A Case of Sarcoidosis Associated with Capecitabine

A Case of Sarcoidosis Associated with Capecitabine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Case of Sarcoidosis Associated with Capecitabine Fatma Didem Birel, Büşra Babahanoğlu Arslan, Emine Argüder This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4385373/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Sarcoidosis is a systemic disease of unknown cause with multiorgan involvement, characterized by a noncaseating granulomatous reaction. There are four groups of drugs that have been associated with the development of drug-induced sarcoid-like reactions. These are immune checkpoint inhibitors, highly active antiretroviral drugs, interferons and tumor necrosis factor-alpha antagonists. A case of sarcoidosis due to capecitabine in a patient with colorectal cancer has previously been reported in the literature. Here, we aimed to present a case of sarcoidosis that developed after adjuvant capecitabine treatment in a patient diagnosed with breast cancer. Sarcoidosis Capecitabine Drug-induced Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Sarcoidosis is a systemic disease of unknown cause with multiorgan involvement, characterized by a noncaseating granulomatous reaction ( 1 ). Sarcoidosis is a complex systemic disease with varying phenotypes and clinical heterogeneity based on its natural history. The etiology of sarcoidosis is not clearly known. However, it is thought to occur under the influence of exposure to certain environmental factors. Among these factors, various agents have been mentioned: pine pollen, wood or metal dust, infectious agents, agricultural employment insecticides and mold/mildew ( 2 , 3 ). Drug-induced sarcoid-like reaction is a systemic granulomatous reaction that is indistinguishable from sarcoidosis and is in a temporal relationship with the initiation of the drug that causes the reaction ( 4 ). Capecitabine is an oral 5-fluorouracil prodrug and is widely used in the treatment of various solid tumors. It is used in breast cancer and colorectal cancer treatments due to its effectiveness, reliability and good tolerability ( 5 , 6 ). To this date there is only one reported case of sarcoidosis that developed after capecitabine treatment in a patient diagnosed with colon cancer ( 7 ). Here, we aimed to present a case of sarcoidosis that developed after adjuvant capecitabine treatment in a patient diagnosed with breast cancer. Case report A 45-year-old female patient was diagnosed with breast cancer (invasive carcinoma, T2N1) two years ago and underwent a right mastectomy operation after receiving 4 cycles of neoadjuvant chemotherapy (adriamycin, cyclophosphamide). Adjuvant 6 cycles of capecitabine, 12 cycles of adjuvant paclitaxel and 25 sessions of radiotherapy were administered. While she was still receiving tamoxifen treatment, she was referred to our clinic after she had mediastinal lymphadenopathies (LAPs) in the thorax computed tomography taken during her routine check-ups. The patient had no respiratory or systemic complaints. She had no history of smoking and no chronic disease. On physical examination, the patient's vital signs were within normal limits and breathing sounds were normal. There was an operation scar in the right breast area. There were no pathological findings in other system examinations. On PA chest radiography (Fig. 1), there was bilateral hilar enlargement and on thorax CT, there were multiple newly developed LAPs in the bilateral hilar region, the largest of which is subcarinal, 25 mm in diameter, sometimes conglomerate, and in the middle lobe of the right lung, subpleural, thin reticular and sometimes minimally consolidated infiltration appearance, possibly secondary to radiotherapy was seen (Fig. 2,3). Positron emission tomography (PET)- CT scan showed enlarged hypermetabolic lymphadenopathies in the mediastinum (SUVmax: 20.59–23.94) (Fig. 4). In laboratory examinations: WBC: 3.25x 109, Hgb: 12.6 g/dl, serum angiotensin converting enzyme (ACE) level: 132 U/L, CRP: < 0.5 mg. No hypercalcemia or hypercalciuria was detected. IGRA was negative with Quantiferon-Tb gold plus test. Respiratory function test and diffusion test were within normal limits. Due to these findings, bronchoscopy, bronchoalveolar lavage (BAL) and endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) were performed with the preliminary diagnoses of breast cancer recurrence, sarcoidosis and tuberculosis. There was no endobronchial lesion on bronchoscopy. Pathological evaluation of mediastinal lymph node samples obtained by EBUS-TBNA was found to be compatible with non-caseating granulomatous inflammation. No malignant cells were found in bronchial lavage or lymph nodes aspiration materials. Bronchial lavage cultures for viruses, bacteria, and fungi were negative. Tuberculosis-polymerase chain reaction (PCR) and acid-fast-bacilli was