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Diagnostic Criteria of Hepatorenal Syndrome (HRS)

Major criteria
1. Low glomerular filtration rate, as indicated by serum creatinine greater than 1.5 mg/dl or
24-hour creatinine clearance lower than 40 ml/minute
2. Absence of shock, ongoing bacterial infection, fluid losses and current treatment with
nephrotoxic drugs
3. No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dl or
less or increase in creatinine clearance to 40 ml/minute or more) following diuretic
withdrawal and expansion of plasma volume with 1.5 l of a plasma expander
4. Proteinuria lower than 500 mg/day and no ultrasonographic evidence of obstructive
uropathy or parenchymal renal disease
Additional criteria
1. Urine volume lower than 500 ml/day
2. Urine sodium lower than 10 mEq/l
3. Urine osmolality greater than plasma osmolality
4. Urine red blood cells less than 50 per high-power field
5. Serum sodium concentration lower than 130 mEq/l
All major criteria must be present for the diagnosis of hepatorenal syndrome. Additional criteria
are not necessary for the diagnosis, but provide supportive evidence.

Clinical types of hepatorenal syndrome

Type I: Rapid and progressive impairment of renal function as defined by a doubling of the
initial serum creatinine to a level higher than 2.5 mg/dl or a 50% reduction of the initial 24-hour
creatinina clearance to a level lower than 20 ml/minute in less than 2 weeks
Type II: Impairment in renal function (serum creatinine 41.5 mg/dl) that does not meet the
criteria of type I
Diagnostic Criteria for Zollinger-Ellison Syndrome (ZES)
Diagnostic criteria for ZES include the following:
1. Elevated levels of Basal Acid Output (BAO), greater than 15 mEq in unoperated patients
and greater than 5 mEq if previous acid-reducing surgery has been performed;
2. Elevated level of fasting serum gastrin (>100 pg/mL until 1994, >200 pg/mL since 1994);
3. Abnormal results from stimulation testing with secretin (an increase of >200 pg/mL
postinjection) or with calcium (an increase >395 pg/mL);
4. Positive histologic confirmation of gastrinoma; or
5. A combination of these criteria.
The tests used most commonly to establish a diagnosis of ZES are the fasting serum gastrin
concentration and BAO evaluation. Measurement of gastric pH is important to exclude
achlorhydria as a cause of secondary hypergastrinemia. Patients taking Proton Pump Inhibitors
(PPIs), those who have undergone massive small bowel resection, or those who have renal
insufficiency, G-cell hyperplasia, or gastric outlet obstruction may have gastrin levels between
150 and 1000 pg/mL Hence, for patients with suspected ZES with an equivocal fasting serum
gastrin concentration, a secretin stimulation test should be performed.
Diagnostic Criteria for Wilson's disease
1. Low serum ceruloplasmin levels < 20 mg/dL (Normal range 20-50 mg/dL).
2. Kayser - Fleischer rings in eyes.
3. High liver copper levels > 250 micrograms/g dry weight (Normal range <35
micrograms/g dry weight).
4. High 24 hr urinary copper levels > 100 micrograms /d or > 1.6 mmol/d (Normal range
<50 micrograms/d or < 0.8 mmol/d).
5. Radioisotope copper studies using 64Cu, 67Cu or 65Cu, which assesses ability to
incorporate copper into ceruloplasmin.
Liver biopsy is very helpful for making the diagnosis of Wilson's disease, especially in patients
with normal ceruloplasmin levels and no evidence of Kayser-Fleischer rings. Hepatic copper
concentrations greater than 250 micrograms/g dry weight (normal is <35 micrograms) are often
found in untreated patients with Wilson's disease.
Identification of the Wilson's disease gene has made molecular diagnosis of this disease possible,
but population-based screening is not feasible or recommended at this time. Genetic testing
probably has had its biggest impact on screening of first-degree relatives of an affected person.
Severity Criteria for Acute Pancreatitis
Ranson Criteria to Predict Severity of Acute Pancreatitis

1. When three or more of the following are present on admission, a severe course complicated by
pancreatic necrosis can be predicted with a sensitivity of 60-80%:
• Age over 55 years.
• White blood cell count over 16,000/uL.
• Blood glucose over 200 mg/dL.
• Serum lactate dehydrogenase (LDH) over 350 units/L.
• Aspartate aminotransferase (AST, SGOT) over 250 units/L.
2. Development of the following in the first 48 hours indicates a worsening prognosis:
• Hematocrit drop of more than ten percentage points.
• Blood urea nitrogen (BUN) rise greater than 5 mg/dL.
• Arterial PO2 of less than 60 mm Hg.
• Serum calcium of less than 8 mg/dL.
• Base deficit over 4 meq/L.
• Estimated fluid sequestration of more than 6 L.
3. Mortality rates correlate with the number of criteria present:

Number of Mortality rate


criteria
0-2 1%
3-4 16%
5-6 40%
7-8 100%
Balthazar CT severity index for acute pancreatitis.

CT Grade Points Necrosis Additional Severity Mortality


(%) Points Index Rate (%)
A Normal 0 0 0 0 0
pancreas
B Pancreatic 1 0 0 1 0
enlargement
C Pancreatic 2 < 30 2 4 0
inflammation
and/or
peripancreatic
fat
D Single 3 30-50 4 7 > 17
peripancreatic
fluid
collection
E Two or 4 > 50 6 10
more fluid
collections or
retroperitoneal
air
Diagnostic Criteria for the Hepatopulmonary Síndrome (HPS)

Variable Criterion
Oxygenation defect Partial pressure of oxygen <80 mm Hg or alveolar–arterial
oxygen gradient ≥15 mm Hg while breathing ambient air
Pulmonary vascular Positive findings on contrast-enhanced echocardiography or
dilatation abnormal uptake in the brain (>6%) with radioactive lung-
perfusion scanning
Liver disease Portal hypertension (most common) with or without cirrhosis
Degree of severity
Mild * Alveolar–arterial oxygen gradient ≥15 mm Hg, partial
pressure of oxygen ≥80 mm Hg
Moderate * Alveolar–arterial oxygen gradient ≥15 mm Hg, partial
pressure of oxygen ≥60 to <80 mm Hg
Severe * Alveolar–arterial oxygen gradient ≥15 mm Hg, partial
pressure of oxygen ≥50 to <60 mm Hg
Very severe * Alveolar–arterial oxygen gradient ≥15 mm Hg, partial
pressure of oxygen <50 mm Hg (<300 mm Hg while the
patient is breathing 100% oxygen)
All criteria were determined by means of positive contrast-enhanced echocardiography (i.e.,
microbubble opacification of the left heart chambers three to six cycles after right atrial passage).
The abbreviated formula for the alveolar–arterial gradient is as follows:
PAO2−PaO2 = (FIO2 [Patm–PH2O] – [PaCO2/0.8]) – PaO2,
where PAO2 denotes partial pressure of alveolar oxygen, PaO2 partial pressure of arterial oxygen,
FIO2 fraction of inspired oxygen, Patm atmospheric pressure, PH2O partial pressure of water vapor
at body temperature, and PaCO2 partial pressure of arterial carbon dioxide (0.8 corresponds to
the standard gas-exchange respiratory ratio at rest); the normal range is 4 to 8 mm Hg (0.5 to 1.1
kPa). The normal range for the partial pressure of oxygen is 80 to 100 mm Hg (10.7 to 13.3 kPa)
at sea level, while the patient is at rest and breathing ambient air. For patients older than 64 years
of age, a value of ≤70 mm Hg (9.3 kPa) for PaO2 or ≥20 mm Hg for the alveolar-arterial gradient
is often used. Ambient air is the respired gas unless otherwise indicated. To convert millimeters
of mercury to kilopascals, multiply by 0.133.
Revised Criteria for the Diagnosis of Celiac Disease (CD) Proposed by the ESPGHAN
Definite diagnosis of CD
History and clinical presentation compatible with CD
1. Serological screening compatible with CD: antigliadin antibody (AGA) antiendomysium
antibody (AEA), tissue transglutaminase (tTG) antibody.
2. Histological findings compatible with CD: villous atrophy
3. Obvious clinical and serological response to a gluten free diet (GFD)
4. Subject >2 years old
5. Rule out other clinical conditions mimicking CD
Possible Clinical Manifestations of CD
A- Typical symptoms
• Chronic diarrhea
• Failure to thrive
• Abdominal distention
B- Atypical symptoms
I- Secondary to malabsorption
• Sideropenic anemia
• Short stature
• Osteopenia
• Recurrent abortions
• Hepatic steatosis
• Recurrent abdominal pain
• Gaseousness
II- Independent of malabsorption
• Dermatitis herpetiformis
• Dental enamel hypoplasia
• Ataxia
• Alopecia
• Primary biliary cirrhosis
• Isolated hypertransaminasemia
• Recurrent aphthous stomatitis
• Myasthenia gravis
• Recurrent pericarditis
• Psoriasis
• Polyneuropathy
• Epilepsy (with or without intracranial calcifications)
• Vasculitis
• Dilatative cardiomyopathy
• Hypo/hyperthyroidism
Serologic Screening Tests for the Diagnosis of CD

Test Sensitivity Specificity PPV NPV


AGA IgG 57–100 42–98 20–95 41–88
AGA IgA 53–100 65–100 28–100 65–100
AEA IgA a 75–98 96–100 98–100 80–95
tTG IgA 90-98 95-97
a
Patients older than 2 years.
Abbreviations: AEA, antiendomysium antibody; AGA, antigliadin antibody; CD, celiac disease;
ESPGHAN, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition; GFD,
gluten-free diet; Ig, immunoglobulin; tTG, tissue transglutaminase; PPV, positive predictive
value; NPV, negative predictive value.
King´s College Hospital Criteria for Liver Transplantation in Fulminant Hepatic Failure
Acetaminophen-induced disease
Arterial pH <7.3 (irrespective of the grade of encephalopathy)
or
Grade III or IV encephalopathy, and
Prothrombin time >100 seconds, and
Serum creatinine >3.4mg/dl (301 μmol/L)
All other causes of fulminant hepatic failure
Prothrombin time >100 seconds (irrespective of the grade of encephalopathy)
Or
Any three of the following variables (irrespective of the grade of encephalopathy)
1. Age <10 years or >40 years
2. Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions
3. Duration of jaundice before onset of encephalopathy >7 days
4. Prothrombin time >50 seconds
5. Serum bilirrubin >18 mg/dl (308 μmol/L)
Criteria for Definite Diagnosis of Crohn's Disease
A. One of the following three conditions should be present:
1. Intestinal longitudinal ulcer or deformity induced by a longitudinal ulcer or cobblestone
pattern
2. Intestinal small aphthous ulcerations arranged in a longitudinal fashion for at least three
months, plus noncaseating granulomas
3. Multiple small aphthous ulcerations in both the upper and lower digestive tract, not
necessarily with longitudinal arrangement, for at least three months, plus noncaseating
granulomas
B. The following diseases should be excluded:
1. Ulcerative colitis
2. Ischemic enterocolitis
3. Acute infectious enterocolitis
Diagnostic Criteria for Cholangitis
The diagnostic criteria for cholangitis are:
a. fever or abdominal pain in the right upper quadrant;
b. endoscopic or radiologic (sonography or CT) evidence of biliary tract obstruction owing
to stones, stricture, or tumor; and
c. laboratory evidence of hyperbilirubinemia and elevated alkaline phosphatase.
Appropriate Indications for Upper Gastrointestinal Endoscopy (UGE)
1. Uncomplicated dyspepsia
2. Frequent symptoms (>= 2/wk) suggesting gastroesophageal reflux disease (GERD) or
history of reflux-associated mucosal disease of the esophagus, without alarm symptoms
and without Barrett's esophagus
3. Known Barrett's esophagus, without alarm symptoms
4. Atypical chest pain
5. Alarm symptoms: recent upper GI bleeding, esophageal dysphagia, unexplained weight
loss, iron deficiency anemia
6. Risk factors and pre-malignant conditions of the UGI tract: pernicious anemia, atrophic
gastritis, status post-gastrectomy, gastric polyps, familial adenomatous polyposis
7. Miscellaneous indications: assess healing of benign gastric ulcer, follow-up of
sclerotherapy/banding, suspected malignant lesion on UGI series, suspected
malabsorption syndrome
Appropriate Indications for Colonoscopy
1. Iron-deficiency anemia (malabsorption syndrome excluded)
2. Hematochezia (without Inflammatory Bowel Disease - IBD).
3. Uncomplicated lower abdominal pain of at least 2 months'duration, without known
inflammatory bowel disease, without anemia and without Fecal Occult Blood Test
(FOBT) positive.
4. Change in bowel habits (predominantly constipation), of at least 2 months'duration,
without known inflammatory bowel disease, without anemia or FOBT-positive stools and
without pain.
5. Uncomplicated diarrhea (infectious or malabsorption origin excluded and without known
IBD). No anemia. No bleeding. No radio-frequency (RF) for Colorectal (CR) cancer.
6. Evaluation of known ulcerative colitis (UC)
7. Evaluation of known Crohn's disease (CD)
8. Screening for colorectal cancer in patients with known inflammatory ulcerative colitis
9. Screening for colorectal cancer in patients with known Crohn's disease
10. Surveillance after colonic polypectomy or curative intent resection of colorectal cancer
11. Screening for colorectal cancer
12. Miscellaneous indications: lesion at recent barium enema or sigmoidoscopy, preoperative
colonoscopy, FOBT-positive stools, fulminant colitis, acute diverticulitis, endometriosis,
unexplained weight loss
13. Histological Scoring System for Nonalcoholic Fatty Liver Disease (NAFLD)
14. Components of NAFLD Activity Score (NAS) and Fibrosis Staging
15. Total NAS score represents the sum of scores for steatosis, lobular inflammation, and
ballooning, and ranges from 0-8. Diagnosis of NASH (or, alternatively, fatty liver not
diagnostic of NASH) should be made first, then NAS is used to grade activity. In the
reference study, NAS scores of 0-2 occurred in cases largely considered not diagnostic of
NASH, scores of 3-4 were evenly divided among those considered not diagnostic,
borderline, or positive for NASH. Scores of 5-8 occurred in cases that were largely
considered diagnostic of NASH.

