COVID-19 and Corticosteroids: Unfamiliar but Potentially Fatal Infections That Can Arise following Short-Course Steroid Treatment.

Corticosteroid use is increasing worldwide as recent studies confer survival benefit of corticosteroids in the management of patients with severe COVID-19. Strongyloides and amebic infections are neglected diseases that can progress to catastrophic complications in patients exposed to corticosteroids, even with short treatment courses. To prevent lethal outcomes, clinicians should be aware of the threat these two parasitic infections pose to at-risk patients receiving corticosteroids, especially in the era of COVID-19.

Discrepancias en la clasificación de los glucocorticoides inhalados entre GEMA y GINA / Discrepancies Between GEMA And GINA In The Classification Of Inhaled Corticosteroids

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Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD.

Inhaled corticosteroids (ICSs) treatment combined with long-acting ß2-adrenoceptor agonists (LABAs) reduces the risk of exacerbations in COPD, but the use of ICSs is associated with increased incidence of pneumonia. There are indications that this association is stronger for fluticasone propionate than for budesonide. We have examined systematic reviews assessing the risk of pneumonia associated with fluticasone propionate and budesonide COPD therapy. Compared with placebo or LABAs, we found that fluticasone propionate was associated with 43%-78% increased risk of pneumonia, while only slightly increased risk or no risk was found for budesonide. We have evaluated conceivable mechanisms which may explain this difference and suggest that the higher pneumonia risk with fluticasone propionate treatment is caused by greater and more protracted immunosuppressive effects locally in the airways/lungs. These effects are due to the much slower dissolution of fluticasone propionate particles in airway luminal fluid, resulting in a slower uptake into the airway tissue and a much longer presence of fluticasone propionate in airway epithelial lining fluid.

Características de los corticoides particulados y no particulados. Condicionantes para su uso en el tratamiento del dolor crónico / Characteristics of particulate and non-particulate corticosteroids. Indications for their use in chronic pain treatments

El uso de corticoides en el tratamiento del dolor ha sido una práctica habitual desde mediados del siglo pasado. A raíz de una revisión de las complicaciones acontecidas con su administración por vía epidural, la Administración de Alimentos y Medicamentos de Estados Unidos (FDA) emitió una «controvertida alerta» solicitando se añada una «advertencia» en el etiquetado de los corticoides inyectables donde se deben describir dichos riesgos (pérdida de la visión, derrame cerebral, parálisis y muerte) al ser suministrados por esta vía. Es importante resaltar la existencia de diferentes clases de corticoides con características diversas que hace, que los potenciales efectos secundarios de su uso también sean distintos. Creemos necesario, en vista de los acontecimientos mencionados, las controversias que se han generado y la falta de estudios bien realizados sobre el uso de los corticoides, tanto en infiltraciones epidurales y como en otros procedimientos, comenzar por realizar una revisión general sobre sus indicaciones, efectos secundarios, complicaciones y características particulares de los diferentes compuestos en diversas enfermedades dolorosas (AU9

Corticosteroids been used frequently in pain treatments since the middle of last century (1952). Due to a review of the complications as a result of their application in epidural injections, the United States of America Food and Drug Administration (FDA) issued an «alert controversy» requesting that a warning label should be added to injectable corticosteroids, where risks must be described (loss of sight, brain damage, paralysis and death) when administering by this route. It must be mentioned that there are different types of corticosteroids with diverse characteristics, which as a result, may produce different side-effects. Due to the aforementioned developments, the controversies that have arisen, and the lack of well-conducted studies on the use of steroids in epidural injections, we must begin by reviewing their indications in different pain conditions (AU)

Reacciones de hipersensibilidad a corticoides / Hipersensitivity Reactions to Corticosteroids

Los corticoides son fármacos ampliamente utilizados en la práctica clínica, especialmente de forma tópica en dermatología. Estas sustancias pueden actuar como alérgenos y producir tanto reacciones de hipersensibilidad inmediata como retardada. La alergia en forma de dermatitis de contacto es la reacción más frecuente, y debe estudiarse mediante pruebas epicutáneas en unidades especializadas. Actualmente la batería estándar española tiene buenos marcadores para su detección, pero no ideales. Por ello, es rentable aplicar una batería específica de corticoides si dichos marcadores son positivos, así como los corticoides propios aportados por los pacientes. En cuanto a las reacciones de hipersensibilidad inmediata, son mucho menos habituales, pero potencialmente más graves. Debido a que estos fármacos son necesarios en múltiples enfermedades, es importante confirmar la sensibilización a estas sustancias, y orientar el uso de corticoides alternativos. En el presente artículo pretendemos revisar los principales conceptos respecto a estos 2 tipos de reacciones de hipersensibilidad en la alergia a corticoides, así como su abordaje en la práctica clínica

Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce immediate and delayed hypersensitivity reactions. Allergic contact dermatitis is the most frequent presentation of corticosteroid allergy and it should be studied by patch testing in specific units. The corticosteroids included in the Spanish standard battery are good markers but not ideal. Therefore, if those makers are positive, it is useful to apply a specific battery of corticosteroids and the drugs provided by patients. Immediate reactions are relatively rare but potentially severe, and it is important to confirm the sensitization profile and to guide the use of alternative corticosteroids, because they are often necessary in several diseases. In this article we review the main concepts regarding these two types of hypersensitivity reactions in corticosteroid allergy, as well as their approach in the clinical practice

Corticosteroid hypersensitivity studies in a skin allergy clinic.

INTRODUCTION: Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. MATERIAL AND METHODS: Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. RESULTS: We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. CONCLUSIONS: The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids.

[Naming and classification of steroids and human stress ulcers. Articles of historic significance published by Hans Selye 70 years ago]. / A szteroidok elnevezése, felosztása és az emberi stresszfekélyek. Selye János 70 éve megjelent történelmi jelentoségu cikkei.

The name of Hans Selye is mostly known worldwide as the discoverer of stress reaction. Yet, he made numerous other seminal and clinically relevant discoveries. Namely, since he had a focused research on steroid hormones originating from the adrenal cortex that play a crucial role in stress response, he was the first who introduced about 70 years ago the first classification of steroids that is still valid nowadays. This is based on three objective facts: (a) the names of steroid groups are identical with their organ of origin (e.g., corticoids from the adrenal cortex, testoids/androgens from the testis); (b) chemical structures of the steroids are identical within a group (e.g., all corticoids have pregnane nucleus with 21 carbon atoms); and (c) the biological effects are homogenous within a group (e.g., all glucocorticoids exert catabolic effect, while androgens are anabolic). It should be emphasized that Selye also discovered in animal models the pro-inflammmatory effect of mineralocorticoids and the anti-inflammatory properties of glucocorticoids, about 8-10 years before Nobel Prize was awarded to a physician for the first clinical use of adrenocorticotrop hormone and cortisone. Last, but not least, Selye was the first who recognized about 70 years ago the occurence of stress ulcers in humans, based on clinical reports on the huge increase in the number of perforated gastric anti-duodenal ulcers during bombings of London in World War II. The subsequent ulcer research by Selye`s former students and their contemporaries resulted in the recognition of anti-duodenal ulcer effect of dopamine, and the central gastroprotective actions of thyreotrop releasing hormone and endogenous opioids. Thus, Hans Selye made much more contributions to medical science and clinical practice than 'just' the discoverer of biologic stress response.

Sarcoidosis con afectación neurológica simulando una esclerosis múltiple: importancia de la imagen torácica / Sarcoidosis with neurological involvement imitating multiple sclerosis: The importance of thoracic imaging

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The topical corticosteroid classification called into question: towards a new approach.

Vasoconstrictor assay described in 1962 was an interesting assessment of potency of topical corticosteroids at the beginning of these new therapies, however knowledge and technology have evolved and the classification should follow. A topical corticosteroids with a strong vasoconstrictor effect, as determined by vasoconstrictor assay, has not necessary a strong anti-inflammatory effect. Therefore a specific classification adapted to the therapeutic target is needed to be more efficient and thus reduce side effects and corticophobia.

[Utility of challenge test in immediate hypersensitivity to hydrocortisone sodium succinate]. / Utilidad de la prueba de reto en hipersensibilidad inmediata a succinato sódico de hidrocortisona.

Corticosteroid hypersensitivity is a complex phenomenon in which many factors interact, such as idiosyncrasy, intolerance or allergic reactions. The prevalence of immediate hypersensitivity reactions to corticosteroids is 0.2%-0.5%. Corticosteroids have major therapeutic implications; thus, when hypersensitivity is suspected, in-vitro and/or in-vivo testing can be performed to confirm diagnosis, being the drug challenge the gold standard. After definitive diagnosis, cross-reactivity among the different corticosteroid groups should be considered, to choose wisely if corticosteroid therapy is still required. In Coopman classification, steroids belonging to groups A, B and D2 have high cross-reactivity, however, more studies are needed to determine the degree of cross-reaction among these drugs. This paper presents the case of a woman, in who hypersensitivity to hydrocortisone succinate was confirmed by drug challenge test.