negative. And, then there was no growth in mycobacterium culture. No other granulomatous diseases were detected in the anamnesis and other examinations. No ocular involvement was detected in the eye examination. Electrocardiography (ECG) and echocardiography findings were normal. The patient was evaluated by the multidisciplinary council with the current findings, and by the decision of the council, it was accepted as capecitabine-related sarcoidosis. Treatment was not started because the patient was asymptomatic and there was no organ involvement that would cause loss of function. It was decided to follow up at 3-month intervals. Figure 1. Chest X-ray shows bilateral hilar enlargement. Figure 2. Thorax computerized tomography shows mediastinal lymphadenopathies (mediastinal window) Figure 3. Thorax computerized tomography shows minimal subpleural infiltration (parenchymal window) Figure 4. PET-CT scan showed enlarged hypermetabolic lymphadenopathies in the mediastinum (SUVmax: 20,59 − 23,94) Discussion Many organic and inorganic antigens and various microorganisms have been implicated as possible causes of sarcoidosis. Especially due to the histological similarity between sarcoidosis and mycobacterial infection, the etiological role of Mycobacterium tuberculosis has been investigated in many studies. Propionibacterium acnes and P. granulosum were also isolated from sarcoidosis samples at significantly higher rates compared to control samples. However, there is no definitive conclusion as to whether infectious agents play a role in pathogenesis. Some occupational exposures, particularly beryllium, can induce sarcoid-like granulomatous inflammation, suggesting that occupational or environmental agents may also trigger the disease in at least a subset of cases ( 8 ). To diagnose sarcoidosis, clinical findings compatible with sarcoidosis must be present, non-caseating granulomas must be demonstrated in histopathological examination, and other granulomatous diseases with known causes must be excluded. Infectious causes such as tuberculosis and fungal infections, autoimmune diseases such as granulomatous polyangiitis, eosinophilic polyangiitis, malignancies, occupational and environmental diseases such as chronic beryllium disease and hypersensitivity pneumonia should be taken into consideration in the differential diagnosis of sarcoidosis. In addition, cases of drug-related sarcoidosis are also encountered ( 1 , 4 ). There are no laboratory findings specific to sarcoidosis that can be used in differential diagnosis. Mild anemia, lymphopenia, hypercalcemia, increase in total protein and increase in liver function tests may be observed. Serum ACE level increases in 50–75% of cases but has low sensitivity and specificity. Lack of response to tuberculin skin test (TCT) due to anergy does not confirm the diagnosis. However, it should not be forgotten that false negativity may occur in cases with tuberculosis or TCT response may not occur in severe forms of tuberculosis ( 1 ). There are four groups of drugs that have been associated with the development of drug-induced sarcoid-like reactions. These are immune checkpoint inhibitors, highly active antiretroviral drugs, interferons and tumor necrosis factor-alpha antagonists ( 4 , 9 ). Capecitabine, the prodrug form of 5-FU, was produced for more appropriate therapy, improving tolerability and intratumoral drug concentration levels. It is an oral chemotherapy agent used in many cancers, primarily in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug that slows the growth of tumor tissue by suppressing DNA synthesis. This prodrug is converted enzymatically in the tumor to fluorouracil, which acts as an antimetabolite. Capecitabine has been reported to show improvements in drug efficacy and survival when administered as monotherapy or in combination with other chemotherapies. The most common side effects are skin reaction on the palms and soles of the feet, diarrhea, nausea, vomiting, mouth sores, abdominal pain and increased risk of bleeding. It does not fall into the four drug categories that cause sarcoid-like reactions in the literature ( 6 , 10 ). However, a case of capecitabine-associated sarcoidosis in a patient with colorectal cancer has previously been reported in the literature ( 7 ). Our case is the first case that developed sarcoidosis due to adjuvant capecitabine used in breast cancer treatment. Drug-associated sarcoidosis is a systemic granulomatous disease that is indistinguishable from sarcoidosis. Like sarcoidosis treatment, it does not necessarily require treatment. It may not always cause symptoms, impairment in quality of life, or organ dysfunction. When treatment is required, standard sarcoidosis treatment regimens are effective. There is a tendency for drug-related sarcoidosis to improve or resolve when the drug responsible is discontinued. For this reason, discontinuing or continuing