Sandbox:Hamid

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Hamid Qazi, MD, BSc [2]

Historical Perspective

===Discovery===

• Peutz-Jeghers syndrome was first discovered by Dr. Connor, a British, in 1895 in identical twin sisters.

• The association between gastrointestinal polyposis with distinctive pigmentation of the skin and Peutz-Jeghers syndrome was made in 1921 by Dr. Johannes Peutz of Holland.
• In 1949, Dr. Harold Jeghers of United States was the first to discover the association between combination of intestinal polyposis and skin pigmentation, and the development of Peutz-Jeghers syndrome.
• In 1954, A. Bruwer used the eponym Peutz-Jeghers syndrome
• In 1998, serine/threonine-protein kinase 11 alias LKB1 (STK11/LKB1) gene mutations were first implicated in the pathogenesis of Peutz-Jeghers syndrome.

Classification

• There is no established system for the classification of Peutz-Jeghers syndrome.

Pathophysiology

Pathogenesis

• It is thought that Peutz-Jeghers syndrome is the result of deletion or partial deletion of STK11 (LBK1) gene, located on chromosome 19p13.3.
• STK11 protein plays an important role in second messenger signal transduction and is found to regulate cellular proliferation, controls cell polarity, and responds to low energy states.
• In Mammalian studies, STK11 is shown in the inhibition of AMP-activated protein kinase (AMPK), and signals downstream to inhibit the mammalian target of rapamycin (mTOR).
  • The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.

Pathology

• Peutz-Jeghers syndrome associated polyps have a unique smooth muscle core that arborizes throughout the polyp.
  • These polyps can only be differentiated from other polyp types by histopathology.

Causes

• Peutz-Jeghers syndrome is caused by STK11 gene mutation
• Variable penetrance

Epidemiology and Demographics

Prevalence

• The prevalence of Peutz-Jeghers syndrome is estimated to be 1 in 8300 to 250000
• Most likely prevalence is 1 in 100000

Age

• Peutz-Jeghers syndrome affects individuals between the ages of 10 to 30 years; average age of diagnosis is 23 years for males and 26 years for females.

Gender

• Males and females are equally affected.

Risk Factors

• There are no established risk factors for Peutz-Jeghers

Screening

• According to the American College of Gastroenterology (ACG) and the National Comprehensive Cancer Network (NCCN), screening for Peutz-Jeghers syndrome by physical exam, complete blood work for iron deficiency anemia, and endoscopy are recommended every year among patients with Peutz-Jeghers Syndrome.

Natural History, Complications, and Prognosis

Natural History

• The symptoms of Peutz-Jeghers syndrome usually develop in the first decade of life, and start with symptoms such as hyperpigmentation, abdominal pain, and rectal bleeding.
• If left untreated, patients with Peutz-Jeghers syndrome may progress to develop colon cancer, breast cancer, and gastrointestinal cancers.
• Extraintestinal manifestation include pancreatic, lung, breast, uterine, ovarian and testicular malignancies.

Complications

• Common complications of Peutz-Jeghers syndrome include:
  • Intussusception
  • Gastric outlet obstruction
  • Extraintestinal polyps

Prognosis

• Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
• Depending on the extent of the [tumor/disease progression/etc.] at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent.
• The presence of [characteristic of disease] is associated with a particularly [good/poor] prognosis among patients with [disease/malignancy].
• [Subtype of disease/malignancy] is associated with the most favorable prognosis.
• The prognosis varies with the [characteristic] of tumor; [subtype of disease/malignancy] have the most favorable prognosis.

Overview

• The page name should be "[Disease name] diagnostic study of choice", with only the first letter of the title capitalized. Note that the page is called "Diagnostic study of choice."
• Goal:
  • To describe the most efficient/sensitive/specific test that is utilized for diagnosis of [disease name].
  • To describe the gold standard test for the diagnosis of [disease name].
  • To describe the diagnostic criteria, which may be based on clinical findings, physical exam signs, pathological findings, lab findings, findings on imaging, or even findings that exclude other diseases.
• As with all microchapter pages linking to the main page, at the top of the edit box put {{CMG}}, your name template, and the microchapter navigation template you created at the beginning.
• Remember to create links within WikiDoc by placing [[square brackets]] around key words which you want to link to other pages. Make sure you makes your links as specific as possible. For example, if a sentence contained the phrase anterior spinal artery syndrome, the link should be to anterior spinal artery syndrome not anterior or artery or syndrome. For more information on how to create links, click here.
• Remember to follow the same format and capitalization of letters as outlined in the template below.
• You should include the name of the disease in the first sentence of every subsection.

