Can i have a tb test while on prednisone.Targeted TB Testing & Interpreting Skin Test Results
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Can i have a tb test while on prednisone
Because of a positive control in this assay, it is possible to identify those patients in which a result of tuberculosis testing is not available due to a lack of stimulation capacity of lymphocytes indeterminate result. Patients suffering from IBD are often treated with immunosuppressive agents, which may influence the results of tuberculosis testing. Methods: 50 consecutive patients were documented before introducing anti-TNF-treatment in this single centre study between April and April Results: For the period of one year data of 45 consecutive patients was available for statistical analysis.
A correlation between the indeterminate result and combination therapy of corticosteroids was found. The concomitant therapy of immunosuppressive agents lead to a lower IFN release but no significance was found. Conclusions: Steroid treatment and further combination therapy with immunosuppressive agents lead to a high risk of indeterminate QuantiFERON test. A common recommendation to exclude tuberculosis infection is to perform a chest radiography, which might exclude granulomas over the size of 1 cm, a detailed travel history and TB exposures as well as to measure the skin reaction of purified protein derivates of M.
The PPD test is a delayed-type-hypersensitivity reaction test towards a mixture of more than different M. An alternative diagnostic approach is to test the interferon gamma release as a specific reaction of T-cells on stimulation with M.
Furthermore, it has a higher sensitivity and the possibility to detect an indeterminate result via a positive reaction control. The therapeutic strategy in Crohn's disease and ulcerative colitis is the use of corticosteroids in the acute phase of inflammation and immunosuppressive agents like azathioprine and 6-mercaptopurine or methotrexate for maintenance of the remission phase.
The immunosuppressive therapy may influence also the test of latent tuberculosis. In the performance of the tuberculin skin test a positive control is not implicated, whereas a false indeterminate result cannot be detected. We assessed the rate of indeterminate results of QuantiFERON test and its association with corticosteroid and immunosuppressive treatment.
Consequently, we excluded these patients from all statistical analysis. This study was approved by the ethical committee of Lower Saxony, Hanover, Germany and was performed in concordance to Helsinki declaration. Laboratory parameters including liver enzymes, CRP, white blood cell count, haemoglobin, thrombocytes etc. In short: one ml of whole venous blood was added to each of the three assay kit-tubes nil, mitogen, antigen.
The tubes were transferred via courier to the performing laboratory for assay. Indeterminate results were defined as increase less than 0. The primary point was to determine the influence of indeterminate results of the QuantiFERON test by immunosuppressive agents. Based on Kolmogorov—Smirmov tests normal distribution could not be assumed.
Therefore we used median and quartile values box-whisker plots for data description. The probability for a valuable test was predicted by a logistic regression model. For the logistic regression we included corticoid therapy immunosuppression, blood cell count of erythrocytes, leucocytes, thrombocytes, C-reactive protein, iron serum level, sex and the diagnosis of Crohn's disease or ulcerative colitis.
The dose depending curve Fig. Further patient data is presented in Table 1. One patient out of 45 corresponding to 2. To describe the difference between the patient group receiving corticosteroid, corticosteroids and immunosuppression in combination or no concomitant medication we used the Mann—Whitney- U -test. The indeterminate results were associated with corticosteroid treatment and stronger association was found in patients with combined immunosuppressive therapy and corticosteroid treatment.
These findings depend upon the dose. A daily dose of 15 mg or more showed a high risk for indeterminate results. We analysed the stimulation capacity in dependence of immunosuppressive therapy.
The presented study shows the effect of anti-inflammatory agents on the outcome of testing the latent tuberculosis infection.
Corticosteroid treatment increases the risk for indeterminate results. Moreover, the combination of immunosuppressive medication with corticosteroids further increases the risk for an indeterminate result of the QuantiFERON test. Until now it is unclear, if this is due to the general immunologic situation of patients suffering from Crohn's disease or ulcerative colitis or not.
In the past the suspicion of modified immunologic reactions against tuberculosis agents in inflammatory bowel disease was discussed Fig. The therapeutic strategy against Crohn's disease and ulcerative colitis is the use of corticosteroids in the acute phase of inflammation and immunosuppressive agents like azathioprine and 6-mercaptopurine or methotrexate for maintenance of remission phase.
In patients with fistula disease and severe inflammation or failure to corticoid and or immunosuppressive therapy the treatment with anti-TNF-antibodies like Infliximab, Adalimuab or Certolizumab will be induced. In the presented patient group, However, in the presented patient population there was only one patient tested positively for latent tuberculosis infection.
