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Clinical and Translational Allergy volume 10Article number: 1 Cite this article. Metrics details. A Correction to this article was published on 28 September Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades.
However, it has been very well documented that—potentially severe—side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking.
Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease. Allergic rhinitis AR is the best-known form of non-infectious rhinitis and is associated with an IgE-mediated immune response against allergens [ 1 ].
However, a substantial group of rhinitis patients has no known allergy and they form a very heterogeneous non-allergic rhinitis NAR patient population suffering from drug-induced rhinitis, occupational rhinitis, irritant-induced rhinitis, hormonally linked rhinitis and idiopathic rhinitis [ 23 ].
When inflammation of the nasal mucosa extends to the mucosa of the paranasal sinuses, the consensus term of rhinosinusitis is used. In addition to rhinitis symptoms, rhinosinusitis is characterized by postnasal drip, facial pressure and reduction or loss of smell [ 5 ].
Acute rhinosinusitis ARS is a very common condition and mostly of viral origin [ 5 ]. About 0. Additionally, chronic upper airway disease often coexists with lower airway problems, most frequently asthma, but also a link with chronic obstructive pulmonary disease COPD and bronchiectasis has been reported [ 6 ].
Glucocorticosteroids GCS are the oldest and most widely used anti-inflammatory therapy. Since their introduction in the s, GCS have played a key role in the treatment of various inflammatory, allergic, and immunologic disorders.
Consequently, they are known as a very effective drug for treating chronic airway inflammatory diseases involving both lower as well as upper airways [ 147 ]. GCS can be administered topical or systemically. Therefore, the risk—benefit ratio of treating non-life-threatening upper airway diseases with systemic GCS remains debatable and needs clarification.
This document summarizes the current evidence for beneficial as well as harmful effects of administration of systemic GCS in the different types of upper airway disease and aims at providing recommendations about its use in rhinitis and rhinosinusitis based on the current evidence. For each topic 2 experts in the field were appointed to review the literature and topics that were appropriate for clinical recommendations were considered as evidence-based reviews with recommendations.
The experts then provided a recommendation based upon the guidelines of the American Academy of Pediatrics following the recommendation strategy used by the International Consensus on Allergy and Rhinology [ 9 ]. Generally, the search was focused on adults. Two experts reviewed the literature specifically for the pediatric population. The search strategy was based on a combination of MeSH-terms and free text words.
Search terms are listed in Additional file 1. Corticosteroids, which are produced by the adrenal glands, can be classified as glucocorticoids and mineralocorticoids. Cortisol is the endogenous glucocorticoid in humans, naturally derived from cholesterol metabolism upon stimulation by the hypothalamic—pituitary—adrenal axis Fig.
The hypothalamic—pituitary—adrenal axis. Stress stimuli induce the production of CRH by the hypothalamus. CRH induces the production of ACTH by the pituitary gland which stimulates the production of glucocorticoids cortisol in the adrenal gland cortex. Cortisol acts on many cells, tissues, and organs including the immune system. The excessive release of cortisol as well as proinflammatory cytokines have a negative feedback on the central nervous system by inhibiting this circadian cycle.
GCS are involved in several physiologic functions. They control the metabolism of carbohydrates, proteins and lipids, as well as the balance of calcium [ 1112 ]. However, the most explored effects of GCS are the anti-inflammatory and immune-suppressive functions. GCS inhibit the activation and survival of inflammatory cells and modulate the activity of structural cells [ 1314 ].
This affects recruitment, localization, protein synthesis, and survival of inflammatory cells such as eosinophils [ 15 ]. The recruitment of inflammatory cells is also diminished by an inhibited expression of adhesion molecules such as ICAM-1 and VCAM-1 [ 16 ], which affects the influx of basophils and mast cells in the epithelial layers of nasal mucosa.
Finally, GCS are involved in the pathological wound repair mechanism called remodelling. Remodelled tissue such as the stroma of nasal polyps contains abundant infiltration of inflammatory cells, increased fibroblasts numbers and increased extra-cellular matrix deposition.