Diagnostic Study of Choice

Gold standard/Study of choice:

• [Name of the investigation] is the gold standard test for the diagnosis of [disease name].
• The following result of [gold standard test] is confirmatory of [disease name]:
  • Result 1
  • Result 2
• The [name of investigation] should be performed when:
  • The patient presented with symptoms/signs 1. 2, 3.
  • A positive [test] is detected in the patient.
• [Name of the investigation] is the gold standard test for the diagnosis of [disease name].
• The diagnostic study of choice for [disease name] is [name of investigation].
• There is no single diagnostic study of choice for the diagnosis of [disease name].
• There is no single diagnostic study of choice for the diagnosis of [disease name], but [disease name] can be diagnosed based on [name of the investigation 1] and [name of the investigation 2].
• [Disease name] is mainly diagnosed based on clinical presentation.
• Investigations:
  • Among patients who present with clinical signs of [disease name], the [investigation name] is the most specific test for the diagnosis.
  • Among patients who present with clinical signs of [disease name], the [investigation name] is the most sensitive test for diagnosis.
  • Among patients who present with clinical signs of [disease name], the [investigation name] is the most efficient test for diagnosis.

The comparison table for diagnostic studies of choice for [disease name]

	Sensitivity	Specificity
Test 1	✔	...%
Test 2	...%	✔

✔= The best test based on the feature

Diagnostic results

The following result of [investigation name] is confirmatory of [disease name]:

• Result 1
• Result 2

Sequence of Diagnostic Studies

The [name of investigation] should be performed when:

• The patient presented with symptoms/signs 1, 2, and 3 as the first step of diagnosis.
• A positive [test] is detected in the patient, to confirm the diagnosis.

Diagnostic Criteria

• Here you should describe the details of the diagnostic criteria.
• Always mention the name of the criteria/definition you are about to list (e.g. modified Duke criteria for diagnosis of endocarditis / 3rd universal definition of MI) and cite the primary source of where this criteria/definition is found.
• Although not necessary, it is recommended that you include the criteria in a table. Make sure you always cite the source of the content and whether the table has been adapted from another source.
• Be very clear as to the number of criteria (or threshold) that needs to be met out of the total number of criteria.
• Distinguish criteria based on their nature (e.g. clinical criteria / pathological criteria/ imaging criteria) before discussing them in details.
• To view an example (endocarditis diagnostic criteria), click here
• If relevant, add additional information that might help the reader distinguish various criteria or the evolution of criteria (e.g. original criteria vs. modified criteria).
• You may also add information about the sensitivity and specificity of the criteria, the pre-test probability, and other figures that may help the reader understand how valuable the criteria are clinically.
• [Disease name] is mainly diagnosed based on clinical presentation. There are no established criteria for the diagnosis of [disease name].
• There is no single diagnostic study of choice for [disease name], though [disease name] may be diagnosed based on [name of criteria] established by [...].

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
• The diagnosis of [disease name] is based on the [criteria name] criteria, which includes [criterion 1], [criterion 2], and [criterion 3].

• [Disease name] may be diagnosed at any time if one or more of the following criteria are met:
  • Criteria 1
  • Criteria 2
  • Criteria 3

IF there are clear, established diagnostic criteria:

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
• The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
• The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

IF there are no established diagnostic criteria: 

• There are no established criteria for the diagnosis of [disease name].

References

• References should be cited for the material that you have put on your page. Type in {{reflist|2}}.This will generate your references in small font, in two columns, with links to the original article and abstract.
• For information on how to add references into your page, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief:

Overview

The majority of patients with [disease name] are asymptomatic.

OR

The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].

History and Symptoms

• Symptoms of Peutz-Jegher syndrome include abnormal pigmentation of the oral mucosa, abdominal pain, blood in stool, and extrusion of anal polyp. 

History

Patients with Peutz-Jegher syndrome may have a positive history of:

• Intussesception at a young age

References

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief:

Overview

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Physical Examination

• Physical examination of patients with [disease name] is usually remarkable for:[finding 1], [finding 2], and [finding 3].
• The presence of [finding(s)] on physical examination is diagnostic of [disease name].
• The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Appearance of the Patient

• Patients with [disease name] usually appear [general appearance].

Vital Signs

• High-grade / low-grade fever
• Hypothermia / hyperthermia may be present
• Tachycardia with regular pulse or (ir)regularly irregular pulse
• Bradycardia with regular pulse or (ir)regularly irregular pulse
• Tachypnea / bradypnea
• Kussmal respirations may be present in _____ (advanced disease state)
• Weak/bounding pulse / pulsus alternans / paradoxical pulse / asymmetric pulse
• High/low blood pressure with normal pulse pressure / wide pulse pressure / narrow pulse pressure

Skin

• Cyanosis
• Jaundice
• Pallor
• Bruises

• Description (Adapted from Dermatology Atlas)

  Description (Adapted from Dermatology Atlas)

• 

  Description (Adapted from Dermatology Atlas)

