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{{Hereditary pancreatitis}}
{{Hereditary pancreatitis}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}}{{IQ}}


==Overview==
==Overview==
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
Serum [[amylase]] and [[lipase]] are usually normal but may be slightly elevated (neither diagnostic nor prognostic). Serum [[bilirubin]] and [[alkaline phosphatase]] levels may be elevated in case of intra-pancreatic [[biliary duct]] obstruction. Fecal tests include Sudan staining of faeces, 72-hour quantitative fecal fat, and faecal elastase measurement. Pancreatic function tests include direct and indirect tests.  Genetic testing is generally done for the following genes; ''PRSS1,'' ''CFTR,'' ''SPINK1'' ''and'' ''CTRC.''


OR
==Laboratory Findings==
* Serum [[amylase]] and [[lipase]] are usually normal but may be slightly elevated (neither diagnostic nor prognostic).
* Serum [[bilirubin]] and [[alkaline phosphatase]] levels may be elevated in case of intra-pancreatic [[biliary duct]] obstruction.
* The following lab tests are usually normal:
** [[CBC]]
** [[LFTs]]
** [[Electrolyte|Electrolytes]]


Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
==== Fecal tests: ====


OR
===== (a) Sudan staining of feces: =====
* A non-specific, qualitative test that is no longer used for the diagnosis of [[steatorrhea]].


[Test] is usually normal among patients with [disease name].
===== (b) 72-hour quantitative fecal fat (Gold standard): =====
* A quantitaive test that determines [[fecal]] fat excretion for over 24hrs.
* [[Fecal]] fat excretion of >7g/day is diagnostic of [[malabsorption]].
* Patients with [[steatorrhea]] usually have an [[excretion]] of >10g of fat per day.


OR
===== (c) Faecal elastase measurement (Test of choice): =====
*The most sensitive and specific test for [[pancreatic]] [[exocrine]] dysfunction.
*It can be done with a single random stool sample.
*The results are independent of pancreatic enzyme replacement therapy.
*A value of less than 200 ug/g indicates [[pancreatic insufficiency]].<ref name="UpTo">{{cite web |author=Freedman SD |url=http://www.uptodate.com/patients/content/topic.do?topicKey=~EzkfCtNwumVrg |title=Clinical manifestations and diagnosis of chronic pancreatitis in adults |format= |work=UpToDate  |accessdate=}}</ref><ref name="pmid15285176">{{cite journal |vauthors=Keim V, Teich N, Moessner J |title=Clinical value of a new fecal elastase test for detection of chronic pancreatitis |journal=Clin. Lab. |volume=49 |issue=5-6 |pages=209–15 |year=2003 |pmid=15285176 |doi= |url=}}</ref><ref name="pmid12093988">{{cite journal |vauthors=Walkowiak J, Herzig KH, Strzykala K, Przyslawski J, Krawczynski M |title=Fecal elastase-1 is superior to fecal chymotrypsin in the assessment of pancreatic involvement in cystic fibrosis |journal=Pediatrics |volume=110 |issue=1 Pt 1 |pages=e7 |year=2002 |pmid=12093988 |doi= |url=}}</ref><ref name="pmid15343184">{{cite journal |vauthors=Borowitz D, Baker SS, Duffy L, Baker RD, Fitzpatrick L, Gyamfi J, Jarembek K |title=Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis |journal=J. Pediatr. |volume=145 |issue=3 |pages=322–6 |year=2004 |pmid=15343184 |doi=10.1016/j.jpeds.2004.04.049 |url=}}</ref>
=== Pancreatic function tests: ===


Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
===== (a) Direct/ Invasive tests: =====
* Direct tests are used to assess [[pancreatic insufficiency]] in the early course of disease when patient has clinical symptoms but no radiology findings.
* Direct tests involve pancreatic stimulation via meal or hormonal secretagogues and assessment of pancreatic secretions in the duodenal fluid.
* Direct tests along with radiographic findings (pancreatic calcifications) are still considered to be the gold standard for the diagnosis of hereditary pancreatitis.<ref name="pmid11276375">{{cite journal |vauthors=Boeck WG, Adler G, Gress TM |title=Pancreatic function tests: when to choose, what to use |journal=Curr Gastroenterol Rep |volume=3 |issue=2 |pages=95–100 |year=2001 |pmid=11276375 |doi= |url=}}</ref><ref name="pmid12641496">{{cite journal |vauthors=Chowdhury RS, Forsmark CE |title=Review article: Pancreatic function testing |journal=Aliment. Pharmacol. Ther. |volume=17 |issue=6 |pages=733–50 |year=2003 |pmid=12641496 |doi= |url=}}</ref><ref name="pmid15508057">{{cite journal |vauthors=Siegmund E, Löhr JM, Schuff-Werner P |title=[The diagnostic validity of non-invasive pancreatic function tests--a meta-analysis] |language=German |journal=Z Gastroenterol |volume=42 |issue=10 |pages=1117–28 |year=2004 |pmid=15508057 |doi=10.1055/s-2004-813604 |url=}}</ref><ref name="pmid16633964">{{cite journal |vauthors=Ammann RW |title=Diagnosis and management of chronic pancreatitis: current knowledge |journal=Swiss Med Wkly |volume=136 |issue=11-12 |pages=166–74 |year=2006 |pmid=16633964 |doi=2006/11/smw-11182 |url=}}</ref>
* The limitation of direct tests is that they are costly and cumbersome.<ref name="pmid11276375">{{cite journal |vauthors=Boeck WG, Adler G, Gress TM |title=Pancreatic function tests: when to choose, what to use |journal=Curr Gastroenterol Rep |volume=3 |issue=2 |pages=95–100 |year=2001 |pmid=11276375 |doi= |url=}}</ref><ref name="pmid12641496">{{cite journal |vauthors=Chowdhury RS, Forsmark CE |title=Review article: Pancreatic function testing |journal=Aliment. Pharmacol. Ther. |volume=17 |issue=6 |pages=733–50 |year=2003 |pmid=12641496 |doi= |url=}}</ref><ref name="pmid15508057">{{cite journal |vauthors=Siegmund E, Löhr JM, Schuff-Werner P |title=[The diagnostic validity of non-invasive pancreatic function tests--a meta-analysis] |language=German |journal=Z Gastroenterol |volume=42 |issue=10 |pages=1117–28 |year=2004 |pmid=15508057 |doi=10.1055/s-2004-813604 |url=}}</ref><ref name="pmid16633964">{{cite journal |vauthors=Ammann RW |title=Diagnosis and management of chronic pancreatitis: current knowledge |journal=Swiss Med Wkly |volume=136 |issue=11-12 |pages=166–74 |year=2006 |pmid=16633964 |doi=2006/11/smw-11182 |url=}}</ref>
* Direct tests include:
** [[Secretin]] stimulation test
** Pancreozymin-secretin test
*[[Secretin]] stimulation test is considered the gold standard functional test for diagnosis of chronic pancreatitis.
**The observation that [[bicarbonate]] production is impaired early in chronic hereditary pancreatitis has led to the rationale of use of this test in early stages of disease.
***Sensitivity - 82%<ref name="pmid23711627">{{cite journal |vauthors=Ketwaroo G, Brown A, Young B, Kheraj R, Sawhney M, Mortele KJ, Najarian R, Tewani S, Dasilva D, Freedman S, Sheth S |title=Defining the accuracy of secretin pancreatic function testing in patients with suspected early chronic pancreatitis |journal=Am. J. Gastroenterol. |volume=108 |issue=8 |pages=1360–6 |year=2013 |pmid=23711627 |pmc=5388854 |doi=10.1038/ajg.2013.148 |url=}}</ref>
***Specificity- 86%<ref name="pmid23711627">{{cite journal |vauthors=Ketwaroo G, Brown A, Young B, Kheraj R, Sawhney M, Mortele KJ, Najarian R, Tewani S, Dasilva D, Freedman S, Sheth S |title=Defining the accuracy of secretin pancreatic function testing in patients with suspected early chronic pancreatitis |journal=Am. J. Gastroenterol. |volume=108 |issue=8 |pages=1360–6 |year=2013 |pmid=23711627 |pmc=5388854 |doi=10.1038/ajg.2013.148 |url=}}</ref>


OR
===== (b) Indirect/ Non-invasive tests: =====
* Indirect tests are used to assess the complications of chronic hereditary pancreatitis.
* Indirect tests include:
** Faecal chymotrypsin, PABA-, pancreolauryl-
** Faecal elastase test
* Indirect tests are not sensitive to assess [[pancreatic insufficiency]] in the early course of disease.<ref name="pmid16633964">{{cite journal |vauthors=Ammann RW |title=Diagnosis and management of chronic pancreatitis: current knowledge |journal=Swiss Med Wkly |volume=136 |issue=11-12 |pages=166–74 |year=2006 |pmid=16633964 |doi=2006/11/smw-11182 |url=}}</ref><ref name="pmid11179244">{{cite journal |vauthors=Etemad B, Whitcomb DC |title=Chronic pancreatitis: diagnosis, classification, and new genetic developments |journal=Gastroenterology |volume=120 |issue=3 |pages=682–707 |year=2001 |pmid=11179244 |doi= |url=}}</ref>