However, GCS appear to be minimally effective in reversing the structural changes resulting from remodelling [ 17 ]. All these effects are exerted by intracellular activation of the glucocorticoid receptor GR [ 18 ]. Molecular mechanisms of glucocorticoid action. The anti-inflammatory effects of GCS are explained by three broad molecular mechanisms: the decreased expression of pro-inflammatory genes trans-repressionthe increased expression of anti-inflammatory genes trans-activationand non-genomic mechanisms.
AR is the most prevalent presentation form of all allergic diseases and the most com-mon chronic disorder in children. Moderate to severe disease not responsive to intranasal GCS, should be treated with additional pharmacological therapies including cromolyns and leukotriene receptor antagonistsallergen immunotherapy AIT and non-pharmacologic therapies such as nasal irrigation [ 3031 ].
Usually a combination of intranasal GCS and a topical or oral antihistamine is used for moderate to severe AR. The first randomized controlled trial RCT from showed a beneficial effect of a depot injection of 80 mg methylprednisolone MP vs. The second study by Brooks et al. Thirty-one patients were randomized to receive 0, 6, 12, or 24 mg MP. Oral GCS produced dose-related reduction in all symptoms. The difference between placebo and 24 mg MP was significant for all the symptoms monitored, except itching, which benefited marginally.
The third study by Laursen et al. This study showed a therapeutic index in favour of the depot injection versus oral treatment in AR [ 33 ]. These cases include patients with severe symptoms who do not respond to other drugs, or those who are intolerant to intranasal drugs [ 135 ].
Consequently, oral GCS can be used for a few days as in carefully selected cases when other medical treatment options have failed. Recommendation: Strong recommendation against. Option in patients suffering from very severe and therapy-resistant symptoms. NAR comprises a heterogeneous group of chronic rhinitis subtypes, such as drug-induced rhinitis, hormonal-induced rhinitis, some forms of occupational rhinitis and rhinitis linked to systemic diseases [ 37 ].
Up till now, no studies are available that investigate the effectiveness of systemic steroids in NAR or IR patients. However, since it is believed that in IR neurogenic pathways are involved, rather than classical inflammatory pathways [ 38 ], systemic GCS are not the therapy of choice. Of note, all IR patients included in a recent study investigating the effect of capsaicin in IR, reported lack of clinical response to intranasal GCS [ 38 ].
By extrapolation, there is a low likelihood of oral GCS being effective in this patient population, unless more than one etiologic or inflammatory mechanism underlies the development of rhinitis. Only in selected cases of other subtypes of NAR, such as rhinitis linked to vasculitic or systemic diseases, oral GCS might play a role in the treatment strategy see below [ 39 ].
Although oral GCS are often prescribed in patients suffering from rhinitis medicamentosa to overcome the withdrawal period of topical decongestants, there are no valuable studies supporting this clinical practice.
In an update of a Cochrane review was published [ 40 ] concluding that systemic GCS as a monotherapy are ineffective compared to placebo in ARS patients, but might have a beneficial effect on short-term symptom relief when used as an adjunctive therapy to antibiotics.
Up to date, five randomized, placebo-controlled trials investigating the effect of oral GCS in adults with ARS are available and included in the Cochrane meta-analysis Table 3. From those, only one focused on systemic GCS as a monotherapy [ 41 ].
In the patients who completed the trial, no clinically relevant benefit of prednisolone over placebo was found regarding facial pain or pressure, other nasal symptoms or quality of life. Gehanno et al. On day four, patients showed significantly less pain in the steroid group whereas nasal discharge did not significantly improve.
The use of additional medication was not reported. Intwo similar studies were published; a French study [ 43 ] showed a beneficial effect on pain with oral prednisone as an add-on therapy to cefpodoxime in ARS patients. Also Ratau et al. However, oral GCS in combination with antibiotics may be modestly beneficial for short-time symptom relief in adults suffering from ARS, compared to antibiotics alone, with a number needed to treat of seven [ 40 ].
Recommendation: Strong recommendation against when only mild to moderate symptoms. CRSsNP is characterized by basement membrane thickening, goblet cell hyperplasia, fibrosis, subepithelial oedema and influx of inflammatory cells that are mainly of the neutrophilic subtype with a cytokine pattern deviated towards the Th1 subtype [ 5 ].
