- Email: [email protected]
New-Onset Paresthesias in Inflammatory Bowel Disease
CLINICAL CHALLENGES AND IMAGES IN GI New-Onset Paresthesias in Inflammatory Bowel Disease Douglas A. Simonetto and Konstantinos A. Papadakis Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
Question: A 44-yearold Caucasian woman with a history of ileocolonic Crohn’s disease, currently in remission on infliximab and 6mercaptopurine for the last 5 years, presented with paresthesias on her left below the waist, left lower extremity, and severe back pain. On examination, she demonstrated dysesthesia and hyperesthesia in the left hemibody below T4 level. Strength was normal. PET (Figure A) revealed moderately intense fluorodeoxyglucose activity (maximum standardized uptake value of 4.9) in the thoracic spinal cord extending from T3 to T9 correlating with the enhancing lesion seen on MRI (Figure B). Spinal cord biopsy was obtained. Extensive workup for infections including Mycobacterium tuberculosis by culture, polymerase chain reaction, and acid-fast smear was negative. QuantiFERON before initiation of infliximab 5 years ago had been negative. Chest CT and conjunctival biopsy were negative. What is the diagnosis? Look on page 907 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.12.040
Gastroenterology 2015;148:906–907
CLINICAL CHALLENGES AND IMAGES IN GI Answer to Image 2 (page 906): Spinal Cord Neurosarcoidosis Associated with Tumor Necrosis Factor-a Inhibitor
The presence of nonnecrotizing granulomas on the spinal cord biopsy (Figure C) combined with the enhancing lesion seen on MRI (Figure B) and PET scan (Figure A) and in the absence of an infectious agent, is consistent with the diagnosis of neurosarcoidosis. Infliximab was discontinued immediately and high-dose glucocorticoids initiated. Follow-up in 3 months showed improvement of her neuroimaging (Figure D). Her Crohn’s disease has remained in remission while on high-dose prednisone and 6-mercaptopurine. Tumor necrosis factor (TNF)-a is a proinflammatory cytokine that plays a major role in the pathogenesis of inflammatory bowel diseases (IBD). Anti–TNF-a therapy is recommended for treatment of moderate to severe IBD, either as monotherapy or in combination with thiopurines. Infliximab has been used for treatment of steroid-refractory neurosarcoidosis as well as cutaneous and joint involvement in this condition.1 Recently, however, several case reports and series have demonstrated the development of sarcoidosis during treatment with TNF antagonists, with the most commonly affected organs including lungs, lymph nodes, and skin.2 TNF-a inhibitors have also been implicated in several other neurologic complications, including peripheral neuropathy, central demyelination, transverse myelitis, optic neuritis, leukoencephalopathy, chronic inflammatory demyelinating polyneuropathy, and posterior reversible encephalopathy syndrome.3 A 10-year review of the neurological complications of TNF alpha inhibitors from the Food Drug Administration Adverse Event Report System identified 528 cases, of which 17.4% were in patients with IBD. This case highlights the importance of recognizing the neurologic complications associated with TNF inhibitors, which are commonly prescribed in patients with IBD. Sarcoidosis is emerging as a new potential complication of this class of drugs and therefore should be considered in the differential of new-onset neurological symptoms.
References 1. 2. 3.
Pereira J, Anderson NE, McAuley D, et al. Medically refractory neurosarcoidosis treated with infliximab. Int Med J 2011; 41:354–357. Cathcart S, Sami N, Elewski B. Sarcoidosis as an adverse effect of tumor necrosis factor inhibitors. J Drugs Dermatol 2012;11:609–612. Singh S, Kumar N, Loftus EV Jr, et al. Neurologic complications in patients with inflammatory bowel disease: increasing relevance in the era of biologics. Inflamm Bowel Dis 2013;19:864–872.
For submission instructions, please see the Gastroenterology web site (www.gastrojournal.org).
907
Question: A 44-yearold Caucasian woman with a history of ileocolonic Crohn’s disease, currently in remission on infliximab and 6mercaptopurine for the last 5 years, presented with paresthesias on her left below the waist, left lower extremity, and severe back pain. On examination, she demonstrated dysesthesia and hyperesthesia in the left hemibody below T4 level. Strength was normal. PET (Figure A) revealed moderately intense fluorodeoxyglucose activity (maximum standardized uptake value of 4.9) in the thoracic spinal cord extending from T3 to T9 correlating with the enhancing lesion seen on MRI (Figure B). Spinal cord biopsy was obtained. Extensive workup for infections including Mycobacterium tuberculosis by culture, polymerase chain reaction, and acid-fast smear was negative. QuantiFERON before initiation of infliximab 5 years ago had been negative. Chest CT and conjunctival biopsy were negative. What is the diagnosis? Look on page 907 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.12.040
Gastroenterology 2015;148:906–907
CLINICAL CHALLENGES AND IMAGES IN GI Answer to Image 2 (page 906): Spinal Cord Neurosarcoidosis Associated with Tumor Necrosis Factor-a Inhibitor
The presence of nonnecrotizing granulomas on the spinal cord biopsy (Figure C) combined with the enhancing lesion seen on MRI (Figure B) and PET scan (Figure A) and in the absence of an infectious agent, is consistent with the diagnosis of neurosarcoidosis. Infliximab was discontinued immediately and high-dose glucocorticoids initiated. Follow-up in 3 months showed improvement of her neuroimaging (Figure D). Her Crohn’s disease has remained in remission while on high-dose prednisone and 6-mercaptopurine. Tumor necrosis factor (TNF)-a is a proinflammatory cytokine that plays a major role in the pathogenesis of inflammatory bowel diseases (IBD). Anti–TNF-a therapy is recommended for treatment of moderate to severe IBD, either as monotherapy or in combination with thiopurines. Infliximab has been used for treatment of steroid-refractory neurosarcoidosis as well as cutaneous and joint involvement in this condition.1 Recently, however, several case reports and series have demonstrated the development of sarcoidosis during treatment with TNF antagonists, with the most commonly affected organs including lungs, lymph nodes, and skin.2 TNF-a inhibitors have also been implicated in several other neurologic complications, including peripheral neuropathy, central demyelination, transverse myelitis, optic neuritis, leukoencephalopathy, chronic inflammatory demyelinating polyneuropathy, and posterior reversible encephalopathy syndrome.3 A 10-year review of the neurological complications of TNF alpha inhibitors from the Food Drug Administration Adverse Event Report System identified 528 cases, of which 17.4% were in patients with IBD. This case highlights the importance of recognizing the neurologic complications associated with TNF inhibitors, which are commonly prescribed in patients with IBD. Sarcoidosis is emerging as a new potential complication of this class of drugs and therefore should be considered in the differential of new-onset neurological symptoms.
References 1. 2. 3.
Pereira J, Anderson NE, McAuley D, et al. Medically refractory neurosarcoidosis treated with infliximab. Int Med J 2011; 41:354–357. Cathcart S, Sami N, Elewski B. Sarcoidosis as an adverse effect of tumor necrosis factor inhibitors. J Drugs Dermatol 2012;11:609–612. Singh S, Kumar N, Loftus EV Jr, et al. Neurologic complications in patients with inflammatory bowel disease: increasing relevance in the era of biologics. Inflamm Bowel Dis 2013;19:864–872.
For submission instructions, please see the Gastroenterology web site (www.gastrojournal.org).
907