We cannot comment on the risk for undiagnosed latent tuberculosis reaction because of the low number of patients with latent tuberculosis. We performed risk factors for the development of an indeterminate result and found that the corticosteroid therapy is the main risk factor for false negative results.
The risk increases with higher doses of corticosteroids and is supported by immunosuppressive agents. This is related to the reduced stimulation capacity of lymphocytes when patients receive corticoid treatment and is further reduced in case of concomitant therapy with immunosuppressive agents. The stimulation capacity is significantly higher in patients under immunosuppressive therapy when the daily corticoid dose is less than 15 mg prednisolone equivalent.
However, the presented study population might show a low rate of latent tuberculosis infections compared to other studies, 14,15,22 but, nonetheless, our data represents the low incidence of tuberculosis infection in the northwest of Germany. In the presented study a high rate of an indeterminate results occurred compared to the studies of Schoepfer at al. This might be due to the German recommendation of use of anti-TNF-therapy in patients with refractory disease to immunosuppressive agents or corticosteroids.
A couple of months ago Papay et al. However, in the IBD-cohort no data on the combined therapy with immunosuppressive agents and corticosteroids was available whereas in the second cohort data on corticosteroids is available and leads to similar results as the main risk factor for indeterminate results of the IFN-gamma release assay. Moreover we could show in the presented study an influence depending on the dose of corticosteroids on the results of QuantiFERON-test. In conclusion, we can confirm the data of Papay et al.
Moreover, we found a high correlation between the combination of immunosuppressive agents and corticosteroids in the presented study. Therefore, we recommend reducing the corticosteroid treatment to less than 15 mg prednisolone per day if corticosteroid treatment is combined with immunosuppressive agents before starting the QuantiFERON-test. If the clinical situation of the patient requires a high dose of corticosteroid treatment and does not allow a dose reduction of corticosteroids, we recommend excluding latent tuberculosis infection by chest-x-ray and detailed medical history.
The study-setup and the low patient number do not allow a comment on the risk for false negative results and no comparison to the tuberculin skin test. Travis S. Stange E. Lemann M. Oresland T. Chowers Y. Forbes A. European evidence based consensus on the diagnosis and management of Crohn's disease: current management Gut 55 Suppl. Google Scholar. Lin J. Ziring D. Desai S.
Kim S. Wong M. Korin Y. TNFalpha blockade in human diseases: an overview of efficacy and safety Clin Immunol 13 — Furst D. Problems encountered during anti-tumour necrosis factor therapy Best Pract Res Clin Rheumatol 20 — Keane J. Gershon S. Wise R. Mirabile-Levens E. Kasznica J. Schwieterman W.
Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent N Engl J Med — Malipeddi A. Rajendran R. Kallarackal G. Disseminated tuberculosis after anti-TNFalpha treatment Lancet Hoffmann J. Preiss J. Autschbach F. Buhr H. Hauser W. Herrlinger K. Clinical practice guideline on diagnosis and treatment of Crohn's disease Z Gastroenterol 46 — Zeitz M. Bischoff S. Brambs H. Bruch H. Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of Digestive and Metabolic Diseases and the competence network on inflammatory bowel disease Z Gastroenterol 42 —
❾-50%}- 1 Introduction
For the logistic regression we included corticoid therapy immunosuppression, blood cell count of erythrocytes, leucocytes, thrombocytes, C-reactive protein, iron serum level, sex and the diagnosis of Crohn's disease or ulcerative colitis.
The dose depending curve Fig. Further patient data is presented in Table 1. One patient out of 45 corresponding to 2. To describe the difference between the patient group receiving corticosteroid, corticosteroids and immunosuppression in combination or no concomitant medication we used the Mann—Whitney- U -test. The indeterminate results were associated with corticosteroid treatment and stronger association was found in patients with combined immunosuppressive therapy and corticosteroid treatment.
These findings depend upon the dose. A daily dose of 15 mg or more showed a high risk for indeterminate results. We analysed the stimulation capacity in dependence of immunosuppressive therapy. The presented study shows the effect of anti-inflammatory agents on the outcome of testing the latent tuberculosis infection.
Corticosteroid treatment increases the risk for indeterminate results. Moreover, the combination of immunosuppressive medication with corticosteroids further increases the risk for an indeterminate result of the QuantiFERON test. Until now it is unclear, if this is due to the general immunologic situation of patients suffering from Crohn's disease or ulcerative colitis or not.
