Microproteinuria in patients with inflammatory bowel disease:Is it associated with the disease activity or the treatment with 5-aminosalicylic acid?

AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis （UC） and 25 with Crohn＇s disease （CD）, before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months （range 1-168 too）. Microalbuminuria （mALB） and urine levels of the renal tubular proteins β2-microglobulin （β2mGLB） and β-N-acetyI-D-glucosamidase （β-NAG） as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α （TNF-α） serum levels were also measured. RESULTS： A total of 277 measurements （194 in UC patients and 83 in CD patients） were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity （UCAI： P〈0.01; UCEI： P〈0.005）. mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION： Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.

5-aminosalicylicacid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.

Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.

Epstein-Barr virus is related with 5-aminosalicylic acid, tonsillectomy, and CD19^+ cells in Crohn's disease

AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals(controls), and evaluated different clinical scenarios(new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal(tonsillectomy and appendectomy) and therapeutic regimens(5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry(markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV Ig G antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV Ig G levels were observed in the group of patients that were not in a specific treatment(95.4 ± 53.9 U/m L vs 131.5 ± 46.2 U/m L, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV Ig G values(144.3 U/m L vs 102.6 U/m L, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment(138.6 vs 223.9; P = 0.022). The analysis of anti-EBV Ig G with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients(169.2 ± 20.7 U/m L vs 106.1 ± 50.3 U/m L, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on(134.0 ± 52.5 U/m L vs 127.7 ± 48.1 U/m L, P = 0.523).CONCLUSION: High anti-EBV Ig G levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.

5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro

AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining,respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122,P < 0.05; t = 3.086,P < 0.05,respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h,which showed an obvious time-effect relationship (t = 6.149,P < 0.05; t = 4.159,P < 0.05,respectively). At the concentration of 10-500 μmol/L,the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156,P < 0.001; t = 19.983,P < 0.001,respectively),while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828,P < 0.05; t = 14.024,P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448,P < 0.05; t = 4.428,P < 0.05,respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.

Duration of treatment with 5-aminosalicylic acid compounds

The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis,but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962,the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973,the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However,in 1985,a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.

Colon-specific drug delivery systems based on cyclodextrin prod rugs: In vivo evaluation of 5-aminosalicylic acid from its cyclodextrin conjugates

AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextrins （CyDs） through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat＇ s gastrointestinal tract after the oral administration was investigated. RESULTS： The 5-ASA concentration in the rat＇s stomach and small intestine after the oral administration of CyD- 5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-S-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone. CONCLUSION： CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.

Can 5-aminosalicylic acid suppository decrease the pain after rectal band ligation?

AIM: To investigate the effect of 5-aminosalicylic acid (5-ASA) suppositories on rectal band ligation-induced pain. METHODS: Sixty patients were randomized into two treatment groups. RESULTS: Our results showed that there was no difference between 5-ASA suppository group and the control group for pain control. CONCLUSION: 5-ASA may be an alternative treatment for hemorrhoids; however, it does not affect the rectal band ligation-induced pain.

Efficacy of Topical versus Oral 5-Aminosalicylate for Treatment of 2,4,6-Trinitrobenzene Sulfonic Acid-induced Ulcerative Colitis in Rats

5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.

5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis

AIM:To compare the mucosal concentrations of 5-aminosalicylic acid(5-ASA)resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.METHODS:The study included 130 inflammatory bowel disease(IBD)patients receiving 5-ASA as pH-dependent-release formulations(73 patients),time-dependent-release formulations(11 patients),or pro-drugs(18patients).In addition,28 patients were receiving topical treatment(2-4 g/d)with pH-dependent-release formulations.Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy.The 5-ASA concentrations(ng/mg)were measured in tissue homogenatesusing high-pressure liquid chromatography with electrochemical detection.The t test and Mann-Whitney test,when appropriate,were used for statistical analysis.RESULTS:Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA(51.75±5.72 ng/mg)compared with patients receiving pro-drugs(33.35±5.78 ng/mg,P=0.01)or time-dependent-release formulations(38.24±5.53 ng/mg,P=0.04).Patients with endoscopic remission had significantly higher mucosal concentrations of5-ASA than patients with active disease(60.14±7.95ng/mg vs 35.66±5.68 ng/mg,P=0.02).Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation(67.53±9.22 ng/mg vs 35.53±5.63 ng/mg,P<0.001).Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone(72.33±11.23 ng/mg vs 51.75±5.72 ng/mg,P=0.03).CONCLUSION:IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation,and the highest mean concentration was achieved using pH-dependent-release formulations.

Colon-specific prodrugs of 4-aminosalicylic acid for inflammatory bowel disease

Despite the advent of biological products, such as anti-tumor necrosis factor-&#x003b1; monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.