NAS Components (see scoring interpretation)


Item Score Extent Definition and Comment
Steatosis 0 <5% Refers to amount of surface area
involved by steatosis as evaluated
on low to medium power
examination; minimal steatosis
(<5%) receives a score of 0 to avoid
giving excess weight to biopsies
with very little fatty change
1 5-33%
2 >33-66%
3 >66%

Lobular 0 No foci Acidophil bodies are not included


Inflammation in this assessment, nor is portal
inflammation
1 <2 foci/200x
2 2-4 foci/200x
3 >4 foci/200x

Hepatocyte 0 None
Ballooning 1 Few balloon The term "few" means rare but
cells definite ballooned hepatocytes as
well as cases that are diagnostically
borderline
2 Many Most cases with prominent
cells/prominent ballooning also had Mallory's
ballooning hyalin, but Mallory's hyaline is not
scored separately for the NAS

Fibrosis Stage (Evaluated separately from NAS)


Fibrosis 0 None
1 Perisinusoidal
or periportal
1A Mild, zone 3, "delicate" fibrosis
perisinusoidal
1B Moderate, zone "dense" fibrosis
3,
perisinusoidal
1C Portal/periporta This category is included to
l accommodate cases with portal
and/or peri portal fibrosis without
accompanying
pericellular/perisinusoidal fibrosis
2 Perisinusoidal
and
portal/periportal
3 Bridging
fibrosis
4 Cirrhosis
16. Total NAS score represents the sum of scores for steatosis, lobular inflammation, and
ballooning, and ranges from 0-8. Diagnosis of NASH (or, alternatively, fatty liver not
diagnostic of NASH) should be made first, then NAS is used to grade activity. In the
reference study, NAS scores of 0-2 occurred in cases largely considered not diagnostic of
NASH, scores of 3-4 were evenly divided among those considered not diagnostic,
borderline, or positive for NASH. Scores of 5-8 occurred in cases that were largely
considered diagnostic of NASH.
Diagnosis of Spontaneous Bacterial Peritonitis (SBP)
Indications for diagnostic paracentesis.
• Cirrhotic patients with ascites at admission
• Cirrhotic patients with ascites and signs or symptoms of infection: fever, leukocytosis,
abdominal pain
• Cirrhotic patients with ascites who present with a clinical condition that is deteriorating
during hospitalization: renal function impairment, hepatic encephalopathy,
gastrointestinal bleeding
• Patients with new-onset ascites
Analysis of Peritoneal Fluid

Test and Ascitic-Fluid Comments


Container
Albumin Differential diagnosis of ascites according to the serum–
ascites albumin gradient
Cell Cell count and differential count
Culture Aerobic- and anaerobic-culture
Additional Analyses of Ascitic Fluid

Test and Ascitic-Fluid Comments


Container
Tube without additives
Total protein Values >1 g/dl suggest secondary peritonitis instead of SBP
Lactate dehydrogenase Values greater than the upper limit of normal for serum
suggest secondary peritonitis instead of SBP
Glucose Values <50 mg/dl suggest secondary peritonitis instead of
SBP
Carcinoembryonic antigen Values >5 ng/ml suggest hollow viscus perforation
Alkaline phosphatase Values >240 U/liter suggest hollow viscus perforation
Amylase Values markedly elevated (often >2000 U/liter or five times
serum levels) in patients with pancreatic ascites or hollow
viscus perforation
Triglyceride Values >200 mg/dl suggest chylous ascites
Syringe or evacuated container
Cytology Sensitivity increased if three samples submitted and promptly
evaluated
Mycobacterial culture Sensitivity only 50%

Differential Diagnosis of Ascites According to the Serum–Ascites Albumin Gradient

Gradient >1.1 g/dl (portal hypertension) Gradient <1.1 g/dl


Cirrhosis Peritoneal carcinomatosis
Alcoholic hepatitis Tuberculous peritonitis
Cardiac ascites Pancreatic ascites
Portal-vein thrombosis Biliary ascites
Budd-Chiari syndrome Nephrotic syndrome
Liver metastases Serositis
The diagnosis of SBP is suggested by a polymorphonuclear (PMN) cell count in excess of 250
cells per cubic millimeter in the absence of evidence of an alternative source of infection
(secondary peritonitis), such as viscus perforation or intraabdominal abscess.
Determination of total protein, lactate dehydrogenase, and glucose levels in ascitic fluid may aid
in the differentiation between SBP and secondary peritonitis. Culture is used to confirm the
diagnosis of SBP
Child-Pugh Classification of Severity of Liver Disease
Modified Child-Pugh classification of severity of liver disease according to the degree of ascites,
the plasma concentrations of bilirrubin and albumin, the prothrombin time, and the degree of
encephalopathy.

Parameter Points assigned


1 2 3

Ascites Absent Slight Moderate


Bilirrubin, mg/dL </= 2 2-3 >3
Albumin, g/dL >3.5 2.8-3.5 <2.8
Prothrombin time
* Seconds over control 1-3 4-6 >6
* INR <1.8 1.8-2.3 >2.3
Encephalopathy None Grade 1-2 Grade 3-4

A total score of 5-6 is considered grade A (well-compensated disease); 7-9 is grade B (significant
functional compromise); and 10-15 is grade C (descompensated disease). These grades correlate
with one- and two-year patient survival.

Grade Points One-year patient Two-year patient


survival (%) survival (%)
A: well- 5-6 100 85
compensated disease
B: significant 7-9 80 60
functional
compromise
C: descompensated 10-15 45 35
disease
Diagnostic Criteria for Autoimmune Pancreatitis
Diagnostic Criteria for Autoimmune Pancreatitis by the Japan Pancreas Society

Findings on Imaging Serologic and Histologic Findings (One Required)


Radiography (One Required)
Cross-sectional ERCP or MRCP Serologic Pancreatic- Nongastrointestinal
Imaging Analysis Biliary Histologic
Histologic Analysis
Analysis
Diffusely Segmental Elevated serum Periductal Tubulointerstitial
enlarged pancreatic IgG4 level lympho- nephritis with
pancreas ductal plasmacytic immune deposits
narrowing infiltration or within tubular
fibrosis basement
membranes
Enhanced Focal Elevated serum Obliterative Pulmonary
peripheral rim pancreatic IgG or gamma phlebitis interstitial
of ductal globulin level lymphoplasmacytic
hypoattenuation narrowing infiltration with
“halo” IgG4-positive
plasma cells
Low- Diffuse Presence of IgG4-positive Chronic
attenuation pancreatic ALA, ACA II, plasma cells in sialadenitis with
mass in head of ductal ASMA, or tissue IgG4-positive
pancreas narrowing ANA plasma cells
Criteria were modified from those of the Japan Pancreas Society. ERCP denotes endoscopic
retrograde cholangiopancreatography, MRCP magnetic resonance cholangiopancreatography,
ALA antilactoferrin antibody, ACA II anti-carbonic anhydrase II antibody, ASMA anti-smooth-
muscle antibody, and ANA antinuclear body.
The presence of tissue IgG4-positive cells is not necessarily abnormal, but an increased number
of infiltrating IgG4-positive plasma cells is abnormal.

Diagnostic Criteria for Autoimmune Pancreatitis in Asan Medical Center


Inclusion Criteria
Criterion I. Pancreatic imaging (essential)
1. CT: Diffuse enlargement (swelling) of pancreas, and
2. ERCP: Diffuse or segmental irregular narrowing of main pancreatic duct
Criterion II. Laboratory findings
1. elevated levels of IgG and/or IgG4. or
2. detected autoantibodies
Criterion III. Histopathologic findings: Fibrosis and lymphoplasmacytic infiltration
Criterion IV. Response to the steroid
Definite diagnosis: Criterion I and any of criterion II-IV