the medication can be necessary, depending on the benefit-harm ratio. In this case, approximately one year had passed since the drug was discontinued, and findings were found on thorax CT during routine check-ups. Since it did not cause any deterioration in quality of life or organ dysfunction, treatment was not started and an observation decision was made ( 9 ). As a result, knowing what drugs cause drug-related sarcoidosis and understanding the mechanisms that cause it may enable prevention, timely diagnosis and effective treatment. Declarations Ethical Approval An informed consent form was obtained from our case agreeing to participate. Consent for publication Written informed consent was obtained from the participant for the publication of the information. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Competing interests The authors declare that they have no competing interests Funding We don’t have any financial support Authors’ contributions All authors contributed and reviewed the case report Acknowledgements Not applicable References Singha A, Liao SY, Herman DD, Crouser ED, Maier LA, Baughman RP, et al. Summary for Clinicians: Clinical Practice Guideline for the Diagnosis and Detection of Sarcoidosis. Ann Am Thorac Soc. 2020; 17:1510-1515. Doi: 10.1513/AnnalsATS.202007-874CME. Newman LS, Rose CS, Bres Nitz EA, Rossman MD, Barnard J, Frederick M, et al. ACCESS Research Group. A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med. 2004; 170:1324-30. Doi: 10.1164/rccm.200402-249OC. Liao SY, Fingerlin T, Maier L. Genetic predisposition to sarcoidosis. J Autoimmune. 2023:103122. Doi: 10.1016/j.jaut.2023.103122. Miedema J, Nunes H. Drug-induced sarcoidosis-like reactions. Curr Opin Pulm Med. 2021; 27:439-447. Doi: 10.1097/MCP.0000000000000800. Wang S, Deng L, Chen J, Li Y, Zhong Y, Wang Y, et al. Role and efficacy of capecitabine in the anthracycline-free regimen in breast cancer patients: a systematic review and meta-analysis. J Cancer Res Clin Oncol. 2023; 149:17671-17682. doi: 10.1007/s00432-023-05459-7. Alzahrani SM, Al Doghaither HA, Al-Ghafari AB, Pushparaj PN. 5 Fluorouracil and capecitabine therapies for the treatment of colorectal cancer (Review). Oncol Rep. 2023; 50:175. Doi: 10.3892/or.2023.8612. Kang SM, Baek JY, Hwangbo B, Kim HY, Lee GK, Lee HS. A case of capecitabine-induced sarcoidosis. Tuberc Respir Dis (Seoul). 2012; 72:318-22. Doi: 10.4046/trd.2012.72.3.318. Spagnolo P, Bernardinello N. Sarcoidosis. Immunol Allergy Clin North Am. 2023; 43:259-272. Doi: 10.1016/j.iac.2023.01.008. Chopra A, Nautiyal A, Kalkanis A, Judson MA. Drug-Induced Sarcoidosis-Like Reactions. Chest. 2018 Sep;154(3):664-677. doi: 10.1016/j.chest.2018.03.056. Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021;5:CD011220. Doi: 10.1002/14651858. Additional Declarations No competing interests reported. Supplementary Files theavailabilityofdataandmaterials.doc Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4385373","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":301787269,"identity":"795e55e6-4312-4fc3-a90c-a5042429e621","order_by":0,"name":"Fatma Didem Birel","email":"","orcid":"","institution":"Ankara City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fatma","middleName":"Didem","lastName":"Birel","suffix":""},{"id":301787270,"identity":"a19b3f88-71cf-438f-89d2-6dd3c2f4565b","order_by":1,"name":"Büşra Babahanoğlu 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20:57:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":51839,"visible":true,"origin":"","legend":"\u003cp\u003eThorax computerized tomography shows mediastinal lymphadenopathies (mediastinal window)\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4385373/v1/b5c706047ed843a897d2d247.jpg"},{"id":56487191,"identity":"bd0037cf-a3ad-4afb-adf9-a21aa0f91693","added_by":"auto","created_at":"2024-05-14 20:57:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69618,"visible":true,"origin":"","legend":"\u003cp\u003eThorax computerized tomography shows minimal subpleural infiltration (parenchymal window)\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4385373/v1/2bcd84cdac8c2a3fe5ea7e7a.jpg"},{"id":56487190,"identity":"3e7c59d5-bf94-4eab-81b6-d539db3a6bc5","added_by":"auto","created_at":"2024-05-14 20:57:09","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":28182,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT scan showed enlarged hypermetabolic lymphadenopathies in the mediastinum (SUVmax: 20,59- 23,94)\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4385373/v1/e6b7bffc8ebf583b1d53f4db.jpg"},{"id":58232319,"identity":"0252c344-f65e-4e41-9bbf-e7e1d5061813","added_by":"auto","created_at":"2024-06-12 19:44:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":508861,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4385373/v1/8b025a0b-f40a-4d6e-8314-399c2572c5df.pdf"},{"id":56487172,"identity":"86ff7b76-9b6a-48d5-a2ff-b70b3b663da6","added_by":"auto","created_at":"2024-05-14 20:57:02","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":27136,"visible":true,"origin":"","legend":"","description":"","filename":"theavailabilityofdataandmaterials.doc","url":"https://assets-eu.researchsquare.com/files/rs-4385373/v1/8bfc4093f011254f9e26d5f5.