Both retrospective studies investigated the effects of oral prednisone in conjunction with 1 month of oral antibiotics added to intranasal steroids and irrigations. Improved subjective and objective outcomes were seen after multimodality treatment schemes in both studies for CRSsNP.
The study of Subramamian et al. Lal et al. Two reviews were performed with respect to short-term oral GCS; one comparing oral GCS alone versus placebo or other treatment [ 55 ], and a second comparing oral GCS used as an adjunct to other treatments, versus control [ 56 ].
For oral GCS alone, 8 trials with a total of participants, all of whom were adult patients CRSwNP, were identified [ 5758596061626364 ]. All studies followed up patients to the end of the treatment course, and 3 followed patients for 3 to 6 months after completion. However, there was no difference between groups at 3 to 6 months after the course of treatment. Treatment doses utilized in included studies included prednisone at 30 mg and reduced over 14 days, prednisolone at 60 mg reducing over 17 days, or at constant dosage of 50 mg or 25 mg for 14 days, or reducing dosages of MP over 20 days.
Of the three studies that followed patients beyond the course of treatment, 2 prescribed ongoing intranasal GCS after completion of the systemic dose to both groups while one did not [ 586263 ]. Included trials were considered to be at low risk of bias, but overall the quality of evidence was rated as low due to the small numbers of participants, heterogeneity of outcome measures and limited follow-up time in most studies.
This study recruited 30 participants and was considered at high risk of bias because of lack of blinding and lack of information on randomization. One trial included in the Cochrane review of oral GCS as an adjunctive treatment recruited children [ 66 ] and is therefore considered later in this document. They can be used in a short course during 2—3 weeks as a last resort of treatment when combinations of other medications are ineffective.
Option for a short-term course in patients with severe symptoms and therapy-resistance. A separate indication, for which oral GCS have been prescribed in CRSwNP patients, is the preoperative setting, in order to reduce perioperative bleeding and improve surgical conditions for the surgeon during endoscopic sinus surgery ESS. Of the five studies that have been performed studying this topic in adults Table 6four are RCTs, however, their outcomes are not conclusive The study from Ecevit demonstrated a significant improvement on all perioperative variables studied perioperative bleeding, visibility of the operative field, operative time, hospital stay after a preoperative course of GCS in CRSwNP patients [ 59 ].
However, while some other studies confirm a significant improvement of intraoperative bleeding time [ 67 ] or quality of the operating field [ 68 ] and surgical time [ 69 ], these differences were not found to be significant by their colleagues [ 67686970 ]. A recent meta-analysis reported on a significant reduction in operating time, perioperative blood loss and improved surgical field quality when patients were given preoperative steroid treatment, however, the result was mainly based on a large RCT reporting on intranasal GCS [ 71 ].
Allergic fungal rhinosinusitis AFRS is a form of a non-invasive fungal rhinosinusitis and although it is not characterized by a specific phenotype, it seems to be an immunologically distinct subtype of CRS [ 72 ]. The diagnosis is based on the criteria proposed by Bent and Kuhn: 1 production of eosinophilic mucin without fungal invasion into sinonasal tissue; 2 positive fungal stain of sinus contents; 3 nasal polyposis; 4 characteristic radiographic findings; and 5 allergy to fungi [ 73 ].
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Does prednisone cause stuffy nose -
The incidence of gastrointestinal complaints did not differ between treatment groups. In a large nested case—control analysis based on the UK General Practice Research Database, cases of upper gastro-intestinal complications were compared to 11, controls and then evaluated for exposure to certain drugs e. No statistically significant difference could be objectified for lower versus higher dosage of GCS. To our knowledge no studies in upper airway disease patients report on systemic steroid treatment and peptic ulceration.
GCS have been described to induce the formation of posterior subcapsular cataract or glaucoma. The risk for patients using repeated short courses of systemic GCS for upper airway disease is currently unknown.
There is evidence in rheumatoid arthritis patients that this risk is enhanced after therapy lasting more than 1 year [ ]. Another study by Huscher et al. These symptom patterns were compared to non-users no systemic GCS for at least 12 months.