5-ASA in ulcerative colitis:Improving treatment compliance

5-aminosalicylic acid(5-ASA)compounds are a highly effective treatment for ulcerative colitis(UC).While UC patient compliance in clinical studies is over 90%, only 40%of patients in every day life take their prescribed therapy.Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration.Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine,it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon.5-ASA Multi matrix(MMx)is a novel,high strength(1.2 g),oral formulation designed for oncedaily dosing.It releases the active moiety throughout the colon.Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate,left-sided UC,and is comparable to a pH-dependent,delayed release 5-ASA (Asacol ),even if given once daily.Recently,the effectiveness in the acute phase of UC has been confirmed also in maintenance.In conclusion,at present,5-ASA MMx seems theoretically the best agent for maintaining patient compliance,and consequently,treatment effectiveness.

Current medical therapy of inflammatory bowel disease

INTRODUCTIONThe 1990’s have brought a significant promise and the hopefor a better and brighter future in the new millennium forpatients with inflammatory bowel disease(IBD).A betterunderstanding of the pathophysiology of IBD symptoms hasled to newer treatment modalities and streamlining oftherapy for specific subsets of patients.

Higher platelet P-selectin in male patients with inflammatory bowel disease compared to healthy males

AIM： To observe if the total amount of platelet P-selectin （tP-selectin） in patients with inflammatory bowel disease （IBD） was related to disease entity or activity, 5-aminosalicylic acid （5-ASA） medication or gender. METHODS： tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls. RESULTS： Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication. When the groups were split according to gender the male patient group showed higher levels of tP-selectin compared to male controls （153 ng/mL vs 94 ng/mL, P〈 0.05）. CONCLUSION： Increased tP-selectin levels may alter the inflammatory response and susceptibility to thromboembolic disease. As previously shown with soluble P-selectin, tP-selectin shows gender dependent differences important to consider in future studies.

Understanding of chemoprophylaxis and concordance in inflammatory bowel disease

AIM:To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with in? ammatory bowel disease (IBD). METHODS: A questionnaire-based study using a 5 point opinion scale was performed. One hundred and ninety-two patients with colitis only and 74 patients with primary sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall response rate was 58%. Sixtyfour percent of patients claimed full concordance with chemoprophylaxis for maintenance of remission. Eightyfour percent of patients considered daily concordance during remission to be very important. Seventy-five percent stated they understood the reasons for taking the drugs. However, only 50% of the patients were aware of any link of their condition to bowel cancer. Seventy-nine percent of patients felt their concordance and understanding would be improved if they were informed of the chemoprophylactic potential of the medication.

Isolated fever induced by mesalamine treatment

Adverse reactions to mesalamine,a treatment used to induce and maintain remission in inflammatory bowel diseases,particularly ulcerative colitis,have been described in the literature as case reports.This case illustrates an unusual adverse reaction.Our patient developed an isolated fever of unexplained etiology,which was found to be related to mesalamine treatment.A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving.Testing revealed no infection.A mesalamineinduced fever was considered,and treatment was stopped,which led to spontaneous resolution of the fever.The diagnosis was confirmed by reintroducing the mesalamine.One year later,this side effect was noticed again in the same patient after he was administered topical mesalamine.This reaction to mesalamine seems to be idiosyncratic,and the mechanism that induces fever remains unclear.Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity,an associated extraintestinal manifestation,or an infectious etiology.

Role of conventional therapies in the era of biological treatment in Crohn’s disease

Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized,placebo-controlled trials,and meta-analyses when available,that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD,modifying the treatment goals. However,the large majority of patients with CD will be managed through conventional therapy,even if they are a prelude to biological therapy.

Diverticular disease: A therapeutic overview

Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis. When diverticulosis becomes symptomatic, it becomes diverticular disease. Diverticular disease is common in Western and industrialized countries, and it is associated with numerous abdominal symptoms (including pain, bloating, nausea, diarrhea, and constipation). Standard medical therapies with antibiotics are currently recommended for patients affected by diverticular disease. However, changing concepts on the pathophysiology of the disease suggest that diverticular disease may share many of the hallmarks of inflammatory bowel diseases. On this basis, the addition of therapies using mesalazine and probiotics may enhance treatment eff icacy by shortening the course of the disease and preventing recurrences.

Current therapy of pediatric Crohn's disease

Inflammatory bowel diseases(IBD), including Crohn's disease(CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate,antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor(TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy- induction and maintenance of remission while improving the patient's growth and overall well-being.

Mesalamine treatment mimicking relapse in a child with ulcerative colitis

Background:There are reports on mesalamine-induced bloody diarrhea mimicking ulcerative colitis(UC)relapse,mostly in adults.Methods:Herein we present a case of a child with UC who developed relapse of hemorrhagic colitis related to mesalamine.Results:A 10-year-old girl developed severe symptoms mimicking UC relapse 3 weeks after introduction of mesalamine therapy.After mesalamine was withdrawn,her symptoms improved,but deteriorated again during the challenge of mesalamine despite concomitant use of corticosteroids.Conclusion:This is the fi rst case report on such a young child during the concomitant use of corticosteroids.