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A 44-Year-Old Patient With Fever, Night Sweats, and Arthralgia
Electronic Clinical Challenges and Images in GI Grace Elta and Robert J. Fontana, Section Editors
A 44-Year-Old Patient With Fever, Night Sweats, and Arthralgia Thomas Karlas,1,2 Joachim Mössner,2 and Volker Keim2,3 1 Leipzig University Medical Center, IFB Adiposity Diseases, 2University Hospital Leipzig, Department of Internal Medicine, Dermatology and Neurology, Division of Gastroenterology and Rheumatology, and 3University Hospital Leipzig, Interdisciplinary Ultrasound Unit, Leipzig, Germany
Question: A 44-year old man presented with fatigue, intermittent fever, and night sweats. His symptoms started 10 days earlier. Furthermore, he reported painful knee joints after physical exercise for the last week. He experienced similar, self-limiting episodes of arthralgia 1 and 2 years ago. The patient stopped smoking 10 years earlier (20 pack-years). Further personal medical and travel history were uneventful. On admission, physical examination was unremarkable, except for a slight swelling of both knees. C-reactive protein level was 160 mg/L (normal, <5) and both alanine and aspartate aminotransferases were elevated (174 and 120 U/L; normal, <51). Alkaline phosphatase was 145 U/L (normal, <129); gamma-glutamyl transferase and bilirubin were within normal ranges. Hemoglobin was 7.9 mmol/L (normal, >9.2) and there was mild thrombocytosis (465 Gpt/L). The further blood count was within normal limits. A chest x-ray and urinalysis did not reveal any pathological findings. Abdominal ultrasound detected a central liver lesion (23 19 mm) with a hyperechoic halo (subcostal view, Figure A). Alpha-fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, prostate-specific antigen, and liver autoantibodies were within normal limits. Serology and polymerase chain reaction were negative for HIV, hepatotropic viruses (hepatitis B and C; herpes simplex, varicella, Epstein–Barr virus, and cytomegalovirus), mycoplasma and Borrelia burgdorferi. The clinical suspicion of malignancy was supported by predominant arterial tumor perfusion and lack of perfusion in the portal venous phase in contrast-enhanced ultrasound (Figure B, C, respectively). Whereas on computed tomography (CT) barely any lesion was detectable (Figure D), magnetic resonance imaging (MRI) showed a signal decrease in the late phase after injection of contrast agent (T1 20 minutes after gadoxetate disodium injection; Figure E). Positron emission tomography (PET) revealed an intense glucose
GASTROENTEROLOGY 2013;145:e1–e3
Electronic Clinical Challenges and Images in GI, continued metabolism at a site corresponding with the ultrasound and MRI findings (Figure F). Owing to the highly discrepant results of the imaging procedures, a liver biopsy was performed. What is the diagnosis? What treatment should be initiated? See the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Acknowledgments: The authors thank Prof Dr T. Kahn (Diagnostic and Interventional Radiology Clinic, University Hospital Leipzig), Prof Dr O. Sabri (Clinic of Nuclear Medicine, University Hospital Leipzig) and Prof Dr C. Wittekind (Institute of Pathology, University Hospital Leipzig) for providing the CT, MRI and PET-CT scans and the histology images. Conflicts of interest: The authors disclose no conflicts. Funding: TK was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001. © 2013 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2013.03.028
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Electronic Clinical Challenges and Images in GI, continued Answer to the Clinical Challenges and Images in GI Question: Image 1: Inflammatory Pseudotumor of the Liver
Liver histology showed no signs of malignancy (Figure G; stain, hematoxylin and eosin; original magnification, 100). However, there was a dense lymphoplasmacytic infiltration (Figure H, left side) with 40% immunoglobulin (Ig)G4-positive cells (Figure H, I) and a mild fibrosis. Thus, although serum IgG4 levels were not elevated, the diagnosis of an IgG4-associated inflammatory pseudotumor (IPT) of the liver was established. The patient was treated with 100 mg prednisolone daily: Symptoms declined and the C-reactive protein-level decreased rapidly. However, after stepwise steroid reduction and change to budesonide maintenance therapy (9 mg/d), a febrile relapse occurred. After a successful second course of prednisolone, the patient is now on maintenance therapy with azathioprine (75 mg/d) and in good clinical condition. Repeat ultrasound controls show a slight increase of echo pattern and a stable size of the lesion, indicating a likely regression of inflammatory activity. IPT are rare autoimmune disorders.1,2 Several organs such as the liver, pancreas, lung, and intestine may be affected. Symptoms are usually unspecific and comprise fever, fatigue and arthralgia. There are no characteristic radiological findings for IPT.3 Histology shows mainly nonspecific inflammatory cell infiltration and fibrosis.1 IgG4-positive IPTs are rare and have been described predominantly in association to autoimmune pancreatitis. Although some IPT regress spontaneously steroid, therapy is successful in the majority of cases. Operative resection should be limited to patients not responding to medical treatment. References 1. Zen Y, Fujii T, Sato Y, et al. Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Modern Pathol 2007;20:884–894. 2. Ahn KS, Kang KJ, Kim YH, et al. Inflammatory pseudotumors mimicking intrahepatic cholangiocarcinoma of the liver; IgG4positivity and its clinical significance. J Hepatobil Pancreat Sci 2012;4:405–412. 3. Goldsmith PJ, Loganathan A, Jacob M, et al. Inflammatory pseudotumours of the liver: a spectrum of presentation and management options. Eur J Surg Oncol 2009;35:1295–1298.