Diagnostic Criteria for Autoimmune Pancreatitis by Italian Group


Diagnostic criteria
1. Histology and cytology
2. The association with other postulated autoimmune disease
3. Response to the steroid therapy
ROME II Diagnostic Criteria for Functional Abdominal Pain
The diagnosis of Functional Abdominal Pain always presumes the absence of a structural or
biochemical explanation for the symptoms.
D1. Functional Abdominal Pain Syndrome
At least 6 months of:
1. Continuous or nearly continuous abdominal pain; and
2. No or only occasional relationship of pain with physiological events (e.g., eating,
defecation, or menses); and
3. Some loss of daily functioning; and
4. The pain is not feigned (e.g., malingering), and
5. Insufficient criteria for other functional gastrointestinal disorders that would explain the
abdominal pain.
D2. Unspecified Functional Abdominal Pain
This is functional abdominal pain that fails to reach criteria for functional abdominal pain
syndrome.
ROME II Diagnostic Criteria for Functional Gastroduodenal Disorders
The diagnosis of a Functional Gastroduodenal Disorder always presumes the absence of a
structural or biochemical explanation for the symptoms.
B1. Functional Dyspepsia
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Persistent or recurrent symptoms (pain or discomfort centered in the upper abdomen);
2. No evidence of organic disease (including at upper endoscopy) that is likely to explain
the symptoms; and
3. No evidence that dyspepsia is exclusively relieved by defecation or associated with the
onset of a change in stool frequency or stool form (i.e., not irritable bowel).
B1a. Ulcer-like Dyspepsia
Pain centered in the upper abdomen is the predominant (most bother-some) symptom.
B1b. Dysmotility-like Dyspepsia
An unpleasant or troublesome nonpainful sensation (discomfort) centered in the upper abdomen
is the predominant symptom; this sensation may be characterized by or associated with upper
abdominal fullness, early satiety, bloating, or nausea.
B1c. Unspecified (Nonspecific) Dyspepsia
Symptomatic patients whose symptoms do not fulfill the criteria for ulcer-like or dysmotility-like
dyspepsia.
B2. Aerophagia
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Air swallowing that is objectively observed; and
2. Troublesome repetitive belching.
B3. Functional Vomiting
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Frequent episodes of vomiting, occurring on at least three separate days in a week over
three months;
2. Absence of criteria for an eating disorder, rumination, or major psychiatric disease
according to DSM-IV;
3. Absence of self-induced and medication-induced vomiting; and
4. Absence of abnormalities in the gut or central nervous system, and metabolic diseases to
explain the recurrent vomiting.
ROME II Diagnostic Criteria for Functional Esophageal Disorders
The diagnosis of a Functional Esophageal Disorder always presumes the absence of a structural
or biochemical explanation for the symptoms.
A1. Globus
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. The persistent or intermittent sensation of a lump or foreign body in the throat;
2. Occurrence of the sensation between meals;
3. Absence of dysphagia and odynophagia; and
4. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with
a recognized pathologic basis (e.g., scleroderma of the esophagus).
A2. Rumination Syndrome
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Persistent or recurrent regurgitation of recently ingested food into the mouth with
subsequent remastication and swallowing or spitting it out;
2. Absence of nausea and vomiting;
3. Cessation of the process when the regurgitated material becomes acidic; and
4. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with
a recognized pathologic basis as the primary disorder.
A3. Functional Chest Pain of Presumed Esophageal Origin
At least 12 weeks, which need not be consecutive, within the preceding 12 months of:
1. Midline chest pain or discomfort that is not of burning quality; and
2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with
a recognized pathologic basis.
A4. Functional Heartburn
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Burning retrosternal discomfort or pain; and
2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with
a recognized pathologic basis.
A5. Functional Dysphagia
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Sense of solid and/or liquid foods sticking, lodging, or passing abnormally through the
esophagus; and
2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with
a recognized pathologic basis.
A6. Unspecified Functional Esophageal Disorder
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Unexplained symptoms attributed to the esophagus that do not fit into the previously
described categories; and
2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with
a recognized pathologic basis.
ROME II Diagnostic Criteria for Functional Disorders of the Biliary Tract and the
Pancreas
The diagnosis of a Functional Disorder of the Biliary Tract and Pancreas always pre-sumes the
absence of a structural or biochemical explanation for the symptoms.
E1. Gallbladder Dysfunction
Episodes of severe steady pain located in the epigastrium and right upper quadrant, and all of the
following:
1. Symptom episodes last 30 minutes or more, with pain-free intervals;
2. Symptoms have occurred on one or more occasions in the previous 12 months;
3. The pain is steady and interrupts daily activities or requires consultation with a physician;
4. There is no evidence of structural abnormalities to explain the symptoms; and
5. There is abnormal gallbladder functioning with regard to emptying.
E2. Sphincter of Oddi Dysfunction
Episodes of severe steady pain located in the epigastrium and right upper quadrant, and all of the
following:
1. Symptom episodes last 30 minutes or more, with pain-free intervals;
2. Symptoms have occurred on one or more occasions in the previous 12 months;
3. The pain is steady and interrupts daily activities or requires consultation with a physician;
and
4. There is no evidence of structural abnormalities to explain the symptoms.
ROME II Diagnostic Criteria for Functional Disorders of the Anus and Rectum
The diagnosis of a Functional Disorder of the Anus and Rectum always presumes the absence of
a structural or biochemical explanation for the symptoms.
F1. Functional Fecal Incontinence
Recurrent uncontrolled passage of fecal material for at least one month, in an individual with a
developmental age of at least 4 years, associated with:
1. Fecal impaction; or
2. Diarrhea; or
3. Nonstructural anal sphincter dysfunction.
F2. Functional Anorectal Pain
F2a. Levator Ani Syndrome
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Chronic or recurrent rectal pain or aching;
2. Episodes last 20 minutes or longer; and
3. Other causes of rectal pain such as ischemia, inflammatory bowel disease, cryptitis,
intramuscular abscess, fissure, hemorrhoids, prostatitis, and solitary rectal ulcer have
been excluded.
F2b. Proctalgia Fugax
1. Recurrent episodes of pain localized to the anus or lower rectum;
2. Episodes last from seconds to minutes; and
3. There is no anorectal pain between episodes.
F3. Pelvic Floor Dyssynergia
1. The patient must satisfy diagnostic criteria for functional constipation in Diagnostic
Criteria C3;
2. There must be manometric, EMG, or radiologic evidence for inappropriate contraction or
failure to relax the pelvic floor muscles during repeated at-tempts to defecate;
3. There must be evidence of adequate propulsive forces during attempts to defecate, and
4. There must be evidence of incomplete evacuation.
ROME II Diagnostic Criteria for Childhood Functional Gastrointestinal Disorders
The diagnosis of a Childhood Functional Gastrointestinal Disorder always presumes the absence
of a structural or biochemical explanation for the symptoms.
G1.Vomiting
G1a. Infant Regurgitation
1. Regurgitation 2 or more times per day for 3 or more weeks;
2. There is no retching, hematemesis, aspiration, apnea, failure-to-thrive, or abnormal
posturing;
3. The infant must be 1 to 12 months of age and otherwise healthy; and
4. There is no evidence of metabolic, gastrointestinal, or central nervous system disease to
explain the symptom.
G1b. Infant Rumination Syndrome
1. At least 3 months of stereotypical behavior beginning with repetitive contractions of the
abdominal muscles, diaphragm, and tongue, and culminating in regurgitation of gastric contents
into the mouth, which is either expectorated or rechewed and reswallowed, and 3 or more of the
following:
a. Onset between 3 and 8 months of age;
b. Does not respond to management for gastroesophageal reflux disease, anticholinergic
drugs, hand restraints, formula changes, and gavage or gastrostomy feedings;
c. Unaccompanied by signs of nausea or distress; and/or
d. Does not occur during sleep and when the infant is interacting with in-dividuals in the
environment.
G1c. Cyclic Vomiting Syndrome
1. A history of 3 or more periods of intense, acute nausea, and unremitting vomiting lasting
hours to days, with intervening symptom-free intervals lasting weeks to months.
2. There is no metabolic, gastrointestinal, or central nervous system structural or
biochemical disease.
G2. Abdominal Pain
G2a. Functional Dyspepsia
In children mature enough to provide an accurate pain history, at least 12 weeks, which need not
be consecutive, in the preceding 12 months of:
1. Persistent or recurrent pain or discomfort centered in the upper abdomen (above the
umbilicus);
2. No evidence of organic disease (including at upper endoscopy) that is likely to explain
the symptoms; and
3. No evidence that dyspepsia is exclusively relieved by defecation or associated with onset
of a change in stool frequency or stool form (i.e., not irritable bowel).
G2a1. Ulcer-like Dyspepsia: Pain centered in the upper abdomen is the predominant (most
bothersome) symptom.
G2a2. Dysmotility-like Dyspepsia: An unpleasant or troublesome nonpainful sensation
(discomfort) centered in the upper abdomen is the predominant symptom; this sensation may be
characterized by early satiety, upper abdominal fullness, bloating, or nausea.
G2a3. Unspecified (Nonspecific) Dyspepsia: Symptomatic patients whose symptoms do not
fulfill the criteria for either ulcer-like or dysmotility-like dyspepsia.
G2b. Irritable Bowel Syndrome
In children old enough to provide an accurate pain history, at least 12 weeks, which need not be
consecutive, of continuous or recurrent symptoms during the preceding 12 months of:
1. Abdominal discomfort or pain that has two out of three features:
a. Relieved with defecation; and/or
b. Onset associated with a change in frequency of stool; and/or
c. Onset associated with a change in form (appearance) of stool.
2. There are no structural or metabolic abnormalities to explain the symptoms.
Symptoms that Cumulatively Support the Diagnosis of Irritable Bowel Syndrome
• Abnormal stool frequency (for research purposes “abnormal” may be defined as greater
than 3 bowel movements per day and less than 3 bowel movements per week);
• Abnormal stool form (lumpy/hard or loose/watery stool);
• Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation);
• Passage of mucus;
• Bloating or feeling of abdominal distension.
G2c. Functional Abdominal Pain
At least 12 weeks of:
1. Continuous or nearly continuous abdominal pain in a school-aged child or adolescent;
and
2. No or only occasional relationship of pain with physiological events (e.g., eating, menses,
defecation); and
3. Some loss of daily functioning; and
4. The pain is not feigned (e.g., malingering); and
5. Insufficient criteria for other functional gastrointestinal disorders that would explain the
abdominal pain.
G2d. Abdominal Migraine
1. In the preceding 12 months, 3 or more paroxysmal episodes of intense, acute midline
abdominal pain lasting 2 hours to several days, with intervening symptom-free intervals of weeks
to months; and
2. Evidence of metabolic, gastrointestinal, and central nervous system structural or biochemical
diseases is absent; and
3. Two of the following features:
a. Headache during episodes;
b. Photophobia during episodes;
c. Family history of migraine;
d. Headache confined to one side only; and
e. An aura or warning period consisting of either visual symptoms (e.g., blurred or restricted
vision) or sensory symptoms (e.g., numbness or tingling), or motor symptoms (e.g.,
slurred speech, inability to speak, paralysis).
G2e. Aerophagia
At least 12 weeks, which need not be consecutive, in the preceding 12 months of two or more of
the following signs and symptoms:
1. Air swallowing;
2. Abdominal distension due to intraluminal air; and
3. Repetitive belching and/or increased flatus.
G3. Functional Diarrhea (also called Toddler’s Diarrhea, chronic nonspecific diarrhea,
irritable colon of childhood)
For more than 4 weeks, daily painless, recurrent passage of 3 or more large, unformed stools, in
addition to all these characteristics:
1. Onset of symptoms begins between 6 and 36 months of age;
2. Passage of stools occurs during waking hours; and
3. There is no failure-to-thrive if caloric intake is adequate.
G4. Disorders of Defecation
G4a. Infant dyschezia
At least 10 minutes of straining and crying before successful passage of soft stools in an
otherwise healthy infant less than 6 months of age.
G4b. Functional Constipation
In infants and children, at least 2 weeks of:
1. Scybalous, pebble-like, hard stools for a majority of stools; or
2. Firm stools 2 or less times/week; and
3. There is no evidence of structural, endocrine, or metabolic disease.
G4c. Functional Fecal Retention
From infancy to 16 years old, a history of at least 12 weeks of:
1. Passage of large diameter stools at intervals < 2 times per week; and
2. Retentive posturing, avoiding defecation by purposefully contracting the pelvic floor. As
pelvic floor muscles fatigue, the child uses gluteal muscles, squeezing the buttocks
together.
Accompanying symptoms may include fecal soiling, irritability, abdominal cramps, decreased
appetite and/or early satiety. The accompanying symptoms disappear immediately following
passage of a large stool.
G4d. Functional Non-retentive Fecal Soiling
Once a week or more for the preceding 12 weeks, in a child older than 4 years, a history of:
1. Defecation into places and at times inappropriate to the social context;
2. In the absence of structural or inflammatory disease; and
3. In the absence of signs of fecal retention (listed in G4c above).
ROME II Diagnostic Criteria for Functional Bowel Disorders
The diagnosis of a Functional Bowel Disorder always presumes the absence of a structural or
biochemical explanation for the symptoms.
C1. Irritable Bowel Syndrome
At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal
discomfort or pain that has two out of three features:
1. Relieved with defecation; and/or
2. Onset associated with a change in frequency of stool; and/or
3. Onset associated with a change in form (appearance) of stool.
Symptoms that Cumulatively Support the Diagnosis of Irritable Bowel Syndrome
• Abnormal stool frequency (for research purposes “abnormal” may be defined as greater
than 3 bowel movements per day and less than 3 bowel movements per week);
• Abnormal stool form (lumpy/hard or loose/watery stool);
• Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation);
• Passage of mucus;
• Bloating or feeling of abdominal distension.
C2. Functional Abdominal Bloating
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Feeling of abdominal fullness, bloating, or visible distension; and
2. Insufficient criteria for a diagnosis of functional dyspepsia, irritable bowel syndrome, or
other functional disorder.
C3. Functional Constipation
At least 12 weeks, which need not be consecutive, in the preceding 12 months of two or more of:
1. Straining >1/4 of defecations;
2. Lumpy or hard stools >1/4 of defecations;
3. Sensation of incomplete evacuation >1/4 of defecations;
4. Sensation of anorectal obstruction/blockage >1/4 of defecations;
5. Manual maneuvers to facilitate >1/4 of defecations (e.g., digital evacuation, support of
the pelvic floor); and/or
6. < 3 defecations per week.
Loose stools are not present, and there are insufficient criteria for IBS.
C4. Functional Diarrhea
At least 12 weeks, which need not be consecutive, in the preceding 12 months of:
1. Loose (mushy) or watery stools
2. Present >3/4 of the time; and
3. No abdominal pain.
C5. Unspecified Functional Bowel Disorder
Bowel symptoms in the absence of organic disease that do not fit into the previously defined
categories of functional bowel disorders.

