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Autoimmune Pancreatitis (PowerPoint download)

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Autoimmune Pancreatitis (PowerPoint download) Powered By Docstoc
					DOMMR
Week of 9/7-9/11
OBJECTIVES
 Discuss the pathogenesis, etiology, and diagnosis
  of chronic pancreatitis
 Discuss autoimmune pancreatitis focusing on
     Presentation
     Radiologic findings
     Laboratory values
     Treatment
CHRONIC PANCREATITIS
   Irreversible morphologic changes as a response to
    progressive inflammation
       Strictures, calculi, dilation of pancreatic duct (PD)
 Patchy, focal mononuclear infiltrates and fibrosis
 Leads to loss of pancreatic endocrine and
  exocrine function
 Verses Acute Pancreatitis:
     More chronic, less associated with acute pain
     Amylase/Lipase often normal
             Chronic pancreatitis is a patchy, focal disease
             Significant fibrosis decrease the amount of enzymes
CHRONIC PANCREATITIS – PATHOGENESIS
   Proteinaceous ductal plugs
     Protein hypersecretion “plugs” the ducts, acting as a
      nidus for calcification  stone formation
     Chronic inflammation causes scarring of the ducts

   Ischemia
     Leads to chronic inflammatory changes
     Doesn’t initiate, but exacerbates the disease

   Nutritional deficiency
     Specifically in antioxidants such as selenium,
      Vitamin C, Vitamin E, methionine
     Antioxidant deficiency in stressed cells  free
      radicals  lipid peroxidation, cell impairment
CHRONIC PANCREATITIS - ETIOLOGY
 Chronic alcohol abuse
 Ductal obstruction

 Hereditary

 Tropical

 Systemic Diseases

 Idiopathic

 Autoimmune
CHRONIC PANCREATITIS - ETIOLOGY
   Alcohol abuse:
     Alters zymogen activation
     50% of cases in Western countries
     >150g of alcohol daily for > 6yrs, although great
      variability in sensitivity to alcohol
           Only 5-10% of alcoholics develop chronic pancreatitis
   (Pancreatic) Ductal Obstruction:
     Strictures, pseudocysts, stones, tumors
     Sphincter of Oddi obstruction
     Pancreas divisum (although most with this condition
      are not affected by pancreatitis)
CHRONIC PANCREATITIS - ETIOLOGY
   Hereditary:
       Autosomal dominant with only 80% penetrance
       Associated with the trypsinogen genes, trypsin
        inhibitor gene, and CFTR gene
       Symptoms appear by age 20
       High association with pancreatic adenocarcinoma
       Some mutations may be protective against
        pancreatitis
   Systemic diseases:
       SLE, cystic fibrosis, primary hyperparathyroidism
CHRONIC PANCREATITIS - ETIOLOGY
   Tropical
     Seen in South India (most common cause of chronic
      pancreatitis)
     Affects children
           Often die in early adulthood
   Idiopathic:
     Most common cause after alcohol abuse
     Consider:
         Concealed alcohol consumption or hypersensitivity to small
          amounts of alcohol
         Gene mutations

         Unreported pancreatic trauma
CHRONIC PANCREATITIS – DIAGNOSIS
   Classic triad of:
       Steatorrhea, pancreatic calcifications, DM
   Signs/Symptoms
       Chronic abdominal pain radiating to the back
   Labs
       Normal amylase, lipase
       Secretin stimulation test
         Measures pancreatic function by monitoring its response to
          secretin
         Secretin normally causes the pancreas to release digestive

          enzymes
CHRONIC PANCREATITIS –
DIAGNOSIS
 Imaging
    CT
        Calcifications (common with alcohol
         induced), ductal dilitation, enlarged
         pancreas, fluid collections
    ERCP when CT is normal
        Irregular narrowing of the main PD with
         side branches
    EUS
        Lobular architecture, dilation of PD, side
         branches
           Similar to pancreatic cancer
Pancreatic Calcifications




                            Dilated, tortuous PD containing
                            stones or protein plugs
AUTOIMMUNE PANCREATITIS (AIP)
 First described in 1995 to explain a chronic
  pancreatitis associated with autoimmune
  manifestations
 Defined as a type of chronic pancreatitis
  characterized by autoimmune inflammatory
  process where lymphocyte infiltration and
  associated fibrosis cause organ dysfunction
 A heterogeneous disorder known by many names:
  sclerosing pancreatitis, nonalcoholic destructive
  pancreatitis, tumefactive pancreatitis
AIP - EPIDEMIOLOGY
 Occurs in 5-6% of cases of chronic pancreatitis
 Incidence is higher in the Far East, where most
  of the studies on AIP have been done
       Frequency is increasing in Western nations –
        perhaps because of increased awareness
 More common in women
 Usually diagnosed in > 50yrs, although wide age
  variation
AIP – PATHOPHYSIOLOGY
 Increased circulating CD4+ and CD8+ T cells
  bearing HLA-DR4
 CD4+ cells subdivided into Th1 and Th2 cell
     Th1 cells involved in induction and maintenance
     Th2 cells involved in disease progression

 Suggests an autoimmune mechanism causing
  inflammation
 Often associated with other autoimmune
  disorders:
       PSC, PBC, Retroperitoneal fibrosis, RA
       Sarcoidosis, Sjogrens, IBD (Ulcerative colitis >
        Crohns)
AIP - PRESENTATION
 Can have a wide variety of symptoms – although
  typically less severe than acute pancreatitis
 Abdominal pain, weight loss, jaundice,
  obstructive pattern of LFTs
       Presents similar to acute/chronic pancreatitis and
        pancreatic carcinoma
   Extrapancreatic manifestations:
     Lungs: nodules, infiltrates, adenopathy
     Kidneys: mild renal insufficiency, renal lesions
DIAGNOSIS
 Signs/Symptoms suggestive of pancreatic and
  biliary duct disease in a patient with a history of
  autoimmune disorders
 Radiographic imaging

