This article initially classifies the various panniculititides by their primary histopathologic pattern: (1) septal panniculitis without vasculitis, (2) septal panniculitis with vasculitis, (3) lobular panniculitis without vasculitis, and (4) lobular panniculitis with vasculitis. Subsequently, we describe the key clinical findings in the most important forms of panniculitis. We begin with the most common form of panniculitis, erythema nodosum. Indeed, in many patients suspected of having panniculitis, a worthwhile question to consider initially might be, "Is this, or is this not, erythema nodosum?" before engaging in an elaborate (and expensive) exercise in differential diagnosis.

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.

Rigorous new approach to constructing a gold standard for validating new diagnostic criteria, as exemplified by the eosinophilia-myalgia syndrome.

BACKGROUND: Constructing diagnostic criteria, a common problem in clinical medicine, is particularly difficult for diseases that lack a pathognomonic "gold standard." To develop an improved strategy for constructing such criteria, we used the eosinophilia-myalgia syndrome as an example. The goal, for research classifications, was to construct validated clinically sensible criteria and to develop improved methods that can be used for other disorders. METHODS: Using a "pattern-based" approach with data from several separate sources, a committee of investigators first prepared and informally tested criteria for the diagnosis of eosinophilia-myalgia syndrome. A gold standard challenge set of reports of cases and noncases was independently generated and separately validated by an external panel of clinical experts. The criteria were then tested using the gold standard set, and interobserver variability and diagnostic accuracy were determined. RESULTS: Interobserver variability showed the following mean proportionate agreements: 98.7% for the presence of specific criteria elements, 99% to 100% for diagnosis, and 97% to 98% for diagnostic pattern. kappa Values were correspondingly high. Diagnostic accuracy showed sensitivity at 88%, specificity at 97%, and overall accuracy at 92%. CONCLUSIONS: The proposed criteria are accurate and reproducible, and can be used in future clinical investigations of the eosinophilia-myalgia syndrome. The new strategy and methods developed for this challenge can be valuable for solving analogous problems in constructing criteria for other clinical disorders.

[Eosinophilic myositis in a 9 year old boy]. / Miositis eosinofílica en un niño de 9 años.

INTRODUCTION: Eosinophil infiltration of skeletal muscle is rare, but often no etiological factor can be identified and these are isolated eosinophilic myositis. They may be associated with parasite infections or drugs, or be features of rare systemic disorders of hypereosinophilia, such as the myalgia eosinophilia syndrome and the idiopathic hypereosinophilic syndrome. The eosinophilic myopathies should be distinguished from the commoner inflammatory myopathies such as polymyositis and dermatomyositis. CLINICAL CASE: A nine year old boy with slight motor clumsiness but normal psychomotor development and neurological findings. Laboratory findings showed slightly raised serum transaminases (SGOT 271, SGPT 157 UI/L), CPK 7517 UI/L and eosinophilia (707/mL). Investigations for myoglobin cysticercosis, trichinosis, hydatidosis and toxicariasis were negative. No parasites were found in the faeces. The gammaglobulins were normal. Anti smooth muscle, antinuclear and anti KLM antibodies were negative. Cardiological studies were normal. His father, mother and two siblings had normal results of laboratory tests. Muscle biopsy showed inflammatory myopathy with abundant eosinophils, no evidence of parasites, no alteration of membrane proteins: dystrophin, sarcoglycan and merosine. Two years later he remains asymptomatic, maintains raised muscle enzyme levels in all tests with figures for CPK between 3,065 and 9,616UI/L, and eosinophilia ranging between 634 and 1,026/mL. Corticosteroid treatment was tried but no response obtained. CONCLUSION: We consider this to be a case of eosinophilic polymyositis which gives rise to many questions regarding etiopathogenesis, management and prognosis.

Neurologic, MR imaging, and MR spectroscopic findings in eosinophilia myalgia syndrome.

BACKGROUND AND PURPOSE: Eosinophilia myalgia syndrome (EMS), a multisystemic disease induced by exposure to L-tryptophan, may result in serious CNS abnormalities. The purpose of this study was to determine the pattern of neurologic characteristics, MR imaging abnormalities, and brain neurometabolites in EMS. METHODS: Sixteen patients with EMS and CNS abnormalities (CNS-EMS) and 12 control subjects underwent evaluation, including medical and neurologic examination, proton MR spectroscopy, and MR imaging. RESULTS: Neurologic findings that were increased in CNS-EMS included minor depression (100%), amnesia (88%), and intermittent confusion (38%), although fatigue (31%), motor disorders (31%), recurrent headache (19%), major depression (13%), and dementia (6%) also occurred, but at a lesser significance. Self-reported disability was markedly increased in CNS-EMS. MR imaging findings included subcortical focal lesions, focal lesions in deep white matter, cortical atrophy, ventricular dilatation, and diffuse and periventricular white matter abnormalities. MR spectroscopic findings established two distinct spectral patterns: 1) increased choline-containing compounds, decreased N-acetylaspartate, and increased lipid-macromolecules, consistent with inflammatory cerebrovascular disease; and 2) increased glutamine, decreased myo-inositol, and decreased choline, consistent with acute CNS injury or metabolic encephalopathy. CONCLUSION: Neurologic abnormalities, self-reported disability, brain lesions, and MR spectroscopic abnormalities are common in CNS-EMS. The pattern of cerebral lesions and neurometabolites is consistent with widespread inflammatory cerebrovascular disease. However, a subgroup of patients with CNS-EMS have neurometabolic changes consistent with a metabolic encephalopathy identical or similar to hepatic encephalopathy. The neurologic abnormalities in EMS and related hypereosinophilic syndromes should be interpreted cautiously, with the recognition that both cerebrovascular injury and secondary metabolic encephalopathies may be involved.

Pain, fatigue, and sleep in eosinophilia-myalgia syndrome: relationship to neuropsychological performance.

Cognitive problems are frequently reported in patients with eosinophilia-myalgia syndrome (EMS). This is the first study to explore, in EMS, the relationship between specific neuropsychological deficits and fatigue and pain. Relationships among depression, sleep disturbance, and neuropsychological deficits in EMS were also examined. Neither fatigue nor pain was correlated with memory impairment. Sleep disturbance was significantly correlated with verbal memory impairment, but not with deficits in visuospatial memory. These results suggest that cognitive loss in EMS cannot be attributed to pain or fatigue. Although some aspects of memory impairment may be associated with disturbed sleep, visual memory deficits are clearly independent of sleep deficits and may result from direct effects of the disease on the central nervous system.

[Neuromuscular diseases with eosinophilia]. / Les maladies neuromusculaires avec eosinophilie.

Neuromuscular diseases with eosinophilia include a number of disorders associated with variable degrees of muscle, peripheral nerve, and connective tissue involvement. Eosinophilic infiltration in blood and/or tissue is a consistent finding. In addition to the neurologic manifestations of systemic vascularitis, in particular Churg and Strauss syndrome, there are three main forms of neuromuscular disease. Diffuse fasciitis or Shulman syndrome which can be limited to the fascia or associated with perimyositis is sensitive to corticosteroids. Eosinophilic myositis corresponds to focal muscle involvement and is also sensitive to corticosteroids. Eosinophilic polymyositis is a manifestation of essential hypereosinophilic syndrome and is life-threatening. Eosinophilia-myalgia syndrome and toxic oil syndrome are separate entities that occur in outbreaks and involve poisoning by ingestion of L-tryptophan and adulterated oil containing aniline respectively. The key to diagnosis of these neuromuscular diseases is muscle biopsy to detect the presence of polynuclear eosinophils.