Sponsored Links

2001 Bethesda System Terminology


Specimen Type: Indicate conventional smear (Pap smear) vs. liquid based vs. other
Specimen Adequacy
○ Satisfactory for evaluation (describe presence or absence of endocervical/transformation
zone component and any other quality indicators, e.g., partially obscuring blood,
inflammation, etc.)
○ Unsatisfactory for evaluation ... (specify reason)
○ Specimen rejected/not processed (specify reason)
○ Specimen processed and examined, but unsatisfactory for evaluation of epithelial
abnormality because of (specify reason)
General Categorization (optional)
○ Negative for intraepithelial lesion or malignancy
○ Epithelial cell abnormality: See interpretation/result (specify ‘squamous’ or ‘glandular’ as
appropriate)
○ Other: See interpretation/result (e.g. endometrial cells in a woman > 40 years of age)
Automated Review
If case examined by automated device, specify device and result.

Ancillary Testing
Provide a brief description of the test methods and report the result so that it is easily understood
by the clinician.

Interpretation/Result
Negative for Intraepithelial Lesion or Malignancy (when there is no cellular evidence of
neoplasia, state this in the General Categorization above and/or in the Interpretation/Result
section of the report, whether or not there are organisms or other non-neoplastic findings)

Organisms:
• Trichomonas vaginalis
• Fungal organisms morphologically consistent with Candida species
• Shift in flora suggestive of bacterial vaginosis
• Bacteria morphologically consistent with Actinomyces species.
• Cellular changes consistent with Herpes simplex virus
Other non neoplastic findings (Optional to report; list not inclusive):
• Reactive cellular changes associated with
• inflammation (includes typical repair)
• radiation
• intrauterine contraceptive device (IUD)
• Glandular cells status post hysterectomy
• Atrophy

Other
• Endometrial cells (in a woman > 40 years of age)
(Specify if ‘negative for squamous intraepithelial lesion’)

Epithelial Cell Abnormalities


SQUAMOUS CELL
• Atypical squamous cells (ASC)
• of undetermined significance (ASC-US)
• cannot exclude HSIL (ASC-H)
• Low grade squamous intraepithelial lesion (LSIL)
encompassing: HPV/mild dysplasia/cervical intraepithelial neoplasia (CIN) 1
• High grade squamous intraepithelial lesion (HSIL)
encompassing: moderate and severe dysplasia, carcinoma in situ (CIS)/CIN 2 and CIN 3
• with features suspicious for invasion (if invasion is suspected)
• Squamous cell carcinoma

GLANDULAR CELL
• Atypical
• endocervical cells (NOS or specify in comments)
• endometrial cells (NOS or specify in comments)
• glandular cells (NOS or specify in comments)
• Atypical
• endocervical cells, favor neoplastic
• glandular cells, favor neoplastic
• Endocervical adenocarcinoma in situ (AIS)
• Adenocarcinoma
• endocervical
• endometrial
• extrauterine
• not otherwise specified (NOS)
Other Malignant Neoplasms: (specify)

Educational Notes and Suggestions (optional)


Suggestions should be concise and consistent with clinical follow-up guidelines published by
professional organizations (references to relevant publications may be included).
Diagnostic Criteria for DiGeorge Syndrome (DGS)
Definitive diagnosis
Male or female patient with reduced numbers of CD3+ T cells (less than 500/mm3) and two of
the three following characteristics:
1. Conotruncal cardiac defect (truncus arteriosus, tetralogy of Fallot, interrupted aortic arch,
or aberrant right subclavian).
2. Hypocalcemia of greater than 3 weeks' duration that requires therapy.
3. Deletion of chromosome 22q11.2.
Probable diagnosis
Male or female patient with reduced numbers of CD3+ T cells (less than 1500/mm3) and a
deletion of chromosome 22q11.2.
Possible diagnosis
Male or female patient with reduced numbers of CD3+ T cells (less than 1500/mm3) and at least
one of the following:
1. Cardiac defect.
2. Hypocalcemia of greater than 3 weeks' duration that requires therapy.
3. Dysmorphic facies or palatal abnormalities.
Patients with a definitive or probable diagnosis are assumed to have a greater than 98 and 85
percent probability, respectively, that in 20 years they will still have the same diagnosis. Patients
with a possible diagnosis are those that have some but not all of the characteristic clinical or
laboratory findings of a particular disorder.
Framingham Criteria for Congestive Heart Failure
Diagnosis of CHF requires the simultaneous presence of at least 2 major criteria or 1 major
criterion in conjunction with 2 minor criteria.
Major criteria:
• Paroxysmal nocturnal dyspnea
• Neck vein distention
• Rales
• Radiographic cardiomegaly (increasing heart size on chest radiography)
• Acute pulmonary edema
• S3 gallop
• Increased central venous pressure (>16 cm H2O at right atrium)
• Hepatojugular reflux
• Weight loss >4.5 kg in 5 days in response to treatment

Minor criteria:
• Bilateral ankle edema
• Nocturnal cough
• Dyspnea on ordinary exertion
• Hepatomegaly
• Pleural effusion
• Decrease in vital capacity by one third from maximum recorded
• Tachycardia (heart rate>120 beats/min.)
Minor criteria are acceptable only if they can not be attributed to another medical condition (such
as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or the nephrotic syndrome).
The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying
persons with definite congestive heart failure.
Diagnostic Criteria for Cystic Fibrosis (CF)
One or more typical phenotypic features of CF:
• Chronic sinopulmonary disease
• Characteristic gastrointestinal and nutritional abnormalities
• Salt loss syndromes
• Obstructive azoospermia
or

A history of cystic fibrosis in a sibling

or

A positive newborn screening test

PLUS

An elevated sweat chloride concentration (greater than 60 meq/L) on two or more occasions

or

Identification of mutations in each cystic fibrosis transmembrane conductance regulator (CFTR)


protein gene known to cause CF

or

In vivo demonstration of characteristic abnormalities in ion transport across the nasal epithelium

Clinical Manifestations of Cystic Fibrosis


• Respiratory
• Bronchiolitis / asthma
• Psudomonas aeruginosa colonization of the respiratory tract
• Staphylococcal pneumonia
• Nasal polyposis
• Sinusitis
Gastrointestinal
• Meconium ileus
• Rectal prolapse
• Recurrent abdominal pain and/or right lower quadrant mass
• Hypoproteinemic edema
• Prolonged neonatal jaundice
• Biliary cirrhosis with portal hypertension
• Vitamin deficiency states (A, D, E, K)
• Acrodermatitis enterophatica-like eruption with fatty acid and zinc deficiency
• Recurrent pancreatitis
• Volvulus in fetal life
Genitourinary
• Congenital bilateral absence of the vas deferens (CBAVD)
• Male infertility
• Female infertility
Other
• Hypochloremic, hyponatremic alkalosis
• Mother of child with cystic fibrosis
• Pseudotumor cerebri
Duke Criteria for Infective Endocarditis (IE)
Major criteria:
A. Positive blood culture for Infective Endocarditis
1- Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:
• viridans streptococci, Streptococcus bovis, or HACEK* group, or
• community-acquired Staphylococcus aureus or enterococci, in the absence of a primary
focus
or
2- Microorganisms consistent with IE from persistently positive blood cultures defined as:
• 2 positive cultures of blood samples drawn >12 hours apart, or
• all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1
hour apart)
B. Evidence of endocardial involvement
1- Positive echocardiogram for IE defined as :
• oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant
jets, or on implanted material in the absence of an alternative anatomic explanation, or
• abscess, or
• new partial dehiscence of prosthetic valve
or
2- New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)
Minor criteria:
• Predisposition: predisposing heart condition or intravenous drug use
• Fever: temperature > 38.0° C (100.4° F)
• Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
• Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth spots, and rheumatoid
factor
• Microbiological evidence: positive blood culture but does not meet a major criterion as
noted above¹ or serological evidence of active infection with organism consistent with IE
• Echocardiographic findings: consistent with IE but do not meet a major criterion as noted
above
Clinical criteria for infective endocarditis requires:
• Two major criteria, or
• One major and three minor criteria, or
• Five minor criteria
*HACEK group: Haemophilus sp, Actinobacilius actinomycetemcomitans, Cardiobacterium
hominis, Eikenella rodens y Kingella sp
Causes of Bacteraemia and Meningitis in Young Children
Under 1 month old
• Group B streptococcus
• Escherichia coli (and other enteric Gram negative bacilli)
• Listeria monocytogenes
• Streptococcus pneumoniae
• Haemophilus influenzae
• Staphylococcus aureus
• Neisseria meningitides
• Salmonella spp
1-3 months old
• Streptococcus pneumoniae
• Group B streptococcus
• Neisseria meningitides
• Salmonella spp
• Haemophilus influenzae
• Listeria monocytogenes
Over 3 months old
• Streptococcus pneumoniae
• Haemophilus influenzae
• Neisseria meningitides
• Salmonella spp
CDC Diagnostic Criteria for the Diagnosis of Pelvic Inflammatory Disease (PID)
Minimal criteria*
• Lower abdominal tenderness
• Uterine/adnexal tenderness
• Cervical motion tenderness
Additional criteria
• Oral temperature > 38.3°C (101°F)
• Abnormal cervical or vaginal mucopurulent discharge
• Presence of white blood cells (WBCs) on saline microscopy of vaginal secretions
• Elevated erythrocyte sedimentation rate
• Elevated C-reactive protein level
• Laboratory documentation of cervical infection with Neisseria gonorrhoeae or Chlamydia
trachomatis
Definitive criteria
• Histopathologic evidence of endometritis on endometrial biopsy
• Transvaginal sonography or magnetic resonance imaging techniques showing thickened,
fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex
• Laparoscopic abnormalities consistent with PID
PID, pelvic inflammatory disease
* Empiric treatment is indicated in sexually active women considered at risk for PID if all three
findings are present.
Revised Jones Criteria for Acute Rheumatic Fever (ARF)
A firm diagnosis requires that two major or one major and two minor criteria are satisfied, in
addition to evidence of recent streptococcal infection.
Major Criteria
1. Carditis: All layers of cardiac tissue are affected (pericardium, epicardium, myocardium,
endocardium) The patient may have a new or changing murmur, with mitral regurgitation
being the most common followed by aortic insufficiency.
2. Polyarthritis: Migrating arthritis that typically affects the knees, ankles, elbows and
wrists. The joints are very painful and symptoms are very responsive to anti-
inflammatory medicines.
3. Chorea: Also known as Syndenham´s chorea, or "St. Vitus´ dance". There are abrupt,
purposeless movements. This may be the only manifestation of ARF and is its presence is
diagnostic. May also include emotional disturbances and inappropriate behavior.
4. Erythema marginatum: A non-pruritic rash that commonly affects the trunk and proximal
extremities, but spares the face. The rash typically migrates from central areas to
periphery, and has well-defined borders.
5. Subcutaneous nodules: Usually located over bones or tendons, these nodules are painless
and firm.
Minor Criteria:
1. Fever
2. Arthralgia
3. Previous rheumatic fever or rheumatic heart disease
4. Acute phase reactants: Leukocytosis, elevated eritrosedimentation rate (ESR) and C-
reactive protein (CRP)
5. Prolonged P-R interval on electrocardiogram (ECG)
Evidence of preceding streptococcal infection: Any one of the following is considered
adequate evidence of infection:
• Increased antistreptolysin O or other streptococcal antibodies
• Positive throat culture for Group A beta-hemolytic streptococci
• Positive rapid direct Group A strep carbohydrate antigen test
• Recent scarlet fever.
Diagnostic Criteria for Thromboangiitis Obliterans (Buerger’s Disease)
Since specificity of Buerger’s disease is characterized by peripheral ischemia of an inflammatory
nature and with a self-limiting course, diagnostic criteria should be discussed from clinical of
view.
Several different criteria have been proposed for the diagnosis of thromboangiitis obliterans:
Diagnostic Criteria of Shionoya:
• Smoking history;
• Onset before the age of 50 years;
• Infrapopliteal arterial occlusions;
• Either arm involvement or phlebitis migrans;
• Absence of atherosclerotic risk factors other than smoking.
Diagnostic Criteria of Olin
• Age younger than 45 years
• Current or recent history of tobacco use
• Presence of distal extremity ischemia indicated by claudication, pain at rest, ischemic
ulcers or gangrenes, and documented by non-invasive vascular testing;
• Exclusion of autoimmune diseases, hypercoagulable states and diabetes mellitus;
• Exclusion of a proximal source of embolization by echocardiography and arteriography;
• Consistent arteriographic findings in the clinically involved and noninvolved limbs
Diagnostic Criteria for HELLP Syndrome
The diagnosis of HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)
is based upon the presence of the characteristic laboratory findings in patients of appropriate
gestational age. Imaging tests, particularly CT or MRI scanning, are useful when complications
such as hepatic infarction, hematoma, or rupture are suspected.
The diagnosis is established by the presence of preeclampsia and the following criteria:
• Microangiopathic hemolytic anemia with characteristic schistocytes on blood smear
• Platelet count <100,000 cells/µL
• Serum lactate dehydrogenase >600 IU/L or total bilirubin >1.2 mg/dL
• Serum aspartate aminotransferase (AST) >70 IU/L
Diagnostic Criteria for Alzheimer's Disease (AD)

