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Still, Fried said the conclusions are in line with September guidelines from a group of head and neck doctors, whose treatment options included observation without antibiotics for mild sinus infections. IE 11 is not supported. For an optimal experience visit our site on another browser. NBC News Logo. Politics Plan Your Vote U. News World Covid Business Opinion.

Acute sinusitis is on the rise again this time of year. Most sinus infections start as a virus, usually a common respiratory virus causing symptoms for around a week before resolving. The unlucky of us will then get a secondary bacterial infection that may warrant additional treatment.

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 6 , four 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 [ 67 , 68 , 69 , 70 ]. 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 ].

In view of the locally aggressive character of the disease, the cornerstone of AFRS treatment is surgery [ 74 ]. However, a lot of uncertainty remains concerning the medical options and postoperative therapy. Woodworth showed a significant reduction in nasal endoscopy scores and inflammatory markers in the AFRS group after 18 days of prednisone [ 76 ].

An older retrospective study from Kupferberg [ 77 ] in 26 AFRS patients, found that patients who received postoperative GCS showed more symptom improvement and less endoscopic disease compared to treatment with oral antifungals or no treatment. However, disease recurrence was noted after cessation of GCS.

Similar findings were seen in a non-controlled retrospective study from Kuhn and Javer [ 78 ] who showed a maintenance of low endoscopic scores in AFRS patients, only after long-term GCS use.

It has to be noted that all of these studies have a high risk of bias and the level of evidence for the use of oral GCS in AFRS patients remains at level C. GCS have been the major therapeutic option for some of these diseases as an immune suppressant for the past decades, probably being most effective where eosinophils, which are exquisitely steroid-sensitive, are involved [ 79 ]. The reasons for this include not only time-hallowed use, but also difficulty in undertaking placebo-controlled trials in severe diseases, differences in the manifestations and their intensity between individual patients, disease complexity and plasticity and probably lack of interest in funding.

This situation is now changing with the advent of newer therapies, particularly monoclonal antibodies, which are being trialled against older therapies including GCS [ 83 ]. Treatment must be tailored according to prognostic factors identified by the French Vasculitis Study Group [ 84 ].

GCS alone are used for mild disease, high-dose GCS and cyclophosphamide is still the gold standard for severe cases [ 85 ], but biological agents such as rituximab or anti-IL-5 biologicals are promising, though costly, alternatives [ 86 ]. GCS alone are insufficiently effective: the induction treatment for severe GPA comprises GCS combined with another immunosuppressant, cyclophosphamide or rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate.

GCS decrease the frequency, duration, and severity of flares in relapsing polychondritis, but do not stop disease progression in severe cases [ 88 ]. The presence of sino-nasal disease is associated with more severe sarcoidosis and the need for systemic GCS therapy [ 89 ]. Treatment for systemic lupus erythematosus SLE by various organ systems is not evidence-based beyond the usual first- or second-line treatment, however a recent meeting achieved consensus in several scenarios, including anti-phospholipid syndrome [ 90 ].

Table 8 shows the evidence available for auto-immune disorders for which GCS are frequently used. Recommendation: Following the recommendation for the management of the specific auto-immune disease.

AR and asthma often coexist and AR is regarded as a risk factor for the development of asthma. Uncontrolled rhinitis impacts asthma control. Asthmatic patients have a higher CRS severity score than non-asthmatic patients, and more nasal polyps, indicative of a strong relationship between CRS severity and asthma [ 93 ].

The first use of GCS to treat acute asthma exacerbation was in [ 96 ]. Development of GCS that have less mineralocorticoid activity, like prednisone, and later those that have no mineralocorticoid activity, like dexamethasone, made steroid use more attractive therapies to use in asthma. Prescribing a short course of oral GCS following the treatment of acute asthma exacerbations was found to reduce the rate of relapse [ 97 ].

However, courses longer than 5 days were not found to provide any additional benefit [ 98 ]. We could not identify any systematic review, randomized trial, or controlled study that evaluated the use of systemic GCS in patients with AR with concomitant asthma not responding to other therapy. When analysing the evidence of oral GCS for patients with CRS and coexisting asthma there are a few randomized controlled trials and uncontrolled prospective interventional studies that evaluated the efficacy of different treatments Table 9 of which only one looked at systemic GCS use.

This study was carried out in adults by Ikeda et al. Fifteen patients underwent ESS, and 6 other patients remained on medical therapy. Seven patients of the ESS group showed a reduction in the need for GCS during the 6 months following surgery, whereas two patients were unchanged and two patients required larger dosages.