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A 44-Year-Old Patient With Fever, Night Sweats, and Arthralgia Thomas Karlas,1,2 Joachim Mössner,2 and Volker Keim2,3 1 Leipzig University Medical Center, IFB Adiposity Diseases, 2University Hospital Leipzig, Department of Internal Medicine, Dermatology and Neurology, Division of Gastroenterology and Rheumatology, and 3University Hospital Leipzig, Interdisciplinary Ultrasound Unit, Leipzig, Germany
Question: A 44-year old man presented with fatigue, intermittent fever, and night sweats. His symptoms started 10 days earlier. Furthermore, he reported painful knee joints after physical exercise for the last week. He experienced similar, self-limiting episodes of arthralgia 1 and 2 years ago. The patient stopped smoking 10 years earlier (20 pack-years). Further personal medical and travel history were uneventful. On admission, physical examination was unremarkable, except for a slight swelling of both knees. C-reactive protein level was 160 mg/L (normal, <5) and both alanine and aspartate aminotransferases were elevated (174 and 120 U/L; normal, <51). Alkaline phosphatase was 145 U/L (normal, <129); gamma-glutamyl transferase and bilirubin were within normal ranges. Hemoglobin was 7.9 mmol/L (normal, >9.2) and there was mild thrombocytosis (465 Gpt/L). The further blood count was within normal limits. A chest x-ray and urinalysis did not reveal any pathological findings. Abdominal ultrasound detected a central liver lesion (23 19 mm) with a hyperechoic halo (subcostal view, Figure A). Alpha-fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, prostate-specific antigen, and liver autoantibodies were within normal limits. Serology and polymerase chain reaction were negative for HIV, hepatotropic viruses (hepatitis B and C; herpes simplex, varicella, Epstein–Barr virus, and cytomegalovirus), mycoplasma and Borrelia burgdorferi. The clinical suspicion of malignancy was supported by predominant arterial tumor perfusion and lack of perfusion in the portal venous phase in contrast-enhanced ultrasound (Figure B, C, respectively). Whereas on computed tomography (CT) barely any lesion was detectable (Figure D), magnetic resonance imaging (MRI) showed a signal decrease in the late phase after injection of contrast agent (T1 20 minutes after gadoxetate disodium injection; Figure E). Positron emission tomography (PET) revealed an intense glucose
GASTROENTEROLOGY 2013;145:e1–e3
Electronic Clinical Challenges and Images in GI, continued metabolism at a site corresponding with the ultrasound and MRI findings (Figure F). Owing to the highly discrepant results of the imaging procedures, a liver biopsy was performed. What is the diagnosis? What treatment should be initiated? See the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Acknowledgments: The authors thank Prof Dr T. Kahn (Diagnostic and Interventional Radiology Clinic, University Hospital Leipzig), Prof Dr O. Sabri (Clinic of Nuclear Medicine, University Hospital Leipzig) and Prof Dr C. Wittekind (Institute of Pathology, University Hospital Leipzig) for providing the CT, MRI and PET-CT scans and the histology images. Conflicts of interest: The authors disclose no conflicts. Funding: TK was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001. © 2013 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2013.03.028
e2
Electronic Clinical Challenges and Images in GI, continued Answer to the Clinical Challenges and Images in GI Question: Image 1: Inflammatory Pseudotumor of the Liver
Liver histology showed no signs of malignancy (Figure G; stain, hematoxylin and eosin; original magnification, 100). However, there was a dense lymphoplasmacytic infiltration (Figure H, left side) with 40% immunoglobulin (Ig)G4-positive cells (Figure H, I) and a mild fibrosis. Thus, although serum IgG4 levels were not elevated, the diagnosis of an IgG4-associated inflammatory pseudotumor (IPT) of the liver was established. The patient was treated with 100 mg prednisolone daily: Symptoms declined and the C-reactive protein-level decreased rapidly. However, after stepwise steroid reduction and change to budesonide maintenance therapy (9 mg/d), a febrile relapse occurred. After a successful second course of prednisolone, the patient is now on maintenance therapy with azathioprine (75 mg/d) and in good clinical condition. Repeat ultrasound controls show a slight increase of echo pattern and a stable size of the lesion, indicating a likely regression of inflammatory activity. IPT are rare autoimmune disorders.1,2 Several organs such as the liver, pancreas, lung, and intestine may be affected. Symptoms are usually unspecific and comprise fever, fatigue and arthralgia. There are no characteristic radiological findings for IPT.3 Histology shows mainly nonspecific inflammatory cell infiltration and fibrosis.1 IgG4-positive IPTs are rare and have been described predominantly in association to autoimmune pancreatitis. Although some IPT regress spontaneously steroid, therapy is successful in the majority of cases. Operative resection should be limited to patients not responding to medical treatment. References 1. Zen Y, Fujii T, Sato Y, et al. Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Modern Pathol 2007;20:884–894. 2. Ahn KS, Kang KJ, Kim YH, et al. Inflammatory pseudotumors mimicking intrahepatic cholangiocarcinoma of the liver; IgG4positivity and its clinical significance. J Hepatobil Pancreat Sci 2012;4:405–412. 3. Goldsmith PJ, Loganathan A, Jacob M, et al. Inflammatory pseudotumours of the liver: a spectrum of presentation and management options. Eur J Surg Oncol 2009;35:1295–1298.
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