NINDS-ADRDA Diagnostic criteria for Alzheimer's Disease (AD)


Probable AD: A plus one or more supportive features B, C, D, or E
Core diagnostic criteria
A. Presence of an early and significant episodic memory impairment that includes the following
features:
1. Gradual and progressive change in memory function reported by patients or informants
over more than 6 months
2. Objective evidence of significantly impaired episodic memory on testing: this generally
consists of recall deficit that does not improve significantly or does not normalise with
cueing or recognition testing and after effective encoding of information has been
previously controlled
3. The episodic memory impairment can be isolated or associated with other cognitive
changes at the onset of AD or as AD advances
Supportive features
B. Presence of medial temporal lobe atrophy
• Volume loss of hippocampi, entorhinal cortex, amygdala evidenced on MRI with
qualitative ratings using visual scoring (referenced to well characterised population with
age norms) or quantitative volumetry of regions of interest (referenced to well
characterised population with age norms)
C. Abnormal cerebrospinal fluid biomarker
• Low amyloid β1–42 concentrations, increased total tau concentrations, or increased
phospho-tau concentrations, or combinations of the three
• Other well validated markers to be discovered in the future
D. Specific pattern on functional neuroimaging with PET
• Reduced glucose metabolism in bilateral temporal parietal regions
• Other well validated ligands, including those that foreseeably will emerge such as
Pittsburg compound B or FDDNP
E. Proven AD autosomal dominant mutation within the immediate family
Exclusion criteria
History
• Sudden onset
• Early occurrence of the following symptoms: gait disturbances, seizures, behavioural
changes
Clinical features
• Focal neurological features including hemiparesis, sensory loss, visual field deficits
• Early extrapyramidal signs
Other medical disorders severe enough to account for memory and related symptoms
• Non-AD dementia
• Major depression
• Cerebrovascular disease
• Toxic and metabolic abnormalities, all of which may require specific investigations
• MRI FLAIR or T2 signal abnormalities in the medial temporal lobe that are consistent
with infectious or vascular insults
Criteria for definite AD
AD is considered definite if the following are present:
• Both clinical and histopathological (brain biopsy or autopsy) evidence of the disease, as
required by the NIA-Reagan criteria for the post-mortem diagnosis of AD; criteria must
both be present
• Both clinical and genetic evidence (mutation on chromosome 1, 14, or 21) of AD; criteria
must both be present

DSM-IV-TR Diagnostic criteria for Alzheimer's Disease (AD)


A. The development of multiple cognitive deficits manifested by both memory impairment and
one or more of the following
• Aphasia
• Apraxia
• Agnosia
• and disturbances in executive functioning
B. The cognitive deficits represent as decline from previous functioning and cause significant
impairment in social or occupational functioning
C. The course is characterized by gradual onset and continuing decline
D. The cognitive deficits are not due to other central nervous system, systemic, or substance-
induced conditions that cause progressive deficits in memory and cognition
E. The disturbance is not better accounted for by another psychiatric disorder.
Diagnostic Criteria for Preeclampsia
Preeclampsia: For the diagnosis of preeclampsia, both hypertension and proteinuria must be
present.
• Blood pressure: 140 mm Hg or higher systolic or 90 mm Hg or higher diastolic after 20
weeks of gestation in a woman with previously normal blood pressure. Systolic increased
> 30 mm Hg or diastolic increased > 15 mm Hg in a patient with preexisting chronic
hypertension.
• Proteinuria: 0.3 g or more of protein in a 24-hour urine collection (usually corresponds
with 1+ or greater on a urine dipstick test)
Severe preeclampsia
• Blood pressure: 160 mm Hg or higher systolic or 110 mm Hg or higher diastolic on two
occasions at least six hours apart in a woman on bed rest
• Proteinuria: 5 g or more of protein in a 24-hour urine collection or 3+ or greater on urine
dipstick testing of two random urine samples collected at least four hours apart
• Other features: oliguria (less than 500 mL of urine in 24 hours), cerebral or visual
disturbances, pulmonary edema or cyanosis, epigastric or right upper quadrant pain,
impaired liver function, thrombocytopenia, intrauterine growth restriction
Risk Factors for Preeclampsia
Pregnancy-associated factors
• Chromosomal abnormalities
• Hydatidiform mole
• Hydrops fetalis
• Multifetal pregnancy
• Oocyte donation or donor insemination
• Structural congenital anomalies
• Urinary tract infection
Maternal-specific factors
• Age greater than 35 years
• Age less than 20 years
• Black race
• Family history of preeclampsia
• Nulliparity
• Preeclampsia in a previous pregnancy
• Specific medical conditions: gestational diabetes, type I diabetes, obesity, chronic
hypertension, renal disease, thrombophilias
• Stress
Paternal-specific factors
• First-time father
• Previously fathered a preeclamptic pregnancy in another woman
• Criteria for the Diagnosis of Behçet’s Disease
• For the diagnosis to be made, a patient must have recurrent oral ulceration plus at least
two of the other findings in the absence of other clinical explanations.
• Clinical Criteria for Do-Not-Resuscitate (DNR) Orders in Acute Stroke
• A DNR order may be written any time that two of the following clinical criteria are
present and the prognosis has become clear for and shared whenever possible between
physician(s), patient, and family (or appropriate surrogate).
• 1. Severe Stroke
Clinically severe stroke produces persisting (more than 24 hours) and sometimes
deteriorating neurological deficit, often with early impairment of consciousness leading
to total dependency of the patient in activities of daily living. The patient must have little
or no active movement on at least one side of the body, with either impaired
consciousness, global aphasia, or lack of response indicating cognition (Glasgow Coma
Scale score of less than 9, Canadian Neurological Scale score of less than 5.0).
• 2. Life-Threatening Brain Damage
Life-threatening brain damage is associated with brain stem compression caused by large
intracerebral hemorrhage (ICH), usually with intraventricular extension; large
hemispheric infarction with midline shift; infratentorial strokes involving multiple levels
in the brain stem; or cerebellar lesions.*
• 3. Significant Comorbidities
The following nonneurological conditions are important risk factors for death within the
first month after stroke: pneumonia, pulmonary embolism, sepsis, recent myocardial
infarction, cardiomyopathy, and life-threatening arrhythmias. These comorbid factors
should be considered part of expected consequences of severe stroke pointing to an
increased likelihood of death in the subacute phase of stroke.
• *Fatal outcome of ICH is associated with a volume of > 60 mL on CT scans. Currently
available data lack precision in quantifying imaging criteria and size of life-threatening
hemispheric infarctions and infratentorial lesions.

Finding Definition
Recurrent oral Minor aphthous, major aphthous, or herpetiform ulcers observed
ulceration by the physician or patient, which have recurred at least three
times over a 12-month period
Recurrent genital Aphthous ulceration or scarring observed by the physician or
ulceration patient
Eye lesions Anterior uveitis, posterior uveitis, or cells in the vitreous on slit-
lamp examination; or retinal vasculitis detected by an
ophthalmologist
Skin lesions Erythema nodosum observed by the physician or patient,
pseudofolliculitis, or papulopustular lesions; or acneiform nodules
observed by the physician in a postadolescent patient who is not
receiving corticosteroids
Positive pathergy test Test interpreted as positive by the physician at 24 to 48 hours
• For the diagnosis to be made, a patient must have recurrent oral ulceration plus at least
two of the other findings in the absence of other clinical explanations.
• Clinical Criteria for Do-Not-Resuscitate (DNR) Orders in Acute Stroke
• A DNR order may be written any time that two of the following clinical criteria are
present and the prognosis has become clear for and shared whenever possible between
physician(s), patient, and family (or appropriate surrogate).
• 1. Severe Stroke
Clinically severe stroke produces persisting (more than 24 hours) and sometimes
deteriorating neurological deficit, often with early impairment of consciousness leading
to total dependency of the patient in activities of daily living. The patient must have little
or no active movement on at least one side of the body, with either impaired
consciousness, global aphasia, or lack of response indicating cognition (Glasgow Coma
Scale score of less than 9, Canadian Neurological Scale score of less than 5.0).
• 2. Life-Threatening Brain Damage
Life-threatening brain damage is associated with brain stem compression caused by large
intracerebral hemorrhage (ICH), usually with intraventricular extension; large
hemispheric infarction with midline shift; infratentorial strokes involving multiple levels
in the brain stem; or cerebellar lesions.*
• 3. Significant Comorbidities
The following nonneurological conditions are important risk factors for death within the
first month after stroke: pneumonia, pulmonary embolism, sepsis, recent myocardial
infarction, cardiomyopathy, and life-threatening arrhythmias. These comorbid factors
should be considered part of expected consequences of severe stroke pointing to an
increased likelihood of death in the subacute phase of stroke.
• *Fatal outcome of ICH is associated with a volume of > 60 mL on CT scans. Currently
available data lack precision in quantifying imaging criteria and size of life-threatening
hemispheric infarctions and infratentorial lesions.
ACR Criteria for the Classification of Giant-Cell Arteritis
Three of the following five criteria were required to meet American College of Rheumatology
(ACR) classification criteria for giant-cell arteritis:
1. Age 50 years or older,
2. New-onset localized headache,
3. Temporal artery tenderness or decreased temporal artery pulse,
4. Erythrocyte sedimentation rate of at least 50 mm/h, and
5. Abnormal artery biopsy specimen characterized by mononuclear infiltration or
granulomatous inflammation.
These criteria have a reported sensitivity of 93.5% and a reported specificity of 91.2% for the
classification of giant-cell arteritis compared with other vasculitides.
Diagnostic Criteria for Cholangitis
The diagnostic criteria for cholangitis are:
a. fever or abdominal pain in the right upper quadrant;
b. endoscopic or radiologic (sonography or CT) evidence of biliary tract obstruction owing
to stones, stricture, or tumor; and
c. laboratory evidence of hyperbilirubinemia and elevated alkaline phosphatase.
Definition and Stages of Chronic Kidney Disease (CKD)
NKF Definition of Chronic Kidney Disease
• Kidney damage for three or more months, as defined by structural or functional
abnormalities of the kidney, with or without decreased GFR, manifested by pathologic
abnormalities or markers of kidney damage, including abnormalities in the composition
of the blood or urine or abnormalities in imaging tests
• GFR < 60 mL per minute per 1.73 m2 for three months or more, with or without kidney
damage

NKF Classification of Chronic Kidney Disease


Stage Description† GFR (mL per Action plan
minute per 1.73
m2)
- At increased > 60 (with risk Screening, reduction of risk factors for
risk for chronic factors for chronic chronic kidney disease
kidney disease kidney disease)
1 Kidney > 90 Diagnosis and treatment, treatment of
damage with comorbid conditions, interventions to
normal or slow disease progression, reduction of
elevated GFR risk factors for cardiovascular disease
2 Kidney 60 to 89 Estimation of disease progression
damage with
mildly
decreased GFR
3 Moderately 30 to 59 Evaluation and treatment of disease
decreased GFR complications
4 Severely 15 to 29 Preparation for kidney replacement
decreased GFR therapy (dialysis, transplantation)
5 Kidney failure < 15 (or dialysis) Kidney replacement therapy if uremia is
present