This meta-analysis included a wide variety of diseases warranting systemic GCS. The true risk of developing infection in patients using short courses for upper airway disease remains uncertain. We found one case report on gluteal subcutaneous atrophy that was seen after a depot steroid injection of triamcinolone for AR [ ].
A study of Laursen et al. The study demonstrated that one out of 11, injections came with any local AE. Cardiovascular disease is mainly associated with high dose and long-term use, primarily hypertension and acute myocardial infarction are described [ , ]. Current use in the 3 months before the registration of an event and highest average daily dose give a much stronger association. Current use is also associated with a significantly increased risk of heart failure adjusted OR of 2.
Cardiovascular risk showed a clear dose—response relationship [ ]. A study from Hissaria et al. In the above-mentioned controlled trial by Venekamp et al. Two studies in asthmatic and ophthalmologic patients receiving short-courses of GCS, showed a development of hypo mania [ , ] as well as depression symptoms [ ]. Naber et al. The onset of symptoms was within 3 days of use and there was no correlation between daily dose and daily ratings of mood.
Brown et al. Mood changes returned back to normal after discontinuation of therapy. A randomised controlled trial by Campieri et al. Mean body weight increased with 2. Bar-Meir et al. Inflammatory diseases of the nose and paranasal sinuses in children include upper respiratory tract infections, chronic rhinitis, ARS and CRS.
Bacterial infection is expected when at least 3 symptoms are present among which discoloured discharge, purulent secretion in nasal cavity, severe local pain with a unilateral predominance, fever, elevated C-reactive protein or erythrocyte sedimentation rate, and double sickening i. The diagnosis is confirmed by either nasal endoscopy showing edema, purulent drainage or nasal polyps in the middle meatus or CT scan showing ostiomeatal complex or sinus opacification.
Of note, the presence of nasal polyps is much less common in pediatric patients than in adult patients with CRS [ ]. Three clinical trials can be found in literature that investigated the use of oral GCS in the pediatric rhinosinusitis population, of which only one is controlled Table There was also a significant beneficial effect of oral GCS in cough, nasal obstruction and post-nasal drainage symptom scores.
Recurrence of symptoms 6 months after the end of treatment was not statistically significant between the groups. Additionally, a retrospective study involving 35 young CRS patients 1—21 years undergoing serial sinus CT scans due to medical reasons, evaluated Lund Mackay ostiomeatal complex score in relation to three different treatment schemes [ ] antibiotics, intranasal topical GCS and oral systemic GCS. The data suggested that the use of systemic GCS was associated with a significant increase in the likelihood of radiologic improvement.
The retrospective study design, the small and heterogeneous population, heterogeneous treatment modalities, and the lack of adjustments, limit the possibilities to assess clinical significance of the findings. A second uncontrolled study [ 5 ] evaluated cytokine pattern of 30 asthmatic CRS patients 4—12 years before and after the treatment of amoxicillin—clavulanate, fluticasone propionate aqueous nasal spray and a short course of oral deflazacort. The uncontrolled study design and uncertainty whether the patients used prescribed drugs, limits the possibilities to assess effect of systemic GCS.
As an example, the Childhood Asthma Management Program trial followed the annual bone mineral accretion of children 5—12 years with mild-to-moderate asthma [ , ]. Oral GCS bursts produced a dosage-dependent reduction in bone mineral accretion 0. The authors conclude that multiple oral GCS bursts over a period of years can produce a dosage-dependent reduction in bone mineral accretion and increased risk for osteopenia in children with asthma. At the end of the treatment, the mean weight change did not differ statistically significantly between the groups.
A systematic review has been performed to determine the most common and serious drug-related AE of long courses of oral GCS in children [ ]. Literature search of several databases was performed to identify all studies in which systemic GCS had been administered to pediatric patients ranging from 28 days to 18 years of age for at least 15 days of treatment.
The group found 91 studies that represented a total of children and contained reports of adverse drug reactions, the majority in patients with leukaemia, haemangioma and asthma. The three most frequent adverse drug reactions were weight gain Increased susceptibility to infection was the most serious adverse drug reaction.
