How 5 Diseases Became One. Moez Tajdin R3 McGill University
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1 How 5 Diseases Became One Moez Tajdin R3 McGill University
2 Conflicts of Interest None!
3 Mr. M. ID: 65 M PMH Benign prostatic hyperplasia Prostate cancer Awaiting biopsy Skin rash Dyslipidemia Hypertension Remote appendectomy Home meds Simvastatin Irbesartan-hctz Allergies: Penicillin Habits: None Social Lives with wife, 3 children independent Family history 2 paternal uncles and 1 paternal aunt with pancreatic cancer
4 Initial Presentation June 2013: Presents with weight loss of 30 lbs x 6 months Occasional loose stools Normal appetite No other constitutional symptoms Negative review of symptoms otherwise
5 Investigations In the community: Abdo US and CT Abdo (Aug 2013) Pancreatic mass in the head and tail, suspicious lesion bile duct At McGill University Health Center G and C-scope (Oct 2013): no significant findings EUS (Oct 2013) Mass in head of pancreas invading the CBD Suspicious for adenocarcinoma Cystic mass in the tail of the pancreas Suspicious for cystadenoma / cystadenocarcinoma vs. an intraductal papillary mucinous neoplasm with malignant transformation EUS Repeat (Oct 2013) FNA biopsy: insufficient sample
6 CT Abdo/Pelvis (Nov 2013) Pancreatitis with cystic lesions Peripancreatic lymph nodes Sclerosing cholangitis R/o cholangiocarcinoma
7 CT Abdo Pelvis (Nov 2013)
8 Investigations CT Pancreas (Nov 2013) and MRI (Dec 2013) R/o lymphoma Labs: N Ca 19-9, Ca-125, CEA and AFP Elevated ALP and GGT ERCP (Jan 2014) Suspicious ampulary lesion Evidence of pancreatitis Difficult to cannulate
9 Renal Biopsy (Jan 2014)
10
11
12 CD138
13 IgG-4
14 Clinical Evolution PET scan (Feb 2014) Increased uptake in the pancreas and kidneys bilaterally IgG-4 level 5.65 g/l [ g/l] Started on Prednisone 40mg qd for a diagnosis of IgG-4 related disease
15 IgG4-Related Disease P. Briton-Zeron. Autoimmunity Reviews 13 (2014)
16 IgG4-Related Disease Objectives Recognize IgG-4 related disease and the importance of prompt therapeutic measures Diagnose IgG-4 related disease by examining key clinical features and using specific diagnostic tests. Manage the disease using steroids and other immune modulators
17 IgG-4 Related Disease Systemic fibroinflammatory condition that can affect multiple organs and lead to tissue destruction and organ failure. IgG-4 disease has been unrecognized for a very long time. It was first described in Japan in early 21 st century. It has been recently recognized as a unified systemic disease that links many individual ogran conditions once considered to be unrelated.
18 Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366:
19 Clinical Presentation Often identified incidentally on imaging studies or on pathological specimens performed for other reasons. Sub-acute presentation Weight loss, fever, fatigue, arthralgia Eosinophilia on blood test
20 P. Briton-Zeron. Autoimmunity Reviews 13 (2014)
21 Diagnosis Organ dysfunction Serologic testing: IgG-4 levels > 135 mg/dl Tissue diagnosis is of paramount importance IgG-4 plasma cells >10/hpf Ratio of IgG-4 + plasma cells to IgG-4 plasma cells > 50%
22 Management Induction: Corticosteroids Steroid-sparing agents (in addition to steroids) Rituximab. Assessment of treatment response. Maintenance therapy. Relapse.
23 Clinical Evolution Diabetes CT Abdo (March 2014) and MRI (June 2014) Reduction in size of pancreatic and kidney lesions Prednisone tapered until May 2014 July 2014: IgG-4 levels 1.54 g/l Sep 2014: IgG-4 levels rising to 2.23 g/l Oct 2014: Given Rituximab 2 cycles Restarted on Prednisone 40mg Nov 2014: IgG-4 levels down to g/l MRI (Feb 2015): Regression of peripancreatic involvement Prednisone tapered until March 2015
24 Admission to the Medical Ward Off all immunosuppression Feb 4 th 2016: presented with epigastric pain and syncope CT Abdo/Chest C+ Thickened aortic wall suggestive of an intramural aortic hematoma no dissection Patient started on prednisone 40mg for suspected aortitis Pet Scan (1 week later): no FDG uptake Patient discharged
25 Course post discharge Feb 22: Found to have bilateral parotid enlargement Treated as IgG-4 related disease recurrence Despite negative PET and normal IgG-4 levels CT Abdo (Mar 2014) Improvement of aortic wall thickening/hematoma Chronic pancreatitis not active Stable CBD findinfs
26 Summary 65M who presented with weight loss Constellation of findings including Autoimmune pancreatitis Sclerosing cholangitis Interstitial nephritis Suspected aortitis Suspected parotitis On pathology, found to have plasma cell infiltrations expressing IgG-4 and areas of storiform fibrosis Elevated serum IgG-4 levels Treated with prednisone and rituximab with good response Ultimately, saved this gentleman from a diagnosis of cancer and potentially invasive investigations and treatment
27 References Kamisawa et al. IgG4-related disease, Lancet Apr 2015 Kanno A, Nishimori I, Masamune A, et al, and the Research Committee on Intractable Diseases of Pancreas. Nationwide epidemiological survey of autoimmune pancreatitis in Japan. Pancreas 2012; 41: Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366: Shimosegawa T, Chari ST, Frulloni L, et al, and the International Association of Pancreatology. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 2011; 40: Kamisawa T, Shimosegawa T, Okazaki K, et al. Standard steroid treatment for autoimmune pancreatitis. Gut 2009; 58: Khosroshahi A, Bloch DB, Deshpande V, Stone JH. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum 2010; 62: Masaki Y, for the All-Japan Team for the Prospective Treatment Study of IgG4-RD. A trial of corticosteroids for IgG4-related disease. Second International Symposium on IgG4-related Disease & Associated Conditions, Honolulu, HA, USA, February 16 19, Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore) 2012; 91:
28 Merci!
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