There are no diagnostic laboratory findings associated with [disease name].
=== Genetic testing : ===
 
* Genetic testing and genetic counselling is recommended for patients with hereditary pancreatitis.<ref name="pmid24636843">{{cite journal |vauthors=Kumar A, Ajilore O, Zhang A, Pham D, Elderkin-Thompson V |title=Cortical thinning in patients with late-life minor depression |journal=Am J Geriatr Psychiatry |volume=22 |issue=5 |pages=459–64 |year=2014 |pmid=24636843 |pmc=4497565 |doi=10.1016/j.jagp.2012.12.010 |url=}}</ref>
==Laboratory Findings==
* Patients with hereditary pancreatitis who require genetic testing need to be counselled before and after  the genetic testing is done.<ref name="pmid17533082">{{cite journal |vauthors=Fink EN, Kant JA, Whitcomb DC |title=Genetic counseling for nonsyndromic pancreatitis |journal=Gastroenterol. Clin. North Am. |volume=36 |issue=2 |pages=325–33, ix |year=2007 |pmid=17533082 |doi=10.1016/j.gtc.2007.03.007 |url=}}</ref><ref name="pmid24636843">{{cite journal |vauthors=Kumar A, Ajilore O, Zhang A, Pham D, Elderkin-Thompson V |title=Cortical thinning in patients with late-life minor depression |journal=Am J Geriatr Psychiatry |volume=22 |issue=5 |pages=459–64 |year=2014 |pmid=24636843 |pmc=4497565 |doi=10.1016/j.jagp.2012.12.010 |url=}}</ref><ref name="pmid22314809">{{cite journal |vauthors=Solomon S, Whitcomb DC |title=Genetics of pancreatitis: an update for clinicians and genetic counselors |journal=Curr Gastroenterol Rep |volume=14 |issue=2 |pages=112–7 |year=2012 |pmid=22314809 |pmc=5654383 |doi=10.1007/s11894-012-0240-1 |url=}}</ref>
* Genetic testing is generally done for the following genes:<ref name="pmid14641934">{{cite journal |vauthors=Felderbauer P, Hoffmann P, Einwächter H, Bulut K, Ansorge N, Schmitz F, Schmidt WE |title=A novel mutation of the calcium sensing receptor gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations |journal=BMC Gastroenterol |volume=3 |issue= |pages=34 |year=2003 |pmid=14641934 |pmc=317302 |doi=10.1186/1471-230X-3-34 |url=}}</ref>
** ''PRSS1''
** ''CFTR''
** ''SPINK1''
** ''CTRC''


*There are no diagnostic laboratory findings associated with [disease name].
==== In Symptomatic patients: ====
OR
* Patients with any one of the following featires should be considered for genetic testing:<ref name="pmid17533082">{{cite journal |vauthors=Fink EN, Kant JA, Whitcomb DC |title=Genetic counseling for nonsyndromic pancreatitis |journal=Gastroenterol. Clin. North Am. |volume=36 |issue=2 |pages=325–33, ix |year=2007 |pmid=17533082 |doi=10.1016/j.gtc.2007.03.007 |url=}}</ref><ref name="pmid12120217">{{cite journal |vauthors=Ellis I, Lerch MM, Whitcomb DC |title=Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues |journal=Pancreatology |volume=1 |issue=5 |pages=405–15 |year=2001 |pmid=12120217 |doi= |url=}}</ref>
*An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
** A positive history of unexplained documented episode of pancreatitis in childhood
*[Test] is usually normal among patients with [disease name].
** Idiopathic chronic pancreatitis before 25yr age
*Laboratory findings consistent with the diagnosis of [disease name] include:
** Family history of any mutations associated with hereditary pancreatitis
**[Abnormal test 1]
** Recurrent acute attacks of pancreatitis of unknown etiology
**[Abnormal test 2]
** A positive family history of any one of the following with an unknown etiology;
**[Abnormal test 3]
*** Recurrent acute pancreatitis
*** Idiopathic chronic pancreatitis
*** Childhood pancreatitis


*Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
==== In Asymptomatic patients (Predictive testing): ====
* Predictive testing is done only after expert genetic counseling and may be considered for patients who have a first-degree relative with a known ''PRSS1'' mutation.<ref name="pmid12120217">{{cite journal |vauthors=Ellis I, Lerch MM, Whitcomb DC |title=Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues |journal=Pancreatology |volume=1 |issue=5 |pages=405–15 |year=2001 |pmid=12120217 |doi= |url=}}</ref><ref name="pmid17533082">{{cite journal |vauthors=Fink EN, Kant JA, Whitcomb DC |title=Genetic counseling for nonsyndromic pancreatitis |journal=Gastroenterol. Clin. North Am. |volume=36 |issue=2 |pages=325–33, ix |year=2007 |pmid=17533082 |doi=10.1016/j.gtc.2007.03.007 |url=}}</ref>
* Predictive testing is not done for patients below 16 yr age.
* Predictive testing is usually not recommended for patients with ''SPINK1'' or ''CFTR'' mutations.


==References==
==References==

Latest revision as of 19:42, 25 January 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

Serum amylase and lipase are usually normal but may be slightly elevated (neither diagnostic nor prognostic). Serum bilirubin and alkaline phosphatase levels may be elevated in case of intra-pancreatic biliary duct obstruction. Fecal tests include Sudan staining of faeces, 72-hour quantitative fecal fat, and faecal elastase measurement. Pancreatic function tests include direct and indirect tests. Genetic testing is generally done for the following genes; PRSS1, CFTR, SPINK1 and CTRC.

Laboratory Findings

Fecal tests:

(a) Sudan staining of feces:
  • A non-specific, qualitative test that is no longer used for the diagnosis of steatorrhea.
(b) 72-hour quantitative fecal fat (Gold standard):
(c) Faecal elastase measurement (Test of choice):
  • The most sensitive and specific test for pancreatic exocrine dysfunction.
  • It can be done with a single random stool sample.
  • The results are independent of pancreatic enzyme replacement therapy.
  • A value of less than 200 ug/g indicates pancreatic insufficiency.[1][2][3][4]

Pancreatic function tests:

(a) Direct/ Invasive tests:
  • Direct tests are used to assess pancreatic insufficiency in the early course of disease when patient has clinical symptoms but no radiology findings.
  • Direct tests involve pancreatic stimulation via meal or hormonal secretagogues and assessment of pancreatic secretions in the duodenal fluid.
  • Direct tests along with radiographic findings (pancreatic calcifications) are still considered to be the gold standard for the diagnosis of hereditary pancreatitis.[5][6][7][8]
  • The limitation of direct tests is that they are costly and cumbersome.[5][6][7][8]
  • Direct tests include:
    • Secretin stimulation test
    • Pancreozymin-secretin test
  • Secretin stimulation test is considered the gold standard functional test for diagnosis of chronic pancreatitis.
    • The observation that bicarbonate production is impaired early in chronic hereditary pancreatitis has led to the rationale of use of this test in early stages of disease.
      • Sensitivity - 82%[9]
      • Specificity- 86%[9]
(b) Indirect/ Non-invasive tests:
  • Indirect tests are used to assess the complications of chronic hereditary pancreatitis.
  • Indirect tests include:
    • Faecal chymotrypsin, PABA-, pancreolauryl-
    • Faecal elastase test
  • Indirect tests are not sensitive to assess pancreatic insufficiency in the early course of disease.[8][10]

Genetic testing :

  • Genetic testing and genetic counselling is recommended for patients with hereditary pancreatitis.[11]
  • Patients with hereditary pancreatitis who require genetic testing need to be counselled before and after the genetic testing is done.[12][11][13]
  • Genetic testing is generally done for the following genes:[14]
    • PRSS1
    • CFTR
    • SPINK1
    • CTRC

In Symptomatic patients:

  • Patients with any one of the following featires should be considered for genetic testing:[12][15]
    • A positive history of unexplained documented episode of pancreatitis in childhood
    • Idiopathic chronic pancreatitis before 25yr age
    • Family history of any mutations associated with hereditary pancreatitis
    • Recurrent acute attacks of pancreatitis of unknown etiology
    • A positive family history of any one of the following with an unknown etiology;
      • Recurrent acute pancreatitis
      • Idiopathic chronic pancreatitis
      • Childhood pancreatitis

In Asymptomatic patients (Predictive testing):

  • Predictive testing is done only after expert genetic counseling and may be considered for patients who have a first-degree relative with a known PRSS1 mutation.[15][12]
  • Predictive testing is not done for patients below 16 yr age.
  • Predictive testing is usually not recommended for patients with SPINK1 or CFTR mutations.