With regards to the morbidity and potential mortality that is associated with asthma, the use of GCS in asthmatic CRS patients should be directed in the first place by the severity of the lower airway symptoms. Recommendation: Recommendation against. Option in patients with severe symptoms and therapy-resistance. However, few studies have actually addressed the risk of common GCS-induced AE in upper airway disease. Also, most of the studies available on GCS focus on high dose or long-term usage for at least 6 months or even 1 year consecutively, which is mostly less relevant in the upper airway disease patient group.

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. Studies investigating side-effects in children will be discussed separately in the next chapter. Reductions in the level of plasma cortisol are reported after one injection of GCS. They usually decrease in the first 2 weeks after steroid administration, but slowly return to normal after 3 weeks, as has been demonstrated in patients with AR [ ].

Hedner et al. In a double-blind study by Laursen et al. Only the prednisolone treated patients showed reduction in plasma cortisol levels at 3 weeks. Bonfils et al. A retrospective study based on Danish National Registries, including 47, AR patients, demonstrated that treatment with at least one consecutive injection of depot corticosteroid for 3 years on a row was associated with an increased risk of being diagnosed with diabetes later in life RR 1.

The degree of new-onset diabetes associated with intermittent short-term oral GCS has not been clearly established. In the same Danish epidemiological study, Aasbjerg et al.

Osteopenia of the proximal femur was present in Rajeskaran et al. Overall, low bone mineral densities BMD; osteopenia or osteoporosis was These studies were recently evaluated in a systematic review which was unfortunately not able to quantify the overall risk of osteoporosis induced by oral GCS for CRSwNP, due to the low number of studies [ ]. The effects of short-course oral GCS on bone mineral density BMD have also been investigated in a 4-year longitudinal small study in asthmatic patients.

Asthmatic patients receiving frequent short courses of oral GCS i. Also, a lower Z-score of With regards to avascular necrosis of the femoral head in patients treated with systemic GCS for upper airway disease, we found 1 case report of Nasser et al. More individual case reports highlight the relationship between the use of systemic GCS and avascular necrosis.

The risk to develop osteonecrosis seems to be dependent on the prescribed dose, the cumulative dose and route of administration, as well as underlying disease states SLE patients seem to be particularly at risk [ , , ]. In a randomized double-blind placebo-controlled study by Kirtsreesakul et al. In a double-blind placebo-controlled trial by Venekamp et al. 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.

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.

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One moment, please -



 

The U. Marvin Fried, otolaryngology chairman at Montefiore Medical Center in New York, questioned whether all the patients in the study had true sinus infections. Still, Fried said the conclusions are in line with September guidelines from a group of head and neck doctors, whose treatment options included observation without antibiotics for mild sinus infections.

IE 11 is not supported. For an optimal experience visit our site on another browser. NBC News Logo. 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. Article PubMed Google Scholar. Toxicology of the nose and upper airways. London: Informa Healthcare; Google Scholar.

Idiopathic rhinitis, the ongoing quest. EPOS European position paper on rhinosinusitis and nasal polyps A summary for otorhinolaryngologists. Medical treatment reverses cytokine pattern in allergic and nonallergic chronic rhinosinusitis in asthmatic children.

Pediatr Allergy Immunol. Hens G, Hellings PW. The nose: gatekeeper and trigger of bronchial disease. Mullol J, Alobid I. Combined oral and intranasal corticosteroid therapy: an advance in the management of nasal polyposis? Ann Intern Med. Santiago T, da Silva JA. Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years. Ann N Y Acad Sci. Classifying recommendations for clinical practice guidelines. Article Google Scholar.

The glucocorticoid receptor: a revisited target for toxins. The effects of glucocorticoids on adipose tissue lipid metabolism. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Endocr Rev. Barnes PJ. Glucocorticosteroids: current and future directions. Br J Pharmacol. The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore.

Trends Endocrinol Metab. Effects of topical anti-inflammatory drugs on eosinophil survival primed by epithelial cells. Additive effect of glucocorticoids and nedocromil sodium. Clin Exp Allergy.

Mechanism of action of glucocorticoids in nasal polyposis. Braz J Otorhinolaryngol. Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling. Eur Respir J. Glucocorticoid receptors in human airways. Control of transcription by steroid hormones. Expression of glucocorticoid receptor alpha- and beta-isoforms in human cells and tissues.