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case of Sarcoidosis Associated with Capecitabine","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSarcoidosis is a systemic disease of unknown cause with multiorgan involvement, characterized by a noncaseating granulomatous reaction (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Sarcoidosis is a complex systemic disease with varying phenotypes and clinical heterogeneity based on its natural history. The etiology of sarcoidosis is not clearly known. However, it is thought to occur under the influence of exposure to certain environmental factors. Among these factors, various agents have been mentioned: pine pollen, wood or metal dust, infectious agents, agricultural employment insecticides and mold/mildew (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Drug-induced sarcoid-like reaction is a systemic granulomatous reaction that is indistinguishable from sarcoidosis and is in a temporal relationship with the initiation of the drug that causes the reaction (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Capecitabine is an oral 5-fluorouracil prodrug and is widely used in the treatment of various solid tumors. It is used in breast cancer and colorectal cancer treatments due to its effectiveness, reliability and good tolerability (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). To this date there is only one reported case of sarcoidosis that developed after capecitabine treatment in a patient diagnosed with colon cancer (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Here, we aimed to present a case of sarcoidosis that developed after adjuvant capecitabine treatment in a patient diagnosed with breast cancer.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 45-year-old female patient was diagnosed with breast cancer (invasive carcinoma, T2N1) two years ago and underwent a right mastectomy operation after receiving 4 cycles of neoadjuvant chemotherapy (adriamycin, cyclophosphamide). Adjuvant 6 cycles of capecitabine, 12 cycles of adjuvant paclitaxel and 25 sessions of radiotherapy were administered. While she was still receiving tamoxifen treatment, she was referred to our clinic after she had mediastinal lymphadenopathies (LAPs) in the thorax computed tomography taken during her routine check-ups. The patient had no respiratory or systemic complaints. She had no history of smoking and no chronic disease. On physical examination, the patient's vital signs were within normal limits and breathing sounds were normal. There was an operation scar in the right breast area. There were no pathological findings in other system examinations. On PA chest radiography (Fig.\u0026nbsp;1), there was bilateral hilar enlargement and on thorax CT, there were multiple newly developed LAPs in the bilateral hilar region, the largest of which is subcarinal, 25 mm in diameter, sometimes conglomerate, and in the middle lobe of the right lung, subpleural, thin reticular and sometimes minimally consolidated infiltration appearance, possibly secondary to radiotherapy was seen (Fig.\u0026nbsp;2,3). Positron emission tomography (PET)- CT scan showed enlarged hypermetabolic lymphadenopathies in the mediastinum (SUVmax: 20.59\u0026ndash;23.94) (Fig.\u0026nbsp;4). In laboratory examinations: WBC: 3.25x 109, Hgb: 12.6 g/dl, serum angiotensin converting enzyme (ACE) level: 132 U/L, CRP: \u0026lt; 0.5 mg. No hypercalcemia or hypercalciuria was detected. IGRA was negative with Quantiferon-Tb gold plus test. Respiratory function test and diffusion test were within normal limits. Due to these findings, bronchoscopy, bronchoalveolar lavage (BAL) and endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) were performed with the preliminary diagnoses of breast cancer recurrence, sarcoidosis and tuberculosis. There was no endobronchial lesion on bronchoscopy. Pathological evaluation of mediastinal lymph node samples obtained by EBUS-TBNA was found to be compatible with non-caseating granulomatous inflammation. No malignant cells were found in bronchial lavage or lymph nodes aspiration materials. Bronchial lavage cultures for viruses, bacteria, and fungi were negative. Tuberculosis-polymerase chain reaction (PCR) and acid-fast-bacilli was negative. And, then there was no growth in mycobacterium culture. No other granulomatous diseases were detected in the anamnesis and other examinations. No ocular involvement was detected in the eye examination. Electrocardiography (ECG) and echocardiography findings were normal. The patient was evaluated by the multidisciplinary council with the current findings, and by the decision of the council, it was accepted as capecitabine-related sarcoidosis. Treatment was not started because the patient was asymptomatic and there was no organ involvement that would cause loss of function. It was decided to follow up at 3-month intervals.