In the past the suspicion of modified immunologic reactions against tuberculosis agents in inflammatory bowel disease was discussed Fig. The therapeutic strategy against Crohn's disease and ulcerative colitis is the use of corticosteroids in the acute phase of inflammation and immunosuppressive agents like azathioprine and 6-mercaptopurine or methotrexate for maintenance of remission phase.
In patients with fistula disease and severe inflammation or failure to corticoid and or immunosuppressive therapy the treatment with anti-TNF-antibodies like Infliximab, Adalimuab or Certolizumab will be induced. In the presented patient group, However, in the presented patient population there was only one patient tested positively for latent tuberculosis infection.
We cannot comment on the risk for undiagnosed latent tuberculosis reaction because of the low number of patients with latent tuberculosis. We performed risk factors for the development of an indeterminate result and found that the corticosteroid therapy is the main risk factor for false negative results.
The risk increases with higher doses of corticosteroids and is supported by immunosuppressive agents. This is related to the reduced stimulation capacity of lymphocytes when patients receive corticoid treatment and is further reduced in case of concomitant therapy with immunosuppressive agents.
The stimulation capacity is significantly higher in patients under immunosuppressive therapy when the daily corticoid dose is less than 15 mg prednisolone equivalent.
However, the presented study population might show a low rate of latent tuberculosis infections compared to other studies, 14,15,22 but, nonetheless, our data represents the low incidence of tuberculosis infection in the northwest of Germany. In the presented study a high rate of an indeterminate results occurred compared to the studies of Schoepfer at al. This might be due to the German recommendation of use of anti-TNF-therapy in patients with refractory disease to immunosuppressive agents or corticosteroids.
A couple of months ago Papay et al. However, in the IBD-cohort no data on the combined therapy with immunosuppressive agents and corticosteroids was available whereas in the second cohort data on corticosteroids is available and leads to similar results as the main risk factor for indeterminate results of the IFN-gamma release assay. Moreover we could show in the presented study an influence depending on the dose of corticosteroids on the results of QuantiFERON-test.
In conclusion, we can confirm the data of Papay et al. Moreover, we found a high correlation between the combination of immunosuppressive agents and corticosteroids in the presented study. Therefore, we recommend reducing the corticosteroid treatment to less than 15 mg prednisolone per day if corticosteroid treatment is combined with immunosuppressive agents before starting the QuantiFERON-test.
If the clinical situation of the patient requires a high dose of corticosteroid treatment and does not allow a dose reduction of corticosteroids, we recommend excluding latent tuberculosis infection by chest-x-ray and detailed medical history.
The study-setup and the low patient number do not allow a comment on the risk for false negative results and no comparison to the tuberculin skin test.
Travis S. Stange E. Lemann M. Oresland T. Chowers Y. Forbes A. European evidence based consensus on the diagnosis and management of Crohn's disease: current management Gut 55 Suppl. Google Scholar. Lin J. Ziring D. Desai S. Kim S. Wong M. Korin Y.
TNFalpha blockade in human diseases: an overview of efficacy and safety Clin Immunol 13 — Furst D. Problems encountered during anti-tumour necrosis factor therapy Best Pract Res Clin Rheumatol 20 — Keane J. Gershon S. Wise R. Mirabile-Levens E. Kasznica J. Schwieterman W. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent N Engl J Med — Malipeddi A. Rajendran R. Kallarackal G. Disseminated tuberculosis after anti-TNFalpha treatment Lancet Hoffmann J.
Preiss J. Autschbach F. Buhr H. Hauser W. Herrlinger K. Clinical practice guideline on diagnosis and treatment of Crohn's disease Z Gastroenterol 46 — Zeitz M. Bischoff S. Brambs H. Bruch H. Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of Digestive and Metabolic Diseases and the competence network on inflammatory bowel disease Z Gastroenterol 42 — Tissot F. Zanetti G. Francioli P. Zellweger J.
Zysset F. Influence of bacille Calmette-Guerin vaccination on size of tuberculin skin test reaction: to what size? Clin Infect Dis 40 — Mow W. Abreu-Martin M. Immunocompromised patients or individuals with no information regarding immune status were excluded from the present study. Immunocompetent children were defined as patients without the immunocompromised factors as described above. The demographic and clinical characteristics of children receiving low-dose systemic steroids included in the present study are presented in Supplementary Table S1.