Am J Physiol Cell Physiol. Glucocorticoid receptor physiology. Rev Endocr Metab Disord. Mol Biol Cell. Alpha and beta glucocorticoid receptors: relevance in airway diseases. Curr Allergy Asthma Rep. Ray A, Prefontaine KE. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases.

Life Sci. Importance of glucocorticoid receptors in upper and lower airways. Front Biosci. Expression of the glucocorticoid receptor alpha and beta isoforms in human nasal mucosa and polyp epithelial cells. Respir Med. 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. In general, uncomplicated acute sinusitis is treated conservatively for days, assuming a self-resolving viral infection is to blame.

When symptoms are persisting longer than expected for a viral illness then generally we turn to an appropriate antibiotic class and duration. Relapsing infections should consider early sinus CT imaging to confirm diagnosis.

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    Naber et al. Stress stimuli induce the production of CRH by the hypothalamus. Also Ratau et al.

Acute sinusitis is on the rise again this time of year. Most sinus infections start as a virus, usually a common respiratory virus causing symptoms for around a week before resolving. The unlucky of us will then get a secondary bacterial infection that may warrant additional treatment.

Here is a Link to the Otolaryngology Practice Guideline on Adult Sinusitis which is helpful for physicians to review for proper evidence-based treatment of sinusitis this covers acute and chronic infections, but admittedly little attention is given to the first seven days of sickness.

Clinical efficacy of a short course of systemic steroids in nasal polyposis. Treatment of chronic rhinosinusitis with nasal polyposis with oral steroids followed by topical steroids: a randomized trial. Oral steroids and doxycycline: two different approaches to treat nasal polyps.

Effect of glucocorticoids on nasal polyposis, with detection of inflammatory response by measurement of nitric oxide levels in nasal polyp tissue. J Laryngol Otol. Efficacy and tolerability of systemic methylprednisolone in children and adolescents with chronic rhinosinusitis: a double-blind, placebo-controlled randomized trial.

Effect of premedication with systemic steroids on surgical field bleeding and visibility during nasosinusal endoscopic surgery. Acta Otorrinolaringol Espanola. Wright ED, Agrawal S. Impact of perioperative systemic steroids on surgical outcomes in patients with chronic rhinosinusitis with polyposis: evaluation with the novel perioperative sinus endoscopy POSE scoring system. Preoperative corticosteroid oral therapy and intraoperative bleeding during functional endoscopic sinus surgery in patients with severe nasal polyposis: a preliminary investigation.

Ann Otol Rhinol Laryngol. Oral steroids and intraoperative bleeding during endoscopic sinus surgery. Role of corticosteroids in functional endoscopic sinus surgery—a systematic review and meta-analysis.

Role of fungi in pathogenesis of chronic rhinosinusitis: the hypothesis rejected. Diagnosis of allergic fungal sinusitis. Luong A, Marple BF. Allergic fungal rhinosinusitis. Systemic corticosteroids for allergic fungal rhinosinusitis and chronic rhinosinusitis with nasal polyposis: a comparative study.

Alterations in eotaxin, monocyte chemoattractant protein-4, interleukin-5, and interleukin after systemic steroid treatment for nasal polyps. Prognosis for allergic fungal sinusitis.

Allergic fungal sinusitis: a four-year follow-up. Eosinophils in autoimmune diseases. Front Immunol. Arthritis Rheum. Treatment of Churg—Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis Churg—Strauss, EGPA : monocentric experiences in patients. Ann Rheum Dis.

Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol. Ann Med Interne. CAS Google Scholar. Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Sinonasal involvement in sarcoidosis: a case-control study of 20 patients. Treatment algorithms in systemic lupus erythematosus. Arthritis Care Res. Acta Otorhinolaryngol Ital.

Bousquet J. Global initiative for asthma GINA and its objectives. Relationships between severity of chronic rhinosinusitis and nasal polyposis, asthma, and atopy. Prevalence of nasal polyposis in France: a cross-sectional, case-control study. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease.

Corticosteroids for preventing relapse following acute exacerbations of asthma. Duration of systemic corticosteroids in the treatment of asthma exacerbation; a randomized study. Intern Med. Endoscopic sinus surgery improves pulmonary function in patients with asthma associated with chronic sinusitis.

Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data.

Dose-related patterns of glucocorticoid-induced side effects. Martinez-Devesa P, Patiar S. Oral steroids for nasal polyps. Systemic corticosteroid treatment for seasonal allergic rhinitis: a common but poorly documented therapy. Hedner P, Persson G. Suppression of the hypothalamic-pituitary-adrenal axis after a single intramuscular injection of methylprednisolone acetate.