 Labs studies

 Response to steroids

 Biopsy
RADIOGRAPHIC IMAGING
   CT/MRI:
       Pancreas appearance:
           “Sausage shaped”, diffuse enlargement, homogenous
            attenuation
     Minimal pancreatic stranding or peripancreatic fluid
     Lack of pancreatic calcifications
     Peripheral rim of hypoattenuation “halo”
     Focal involvement typically in head of pancreas
           May appear as pancreatic mass
       Pancreatic-duct narrowing (highly diagnostic)
   Abdominal U/S
       Rarely helpful, similar to other types of pancreatitis
ENDOSCOPIC IMAGING
   ERCP:
     Irregular narrowing or stricture of the main
      pancreatic duct
     Narrowing of the intrapancreatic part of the CBD
     Irregular narrowing of hepatic bile ducts

   EUS:
     Diffuse pancreatic enlargement
     Diffusely hypoechoic parenchyma
-“Sausage shaped pancreas”

-Homogeneous attenuation with
peripheral rim of hypoattenuation
“halo”
                                    Pancreatic Duct Narrowing
AIP – DIAGNOSTIC CRITERIA
   IgG4
     Cutoff of >135  SN=95%, SP=97%
     May not be elevated initially
     Other conditions cause IgG4 elevated:
           Atopic dermatitis, asthma, pemphigus vulgaris, certain
            parasitic diseases
              Usually accompanied by elevated IgE


 Antilactoferrin antibody (ALA)
 Anticarbonic anhydrase II antibody (ACA II)

 Anti-smooth muscle antibody (ASMA)

 Antinuclear antibody (ANA)

 Rheumatoid Factor (RF)
AIP - BIOPSY
 Ultimately confirms the diagnosis
 Done when imaging and labs do not establish a
  diagnosis (or if treatment fails)
 Periductal collar of lymphocytes and plasma cells
       “Lymphocytoplasmic infiltrate”
   Dense fibrosis
AIP – DIAGNOSTIC CRITERIA
 Japan Pancreas Society
 Frulloni et al.

 Aparisi et al.

 Mayo Clinic
       Suggest “response to steroids” as a an addition to
        diagnostic criteria
   Most important to rule out alcohol-induced
    chronic pancreatitis or pancreatic ca
                         Diagnostic Criteria for Autoimmune Pancreatitis




Med 2006;355:2670-2676
AIP - TREATMENT
   Diagnostic findings on imaging with supportive lab results
    warrants a trial of steroids
   Rarely, AIP resolves spontaneously
   Prednisone 40mg/day
       Taper by 5 mg every 1-2 weeks
   Dramatic response often seen in 2-4 weeks
       Monitor response by imaging (labs will also improve)
       Malignant lesions may respond to steroids, so must confirm
        complete resolution
   If response to steroids is poor, consider alternate diagnosis
   Maintenance therapy needed for only a small group
DIFFERENTIATING AIP FROM
OTHER DISORDERS
AIP vs PSC                 AIP vs Pancreatic Ca

 PSC is not steroid          Pancreatic cancer is
  responsive                   not steroid responsive
 “Beaded” ducts with             Can see some
  PSC                              response, but not total

 Changes in intra/extra    Mass in the head of
  hepatic ducts (PSC) vs     the pancreas more
  CBD (AIP)                  typical of pancreatic
                             cancer
 AIP has a more
  insidious presentation    Normal IgG4 in
                             pancreatic cancer
A Diagnostic and Treatment Algorithm for Autoimmune Pancreatitis




Finkelberg D et al. N Engl J Med 2006;355:2670-2676
RECAP OF LEARNING POINTS –
    CHRONIC PANCREATITIS
 Characterized by patchy, focal infiltrates
 Triad:
        Steatorrhea, pancreatic calcification, DM
   Pathogenesis:
        Protein plug, ischemia, nutritional (antioxidant)
         deficiency
   Etiology:
        ETOH, idiopathic, ductal obstruction, hereditary,
         tropical, autoimmune, systemic diseases
   Imaging:
        Calcifications, diffusely enlarged pancreas, ductal
         dilitation
RECAP OF LEARNING POINTS - AIP
   Mild symptoms usually without acute attacks of pancreatitis
   Association with other autoimmune disorders
   Labs:
      Increased levels of IgG4
      ANA, ACA-II, ASMA, ALA, RF
   Imaging:
      Diffuse enlargement of pancreas
      Rare calcification
      Irregular narrowing of the main pancreatic duct
      “Halo” of hypoattenuation
   Biopsy:
      Fibrotic changes with lymphocyte infiltration
   Therapy:
      Dramatic improvement with steroid therapy
Follow up of Patient
   Based on biopsy, was a concern for AIP so checked IgG
    panel (normal, including IgG4), RF (<20), AMSA (negative),
    ANA (1:40)
      GI also recommended ALA, ACA-II, but not done
   Surgery recommend Ca 19-9 (88, normal 1-37) to rule out
    carcinoma
   Liver biopsy showed no intrinsic liver disease
   Subsequent CT showed pancreatic necrosis and wanted to
    proceed with surgery but patient continue to worsen
   Developed sepsis, acute respiratory failure requiring
    intubation, and v.fib arrest, but was resuscitated
   Taken to the OR for pancreatic necrosis, but expired before
    surgery began

				
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