International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 12/2014 (1102-1104)
Lansoprazole-induced acute lung and liver injury: a case report Case Report
Christopher Atkins, Tina Maheswaran, Simon Rushbrook, and Ajay Kamath Norfolk and Norwich University Hospital, Norwich, UK
©2014 Dustri-Verlag Dr. K. Feistle ISSN 0946-1965 DOI 10.5414/CP202110 e-pub: November 5, 2014
Key words lansoprazole – adverse reaction – acute lung injury – acute liver injury
Abstract. A 61-year old woman was admitted with increasing dyspnea and deranged liver function tests. A chest X-ray revealed small volume lungs with reticulo-nodular shadowing. High resolution computed tomography of the chest revealed interlobular septal thickening. The patient subsequently underwent an open lung biopsy and ultrasound-guided liver biopsy, which were consistent with a hypersensitivity pneumonitis and drug-induced liver injury respectively. The patient had previously been commenced on lansoprazole 10 days before the onset of symptoms; this had been stopped at diagnosis. High dose prednisolone was commenced, and the patient went on to make a full recovery. Hypersensitivity pneumonitis is a form of interstitial lung disease that is rarely associated with lansoprazole; this is the first report of it causing an idiosyncratic reaction affecting the lung and liver simultaneously. This case demonstrates the importance of obtaining a full drug history, as early identification of the offending agent will improve outcomes.
Case report
Received January 1, 2014; accepted February 24, 2014 Correspondence to Dr. Christopher Atkins Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk, UK, NR4 7UY christopher.atkins@ nnuh.nhs.uk
A 61-year-old retired female teacher was referred to our medical assessment unit with deranged liver function tests (LFTs) and a 10-day history of breathlessness, jaundice, and fatigue. Her past medical history included polymyalgia rheumatica, Barrett’s esophagus, type 2 diabetes, and hypothyroidism. She had travelled to Egypt 1 month earlier. On admission she had been taking prednisolone (9 mg daily), thyroxin (125 µg daily), aspirin (75 mg daily), metformin (1 g twice daily), and insulin (novomix 30, 30 units twice daily). Ten days prior to the onset of symptoms she had commenced lansoprazole. She had never smoked and drank less than 5 units of alcohol per week. She had
no pets, nor had she been exposed to birds. There was no history of exposure to external airborne allergens or toxins. On clinical examination she was hypoxic, jaundiced, and obese. Chest auscultation revealed bi-basal fine end-inspiratory crepitations. Abdominal examination was unremarkable and palmar erythema was noted. Her body mass index was 32 kg/m2. Initial investigations revealed a bilirubin of 135 (0 – 22 µmol/L; direct (conjugated) bilirubin 101 µmol/L), alkaline phosphatase 267 (38 – 126 IU/L), alanine transaminase 447 (0 – 50 IU/L), γ-glutamyl transpeptidase 1,498 (0 – 60 IU/L), total white cells 7.5 (4 – 11 × 109/L), eosinophils 0.15 (0 – 0.4 × 109/L), and C-reactive protein 8 (0 – 10 mg/ml). An autoimmune screen was negative and immunoglobulin levels were normal. Viral hepatitis and respiratory viral and atypical screens were negative. Alpha1-antitrypsin, ferritin, copper and ceruloplasmin levels were normal. An abdominal ultrasound demonstrated a mildly hyperechoic liver suggestive of hepatic steatosis with no evidence of biliary dilatation. The chest Xray performed on admission demonstrated small volume lungs with reticulo-nodular shadowing. A subsequent high resolution CT scan of the chest revealed subtle interlobular septal thickening, particularly in the upper lobes, and a diffuse increase in lung density (Figure 1). A hypersensitivity reaction to lansoprazole was suspected, which had been discontinued on admission. Her respiratory symptoms continued to deteriorate and by day 8 she was breathless at rest, with a PaO2 of 7.63 kPa on room air. She was considered too hypoxic to safely perform bronchoscopy with transbronchial biopsies, and therefore underwent a video-assisted
1103
Lansoprazole-induced acute lung and liver injury
monary function tests had all returned to the normal range. She was recommended not to take lansoprazole or other proton-pump inhibitors in the future.