Ann Allergy. Intramuscular betamethasone dipropionate vs. Adrenal suppression and osteoporosis after treatment of nasal polyposis. Treating allergic rhinitis with depot-steroid injections increase risk of osteoporosis and diabetes. Prevalence of metabolic bone disease among chronic rhinosinusitis patients treated with oral glucocorticoids. The risk of osteoporosis in oral steroid treatment for nasal polyposis: a systematic review.

Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients: a 4-year longitudinal study. Lesson of the week: depot corticosteroid treatment for hay fever causing avascular necrosis of both hips. Avascular necrosis after oral corticosteroids in otolaryngology: case report and review of the literature.

Allergy Rhinol. Steroid induced osteonecrosis: an analysis of steroid dosing risk. Autoimmun Rev. Richards RN. Short-term corticosteroids and avascular necrosis: medical and legal realities. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. Ameratunga R. Gluteal subcutaneous atrophy after depot steroid injection for allergic rhinitis.

World Allergy Organ J. Medicolegal implications of common rhinologic medications. Otolaryngol Clin North Am. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Mood changes during prednisone bursts in outpatients with asthma. J Clin Psychopharmacol.

A prospective study. The Global Budesonide Study Group. The Israeli Budesonide Study Group. Hamilos DL. Pediatric chronic rhinosinusitis. Radiologic outcomes in children with chronic rhinosinusitis and ostiomeatal complex obstruction after medical management. Ann Allergy Asthma Immunol. Effect of long-term corticosteroid use on bone mineral density in children: a prospective longitudinal assessment in the childhood Asthma Management Program CAMP study.

Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D. Long-course oral corticosteroid toxicity in children. Arch Dis Child. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use.

Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther. The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis. Respir Res. Health care resource use and costs associated with possible side effects of high oral corticosteroid use in asthma: a claims-based analysis. Clinicoecon Outcomes Res. The cost of glucocorticoid-associated adverse events in rheumatoid arthritis.

Cumulative burden of oral corticosteroid adverse effects and the economic implications of corticosteroid use in patients with systemic lupus erythematosus. Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis? Comparison of preseasonal and coseasonal allpyral with Depo-Medrone in summer hay-fever. Specific immunotherapy can greatly reduce the need for systemic steroids in allergic rhinitis.

Rivero A, Liang J. Anti-IgE and anti-IL5 biologic therapy in the treatment of nasal polyposis: a systematic review and meta-analysis. The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps.

Sahota J, Robinson DS. Update on new biologics for intractable eosinophilic asthma: impact of reslizumab. Drug Des Dev Ther. Download references. Hippocrate 10, , Brussels, Belgium. Upper Airway Research Laboratory, Dep. Bispebjerg University Hospital, Copenhagen, Denmark. Center of Rhinology and Allergology, Wiesbaden, Germany. You can also search for this author in PubMed Google Scholar. All authors contributed to the design, drafting, writing and revising of the document.

All authors read and approved the final manuscript. Correspondence to Valerie Hox. All these are outside the submitted work. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Reprints and Permissions. Hox, V. Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper. Clin Transl Allergy 10 , 1 Download citation. Received : 30 November Accepted : 02 December Published : 03 January Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. This article has been updated. Abstract 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. Table 1 American Academy of Pediatrics defined strategy for recommendation development [ 9 ] Full size table.

Mechanisms and actions of GCS Corticosteroids, which are produced by the adrenal glands, can be classified as glucocorticoids and mineralocorticoids.

Full size image. Evidence for efficacy of systemic GCS in different inflammatory upper airway diseases 1. Allergic rhinitis AR is the most prevalent presentation form of all allergic diseases and the most com-mon chronic disorder in children. Table 8 summary of the evidence for efficacy of systemic steroids in the treatment of auto-immune disease Full size table. Hyperglycemia and diabetes A retrospective study based on Danish National Registries, including 47, AR patients, demonstrated that treatment with at least one consecutive injection of depot corticosteroid for 3 years on a row was associated with an increased risk of being diagnosed with diabetes later in life RR 1.

Osteoporosis In the same Danish epidemiological study, Aasbjerg et al. Avascular necrosis With regards to avascular necrosis of the femoral head in patients treated with systemic GCS for upper airway disease, we found 1 case report of Nasser et al. Gastrointestinal disturbances and peptic ulceration In a randomized double-blind placebo-controlled study by Kirtsreesakul et al. Ocular adverse effects GCS have been described to induce the formation of posterior subcapsular cataract or glaucoma.