Risk Factors for Chronic Kidney Disease and Its Outcomes

Type Definition Examples


Susceptibilit Factors that increase Older age, family history of chronic kidney
y factors susceptibility to kidney disease, reduction in kidney mass, low birth
damage weight, U.S. racial or ethnic minority status,
low income or educational level
Initiation Factors that directly initiate Diabetes mellitus, high blood pressure,
factors kidney damage autoimmune diseases, systemic infections,
urinary tract infections, urinary stones,
obstruction of lower urinary tract, drug
toxicity
Progression Factors that cause Higher level of proteinuria, higher blood
factors worsening kidney damage pressure level, poor glycemic control in
and faster decline in kidney diabetes, smoking
function after kidney
damage has started
End-stage Factors that increase Lower dialysis dose (Kt/V)*, temporary
factors morbidity and mortality in vascular access, anemia, low serum albumin
kidney failure level, late referral for dialysis
*-In Kt/V (accepted nomenclature for dialysis dose), "K" represents urea clearance, "t"
represents time, and "V" represents volume of distribution for urea.
NKF = National Kidney Foundation; GFR = glomerular filtration rate.
Diagnostic Criteria for Multiple Myeloma
Presence of an M-componenta in serum and/or urine plus clonal plasma cells in the bone marrow
and/or a documented clonal plasmacytoma
PLUS one or more of the following:b
• Calcium elevation (>11.5 mg/dl) [>2.65 mmol/l]
• Renal insufficiency (creatinine >2 mg/dl) [177 mmol/l or more]
• Anemia (hemoglobin <10 g/dl or 2 g/dl <normal) (hemoglobin <12.5 mmol/lc or 1.25
mmol/l <normal)
• Bone disease (lytic lesions or osteopenia)
a
In patients with no detectable M-component, an abnormal serum FLC ratio on the serum FLC
assay can substitute and satisfy this criterion. For patients, with no serum or urine M-component
and normal serum FLC ratio, the baseline bone marrow must have >10% clonal plasma cells;
these patients are referred to as having ‘non-secretory myeloma’. Patients with biopsy-proven
amyloidosis and/or systemic light chain deposition disease (LCDD) should be classified as
‘myeloma with documented amyloidosis’ or ‘myeloma with documented LCDD,’ respectively if
they have >30% plasma cells and/or myeloma-related bone disease.
b
Must be attributable to the underlying plasma cell disorder.
c
Note: Hemoglobin of 10 g/dl is 12.5 mmol/l [or 100 g/l].
Criteria for the Classification of Systemic Sclerosis (Scleroderma)
1980 Criteria for the Classification of Systemic Sclerosis
The American College of Rheumatology (former American Rheumatism Association - ARA) has
defined criteria, that are 97 % sensitive and 98 % specific for systemic sclerosis (SSc) as follows:
Major criterion:
• Proximal diffuse (truncal) sclerosis (skin tightness, thickening, non-pitting induration)
Minor criteria:
• Sclerodactyly (only fingers and/or toes)
• Digital pitting scars or loss of substance of the digital finger pads (pulp loss)
• Bilateral basilar pulmonary fibrosis
The patient should fulfill the major criterion or two of the three minor criteria. Raynaud's
phenomenon is observed in 90-98 % of SSc patients.
Subsets of Systemic Sclerosis

Diffuse Limited*
Skin involvement Distal and proximal Distal to elbows, face
extremities, face, trunk
Raynaud’s Onset within 1 year or at May precede skin disease
phenomenon time of skin changes by years
Organ Pulmonary (interstitial Gastrointestinal;
involvement fibrosis); renal pulmonary arterial
(renovascular hypertensive hypertension after 10-15
crisis); gastrointestinal; years of disease in <10% of
cardiac patients; biliary cirrhosis
Nail fold Dilatation and dropout Dilatation without
capillaries significant dropout
Antinuclear Anti-topoisomerase 1 Anticentromere
antibodies
* Also referred to as CREST( calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly,
telangiectasia).

ABCDCREST Criteria for the Classification of Systemic Sclerosis


1. Autoantibodies: autoantibodies to centromere proteins (CENPs) detected by indirect
immunofluorescence; anti-Scl-70 (topoisomerase I) detected by double immunodiffusion;
anti-fibrillarin (U3-RNP) detected by immunoprecipitation
2. Bibasilar pulmonary fibrosis detected by chest radiograph: linear shadows or “honey-
comb” reticular appearance most expressed at the periphery of the lungs and at the bases
3. Contracture of the joints defined as permanent limitation of joint motion. The prayer sign
is detected when a patient opposed the palmar surfaces of both hands with extended
wrists. The sign is positive when the patient is unable to oppose the palms. This suggests
joint or skin pathology, or shortening of the forearm flexors
4. Dermal thickening can be defined by the modified Rodnan skin score, which employs
clinical palpation of the skin as described
5. Calcinosis cutis, most often located on the fingers, is intra and/or subcutaneous deposits
of hydroxyapatite that can ulcerate the skin; it can be detected by radiography,
crystallographic or chemical analysis
6. Raynaud’s phenomenon is a sudden pallor of an acral structure (e.g., fingers, whole hand,
toes, tip of nose, earlobe, or tongue). The involved area may subsequently develop
cyanosis and, with re-warming, become erythematous. Determination is by patient’s
history or physician’s observation
7. Esophageal distal hypomotility can be detected by cine/video barium esophagram,
performed in the upright and supine position. Reflux-esophagitis can be detected by
esophagogastroduodenoscopy in the forms of erosive esophagitis or Barret’s esophagus
8. Sclerodactyly is symmetric thickening and tightening of the skin on the digits. Before
sclerodactyly develops there could be a phase of non-pitting digital edema of varying
duration. It is defined as non-pitting increase in soft tissue mass of the digits that extends
beyond the normal confines of the joint capsules
9. Teleangiectasias are visible macular dilatations of superficial cutaneous blood vessels that
collapse upon pressure and fill slowly when pressure is released. Common locations are
the digits, face, lips, tongue
Criteria for Diagnosis of Still's Disease
Yamaguchi criteria for classification of adult Still's disease
Presence of 5 or more criteria, of which at least 2 are Major (96% sensitivity; 92% specificity)
Major Criteria
• Temperature of >39°C for >1 wk
• Leukocytosis >10,000/mm3 with >80% PMNs
• Typical rash
• Arthralgias >2 wk
Minor Criteria
• Sore throat
• Lymph node enlargement
• Splenomegaly
• Liver dysfunction (high AST/ALT)
• Negative ANA, RF
Cush criteria for classification of adult Still's disease
Requires all of the following:
• Fever > 39 degrees
• Arthralgia or arthritis
• Rheumatoid factor < 1:80
• ANA < 1:100
In addition to any two of the following:
• WBC count > 15,000
• Stills rash
• Pleuritis or Pericarditis
• Hepatomegaly, Splenomegaly, or Lymphadenopathy
Abbreviations: ALT, alanine transaminase; ANA, antinuclear antibody; AST, aspartate
transminase; PMN, polymorphonuclear leukocyte; RF, rheumatoid factor; WBC, white blood
cells.
1996 CDC Case Definition for Syphilis (Treponema pallidum)
Syphilis is a complex sexually transmitted disease that has a highly variable clinical course.
Classification by a clinician with expertise in syphilis may take precedence over the following
case definitions developed for surveillance purposes.

Syphilis, primary
Clinical description: A stage of infection with Treponema pallidum characterized by one or
more chancres (ulcers); chancres might differ considerably in clinical appearance.
Laboratory criteria for diagnosis: Demonstration of T. pallidum in clinical specimens by
darkfield microscopy, direct fluorescent antibody (DFA-TP), or equivalent methods.
Case classification:
• Probable: a clinically compatible case with one or more ulcers (chancres) consistent with
primary syphilis and a reactive serologic test (nontreponemal: Venereal Disease Research
Laboratory [VDRL] or rapid plasma reagin [RPR]; treponemal: fluorescent treponemal
antibody absorbed [FTA-ABS] or microhemagglutination assay for antibody to T.
pallidum [MHA-TP])
• Confirmed: a clinically compatible case that is laboratory confirmed

Syphilis, secondary
Clinical description: A stage of infection caused by T. pallidum and characterized by localized
or diffuse mucocutaneous lesions, often with generalized lymphadenopathy. The primary chancre
may still be present.
Laboratory criteria for diagnosis: Demonstration of T. pallidum in clinical specimens by
darkfield microscopy, DFA-TP, or equivalent methods
Case classification:
• Probable: a clinically compatible case with a nontreponemal (VDRL or RPR) titer greater
than or equal to 4
• Confirmed: a clinically compatible case that is laboratory confirmed

Syphilis, latent
Clinical description: A stage of infection caused by T. pallidum in which organisms persist in
the body of the infected person without causing symptoms or signs. Latent syphilis is subdivided
into early, late, and unknown categories based on the duration of infection.
Case classification:
Probable: no clinical signs or symptoms of syphilis and the presence of one of the following:
• No past diagnosis of syphilis, a reactive nontreponemal test (i.e., VDRL or RPR), and a
reactive treponemal test (i.e., FTA-ABS or MHA-TP)
• A past history of syphilis therapy and a current nontreponemal test titer demonstrating
fourfold or greater increase from the last nontreponemal test titer

Syphilis, early latent


Clinical description: A subcategory of latent syphilis. When initial infection has occurred
within the previous 12 months, latent syphilis is classified as early latent.
Case classification:
Probable: latent syphilis in a person who has evidence of having acquired the infection within
the previous 12 months based on one or more of the following criteria:
• Documented seroconversion or fourfold or greater increase in titer of a nontreponemal
test during the previous 12 months
• A history of symptoms consistent with primary or secondary syphilis during the previous
12 months
• A history of sexual exposure to a partner who had confirmed or probable primary or
secondary syphilis or probable early latent syphilis (documented independently as
duration less than 1 year)
• Reactive nontreponemal and treponemal tests from a person whose only possible
exposure occurred within the preceding 12 months

Syphilis, late latent


Clinical description: A subcategory of latent syphilis. When initial infection has occurred
greater than 1 year previously, latent syphilis is classified as late latent.
Case classification:
Probable: latent syphilis (see Syphilis, latent) in a patient who has no evidence of having
acquired the disease within the preceding 12 months (see Syphilis, early latent) and whose age
and titer do not meet the criteria specified for latent syphilis of unknown duration.

Syphilis, latent, of unknown duration


Clinical description: A subcategory of latent syphilis. When the date of initial infection cannot
be established as having occurred within the previous year and the patient's age and titer meet
criteria described below, latent syphilis is classified as latent syphilis of unknown duration.
Case classification:
• Probable: latent syphilis (see Syphilis, latent) that does not meet the criteria for early
latent syphilis, and the patient is aged 13-35 years and has a nontreponemal titer greater
than or equal to 32

Neurosyphilis
Clinical description: Evidence of central nervous system infection with T. pallidum
Laboratory criteria for diagnosis: A reactive serologic test for syphilis and reactive VDRL in
cerebrospinal fluid (CSF)
Case classification:
Probable: syphilis of any stage, a negative VDRL in CSF, and both the following:
• Elevated CSF protein or leukocyte count in the absence of other known causes of these
abnormalities
• Clinical symptoms or signs consistent with neurosyphilis without other known causes for
these clinical abnormalities
Confirmed: syphilis of any stage that meets the laboratory criteria for neurosyphilis

Syphilis, late, with clinical manifestations other than neurosyphilis (late benign syphilis and
cardiovascular syphilis)
Clinical description: Clinical manifestations of late syphilis other than neurosyphilis may
include inflammatory lesions of the cardiovascular system, skin, and bone. Rarely, other
structures (e.g., the upper and lower respiratory tracts, mouth, eye, abdominal organs,
reproductive organs, lymph nodes, and skeletal muscle) may be involved. Late syphilis usually
becomes clinically manifest only after a period of 15-30 years of untreated infection.
Laboratory criteria for diagnosis: Demonstration of T. pallidum in late lesions by fluorescent
antibody or special stains (although organisms are rarely visualized in late lesions)
Case classification:
• Probable: characteristic abnormalities or lesions of the cardiovascular system, skin, bone,
or other structures with a reactive treponemal test, in the absence of other known causes
of these abnormalities, and without CSF abnormalities and clinical symptoms or signs
consistent with neurosyphilis
• Confirmed: a clinically compatible case that is laboratory confirmed
Comment: Analysis of CSF for evidence of neurosyphilis is necessary in the evaluation of late
syphilis with clinical manifestations.