The data were analyzed using SAS software, Version 9. Descriptive statistics were used to express continuous variables using median and interquartile range IQR and categorical variables using frequency and percentage. Potential factors associated with the attainment of indeterminate results were identified using univariable logistic regression analysis. Additionally, the Kruskal—Wallis test was used to make comparisons among the three age groups. P values less than 0. This study was performed in accordance with institutional and national regulations and approved by the institutional review board IRB of the Yonsei University Health System IRB approval number that waived requirements for informed consent due to the retrospective nature of the study.
Furin, J. Lancet , — Article Google Scholar. Ghosh, S. Tuberculosis infection in underyear-old refugees: Should we be screening? A systematic review and meta-regression analysis. Child Health 56 , — National Collaborating Centre for Chronic Consortium. Google Scholar. Mazurek, G. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, MMWR Recomm.
PubMed Google Scholar. Tebruegge, M. Lewinsohn, D. Haustein, T. The likelihood of an indeterminate test result from a whole-blood interferon-gamma release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status. Connell, T. Indeterminate interferon-gamma release assay results in children.
Meier, N. Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children—A systematic review and meta-analysis. Fan, P.
Effect of corticosteroids on the human immune response: Comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. Hammerschmidt, D. Corticosteroids inhibit complement-induced granulocyte aggregation.
A possible mechanism for their efficacy in shock states. Youssef, P. Pulse methylprednisolone in rheumatoid arthritis: Effects on peripheral blood and synovial fluid neutrophil surface phenotype. Effect of corticosteroids on the human immune response. Transplantation 26 , — Spika, J. Serum antibody response to pneumococcal vaccine in children with nephrotic syndrome. Pediatrics 69 , — Lahood, N.
Antibody levels and response to pneumococcal vaccine in steroid-dependent asthma. Ann Allergy 70 , — Herron, A. Influenza vaccination in patients with rheumatic diseases.
Safety and efficacy. JAMA , 53—56 Kubiet, M. Serum antibody response to influenza vaccine in pulmonary patients receiving corticosteroids. Chest , — Oliveira, S. Frequency of indeterminate results from an interferon-gamma release assay among HIV-infected individuals. Edwards, A. Thorax 72 , — Clifford, V. Tuberculosis Edinb. Belliere, J. Helwig, U. Crohns Colitis 6 , — Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection.
Bowel Dis. Bua, A. Decker, M. Influence of age and other factors on cytokine expression profiles in healthy children—A systematic review. In this cross-sectional study two hundred and fifty patients of RA above 18 years of age, classified using ACR criteria for RA, were enrolled from rheumatology outdoor. Demographics, disease activity, disease duration, and therapy were recorded. All patients underwent TST. Fifty-one Prevalence of tuberculin positivity in patients with RA was found to be low.
Results were not affected by methotrexate; however tuberculin skin test results in patients with recent use of steroids are likely to be negative. The association between rheumatoid arthritis RA and tuberculosis TB dates back to more than nine decades ago, when several clinicians in Germany and Forrestier in France related the chronic inflammation of tuberculosis to that of rheumatoid arthritis and thus used gold salts for the treatment of RA in the s [ 1 , 2 ] based on the fact that aurothiosulfate sodium was effective in the treatment of pulmonary tuberculosis [ 3 ].
Bahr et al. With time as further researches negated the etiological role of mycobacteria in RA, the relationship between the two took a turn so that the occurrence of two diseases together was not considered to be dependent on each other.
A large observational cohort study from Japan reported a 3. Similar results have been reported from Spain and Sweden even before the anti-TNF era whereas studies from US reveal no difference in incidence of tuberculosis between the general population and those suffering from RA on standard therapy [ 6 — 8 ]. Further with the introduction of biologicals for the treatment of RA, the issue of association between the two again gained acceleration. Various studies suggest 5- to fold increased risk of reactivation of latent TB with the use of anti-TNF antibodies [ 9 — 12 ].
Though there are studies regarding effect of RA therapy on incidence of tuberculosis, effect of DMARDs, which are used as standard therapy in patients of RA, on the result of tuberculin test is not known. This effect may have important implications on interpretation of results of tuberculin test prior to biological therapy. Prevalence of tuberculosis in India has been reported as per one hundred thousand population by Central TB Division, India, in its annual status report [ 13 ].