However, based on studies on pediatric asthma, a single short-term systemic GCS course could be considered in pediatric patients suffering from CRS that is not responding to other therapies such as intranasal GCS, antibiotics, supporting therapy saline douchings, decongestants and adenoidectomy.
Option in patients suffering from very severe and therapy-resistant disease, in combination with antibiotics. Besides clinical consequences, systemic GCS use may also have some health economic implications that should be considered in its benefit-harm trade-off. Generally, the direct costs for systemic GCS are among the lowest quartile of prices of medications available worldwide. However, the indirect costs due to adverse events of especially long-term, high-dose systemic GCS use could be more substantial.
Two industry-funded studies have assessed the cumulative economic burden of GCS associated adverse events regardless of dose, duration or indication [ , ].
Manson et al. A second review [ ] included 47 studies reporting on adverse events of systemic GCS. Subsequently, a cost analysis was undertaken from the US perspective. It was unclear whether any patients with allergic rhinitis or rhinosinusitis were included. Most frequently reported adverse events were psychiatric and gastric conditions, infections and fractures.
The authors estimated the potential cost reductions if the daily GCS dose would be reduced. The findings from both reviews should be interpreted with caution given the heterogeneous and often low-quality and retrospective nature of the studies included and the difficulty in excluding confounding due to underlying disease activity.
Besides these two reviews with no particular disease focus, some studies focused on the costs of systemic GCS related adverse events within a specific population such as asthma [ , ] or rheumatologic diseases [ , ] and found increased costs in the GCS exposed populations. None were specifically focusing on rhinitis or rhinosinusitis. We conclude that given the limited amount of current evidence, more studies on the economic burden and cost-effectiveness of systemic GCS use in rhinitis and rhinosinusitis treatment are required.
However, in AR, allergen immunotherapy AIT is an alternative option for patients suffering from uncontrolled symptoms.
AIT modifies the natural disease course and recent well-performed trials have demonstrated reductions in both symptoms and use of rescue medication in patients with AR for both the subcutaneous as well as sublingual administration route [ ].
One study from compared the efficacy of one depot MP injection with a pre-seasonal administration of an alum-precipitated pyridine extracted grass pollen immunotherapy and found similar results between the two groups in terms of symptom improvement [ ].
For CRS patients, current alternatives for oral GCS during exacerbations consist of antibiotics and when patients remain uncontrolled, sinus surgery is the next step in line [ 4 ]. Gevaert et al. They found a beneficial effect on NP score of doxycycline that was comparable to MP after 8 weeks. Also, omalizumab and mepolizumab treatment had better results on NP score than the oral GCS treatment. Omalizumab and mepolizumab additionally showed better symptom control compared to MP.
Currently only data on the oral steroid-sparing effects of mepolizumab and benralizumab in asthma are available [ ], but with the increased implementation of these therapies in CRSwNP, studies evaluating the steroid-sparing effect for upper airway exacerbations will be necessary. This manuscript provided an overview of the current evidence for the beneficial effects of systemic GCS in the different subtypes of upper airway diseases, as well as in the pediatric age group and aimed at providing recommendations for the specific disease entities.
However, multiple AEs have been widely described and therefore physicians should be aware of the risks associated with oral GCS and make a good risk—benefit assessment prior to prescribing them. In this paper, we summarize these potential AEs; given the current evidence in literature, a clear assessment of the risks associated with oral steroid use in upper airway disease cannot be made. Currently available data show a wide variability in diseases, patients, duration of treatment and follow-up and therefore this topic needs to be addressed in a systematic way in order to provide a substantiated recommendation for the use and dosing of oral GCS in the upper airway disease population.
We can conclude that, although some beneficial effects of systemic GCS have been demonstrated in chronic upper airway diseases such as AR and CRSwNP, systemic GCS should not be considered as a first line of treatment for these disease types.
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Short-term corticosteroids and avascular necrosis: medical and legal realities. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol. Researchers had suspected that an oral steroid might eliminate infections sooner than letting them run their course, because steroid nasal sprays have shown a small benefit in getting people to feel better a few days earlier see Reuters Health report of May 16, reut.