Syphilitic Stillbirth
Clinical case definition: A fetal death that occurs after a 20-week gestation or in which the fetus
weighs greater than 500 g and the mother had untreated or inadequately treated* syphilis at
delivery
Comment: For reporting purposes, syphilitic stillbirths should be reported as cases of congenital
syphilis.
*Inadequate treatment consists of any non-penicillin therapy or penicillin given less than 30 days
before delivery.
Classification of Neutropenia
Acquired neutropenia
• Postinfectious: varicella, measles, rubella, hepatitis A and B, mononucleosis, influenza,
cytomegalovirus, parvovirus, acquired immunodeficiency syndrome (AIDS), S. aureus,
brucellosis, tularemia, rickettsia, Mycobacterium tuberculosis, sepsis.
• Drug induced: Antineoplastic agents, procainamide, antithyroid drugs, sulphasalazine,
phenothiazines, semisynthetic penicillins, nonsteroidal anti-inflammatory agents,
aminopyrine derivatives, benzodiazepines, barbiturates, gold compounds, sulfonamides,
propranolol, dipyridamole, digoxin, acetyldigoxin, sulfamethoxizole, anticonvulsants
• Benign familial neutropenia
• Chronic benign neutropenia of childhood
• Chronic idiopathic neutropenia
• Autoimmune neutropenia
• Isoimmune neutropenia
• Neutropenia associated with immunologic abnormalities
• Neutropenia associated with metabolic diseases
• Neutropenia due to increased margination
• Nutritional deficiency
Intrinsic defects
• Kostmann syndrome (severe infantile agranulocytosis)
• Myelokathexis/neutropenia with tetraploid nuclei
• Cyclic neutropenia
• Shwachman-Diamond-Oski syndrome
• Chediak-Higashi syndrome
• Reticular dysgenesis
• Dyskeratosis congenital

Clinically Significant Neutrophil Counts

ANC Clinical Significance


>1,500/mm3 Normal
1,000-1,500 No significant propensity to infection.
Fevers can be managed on an outpatient
basis.
500-1,000 Some propensity to infection.
Occasionally fever can be managed on an
outpatient basis.
<500 Significant propensity to infection.
Always should be managed as inpatient
with parenteral antibiotics. Few clinical
signs of infection.
ANC; Absolute Neutrophil Counts
These rules apply strictly for neutropenia with hypoplastic marrow, early myeloid arrest, and
decreased granulocyte reserve pools. There is more latitude for clinical judgment in neutropenias
with normocellular marrow. The only regular exception to these rules is documented chronic
benign neutropenia of childhood.
Classification of Neutrophilia
Primary (no other evident associated disease)
• Hereditary neutrophilia
• Chronic idiopathic neutrophilia
• Chronic myelogenous leukemia (CML) and other myeloproliferative diseases
• Familial myeloproliferative disease
• Congenital anomalies and leukemoid reaction
• Leukocyte adhesion deficiency (LAD)
• Familial cold urticaria and leukocytosis
Secondary
• Infection
• Stress neutrophilia
• Chronic inflammation
• Drug induced: Steroids, lithium, tetracycline, G-CSF.
• Nonhematologic malignancy
• Generalized marrow stimulation as in hemolysis
• Asplenia and hyposplenism
• Serum Levels That Differentiate Anemia of Chronic Disease from Iron-Deficiency
Anemia
• Patients with both conditions include those with anemia of chronic disease and true iron
deficiency.

Variable Anemia of Chronic Iron-Deficiency Both Conditions


Disease Anemia
Iron Reduced Reduced Reduced
Trasnferrin Reduced to normal Increased Reduced
Transferrin saturation Reduced Reduced Reduced
Ferritin Normal to increased Reduced Reduced to normal
Soluble transferrin Normal Increased Normal to increased
receptor
Ratio of soluble Low (<1) High (>2) High (>2)
transferrin receptor to
log ferritin
Cytokine Levels Increased Normal Increased
• Patients with both conditions include those with anemia of chronic disease and true iron
deficiency.
Diagnostic Criteria for Disseminated Intravascular Coagulation (DIC)

Classification Definition Diagnostic criteria


Biological DIC Hemostatic defect without Elevated D-Dimers
clinical manifestations and
1 major criterion for consumption
of platelets or coagulation factors
or
2 minor criteria for consumption
of platelets or coagulation factors
Clinical DIC Hemostatic defect with Same as above + microvascular
hemorrhagic or ischemic bleeding and/or thrombosis
manifestations
Complicated Hemostatic defect with Same as above + organ failure
DIC hemorrhagic or ischemic (single or multiple)
manifestations that jeopardize
organ function or patient
prognosis

Details of laboratory criteria


D-Dimers greater than 500 µg·L–1
Platelet consumption
• Minor: platelet count between 50 and 100,000·/mm3
• Major: platelet count less than 50,000·/mm3
Consumption of coagulation factors
• Minor: INR of the PT between 1.2 and 1.5
• Major: INR of the PT greater than 1.5
INR of the PT = international normalized ratio of the prothrombin time. The elevation of D-
Dimers is not specific to DIC. Similarly, the clinical manifestations of DIC are not specific.
ACR Criteria for the Classification of Giant-Cell Arteritis
Three of the following five criteria were required to meet American College of Rheumatology
(ACR) classification criteria for giant-cell arteritis:
1. Age 50 years or older,
2. New-onset localized headache,
3. Temporal artery tenderness or decreased temporal artery pulse,
4. Erythrocyte sedimentation rate of at least 50 mm/h, and
5. Abnormal artery biopsy specimen characterized by mononuclear infiltration or
granulomatous inflammation.
These criteria have a reported sensitivity of 93.5% and a reported specificity of 91.2% for the
classification of giant-cell arteritis compared with other vasculitides.
Revised ARA Criteria for the Classification of Rheumatoid Arthritis (RA)
For classification purposes, a patient is said to have RA if he or she has satisfied at least 4 of the
following 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients
with 2 clinical diagnoses are not excluded. Designation as classic, definite, or probable RA is not
to be made.
1. Morning stiffness: Morning stiffness in and around the joints, lasting at least 1 hour
before maximal improvement.
2. Arthritis of 3 or more joint areas: At least 3 joint areas simultaneously have had soft
tissue swelling or fluid (not bony overgrowth alone) observed by a physician; the 14
possible joint areas are right or left proximal interphalangeal (PIP) joints,
metacarpophalangeal (MCP) joints, wrist, elbow, knee, ankle, and metatarsophalangeal
(MPT) joints.
3. Arthritis of hand joints: At least I area swollen (as defined above) in a wrist, MCP or PIP
joint.
4. Symmetric arthritis: Simultaneous involvement of the same joint areas (see 2 above) on
both sides of the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable
without absolute symmetry).
5. Rheumatoid nodules: Subcutaneous nodules, over bony prominences, or extensor
surfaces, or in juxta-articular regions, observed by a physician.
6. Serum rheumatoid factor: Demonstration of abnormal amounts of serum rheumatoid
factor by any method for which the result has been positive in <5% of normal control
subjects.
7. Radiographic changes: Radiographic changes typical of RA on posteroanterior hand and
wrist radiographs, which must include erosions or unequivocal bony decalcification
localized to or most marked adjacent to the involved joints (osteoarthritis changes alone
do not qualify).
Revised International Classification Criteria for Sjögren's Syndrome (SS)
I. Ocular symptoms: a positive response to at least one of the following questions:
1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
2. Do you have a recurrent sensation of sand or gravel in the eyes?
3. Do you use tear substitutes more than 3 times a day?

II. Oral symptoms: a positive response to at least one of the following questions:
1. Have you had a daily feeling of dry mouth for more than 3 months?
2. Have you had recurrently or persistently swollen salivary glands as an adult?
3. Do you frequently drink liquids to aid in swallowing dry food?

III. Ocular signs-that is, objective evidence of ocular involvement defined as a positive result for
at least one of the following two tests:
1. Schirmer's I test, performed without anaesthesia (</=5 mm in 5 minutes)
2. Rose bengal score or other ocular dye score (>/=4 according to van Bijsterveld's scoring
system)

IV. Histopathology: In minor salivary glands (obtained through normal-appearing mucosa) focal
lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score >/=1,
defined as a number of lymphocytic foci (which are adjacent to normal-appearing mucous acini
and contain more than 50 lymphocytes) per 4 mm2 of glandular tissue

V. Salivary gland involvement: objective evidence of salivary gland involvement defined by a


positive result for at least one of the following diagnostic tests:
1. Unstimulated whole salivary flow (</=1.5 ml in 15 minutes)
2. Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary or
destructive pattern), without evidence of obstruction in the major ducts
3. Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed
excretion of tracer
VI. Autoantibodies: presence in the serum of the following autoantibodies:
1. Antibodies to Ro(SSA) or La(SSB) antigens, or both

Revised Rules for Classification

For primary SS
In patients without any potentially associated disease, primary SS may be defined as follows:
a. The presence of any 4 of the 6 items is indicative of primary SS, as long as either item IV
(Histopathology) or VI (Serology) is positive
b. The presence of any 3 of the 4 objective criteria items (that is, items III, IV, V, VI)
c. The classification tree procedure represents a valid alternative method for classification,
although it should be more properly used in clinical-epidemiological survey

For secondary SS
In patients with a potentially associated disease (for instance, another well defined connective
tissue disease), the presence of item I or item II plus any 2 from among items III, IV, and V may
be considered as indicative of secondary SS

Exclusion criteria:
• Past head and neck radiation treatment
• Hepatitis C infection
• Acquired immunodeficiency disease (AIDS)
• Pre-existing lymphoma
• Sarcoidosis
• Graft versus host disease
• Use of anticholinergic drugs (since a time shorter than 4-fold the half life of the drug)
• Criteria for the Diagnosis of Behçet’s Disease
• For the diagnosis to be made, a patient must have recurrent oral ulceration plus at least
two of the other findings in the absence of other clinical explanations.

Finding Definition
Recurrent oral Minor aphthous, major aphthous, or herpetiform ulcers observed
ulceration by the physician or patient, which have recurred at least three
times over a 12-month period
Recurrent genital Aphthous ulceration or scarring observed by the physician or
ulceration patient
Eye lesions Anterior uveitis, posterior uveitis, or cells in the vitreous on slit-
lamp examination; or retinal vasculitis detected by an
ophthalmologist
Skin lesions Erythema nodosum observed by the physician or patient,
pseudofolliculitis, or papulopustular lesions; or acneiform nodules
observed by the physician in a postadolescent patient who is not
receiving corticosteroids
Positive pathergy test Test interpreted as positive by the physician at 24 to 48 hours
• For the diagnosis to be made, a patient must have recurrent oral ulceration plus at least
two of the other findings in the absence of other clinical explanations.
Criteria for the Classification of Wegener's Granulomatosis (WG)
1. Nasal or oral inflammation: Development of painful or painless oral ulcers or purulent or
bloody nasal discharge
2. Abnormal chest radiograph: Chest radiograph showing the presence of nodules, fixed
infiltrates, or cavities
3. Urinary sediment: Microhematuria (>5 red blood cells per high power field) or red cell
casts in urine sediment
4. Granulomatous inflammation on biopsy: Histologic changes showing granulomatous
inflammation within the wall of an artery or in the perivascular or extravascular area
(artery or arteriole)
For purposes of classification, a patient shall be said to have Wegener's granulomatosis if at least
2 of these 4 criteria are present. The presence of any 2 or more criteria yields a sensitivity of
88.2% and a specificity of 92.0%
Classification Criteria for Osteoarthritis
ACR Classification Criteria for Osteoarthritis of the Hip

Traditional format
Hip pain plus at least two of the following:
• ESR of less than 20 mm per hour
• Femoral or acetabular osteophytes on radiographs
• Joint space narrowing on radiographs

Classification-tree format
Hip pain plus femoral or acetabular osteophytes on radiographs
or
Hip pain plus joint space narrowing on radiographs and an ESR of less than 20 mm per hour

ESR = erythrocyte sedimentation rate.