Informed consent was obtained from all the patients before any study related procedure. Patients with rheumatoid arthritis RA both males and females above 18 years of age, classified using ACR criteria for RA [ 16 ], were enrolled over a period of 20 months August to March All consecutive patients with RA, not already enrolled in our study, attending the Rheumatology clinic on each clinic day of our unit, giving consent and fulfilling the inclusion and exclusion criteria were enrolled regardless of the intake of therapy.
Patients with any other connective tissue disorder or arthritides other than RA, any immunosuppressive condition, and hematological malignancies, those on biologicals, pregnant females, and patients with active tuberculosis or past history of tuberculosis were excluded. Patients exposed to tobacco in form of tobacco chewing or active or passive smoking were classified as smokers while those not exposed to tobacco were classified as nonsmokers.
All patients were examined clinically, subjected to digital X-ray chest PA view, and investigated as required to exclude active tuberculosis. Every patient underwent tuberculin skin test. Results were read after 72 hours. According to the steroid intake patients were divided into three groups control S-patients without any steroid intake within last three months, I-patients with recent steroid intake defined as intake of any dose of steroid in any form oral, intramuscular, or intra-articular within 1 week prior to tuberculin test, and II-patients with history of steroid intake within last three months but not in last one week.
Statistical analysis was performed using SPSS Chi-square test was used to test the hypothesis about equality of proportion between the groups. A total number of patients, found eligible for the study, were invited to participate in the study from August to March Only patients consented out of which six patients did not turn up for TST reading after 72 hours and were thus excluded making the total number of participants in the study Primarily the patients were middle aged None of the patients had undergone a TST within last two years.
Demographic profile of different groups of patients based on methotrexate dose is given in Table 1. Though tuberculin positivity was not affected by MTX intake in patients Table 3 , it was significantly lower in patients with recent steroid intake Group I , as compared to patients without any steroid intake within 3 months control S.
There was no significant difference between control S and group II Table 4. A prospective study of serial tuberculin skin testing performed on patients from the chronic care wards of a Veterans Administration Hospital revealed a positive test in In a study in Taiwan, From India, Seal et al. In our study, The study was done at a single centre in North India and may need to be replicated on multicentric study.
Comparing the results from our study with the available population data, we can infer that presence of rheumatoid arthritis influences the results of tuberculin test in our population. In a study from Italy also, prevalence of latent tuberculosis using TST, among patients suffering from immunomediated inflammatory diseases, was found to be Lower rates of TST positivity in RA may be attributable to the disease itself or the drugs used for its therapy. Another suggestion from this study was that there is no effect of MTX dose on the results of tuberculin test.
However, even the low doses of recent steroid intake significantly reduce the chances of tuberculin positivity. These results echo the results from the past studies. A study carried out at Florence, Italy, revealed that the proportion of positive scoring for TST was significantly lower in patients on treatment with steroids compared with the proportion of positive results in patients who were not receiving treatment with steroids. Schatz et al. However, it is not statistically significant due to small number of patients but should be explored further in view of its clinical importance.
In this study, consecutive patients with RA, fulfilling the inclusion criteria, were enrolled from the outpatient department and then grouped according to their therapy.
This led to disproportionate groups which is a limitation of the study.
Background Reactivation of latent tuberculosis TB is a major complication of tumor necrosis factor alpha inhibitors TNF-i. Therefore, screening for latent TB is recommended before initiation of this treatment.
Currently, the cut-off size of a positive Tuberculosis skin test TST among immunosuppressed patients is 5 mm. It is vastly described in the literature that Prednisone treatment along with chronic inflammatory disease depresses TST reaction. Nevertheless, few studies reject this hypothesis. TST measurements, Prednisone and Methotrexate doses and treatment durations were recorded. Active tuberculosis TB was excluded by chest X-ray and patient's history. A control group, was randomly selected from healthy patients who had a TST at the pulmonology clinic in our institution.
We compared the results of the mean TST reaction size between the following three groups: RA patients with current prednisone treatment, RA patients without history of prednisone treatment and healthy individuals.
A correlation between this score and the size of the TST reaction was assessed using Pearson's correlation coefficient r. Results 43 mean age There was no significant difference in mean TST between these three groups 5. Therefore, we conclude that the criterion of 5 mm TST reaction defining latent TB infection in our population should be re-evaluated. Larger studies are needed to verify our results. You will be able to get a quick price and instant permission to reuse the content in many different ways.