Local adverse effects of steroid-injections We found one case report on gluteal subcutaneous atrophy that was seen after a depot steroid injection of triamcinolone for AR [ ]. Cardiovascular adverse effects Cardiovascular disease is mainly associated with high dose and long-term use, primarily hypertension and acute myocardial infarction are described [ , ]. To our knowledge, the risk in patients using GCS for intermittent short courses is unknown. Neuropsychiatric effects A study from Hissaria et al.

Benefit and risk of use of GCS in pediatric populations Inflammatory diseases of the nose and paranasal sinuses in children include upper respiratory tract infections, chronic rhinitis, ARS and CRS.

Health economic considerations related to GCS use Besides clinical consequences, systemic GCS use may also have some health economic implications that should be considered in its benefit-harm trade-off. Availability of data and materials Not applicable. Change history 28 September An amendment to this paper has been published and can be accessed via the original article. Acknowledgements Not applicable. View author publications. Ethics declarations Ethics approval and consent to participate Not applicable.

Consent for publication Not applicable. All other authors declare that they have no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information. Additional file 1. Search terms. About this article. Cite this article Hox, V. Copy to clipboard. Contact us Submission enquiries: Access here and click Contact Us General enquiries: info biomedcentral.

Inflammation and excess mucous can cause nose congestion, headaches and eye and face pain. Causes include bacteria, viruses, fungal infections and allergies. The U. Marvin Fried, otolaryngology chairman at Montefiore Medical Center in New York, questioned whether all the patients in the study had true sinus infections. Still, Fried said the conclusions are in line with September guidelines from a group of head and neck doctors, whose treatment options included observation without antibiotics for mild sinus infections.

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In the British study, people suffering from facial pain and a runny nose with greenish or yellowish mucous generally improved within about two weeks — whether they took the standard antibiotic amoxicillin, steroid nose spray or fake medicine. Antibiotics, particularly the penicillin-like drug amoxicillin, are among the most commonly prescribed medicines for sinus infections. Steroid sprays sometimes are used, but the study found they also were no better than dummy drugs, although they appeared to provide some relief for patients with only minor symptoms.

Ian Williamson of the University of Southampton in England. Inhaling steam and squirting salt water into the nose to flush out thick mucous are among other methods that sometimes provide relief, he said.

Researchers randomly assigned adults to receive one of four treatments: milligrams of amoxicillin three times daily for seven days and units of steroid spray for 10 days, only amoxicillin, only steroid spray, or fake medicine.

Sinus infections are diagnosed in about 31 million Americans each year and are among the most common reasons for doctor visits. In the United Kingdom, primary care doctors see 50 or more cases a year, the study authors said. The infections affect air spaces called sinuses around the nose and in the lower forehead. Inflammation and excess mucous can cause nose congestion, headaches and eye and face pain.

Causes include bacteria, viruses, fungal infections and allergies. The U. Marvin Fried, otolaryngology chairman at Montefiore Medical Center in New York, questioned whether all the patients in the study had true sinus infections.

Still, Fried said the conclusions are in line with September guidelines from a group of head and neck doctors, whose treatment options included observation without antibiotics for mild sinus infections. IE 11 is not supported. For an optimal experience visit our site on another browser. NBC News Logo. Politics Plan Your Vote U. News World Covid Business Opinion. Search Search. Profile My News Sign Out.

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localhost › Ear, Nose & Throat › Treatment. A short course of prednisone or methylprednisolone will almost certainly make you feel better. Steroids boost your energy level, alleviate pain and nausea. The changes in nasal symptoms were used for assessing the effect of prednisone treatment in these subjects. Paranasal sinus computed. The steroid prednisolone is no better at reducing the symptoms of a sinus infection than a placebo, according to a new study. Steroids such as prednisone and cortisone help to reduce inflammation and swelling. Steroid injections are typically used for joint and muscle pain. Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review. Bar-Meir et al. Option for a short-term course in patients with severe symptoms and therapy-resistance.

Clinical and Translational Allergy volume 10 , Article 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 [ 2 , 3 ].

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 [ 1 , 4 , 7 ]. 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 [ 11 , 12 ]. 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 [ 13 , 14 ].

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-repression , the increased expression of anti-inflammatory genes trans-activation , and 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 antagonists , allergen immunotherapy AIT and non-pharmacologic therapies such as nasal irrigation [ 30 , 31 ].

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 [ 1 , 35 ]. 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. In , two 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 [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. 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 [ 58 , 62 , 63 ]. 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 6 , four 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 [ 67 , 68 , 69 , 70 ].

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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