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1.\u003c/b\u003e Chest X-ray shows bilateral hilar enlargement.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 2.\u003c/b\u003e Thorax computerized tomography shows mediastinal lymphadenopathies (mediastinal window)\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 3.\u003c/b\u003e Thorax computerized tomography shows minimal subpleural infiltration (parenchymal window)\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 4.\u003c/b\u003e PET-CT scan showed enlarged hypermetabolic lymphadenopathies in the mediastinum (SUVmax: 20,59\u0026thinsp;\u0026minus;\u0026thinsp;23,94)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMany organic and inorganic antigens and various microorganisms have been implicated as possible causes of sarcoidosis. Especially due to the histological similarity between sarcoidosis and mycobacterial infection, the etiological role of \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e has been investigated in many studies. \u003cem\u003ePropionibacterium acnes\u003c/em\u003e and \u003cem\u003eP. granulosum\u003c/em\u003e were also isolated from sarcoidosis samples at significantly higher rates compared to control samples. However, there is no definitive conclusion as to whether infectious agents play a role in pathogenesis. Some occupational exposures, particularly beryllium, can induce sarcoid-like granulomatous inflammation, suggesting that occupational or environmental agents may also trigger the disease in at least a subset of cases (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). To diagnose sarcoidosis, clinical findings compatible with sarcoidosis must be present, non-caseating granulomas must be demonstrated in histopathological examination, and other granulomatous diseases with known causes must be excluded. Infectious causes such as tuberculosis and fungal infections, autoimmune diseases such as granulomatous polyangiitis, eosinophilic polyangiitis, malignancies, occupational and environmental diseases such as chronic beryllium disease and hypersensitivity pneumonia should be taken into consideration in the differential diagnosis of sarcoidosis. In addition, cases of drug-related sarcoidosis are also encountered (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are no laboratory findings specific to sarcoidosis that can be used in differential diagnosis. Mild anemia, lymphopenia, hypercalcemia, increase in total protein and increase in liver function tests may be observed. Serum ACE level increases in 50\u0026ndash;75% of cases but has low sensitivity and specificity. Lack of response to tuberculin skin test (TCT) due to anergy does not confirm the diagnosis. However, it should not be forgotten that false negativity may occur in cases with tuberculosis or TCT response may not occur in severe forms of tuberculosis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are four groups of drugs that have been associated with the development of drug-induced sarcoid-like reactions. These are immune checkpoint inhibitors, highly active antiretroviral drugs, interferons and tumor necrosis factor-alpha antagonists (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Capecitabine, the prodrug form of 5-FU, was produced for more appropriate therapy, improving tolerability and intratumoral drug concentration levels. It is an oral chemotherapy agent used in many cancers, primarily in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug that slows the growth of tumor tissue by suppressing DNA synthesis. This prodrug is converted enzymatically in the tumor to fluorouracil, which acts as an antimetabolite. Capecitabine has been reported to show improvements in drug efficacy and survival when administered as monotherapy or in combination with other chemotherapies. The most common side effects are skin reaction on the palms and soles of the feet, diarrhea, nausea, vomiting, mouth sores, abdominal pain and increased risk of bleeding. It does not fall into the four drug categories that cause sarcoid-like reactions in the literature (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, a case of capecitabine-associated sarcoidosis in a patient with colorectal cancer has previously been reported in the literature (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Our case is the first case that developed sarcoidosis due to adjuvant capecitabine used in breast cancer treatment.