Venekamp and his colleagues asked patients who had come to see their doctors for nasal symptoms to take either 30 milligrams per day of prednisolone or placebo pills for one week. The participants had experienced nasal discharge or congestion and facial pain for at least five days. For two weeks, the people in the study kept a diary of their symptoms. The researchers, who published their findings in the Canadian Medical Association Journal, found that, for the most part, the symptoms lasted just as long in the steroid group as they did in the placebo group, between seven and nine days.
Also, a similar number of patients in each group felt totally free of symptoms within a week. Among those who took steroids, 33 percent reported no symptoms after one week, and among those who took fake pills, 25 percent reported no more symptoms.
Similarly, 63 percent of people in the steroid group reported no facial pain or pressure after one week, as did 56 percent of people in the placebo group.
By Kerry GrensReuters Health. Researchers had suspected that an oral steroid might eliminate infections sooner than letting them run their course, because steroid nasal sprays have shown a small benefit in getting people to feel better a few days earlier see Reuters Health report of May 16, reut.
Venekamp and his colleagues asked patients who had come to see their doctors for nasal symptoms to take either 30 milligrams per day of prednisolone or placebo pills for one week. The participants had experienced nasal discharge or congestion and facial pain for at least five days. For two weeks, the people in the study kept a diary of their symptoms. The researchers, who published their findings in the Canadian Medical Association Journal, found that, for the most part, the symptoms lasted just as long in the steroid group as they did in the placebo group, between seven and nine days.
Also, a similar number of patients in each group felt totally free of symptoms within a week. Among those who took steroids, 33 percent reported no symptoms after one week, and among those who took fake pills, 25 percent reported no more symptoms. Similarly, 63 percent of people in the steroid group reported no facial pain or pressure after one week, as did 56 percent of people in the placebo group. The researchers determined that these differences could have been due to chance, rather than to the medication.
He said that perhaps some types of patients might benefit, but more research is needed to find out who they are. In the meantime, patients are left with few options.
Previous studies have found that nasal spray steroids increase the chances of feeling better by only seven percent - meaning that only one of out 15 people who take them will benefit. Steroids also carry a risk of side effects, such as bone loss, for people who are on them long term, and physicians have expressed concern about the overuse of the medications see Reuters Health report of July 25, reut.
Antibiotics don't seem to offer much help to sinus infections either, and they too carry their own risks, such as stomach upset and drug resistance see Reuters Health report of February 15, reut. Rosenfeld said nasal spray decongestants and saline irrigation products, such as a neti pot, can help relieve symptoms.
Ultimately, patience will help see people through their infection and on to feeling better, said Rosenfeld, whose own research has found that 73 percent of people improve within seven to 12 days without taking antibiotics or steroids.
Nasal congestion (stuffy noses) may be caused by swollen or congested nasal tissues Corticosteroids are commonly used medications to treat many diseases. A short course of prednisone or methylprednisolone will almost certainly make you feel better. Steroids boost your energy level, alleviate pain and nausea. You have a greater chance of developing congestion if your nose is inflamed from allergies. Nasal corticosteroids relieve congestion by decreasing the. A short course of prednisone or methylprednisolone will almost certainly make you feel better. Steroids boost your energy level, alleviate pain and nausea. The steroid prednisolone is no better at reducing the symptoms of a sinus infection than a placebo, according to a new study. Ameratunga R. However, the indirect costs due to adverse events of especially long-term, high-dose systemic GCS use could be more substantial. Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients: a 4-year longitudinal study. Due to the heterogeneity in studies, treatment regimens and patient populations, we classified the side-effects according to the organ-system involved, but no further subdivision was made. Systemic corticosteroids for acute sinusitis. However, courses longer than 5 days were not found to provide any additional benefit [ 98 ].Alla prenotazione on line di andata biology la Sardegna, segnalo due adulti e due piccoli cani. Alla mia richiesta di cabina esterna, mi viene indica. Ero con un neonato e avevo molte cose tra cui anche naturalmente un. Successivamente mi arriva una mail d. Dopo che finalmente ha risposto, h.
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