Discussion
Figure 1. High resolution CT scan of the chest showing subtle interlobular septal thickening, particularly in the upper lobes, and a diffuse increase in lung density.
thoracic surgical lung biopsy. Histology of the lung tissue revealed diffuse widening of the alveolar walls by lymphocytes and occasional neutrophils. Occasional Masson bodies with numerous alveolar macrophages were noted. The appearances were of a diffuse lymphocytic pneumonitis, consistent with hypersensitivity pneumonitis. A subsequent liver biopsy showed focally prominent steatosis, occasional septal fibrosis and mild perivenular fibrosis but no established pericellular fibrosis. Prominent canalicular cholestasis with Kuppfer cell activity was seen. Cytokeratin 7 staining revealed a mild ductular reaction around the portal tracts. The appearances were in keeping with a cholestatic drug-induced liver injury (DILI) on a background of steatosis. On day 11 she commenced 60 mg of prednisolone with ranitidine for gastroprotection. She improved rapidly, oxygen saturations reaching 96% on air by day 19, at which point she was discharged from hospital. Her steroids were subsequently tapered by 10 mg per month. When seen in clinic 1 month after discharge, her LFTs and pul-
This report describes the first case of an idiosyncratic reaction to lansoprazole causing simultaneous cholestatic liver injury and hypersensitivity pneumonitis, with biopsyproven evidence of both processes. There have been other case reports of proton-pump inhibitor-induced hepatitis [1] and a single case report of lansoprazole-induced lung disease [2], but these reactions have never been described as occurring simultaneously in a single patient. Hypersensitivity pneumonitis can involve type III or type IV hypersensitivity reactions, the former mediated by immune complexes and the latter by Th1 T-cells [3]. CD8+ lymphocytes aggregate in the lungs following cytokines and chemokines activating alveolar macrophages. This process promotes the development of pulmonary fibrosis [3]. It may produce either non-specific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) patterns. Our patient had histological and radiological findings consistent with non-specific interstitial pneumonia, which has a better prognosis [4]. Various mechanisms for drug-induced liver injury are described. The presence of hepatic steatosis, as was present in this case, increases the risk of a DILI 4-fold [5]. The cholestatic pattern of liver injury suggests the biliary canaliculi and transport proteins were targeted and disrupted [6]. Conjugated bilirubin was therefore unable to be transported to the main bile ducts from the canaliculi, resulting in the mixed hepatitic and cholestatic LFTs without evidence of biliary tree dilatation seen here. The concurrent injury to the lung would argue for an immunemediated attack triggered by the presence of an external antigen. This case highlights the importance of obtaining a full drug history in patients. The early withdrawal of lansoprazole in this case contributed to the speed with which the LFTs normalized and prevented long-term lung damage.
Atkins, Maheswaran, Rushbrook, and Kamath
Conflict of interest None of the authors have any relevant disclosures or conflicts of interest.
References [1]
[2]
[3] [4]
[5]
[6]
García-Cortés M, Lucena MI, Andrade RJ, Romero-Gómez M, Fernández MC. Lansoprazole-induced hepatic dysfunction. Ann Pharmacother. 2003; 37: 1731.CrossRef PubMed Hwang KW, Woo OH, Yong HS, Shin BK, Shim JJ, Kang E-Y. Reversible lansoprazole-induced interstitial lung disease showing improvement after drug cessation. Korean J Radiol. 2008; 9: 175178. CrossRef PubMed Mohr LC. Hypersensitivity pneumonitis. Curr Opin Pulm Med. 2004; 10: 401-411. CrossRef PubMed Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, Hirani N, Hubbard R, Lake F, Millar AB, Wallace WAH, Wells AU, Whyte MK, Wilsher MLBritish Thoracic Society Interstitial Lung Disease Guideline Group, British Thoracic Society Standards of Care CommitteeThoracic Society of AustraliaNew Zealand Thoracic Society; Irish Thoracic Society. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008; 63 (Suppl 5): v1-v58. CrossRef PubMed Tarantino G, Saldalamacchia G, Conca P, Arena A. Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J Gastroenterol Hepatol. 2007; 22: 293-303. CrossRef PubMed Hussaini SH, Farrington EA. Idiosyncratic druginduced liver injury: an overview. Expert Opin Drug Saf. 2007; 6: 673-684. CrossRef PubMed