HEENT

• Abnormalities of the head/hair may include ___
• Evidence of trauma
• Icteric sclera
• Nystagmus
• Extra-ocular movements may be abnormal
• Pupils non-reactive to light / non-reactive to accomodation / non-reactive to neither light nor accomodation
• Ophthalmoscopic exam may be abnormal with findings of ___
• Hearing acuity may be reduced
• Weber test may be abnormal (Note: A positive Weber test is considered a normal finding / A negative Weber test is considered an abnormal finding. To avoid confusion, you may write "abnormal Weber test".)
• Rinne test may be positive (Note: A positive Rinne test is considered a normal finding / A negative Rinne test is considered an abnormal finding. To avoid confusion, you may write "abnormal Rinne test".)
• Exudate from the ear canal
• Tenderness upon palpation of the ear pinnae / tragus (anterior to ear canal)
• Inflamed nares / congested nares
• Purulent exudate from the nares
• Facial tenderness
• Erythematous throat with/without tonsillar swelling, exudates, and/or petechiae

Neck

• Jugular venous distension
• Carotid bruits may be auscultated unilaterally/bilaterally using the bell/diaphragm of the otoscope
• Lymphadenopathy (describe location, size, tenderness, mobility, and symmetry)
• Thyromegaly / thyroid nodules
• Hepatojugular reflux

Lungs

• Asymmetric chest expansion / Decreased chest expansion
• Lungs are hypo/hyperresonant
• Fine/coarse crackles upon auscultation of the lung bases/apices unilaterally/bilaterally
• Rhonchi
• Vesicular breath sounds / Distant breath sounds
• Expiratory/inspiratory wheezing with normal / delayed expiratory phase
• Wheezing may be present
• Egophony present/absent
• Bronchophony present/absent
• Normal/reduced tactile fremitus

Heart

• Chest tenderness upon palpation
• PMI within 2 cm of the sternum (PMI) / Displaced point of maximal impulse (PMI) suggestive of ____
• Heave / thrill
• Friction rub
• S1
• S2
• S3
• S4
• Gallops
• A high/low grade early/late systolic murmur / diastolic murmur best heard at the base/apex/(specific valve region) may be heard using the bell/diaphgram of the otoscope

Abdomen

• Abdominal distention
• Abdominal tenderness in the right/left upper/lower abdominal quadrant
• Rebound tenderness (positive Blumberg sign)
• A palpable abdominal mass in the right/left upper/lower abdominal quadrant
• Guarding may be present
• Hepatomegaly / splenomegaly / hepatosplenomegaly
• Additional findings, such as obturator test, psoas test, McBurney point test, Murphy test

Back

• Point tenderness over __ vertebrae (e.g. L3-L4)
• Sacral edema
• Costovertebral angle tenderness bilaterally/unilaterally
• Buffalo hump

Genitourinary

• A pelvic/adnexal mass may be palpated
• Inflamed mucosa
• Clear/(color), foul-smelling/odorless penile/vaginal discharge

Neuromuscular

• Patient is usually oriented to persons, place, and time
• Altered mental status
• Glasgow coma scale is ___ / 15
• Clonus may be present
• Hyperreflexia / hyporeflexia / areflexia
• Positive (abnormal) Babinski / plantar reflex unilaterally/bilaterally
• Muscle rigidity
• Proximal/distal muscle weakness unilaterally/bilaterally
• ____ (finding) suggestive of cranial nerve ___ (roman numerical) deficit (e.g. Dilated pupils suggestive of CN III deficit)
• Unilateral/bilateral upper/lower extremity weakness
• Unilateral/bilateral sensory loss in the upper/lower extremity
• Positive straight leg raise test
• Abnormal gait (describe gait: e.g. ataxic (cerebellar) gait / steppage gait / waddling gait / choeiform gait / Parkinsonian gait / sensory gait)
• Positive/negative Trendelenburg sign
• Unilateral/bilateral tremor (describe tremor, e.g. at rest, pill-rolling)
• Normal finger-to-nose test / Dysmetria
• Absent/present dysdiadochokinesia (palm tapping test)

Extremities

• Clubbing
• Cyanosis
• Pitting/non-pitting edema of the upper/lower extremities
• Muscle atrophy
• Fasciculations in the upper/lower extremity

References

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-in-Chief:

Overview

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

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

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Laboratory Findings

• There are no diagnostic laboratory findings associated with [disease name].

OR

• An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
• [Test] is usually normal among patients with [disease name].
• Laboratory findings consistent with the diagnosis of [disease name] include:
  • [Abnormal test 1]
  • [Abnormal test 2]
  • [Abnormal test 3]

• Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

References

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [6]; Associate Editor(s)-in-Chief:

Overview

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Electrocardiogram

• There are no ECG findings associated with [disease name].

OR

• An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include
  • [Finding 1]
  • [Finding 2]
  • [Finding 3]