\u003c/p\u003e \u003cp\u003eDrug-associated sarcoidosis is a systemic granulomatous disease that is indistinguishable from sarcoidosis. Like sarcoidosis treatment, it does not necessarily require treatment. It may not always cause symptoms, impairment in quality of life, or organ dysfunction. When treatment is required, standard sarcoidosis treatment regimens are effective. There is a tendency for drug-related sarcoidosis to improve or resolve when the drug responsible is discontinued. For this reason, discontinuing or continuing the medication can be necessary, depending on the benefit-harm ratio. In this case, approximately one year had passed since the drug was discontinued, and findings were found on thorax CT during routine check-ups. Since it did not cause any deterioration in quality of life or organ dysfunction, treatment was not started and an observation decision was made (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). As a result, knowing what drugs cause drug-related sarcoidosis and understanding the mechanisms that cause it may enable prevention, timely diagnosis and effective treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn informed consent form was obtained from our case agreeing to participate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the participant for the publication of the information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe don’t have any financial support\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed and reviewed the case report\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSingha A, Liao SY, Herman DD, Crouser ED, Maier LA, Baughman RP, et al. Summary for Clinicians: Clinical Practice Guideline for the Diagnosis and Detection of Sarcoidosis. Ann Am Thorac Soc. 2020; 17:1510-1515. Doi: 10.1513/AnnalsATS.202007-874CME.\u003c/li\u003e\n \u003cli\u003eNewman LS, Rose CS, Bres Nitz EA, Rossman MD, Barnard J, Frederick M, et al. ACCESS Research Group. A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med. 2004; 170:1324-30. Doi: 10.1164/rccm.200402-249OC.\u003c/li\u003e\n \u003cli\u003eLiao SY, Fingerlin T, Maier L. Genetic predisposition to sarcoidosis. J Autoimmune. 2023:103122. Doi: 10.1016/j.jaut.2023.103122.\u003c/li\u003e\n \u003cli\u003eMiedema J, Nunes H. Drug-induced sarcoidosis-like reactions. Curr Opin Pulm Med. 2021; 27:439-447. Doi: 10.1097/MCP.0000000000000800.\u003c/li\u003e\n \u003cli\u003eWang S, Deng L, Chen J, Li Y, Zhong Y, Wang Y, et al. Role and efficacy of capecitabine in the anthracycline-free regimen in breast cancer patients: a systematic review and meta-analysis. J Cancer Res Clin Oncol. 2023; 149:17671-17682. doi: 10.1007/s00432-023-05459-7.\u003c/li\u003e\n \u003cli\u003eAlzahrani SM, Al Doghaither HA, Al-Ghafari AB, Pushparaj PN. 5 Fluorouracil and capecitabine therapies for the treatment of colorectal cancer (Review). Oncol Rep. 2023; 50:175. Doi: 10.3892/or.2023.8612.\u003c/li\u003e\n \u003cli\u003eKang SM, Baek JY, Hwangbo B, Kim HY, Lee GK, Lee HS. A case of capecitabine-induced sarcoidosis. Tuberc Respir Dis (Seoul). 2012; 72:318-22. Doi: 10.4046/trd.2012.72.3.318.\u003c/li\u003e\n \u003cli\u003eSpagnolo P, Bernardinello N. Sarcoidosis. Immunol Allergy Clin North Am. 2023; 43:259-272. Doi: 10.1016/j.iac.2023.01.008.\u003c/li\u003e\n \u003cli\u003eChopra A, Nautiyal A, Kalkanis A, Judson MA. Drug-Induced Sarcoidosis-Like Reactions. Chest. 2018 Sep;154(3):664-677. doi: 10.1016/j.chest.2018.03.056.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021;5:CD011220. Doi: 10.1002/14651858.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Sarcoidosis, Capecitabine, Drug-induced","lastPublishedDoi":"10.21203/rs.3.rs-4385373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4385373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSarcoidosis is a systemic disease of unknown cause with multiorgan involvement, characterized by a noncaseating granulomatous reaction. There are four groups of drugs that have been associated with the development of drug-induced sarcoid-like reactions. These are immune checkpoint inhibitors, highly active antiretroviral drugs, interferons and tumor necrosis factor-alpha antagonists. A case of sarcoidosis due to capecitabine in a patient with colorectal cancer has previously been reported in the literature. Here, we aimed to present a case of sarcoidosis that developed after adjuvant capecitabine treatment in a patient diagnosed with breast cancer.\u003c/p\u003e","manuscriptTitle":"A Case of Sarcoidosis Associated with Capecitabine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-14 20:56:30","doi":"10.21203/rs.3.rs-4385373/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"59fb742f-ff49-40b2-9f54-c13bf8cbdde0","owner":[],"postedDate":"May 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-12T19:36:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-14 20:56:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4385373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4385373","identity":"rs-4385373","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}