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Lansoprazole-induced acute lung and liver injury: a case report Case Report
Christopher Atkins, Tina Maheswaran, Simon Rushbrook, and Ajay Kamath Norfolk and Norwich University Hospital, Norwich, UK
©2014 Dustri-Verlag Dr. K. Feistle ISSN 0946-1965 DOI 10.5414/CP202110 e-pub: November 5, 2014
Key words lansoprazole – adverse reaction – acute lung injury – acute liver injury
Abstract. A 61-year old woman was admitted with increasing dyspnea and deranged liver function tests. A chest X-ray revealed small volume lungs with reticulo-nodular shadowing. High resolution computed tomography of the chest revealed interlobular septal thickening. The patient subsequently underwent an open lung biopsy and ultrasound-guided liver biopsy, which were consistent with a hypersensitivity pneumonitis and drug-induced liver injury respectively. The patient had previously been commenced on lansoprazole 10 days before the onset of symptoms; this had been stopped at diagnosis. High dose prednisolone was commenced, and the patient went on to make a full recovery. Hypersensitivity pneumonitis is a form of interstitial lung disease that is rarely associated with lansoprazole; this is the first report of it causing an idiosyncratic reaction affecting the lung and liver simultaneously. This case demonstrates the importance of obtaining a full drug history, as early identification of the offending agent will improve outcomes.
Case report
Received January 1, 2014; accepted February 24, 2014 Correspondence to Dr. Christopher Atkins Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk, UK, NR4 7UY christopher.atkins@ nnuh.nhs.uk
A 61-year-old retired female teacher was referred to our medical assessment unit with deranged liver function tests (LFTs) and a 10-day history of breathlessness, jaundice, and fatigue. Her past medical history included polymyalgia rheumatica, Barrett’s esophagus, type 2 diabetes, and hypothyroidism. She had travelled to Egypt 1 month earlier. On admission she had been taking prednisolone (9 mg daily), thyroxin (125 µg daily), aspirin (75 mg daily), metformin (1 g twice daily), and insulin (novomix 30, 30 units twice daily). Ten days prior to the onset of symptoms she had commenced lansoprazole. She had never smoked and drank less than 5 units of alcohol per week. She had
no pets, nor had she been exposed to birds. There was no history of exposure to external airborne allergens or toxins. On clinical examination she was hypoxic, jaundiced, and obese. Chest auscultation revealed bi-basal fine end-inspiratory crepitations. Abdominal examination was unremarkable and palmar erythema was noted. Her body mass index was 32 kg/m2. Initial investigations revealed a bilirubin of 135 (0 – 22 µmol/L; direct (conjugated) bilirubin 101 µmol/L), alkaline phosphatase 267 (38 – 126 IU/L), alanine transaminase 447 (0 – 50 IU/L), γ-glutamyl transpeptidase 1,498 (0 – 60 IU/L), total white cells 7.5 (4 – 11 × 109/L), eosinophils 0.15 (0 – 0.4 × 109/L), and C-reactive protein 8 (0 – 10 mg/ml). An autoimmune screen was negative and immunoglobulin levels were normal. Viral hepatitis and respiratory viral and atypical screens were negative. Alpha1-antitrypsin, ferritin, copper and ceruloplasmin levels were normal. An abdominal ultrasound demonstrated a mildly hyperechoic liver suggestive of hepatic steatosis with no evidence of biliary dilatation. The chest Xray performed on admission demonstrated small volume lungs with reticulo-nodular shadowing. A subsequent high resolution CT scan of the chest revealed subtle interlobular septal thickening, particularly in the upper lobes, and a diffuse increase in lung density (Figure 1). A hypersensitivity reaction to lansoprazole was suspected, which had been discontinued on admission. Her respiratory symptoms continued to deteriorate and by day 8 she was breathless at rest, with a PaO2 of 7.63 kPa on room air. She was considered too hypoxic to safely perform bronchoscopy with transbronchial biopsies, and therefore underwent a video-assisted
1103
Lansoprazole-induced acute lung and liver injury
monary function tests had all returned to the normal range. She was recommended not to take lansoprazole or other proton-pump inhibitors in the future.