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Conclusions Our results showed that TST reaction distribution among RA patients isn't affect by Prednisone therapy. In addition, RA patients may present TST. Prednisolone treatment was strongly associated with negative TST, AOR ( (p= ), and with an increased risk of indeterminate QFT-IT results AOR . Although skin testing programs should be conducted only among high-risk groups, certain individuals may require TST for employment or school attendance. The presented study shows the effect of anti-inflammatory agents on the outcome of testing the latent tuberculosis infection. Corticosteroid treatment increases. Conclusions Our results showed that TST reaction distribution among RA patients isn't affect by Prednisone therapy. In addition, RA patients may present TST. Further patient data is presented in Table 1. A systematic review and meta-regression analysis. MacDonald T. Search Search articles by subject, keyword or author. Register a new account? Another limitation of the study is that patients were on different forms and doses of different corticosteroids. Reitblat 1T.Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.
In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Multivariable logistic regression analysis identified younger age OR 0. Low-dose steroid therapy had the highest OR for the indeterminate results compared to other significant risk factors.
Our study suggests that screening for steroid doses is important prior to performing interferon-gamma release assays for immunocompetent children. This is higher than the mortality rate for all incident cases, suggesting poorer diagnosis and treatment for children. Therefore, early identification and treatment of LTBI in children is an important priority for effectively controlling TB. Of late, IGRAs are increasingly being used and supported by national guidelines to diagnose TB 3 , 4 ; however, their use in children is still limited.
Indeterminate results can either occur when there is a high response to the negative control or a low response to the positive control.
Therefore, the aim of the present study was to identify the factors associated with indeterminate QFT-GIT assay results in immunocompetent children. A total of samples were excluded based on the medical chart review. The exclusion criteria are presented in Fig. Overall, Of the determinate results, 9. Regarding the indeterminate results, 88 Flow chart presenting the protocol for inclusion in the present study. Comparisons made between the indeterminate and determinate groups are summarized in Table 1.
Univariable logistic regression analysis revealed the number of individuals with suspected active TB and unknown reason for IGRA test, white blood cell WBC count, C-reactive protein CRP , erythrocyte sedimentation rate ESR , and low-dose systemic steroid use was higher in the indeterminate group than that in the determinate group. However, the age at sampling, number of individuals screened for LTBI after exposure to TB patient s , and albumin levels were lower in the indeterminate group than in the determinate group.
Moreover, multivariable logistic regression analysis revealed that age at sampling OR 0. The proportion of indeterminate results was significantly lower in group C than groups A and B 5. Red lines indicate the median values. P values were calculated using the Mann—Whitney U test. The red lines indicate the median values. The median response to the TB antigen did not differ significantly among the three groups.
Individuals in the low-dose steroid group had a significantly higher proportion of indeterminate results than those in the non-steroid group Previous studies have reported that an immunocompromised status contributes to indeterminate QFT-GIT results for children 7.
We found that a younger age, high WBC counts, low albumin levels, and low-dose steroid use were significantly associated with indeterminate QFT-GIT results for immunocompetent children.
Even in healthy children, low-dose steroids are prescribed for a variety of anti-inflammatory therapeutic purposes. The effects of these low-dose steroids on IGRA testing in immunocompetent children can be overlooked. Our study showed that using low doses of steroids had the highest OR for the indeterminate results compared to all the other significant risk factors.
Supplementary Table S1 online demonstrates that the median dose and duration of steroid use was equivalent to 0. As a common cause of pneumonia, Mycoplasma pneumoniae was found in 4 cases, whereas parainfluenza virus was found in 1 case, and Streptococcus pneumoniae was found in 1 case. In the remaining three cases, the causative pathogen was not determined. Nevertheless, most IGRA tests were performed to screen TB as a differential diagnosis in these patients with pneumonia that presented with severe symptoms that did not respond to common antibiotics.
However, adverse effects of glucocorticoids on the immune system are both dose- and duration-dependent 10 , 11 , 12 , Although even low-dose steroids may adversely affect the functioning of the immune system in some individuals, the use of the lowest dose of glucocorticoids for the shortest period of time has not been implicated in increasing the risk of severe immunosuppression.
Therefore, administering killed or attenuated vaccines can proceed normally in children receiving low doses of steroids 14 , 15 , 16 , Several studies in adults have reported that patients receiving at least one immunosuppressive drug, including steroids, were at an increased risk of obtaining indeterminate results 5 , 21 , 22 , 23 , However, these studies were conducted in adult patients with underlying diseases, such as inflammatory bowel disease IBD or autoimmune disease, which have been commonly treated using steroids.