La hipersensibilidad a corticoesteroides es un fenómeno complejo en el que interactúan múltiples factores como idiosincrasia, intolerancia o alergia. La prevalencia de las reacciones de hipersensibilidad inmediata a corticoesteroides es de 0.2 a 0.5%. Debido a la relevancia terapéutica de los esteroides, es importante confirmar el diagnóstico de hipersensibilidad con pruebas in vivo, in vitro, o ambas, el patrón de referencia es la prueba de reto con el fármaco implicado. Una vez realizado el diagnóstico y en caso de que se requiera continuar con el tratamiento con esteroides, deberá considerarse la reactividad cruzada entre los diferentes grupos propuestos en la clasificación de Coopman, en la que los corticoesteroides pertenecientes a los grupos A, B y D2 tienen una elevada reactividad cruzada entre sí; sin embargo, hacen falta más estudios para determinar el grado de reactividad cruzada entre estos fármacos. Comunicamos el caso de una paciente en la que se confirmó el diagnóstico de hipersensibilidad a succinato de hidrocortisona con la prueba de reto.

HANS SELYE 70 YEARS LATER: STEROIDS, STRESS ULCERS & H. PYLORI.

Although Hans Selye is mostly known for his discovery & development of the stress concept, he also introduced the first physiologically sound, structure-activity classification of steroids that was also based on the chemical structure of steroids in 1943. He not only introduced the names of glucocorticoids & mineralocorticoids but discovered the anti- & pro-inflammatory properties, respectively, of these steroids in animal models. Furthermore, he not only described the first stress-induced gastric ulcers in rats (1936) & characterized the first human 'stress ulcers' during the air-raids in London during World War 11 (1943). Thus, Selye was a much more productive & creative scientist than it is generally considered.

New insights about delayed allergic hypersensitivity to corticosteroids.

Corticosteroids are among the most commonly used drugs, both topically and systemically. Although unexpected and paradoxical, allergic hypersensitivity to corticosteroids is a common finding, delayed-type reactions being much more frequently encountered than the immediate-type ones. With regard to cross-reactions between corticosteroids, based on patch-test results and molecular modelling, we were recently able to simplify the previous classification into 3 different groups, i.e., Group 1: the non-methylated, most often non-halogenated molecules (Group A, D2 and budesonide), which produce most of the allergic reactions; Group 2: the halogenated molecules with a C16/C17 cis ketal/diol structure (acetonide Group B); and Group 3: the halogenated and C16-methylated molecules (Group C and D1) that only rarely produce allergy.

Exceso de peso y preguntas frecuentes sobre la alimentación del niño con cáncer / Overweight and frequently asked questions about feeding the child with cancer

Durante el tratamiento del niño con cáncer, es posible requerir el uso de corticoides, los cuales como efecto adverso tienen el aumento en el apetito, que unido al sedentarismo de estos niños, incrementan de peso y pueden concurrir en sobrepeso y obesidad, malnutrición que es tan dañina como la desnutrición. Es necesario un control y seguimiento estricto por parte del pediatra y nutricionista infantil en estos niños con malnutrición.

During the treatment of children with cancer, may require the use of corticosteroids, which have the adverse effect of increased appetite, which together with the inactivity of theses children, increased weight and may attend overweight and obesity, malnutrition that is as harmful as malnutrition. It is necessary to control and closely monitored by the pediatrician and infant nutritionist in these children with malnutrition.

El mejor tratamiento del brote grave es que no exista. El mantenimiento, la clave de la colitis / No best treatment for severe outbreaks: Maintenance, the key in colitis

Esponemos en la actualidad de diferentes fármacos que van a intentar conseguir el mantenimiento de la remisión de los pacientes que han obtenido respuesta tras uno u otro tipo de tratamiento de inducción en dependencia de la gravedad inicial del brote. Así, los salicilatos serán los fármacos de elección en el mantenimiento de la remisión obtenida tras brote leve-moderado controlado con los propios salicilatos o corticoides orales. Los fármacos tiopurínicos serán de elección en el mantenimiento de la remisión obtenida tras brote grave o de aquellos pacientes en situación de corticodependencia o corticorresistencia. Los fármacos biológicos, fundamentalmente infliximab, tienen su papel en el mantenimiento de la remisión de los pacientes tras inducción de brote grave con el propio infliximab en los que los fármacos tiopurínicos han fracasado y en aquellos pacientes con intolerancia a ellos. Pero estos escenarios no siempre coinciden con lo que el especialista en aparato digestivo se encuentra en la práctica clínica diaria y serán fundamentalmente las condiciones del propio paciente (edad, evolución de la enfermedad, tratamientos previos, efectos secundarios y opinión propia), así como el «arte desempeñado por el médico», lo que determinará finalmente la actitud individualizada para cada paciente en particular (AU)