Discussion
Figure 1. High resolution CT scan of the chest showing subtle interlobular septal thickening, particularly in the upper lobes, and a diffuse increase in lung density.
thoracic surgical lung biopsy. Histology of the lung tissue revealed diffuse widening of the alveolar walls by lymphocytes and occasional neutrophils. Occasional Masson bodies with numerous alveolar macrophages were noted. The appearances were of a diffuse lymphocytic pneumonitis, consistent with hypersensitivity pneumonitis. A subsequent liver biopsy showed focally prominent steatosis, occasional septal fibrosis and mild perivenular fibrosis but no established pericellular fibrosis. Prominent canalicular cholestasis with Kuppfer cell activity was seen. Cytokeratin 7 staining revealed a mild ductular reaction around the portal tracts. The appearances were in keeping with a cholestatic drug-induced liver injury (DILI) on a background of steatosis. On day 11 she commenced 60 mg of prednisolone with ranitidine for gastroprotection. She improved rapidly, oxygen saturations reaching 96% on air by day 19, at which point she was discharged from hospital. Her steroids were subsequently tapered by 10 mg per month. When seen in clinic 1 month after discharge, her LFTs and pul-
This report describes the first case of an idiosyncratic reaction to lansoprazole causing simultaneous cholestatic liver injury and hypersensitivity pneumonitis, with biopsyproven evidence of both processes. There have been other case reports of proton-pump inhibitor-induced hepatitis [1] and a single case report of lansoprazole-induced lung disease [2], but these reactions have never been described as occurring simultaneously in a single patient. Hypersensitivity pneumonitis can involve type III or type IV hypersensitivity reactions, the former mediated by immune complexes and the latter by Th1 T-cells [3]. CD8+ lymphocytes aggregate in the lungs following cytokines and chemokines activating alveolar macrophages. This process promotes the development of pulmonary fibrosis [3]. It may produce either non-specific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) patterns. Our patient had histological and radiological findings consistent with non-specific interstitial pneumonia, which has a better prognosis [4]. Various mechanisms for drug-induced liver injury are described. The presence of hepatic steatosis, as was present in this case, increases the risk of a DILI 4-fold [5]. The cholestatic pattern of liver injury suggests the biliary canaliculi and transport proteins were targeted and disrupted [6]. Conjugated bilirubin was therefore unable to be transported to the main bile ducts from the canaliculi, resulting in the mixed hepatitic and cholestatic LFTs without evidence of biliary tree dilatation seen here. The concurrent injury to the lung would argue for an immunemediated attack triggered by the presence of an external antigen. This case highlights the importance of obtaining a full drug history in patients. The early withdrawal of lansoprazole in this case contributed to the speed with which the LFTs normalized and prevented long-term lung damage.
Atkins, Maheswaran, Rushbrook, and Kamath
Conflict of interest None of the authors have any relevant disclosures or conflicts of interest.
References [1]
[2]
[3] [4]
[5]
[6]
García-Cortés M, Lucena MI, Andrade RJ, Romero-Gómez M, Fernández MC. Lansoprazole-induced hepatic dysfunction. Ann Pharmacother. 2003; 37: 1731.CrossRef PubMed Hwang KW, Woo OH, Yong HS, Shin BK, Shim JJ, Kang E-Y. Reversible lansoprazole-induced interstitial lung disease showing improvement after drug cessation. Korean J Radiol. 2008; 9: 175178. CrossRef PubMed Mohr LC. Hypersensitivity pneumonitis. Curr Opin Pulm Med. 2004; 10: 401-411. CrossRef PubMed Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, Hirani N, Hubbard R, Lake F, Millar AB, Wallace WAH, Wells AU, Whyte MK, Wilsher MLBritish Thoracic Society Interstitial Lung Disease Guideline Group, British Thoracic Society Standards of Care CommitteeThoracic Society of AustraliaNew Zealand Thoracic Society; Irish Thoracic Society. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008; 63 (Suppl 5): v1-v58. CrossRef PubMed Tarantino G, Saldalamacchia G, Conca P, Arena A. Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J Gastroenterol Hepatol. 2007; 22: 293-303. CrossRef PubMed Hussaini SH, Farrington EA. Idiosyncratic druginduced liver injury: an overview. Expert Opin Drug Saf. 2007; 6: 673-684. CrossRef PubMed
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