In addition, long-term steroid use is likely responsible for the immunosuppression observed in the aforementioned studies. However, our study revealed the effect of low-dose steroid use on indeterminate QFT-GIT results; patients with underlying diseases and those receiving immunosuppressive treatments were excluded.
Our findings suggest that even low-dose steroids can reduce T cell function and impact the IGRA response; thus, IGRA tests should be performed prior to the use of steroids and in patients that may benefit from its biologics. The results of the present study correspond with those of earlier studies which reported that young age was independently associated with a higher risk of obtaining indeterminate QFT-GIT results 5 , 7 , 8.
In particular, we observed that the response to the mitogen control PHA was significantly higher in children older than 10 years compared with that in children younger than 10 years old. Although it is not clear why this discrepancy occurs, these findings suggest that for children, the QFT-GIT assay requires correction for the positive control Mitogen according to the age group, but a correction is unnecessary for TB antigens.
Regarding the influence of laboratory findings on the QFT-GIT test, our results demonstrated that high WBC counts and low albumin levels were significantly associated with indeterminate results.
However, since the median value for the WBC count falls within the normal range for a child's age in both the indeterminate and determinate groups, and the OR value was not large, the WBC count was considered to have little effect on the IGRA test results.
However, since our study was conducted for immunocompetent children with no evidence of chronic inflammation, hypoalbuminemia may have affected the IGRA test results.
Therefore, further research is needed to elucidate the mechanisms underlying the effects of low albumin levels on IGRA testing. This study had several limitations. First, possible biases may have occurred due to the retrospective and single-center nature of this study. We attempted to reduce this effect by including a large cohort of immunocompetent children in the analysis. Second, we could not evaluate factors external to the patient, such as specimen handling and processing.
In addition, the age window for children in the determinate and indeterminate groups may be too broad to serve as a real representation of the WBC profile that changes significantly between these different age groups. Additional prospective large-scale studies, including assessing factors external to the patients, are required to resolve these limitations.
Nevertheless, our study identified factors associated with inconclusive diagnostic test results from conventional TB tests, which highlights the contribution of our results given the importance of accurate and timely diagnosis of TB. However, the findings from this study should be further verified using other diagnostic methodologies to demonstrate that our results are universally applicable across testing systems and not unique to the IGRA-GIT platform.
In conclusion, we identified that 7. Notably, the highest OR was observed for low-dose steroid use. Therefore, our study highlights the importance of screening for steroid use, even in low doses, prior to performing IGRAs for immunocompetent children.
Using the patient ID number, their charts were reviewed to indicate the initial reason for conducting the QFT-GIT assay, relevant laboratory data, use of systemic steroids or immunosuppressive agents, and immune status. Immunocompromised patients or individuals with no information regarding immune status were excluded from the present study.
Immunocompetent children were defined as patients without the immunocompromised factors as described above. The demographic and clinical characteristics of children receiving low-dose systemic steroids included in the present study are presented in Supplementary Table S1. The data were analyzed using SAS software, Version 9. Descriptive statistics were used to express continuous variables using median and interquartile range IQR and categorical variables using frequency and percentage. Potential factors associated with the attainment of indeterminate results were identified using univariable logistic regression analysis.
Additionally, the Kruskal—Wallis test was used to make comparisons among the three age groups. P values less than 0. This study was performed in accordance with institutional and national regulations and approved by the institutional review board IRB of the Yonsei University Health System IRB approval number that waived requirements for informed consent due to the retrospective nature of the study. Furin, J. Lancet , — Article Google Scholar. Ghosh, S. Tuberculosis infection in underyear-old refugees: Should we be screening?
A systematic review and meta-regression analysis. Child Health 56 , — National Collaborating Centre for Chronic Consortium. Google Scholar. Mazurek, G. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, MMWR Recomm. PubMed Google Scholar. Tebruegge, M. Lewinsohn, D. Haustein, T. The likelihood of an indeterminate test result from a whole-blood interferon-gamma release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status.
Connell, T. Indeterminate interferon-gamma release assay results in children. Meier, N. Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children—A systematic review and meta-analysis.
Fan, P. Effect of corticosteroids on the human immune response: Comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. Hammerschmidt, D. Corticosteroids inhibit complement-induced granulocyte aggregation.
A possible mechanism for their efficacy in shock states.
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