Several drugs are currently available to maintain remission in patients who have responded after one or other type of induction therapy, depending on the initial severity of the outbreak. Salicylates are the drugs of choice to maintain remission after a mild-to-moderate outbreak controlled by salicylates or oral corticosteroids. To maintain remission after a severe outbreak or in patients with corticosteroid dependence or resistance, thiopurines are the drugs of choice. In patients who have failed to respond to thiopurines and in those with thiopurine intolerance, biological agents, mainly infliximab, can be used to maintain remission in patients after induction therapy with infliximab for a severe outbreak. However, these scenarios may not reflect reality of gastroenterologists’ daily clinical practice. Treatment will therefore be based on the patient's individual characteristics (age, clinical course, previous treatment, adverse effects and personal preferences) as well as the physician's medical art (AU)

Immediate and delayed hypersensitivity to corticosteroids.

Corticosteroids are therapeutic agents used in cases of allergy and intolerance. Due to the antiinflammatory effects of the corticosteroids, hypersensitivity reactions often are considered to be a paradox. However, delayed-type reaction to corticosteroids is a frequent phenomenon in the daily routine. Non-responding eczema, development of subacute contact eczema, systemic contact dermatitis or maculopapular exanthemas can be a clinical symptom of a delayed-type hypersensitivity reaction to corticosteroids. Immediate-type hypersensitivity reactions to corticosteroids remain uncommon. Nevertheless, they can take a severe clinical course. Patients react with anaphylaxis after systemic administration or with aggravation of an allergic reaction under therapy with corticosteroids. Allergologic testing is necessary for diagnosis and providing alternative corticosteroids in case of an emergency.

Corticosteroid cross-reactivity: clinical and molecular modelling tools.

BACKGROUND: Corticosteroids have been classified into following four cross-reacting groups in function of their contact-allergenic properties: A, B, C and D, the last subdivided into D1 and D2. Recent data indicate that C(16)-methylated and nonmethylated molecules need to be distinguished, the latter selectively binding with arginine to form stable cyclic adducts and producing considerably more positive reactions than the former. This study compares molecular modelling and patch-test results to determine cross-reactivity patterns. METHODS: The patch-test results obtained with 66 corticosteroid molecules in 315 previously sensitized subjects were analysed and correlated with modelling and clustering in function of the electrostatic and steric fields of these molecules. RESULTS: The classification obtained after in silico hydrolysis of C(21) and C(17) esters was selected with an optimal cut into three clusters: the patients who reacted positively to cluster 2 (halogenated molecules from group B, with C(16)/C(17) cis ketal or diol structure) and cluster 3 (halogenated molecules from groups C and D1, C(16)-methylated) also reacted to cluster 1 (molecules mostly from groups A and D2, without C(16)-methyl substitution or halogenation and budesonide). The reverse, however, was not the case. CONCLUSION: Two patient profiles with probably different areas of immune recognition are identified as follows: the profile 1 patients were allergic to the frequently positively reacting cluster 1 only, for whom electrostatic fields (molecular charge) seem important; the profile 2 patients reacted to clusters 1 and 2 and/or 3, for whom steric fields (structure) are determinant and who probably presented a global recognition of the corticosteroid skeleton. A modified classification is thus proposed.

Pattern of corticosteroid allergy in Thailand.

BACKGROUND: Corticosteroid allergy is a complication of topical therapy detected by patch-testing with corticosteroid allergens. OBJECTIVE AND METHODS: Ten-year retrospective review to study the prevalence and patterns of corticosteroid allergy in Thai patients. RESULTS: Of 882 patients who were patch-tested, 29 (3.29%) had allergic reactions to corticosteroids. Of these 29 patients, 17 (58.62%) had positive reactions to one corticosteroid, and 12 (41.38%) reacted to multiple corticosteroids. Rates of reaction to corticosteroid groups ranged from 31.03 to 80.95%. Concomitant reactions between groups were noted. The prevalence of topical corticosteroid allergy (using two screening allergens, tixocortol pivalate and budesonide) was 2.27% (20 of 882). Testing with additional steroid allergens in suspected cases increased the prevalence to 3.29%. Tixocortol pivalate detected 51.72% of corticosteroid-allergic cases, and budesonide detected 24.14%. Combining both tixocortol and budesonide detected 68.97% of cases. CONCLUSION: Corticosteroid allergy is found to multiple corticosteroids, and concomitant reactions occur across groups. Group D1 corticosteroid esters produced a higher positive reaction rate (61.9%) than groups D2 (52.38%) and A (51.72%). This may be due to different prescribing habits or the easy access to D1 corticosteroids sold over the counter by pharmacies in Thailand.