References

  1. ↑ Freedman SD. "Clinical manifestations and diagnosis of chronic pancreatitis in adults". UpToDate.
  2. ↑ Keim V, Teich N, Moessner J (2003). "Clinical value of a new fecal elastase test for detection of chronic pancreatitis". Clin. Lab. 49 (5–6): 209–15. PMID 15285176.
  3. ↑ Walkowiak J, Herzig KH, Strzykala K, Przyslawski J, Krawczynski M (2002). "Fecal elastase-1 is superior to fecal chymotrypsin in the assessment of pancreatic involvement in cystic fibrosis". Pediatrics. 110 (1 Pt 1): e7. PMID 12093988.
  4. ↑ Borowitz D, Baker SS, Duffy L, Baker RD, Fitzpatrick L, Gyamfi J, Jarembek K (2004). "Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis". J. Pediatr. 145 (3): 322–6. doi:10.1016/j.jpeds.2004.04.049. PMID 15343184.
  5. ↑ 5.0 5.1 Boeck WG, Adler G, Gress TM (2001). "Pancreatic function tests: when to choose, what to use". Curr Gastroenterol Rep. 3 (2): 95–100. PMID 11276375.
  6. ↑ 6.0 6.1 Chowdhury RS, Forsmark CE (2003). "Review article: Pancreatic function testing". Aliment. Pharmacol. Ther. 17 (6): 733–50. PMID 12641496.
  7. ↑ 7.0 7.1 Siegmund E, Löhr JM, Schuff-Werner P (2004). "[The diagnostic validity of non-invasive pancreatic function tests--a meta-analysis]". Z Gastroenterol (in German). 42 (10): 1117–28. doi:10.1055/s-2004-813604. PMID 15508057.
  8. ↑ 8.0 8.1 8.2 Ammann RW (2006). "Diagnosis and management of chronic pancreatitis: current knowledge". Swiss Med Wkly. 136 (11–12): 166–74. doi:2006/11/smw-11182 Check |doi= value (help). PMID 16633964.
  9. ↑ 9.0 9.1 Ketwaroo G, Brown A, Young B, Kheraj R, Sawhney M, Mortele KJ, Najarian R, Tewani S, Dasilva D, Freedman S, Sheth S (2013). "Defining the accuracy of secretin pancreatic function testing in patients with suspected early chronic pancreatitis". Am. J. Gastroenterol. 108 (8): 1360–6. doi:10.1038/ajg.2013.148. PMC 5388854. PMID 23711627.
  10. ↑ Etemad B, Whitcomb DC (2001). "Chronic pancreatitis: diagnosis, classification, and new genetic developments". Gastroenterology. 120 (3): 682–707. PMID 11179244.
  11. ↑ 11.0 11.1 Kumar A, Ajilore O, Zhang A, Pham D, Elderkin-Thompson V (2014). "Cortical thinning in patients with late-life minor depression". Am J Geriatr Psychiatry. 22 (5): 459–64. doi:10.1016/j.jagp.2012.12.010. PMC 4497565. PMID 24636843.
  12. ↑ 12.0 12.1 12.2 Fink EN, Kant JA, Whitcomb DC (2007). "Genetic counseling for nonsyndromic pancreatitis". Gastroenterol. Clin. North Am. 36 (2): 325–33, ix. doi:10.1016/j.gtc.2007.03.007. PMID 17533082.
  13. ↑ Solomon S, Whitcomb DC (2012). "Genetics of pancreatitis: an update for clinicians and genetic counselors". Curr Gastroenterol Rep. 14 (2): 112–7. doi:10.1007/s11894-012-0240-1. PMC 5654383. PMID 22314809.
  14. ↑ Felderbauer P, Hoffmann P, Einwächter H, Bulut K, Ansorge N, Schmitz F, Schmidt WE (2003). "A novel mutation of the calcium sensing receptor gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations". BMC Gastroenterol. 3: 34. doi:10.1186/1471-230X-3-34. PMC 317302. PMID 14641934.
  15. ↑ 15.0 15.1 Ellis I, Lerch MM, Whitcomb DC (2001). "Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues". Pancreatology. 1 (5): 405–15. PMID 12120217.

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