Table 4.

Summary of results: effect of oral systemic corticosteroids.

Name	Author and publication date	Type of study	Number of patients	Investigated drug	Side effects	Conclusions	Quality of evidence
Unexpected effects of systemic steroids on the CRSwNP proteome: is protein upregulation more important than inhibition? [32]	Workman 2020	Case series	12	16-day of oral prednisone 40 mg and decreasing by 10 mg every 4 days.	Not mentioned.	Systemic corticosteroids cause almost uniform upregulation of transcriptionally decreased proteins.	Low
Effect of prednisone on nasal symptoms and peripheral blood T-cell function in chronic rhinosinusitis [33]	Watanabe 2014	Prospective	39	Subjects received oral prednisolone with dose and length solely determined by the surgeon according to clinical judgement.	Not mentioned.	There were reduced sinonasal symptoms and a decrease in peripheral blood CD4+, CD25+, Foxp3+ cells (Tregs) after treatment with prednisolone with evidence of decreased Th1 as well as TH2 function.	Low
Efficacy of intranasal steroid spray (mometasone furoate) on treatment of patients with seasonal allergic rhinitis: comparison with oral corticosteroids [34]	Karaki 2013	Prospective	75	Betamethasone oral tablets 0.25 mg twice daily.	No major adverse events but some minor: stomachaches, sleepiness and slight headache.	No significant differences were found in the therapeutic effects of the topical and systemic corticosteroids tested.	Low
The effects of systemic steroid therapy on macrophage migration inhibitory factor concentrations in patients with nasal polyps [35]	Ekinci 2018	Prospective	49	1 mg/kg methylprednisolone reducing the dose by 10 mg every 3 days.	Not mentioned.	Serum macrophage migration inhibitory factor concentrations were significantly reduced after corticosteroid therapy.	Low
Doxycycline or oral corticosteroids for nasal polyps [36]	Grammer 2013	Randomized controlled trial	47	20 days of methylprednisolone (32 mg on day 1–5, 16 mg on day 6–10, and 8 mg on day 11–20).	Not mentioned.	There is evidence of an oral glucocorticosteroid burst for improvement in the signs and symptoms of nasal polyps. The effect is transient, essentially disappearing by 8 weeks after initiation of therapy.	Moderate
Short-term Oral Steroids Significantly Improves Chronic Rhinosinusitis Without Nasal Polyps [37]	De Silva 2021	Prospective	89	Prednisolone 0.5 mg/kg tapered over 10 days.	Six (8.9%) had side effects (poor sleep (n = 3), gastrointestinal symptoms (n = 2), mood disturbance (n = 1).	Short-term oral prednisolone significantly improved all three clinical measures of disease in CRSsNP patients and avoided surgical intervention in 52.5% of patients in the first 12 months.	Moderate
The effect of corticosteroid on metalloproteinase levels of nasal polyposis [38]	Yigit 2011	Case series	27	1 mg/kg/day methylprednisolone decreased 10 mg every third day.	Not mentioned.	Oral corticosteroid treatment especially reduces tissue matrix metalloproteinase-2 (MMP-2).	Low
Effect of systemic steroids on humming nasal nitric oxide in chronic rhinosinusitis with nasal polyposis [39]	Vaidyanathan 2010	Case series	12	2-week course of oral prednisolone, 25 mg/day.	Not mentioned.	Humming nasal NO increases after 2 weeks of oral corticosteroid therapy for CRSwNP.	Low
Treatment outcomes and predictors for systemic steroids in nasal polyposis [40]	Won 2012	Case series	47	20 mg/day prednisolone for 14 days.	Three dropped out due to abdominal discomfort.	Systemic corticosteroids improve nasal symptoms in patients with nasal polyposis.	Low
The effect of corticosteroid therapy on cyclooxygenase 2, vascular endothelial growth factor, and inducible nitric oxide synthase expression levels in nasal polyposis [41]	Yazici 2014	Case series	21	Oral prednisolone 1 mg/kg for 16 days while the dose reduced ¼ every 4 days.	Not mentioned.	Oral nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) expression levels of the inflammatory, epithelial and endothelial cells decreased.	Low
Clinical efficacy of a short course of systemic steroids in nasal polyposis [7]	Kirtsreesakul 2011	Randomized controlled trial	109	50 mg of prednisolone for 14 days.	Gastrointestinal disturbance (n=10), dyspepsia (n=4), fatigue, acne, sore throat, headache, insomnia and increased appetite (all n=1).	A short course of oral corticosteroids showed good clinical efficacy in the treatment of nasal polyposis.	Moderate
Treatment of chronic rhinosinusitis with pressure-pulsed corticosteroid inhalation [42]	Goektas 2013	Prospective	33	80 mg prednisolone daily decreasing to 10 mg for 12 days.	costiveness (n=1), lassitude (n=1), sleeping disorder (n=2), dry mouth (n=1) and parosmia (n=2).	Sinonasal olfactory disorder due to CRS can be treated with a systematic corticosteroid treatment.	Low
Interleukin-1 beta, interleukin-5, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in chronic sinusitis: response to systemic corticosteroids [43]	Lennard 2000	Prospective	15	Prednisone: day1–3 = 40 mg, day 4–6 =30 mg, 7–8 = 20 mg, 9–10 = 10 mg.	No instances of orbital, intracranial, gastric or metabolic complication due to oral corticosteroids occured.	78.6% reported symptomatic improvement with oral corticosteroids, whereas 3 (21.4%) reported no change in symptoms. No instances of orbital, intracranial, gastric, or metabolic complications due to oral prednisone occurred during the study.	Low
Gene expression analysis in sinonasal polyposis before and after oral corticosteroids: a preliminary investigation [44]	Bolger 2007	Prospective	10	Oral methylprednisolone: 32 mg to 0 mg.	Not mentioned.	There were significant changes in genes that direct expression of Th2 cytokines, chemokines, and receptors in human polyp tissue samples after oral corticosteroid treatment.	Low
The effectiveness of steroid treatment in nasal polyposis [45]	Tuncer 2003	Prospective	17	Oral methylprednisolone: 1 mg/kg reduced every fourth day by a ¼ for 16 days.	No major side effects of steroids were observed.	Corticosteroids can reduce polyp sizes and improve the symptoms but are inadequate to eradicate the polyps. Corticosteroids can delay the necessity for surgical intervention.	Very low
Short course of systemic corticosteroids in sinonasal polyposis: a double-blind, randomized, placebo-controlled trial with evaluation of outcome measures [46]	Hissaria 2006	Randomized controlled trial	40	50 mg oral prednisolone for 14 days.	Insomnia (n=8), mood disturbance (n=5), headache (n=2), dyspepsia (n=3), increased appetite (n=2), fatigue (n=2), backache (n=1), diarrhea (n=2), acne (n=1) and edema feet (n=1).	With a short course of systemic corticosteroids there is significant improvement in the symptoms and pathology of sinonasal polyposis.	High
Efficacy of systemic steroid treatment in sinonasal polyposis [47]	Berkiten 2013	Case series	75	Oral methylprednisolone 20 days (1 mg/kg/day for 5 days and then tapered down.	Not mentioned.	Systemic corticosteroid treatment caused a decrease in all nasal symptoms and polyp size, improved paranasal CT results, shortened the duration, improved the quality of the procedure and contributed to the prevention of recurrence.	Low
Alterations in eotaxin, monocyte chemoattractant protein-4, interleukin-5, and interleukin-13 after systemic steroid treatment for nasal polyps [48]	Woodworth 2004	Case series	21	Oral prednisone 12 days (60 mg daily for 3 days and then tapered down).	Not mentioned.	Corticosteroids significantly decreased all cytokine/chemokine levels.	Low
Treatment of smell loss with systemic methylprednisolone [49]	Schriever 2012	Prospective	425	Oral methylprednisolone 40 mg for 14 days reduced by 5 mg every other day.	No major side effects.	The effectiveness of systemic corticosteroids on olfactory dysfunction in a large patient population is confirmed.	Low
A Short Course of Oral Prednisone Followed by Intranasal Budesonide Is an Effective Treatment of Severe Nasal Polyps [50]	Benitez 2006	Prospective	84	Oral prednisolone 30 mg daily for 4 days, 2-day reduction of 5 mg followed by 400 μg intranasal budesonide twice a day for 12 weeks.	Not mentioned.	A short course of oral steroids improved all nasal symptoms. Intranasal steroid treatment was capable of maintaining the effect of oral steroid treatment, except in the loss of the sense of smell.	Low