ARA Classification Criteria for Idiopathic Osteoarthritis of the Knee

Traditional format
Knee pain plus osteophytes on radiographs and at least one of the following:
• Patient age older than 50 years
• Morning stiffness lasting 30 minutes or less
• Crepitus on motion

Classification-tree format
Knee pain and osteophytes on radiographs
or
Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes or less and
crepitus on motion
ACR Classification Criteria for Osteoarthritis of the Hand

Hand pain, aching or stiffness


plus
Hard tissue enlargement of two or more of 10 selected joints*
plus
Fewer than three swollen metacarpophalangeal joints
plus
Hard tissue enlargement of two or more distal interphalangeal joints
or
Deformity of two or more of 10 selected joints*

* - 10 selected joints are the second and third distal interphalangeal joints, the second and third
proximal interphalangeal joints and the first carpometacarpal joints (of both hands).
Diagnostic Criteria for Adult Respiratory Distress Syndrome (ARDS)
Acute Respiratory Distress Syndrome (ARDS) is a syndrome of inflammation and increased
permeability associated with a constellation of clinical, radiologic, and physiologic abnormalities
unexplained by elevations in left atrial or pulmonary capillary pressure.
All definitions of this syndrome include patients who meet the following criteria:
• Identifiable associated condition
• Acute onset
• Pulmonary artery wedge pressure </=18 mm Hg or absence of clinical evidence of left
atrial hypertension
• Bilateral infiltrates on chest radiography
• Acute lung injury (ALI) is present if Pao2/Fio2 ratio is </= 300
• Acute respiratory distress syndrome is present if Pao2/Fio2 ratio </= 200
ARDS = acute respiratory distress syndrome; Pao2 = partial pressure of arterial oxygen; Fio2 =
percentage of inspired oxygen.
Clinical Conditions Associated with Development of Acute Respiratory Distress Syndrome
Direct lung injury
• Pneumonia
• Aspiration of gastric contents
• Inhalation injury
• Near drowning
• Pulmonary contusion
• Fat embolism
• Reperfusion pulmonary edema post lung transplantation or pulmonary embolectomy
Indirect lung injury
• Sepsis
• Severe trauma
• Acute pancreatitis
• Cardiopulmonary bypass
• Massive transfusions
• Drug overdose
Clinical Conditions Associated with Disseminated Intravascular Coagulation (DIC)

1. Sepsis/severe infection (any microorganism)


2. Trauma (e.g., polytrauma, neurotrauma, fat embolism)
3. Organ destruction (e.g., severe pancreatitis)
4. Malignancy
• solid tumors
• myeloproliferative/lymphoproliferative malignancies
5. Obstetrical calamities
• amniotic fluid embolism
• abruptio placentae
6. Vascular abnormalities
• Kasabach-Merritt syndrome
• large vascular aneurysms
7. Severe hepatic failure
8. Severe toxic or immunologic reactions
• snake bites
• recreational drugs
• transfusion reactions
• transplant rejection
FAB Classification of Myelodysplastic Syndromes (MDS)

Refractory anemia (RA).


• Cytopenia of at least one lineage in the peripheral blood (usually anemia)
• Normal or hypercellular bone marrow with dysplastic changes
• Less than 1 percent blasts in the peripheral blood and less than 5 percent blasts in the
bone marrow
Refractory anemia with ringed sideroblasts (RARS)
• Cytopenia (almost always anemia), dysplastic changes, and the same percentages of
blood and bone marrow blasts as in refractory anemia
• Ringed sideroblasts accounting for more than 15 percent of all nucleated cells in the bone
marrow
Refractory anemia with excess blasts (RAEB)
• Cytopenia of two or more lineages in the peripheral blood
• Dysplastic changes in all three lineages
• Less than 5 percent blasts in the peripheral blood and between 5 and 20 percent blasts in
the bone marrow
Chronic myelomonocytic leukaemia (CML)
• Peripheral-blood monocytosis (monocyte count, >1¬10 9 per liter)
• Less than 5 percent blasts in the peripheral blood and up to 20 percent blasts in the bone
marrow
Refractory anemia with excess blasts in transformation (RAEB-T)
• Hematologic features similar to those of refractory anemia with excess blasts
• More than 5 percent blasts in the peripheral blood or between 21 and 30 percent blasts in
the bone marrow or the presence of Auer rods in the blasts

International Prognostic Scoring System for Myelodysplastic Syndromes

Overall Score Median Survival


(yr)
Low (0) 5.7
Intermediate
1 (0.5 or 1.0) 3.5
2 (1.5 or 2.0) 1.2
High (>/=2.5) 0.4
The overall score is the sum of the scores for bone marrow blasts, karyotype, and cytopenias.
The percentage of blasts is scored as follows: <5 percent, 0; 5 to 10 percent, 0.5; 11 to 20
percent, 1.5; and 21 to 30 percent, 2.0. Cytogenetic features associated with a good prognosis
(normal karyotype, Y-, 5q-, or 20q-) are scored as 0; those associated with a poor prognosis
(abnormal chromosome 7 or three or more abnormalities) are scored as 1.0; and all other
cytogenetic abnormalities, which are associated with an intermediate prognosis, are scored as
0.5. A score of 0 is assigned if the patient has no cytopenia or only one type, and a score of 0.5 is
assigned if the patient has two or three types of cytopenia. The various types of cytopenia are
defined as follows: hemoglobin, <10 g per deciliter; absolute neutrophil count, <1500 per cubic
millimeter; and platelet count, <100,000 per cubic millimeter.
Diagnostic Criteria for Heparin-Induced Thrombocytopenia (HIT)
• Heparin exposure >5 days
• Relative thrombocytopenia: decrease in platelet count by 50% from baseline OR absolute
thrombocytopenia: decrease in platelet count to less than 100 to 150 x 109/L
• Absence of other causes of thrombocytopenia
• Development of new thrombosis, or extension of pre-existing thrombosis, while receiving
heparin therapy
• Confirmation by laboratory testing
• Return to normal platelet count when heparin is discontinued
Serology tests to determine HIT (listed in order of greatest to lowest sensitivity)
• Serotonin release assay
• Heparin/PF 4 ELISA
• Platelet aggregation

Estimating the Pretest Probability of HIT: The "Four T's"


Points (0, 1, or 2 for Each of 4 Categories: Maximum Possible
Score = 8)
2 1 0

Thrombocytopenia >50% Platelet fall 30–50% Platelet <30% Platelet fall,


to nadir >/= 20 fall, or nadir 10-19 or nadir <10
Timing* of onset of Days 5–10, or </= >Day 10 or timing <Day 4 (no recent
platelet fall (or day 1 with recent unclear; or <day 1 heparin)
other sequelae of heparin (past 30 with recent heparin
HIT) days) (past 31–100 days)
Thrombosis or Proven new Progressive or None
other sequelae thrombosis; skin recurrent
necrosis; or acute thrombosis;
systemic reaction erythematous skin
after intravenous lesions; suspected
UFH bolus thrombosis (not
proven)
OTher cause(s) of None evident Possible Definite
platelet fall
UFH, Unfractionated heparin
Pretest probability score: 6–8 indicates high; 4–5, intermediate; and 0–3, low.
*First day of immunizing heparin exposure considered day 0.
Indications for Percutaneous Renal Biopsy
Indications for percutaneous needle biopsy include
1. Unexplained acute renal failure or chronic renal insufficiency;
2. Acute nephritic syndromes;
3. Unexplained proteinuria and hematuria;
4. Previously identified and treated lesions to plan future therapy;
5. Systemic diseases associated with kidney dysfunction, such as systemic lupus
erythematosus (SLE), Goodpasture's syndrome, and Wegener's granulomatosis, to
confirm the extent of renal involvement and to guide management;
6. Suspected transplant rejection, to differentiate it from other causes of acute renal failure;
and
7. To guide treatment.
Relative contraindications include a solitary or ectopic kidney (exception: transplant allografts),
horseshoe kidney, uncorrected bleeding disorder, severe uncontrolled hypertension, renal
infection, renal neoplasm, hydronephrosis, end-stage renal disease (ESRD), congenital
anomalies, multiple cysts, or uncooperative patient.
RIFLE Criteria for Acute Renal Dysfunction

Category GFR Criteria Urine Output (UO)


Criteria
Risk Increased creatinine UO < 0.5ml/kg/h x 6 High
x1.5 or GFR hr Sensitivity
decrease > 25%
Injury Increased creatinine UO < 0.5ml/kg/h x
x2 or GFR decrease 12 hr High
> 50% Specificity
Failure Increase creatinine UO < 0.3ml/kg/h x
x3 or GFR decrease 24 hr or Anuria x 12
> 75% hrs

Loss Persistent ARF = complete loss of kidney


function > 4 weeks
ESKD End Stage Kidney Disease (> 3 months)
GFR; Glomerular Filtration Rate
ARF; Acute Renal Failure
ESKD; End Stage Kidney Disease
ACR Criteria for the Classification of Polyarteritis Nodosa (PAN)
American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa
(PAN). Classified as PAN if at least three of the 10 criteria are present:
1. Weight loss > 4 kg: Loss of >4 kg body weight since illness began, not related to dieting
or other factors.
2. Livedo reticularis: Mottled reticular pattern over the skin of portions of the extremities or
torso.
3. Testicular pain/tenderness: Pain or tenderness of the testicles, not due to infection, trauma
or other causes.
4. Myalgias, weakness or leg tenderness: Diffuse myalgias (excluding shoulder or hip
girdle) or weakness of muscles or tenderness of leg muscles.
5. Mono- or polyneuropathy: Development of mononeuropathy, multiple
mononeuropathies or polyneuropathy.
6. Diastolic BP >90 mmHg: Development of hypertension with the diastolic BP higher than
90 mmHg.
7. Elevated BUN or creatinine: Elevation of BUN >40 mg/dl or creatinine >1.5 mg/dl, not
due to dehydration or obstruction.
8. Hepatitis B virus: Presence of hepatitis B surface antigen or antibody in serum.
9. Arteriographic abnormality: Arteriogram showing aneurysms or occlusions of the
visceral arteries, not due to arteriosclerosis, fibromuscular dysplasia or other non-
inflammatory causes.
10. Biopsy of small or medium-sized artery containing polymorphonuclear cells: Histologic
changes showing the presence of granulocytes or granulocytes and mononuclear
leucocytes in the artery wall.
These criteria have a reported sensitivity of 82.2% and a reported specificity of 86.6% for the
classification of polyarteritis nodosa compared with other vasculitides.
ACR Criteria for the Classification of Churg-Strauss Syndrome (CSS)
American College of Rheumatology 1990 criteria for the classification of Churg-Strauss
syndrome (CSS). Classified as CSS if at least four of six criteria are present
1. Asthma: History of wheezing or diffuse high-pitched expiratory rhonchi.
2. Eosinophilia: Eosinophilia >10% on differential white blood cell count.
3. Mono- or polyneuropathy: Development of mononeuropathy, multiple
mononeuropathies, or polyneuropathy (glove/ stocking distribution) attributable to
systemic vasculitis.
4. Pulmonary infiltrates, non-fixed: Migratory or transitory pulmonary infiltrates (not
including fixed infiltrates). attributable to vasculitis.
5. Paranasal sinus abnormality: History of acute or chronic paranasal sinus pain or
tenderness or radiographic opacification of the paranasal sinuses.
6. Extravascular eosinophils: Biopsy including artery, arteriole or venule showing
accumulations of eosinophils in extravascular areas.
McDonald Diagnostic Criteria for Multiple Sclerosis (MS)
What Is An Attack?
• Neurological disturbance of kind seen in MS
• Subjective report or objective observation
• 24 hours duration, minimum
• Excludes pseudoattacks, single paroxysmal episodes
Determining Time Between Attacks
• 30 days between onset of event 1 and onset of event 2
How Is "Abnormality" In Paraclinical Tests Determined?
A- Magnetic resonance imaging (MRI): Three out of four:
• 1 Gd-enhancing or 9 T2 hyperintense lesions if no Gd-enhancing lesion
• 1 or more infratentorial lesions
• 1 or more juxtacortical lesions
• 3 or more periventricular lesions
(1 spinal cord lesion = 1 brain lesion)
B- Cerebrospinal fluid (CSF)
• Oligoclonal IgG bands in CSF (and not serum)
• or elevated IgG index
C- Evoked potentials (EP)
• Delayed but well-preserved wave form
What Provides MRI Evidence Of Dissemination In Time?
A Gd-enhancing lesion demonstrated in a scan done at least 3 months following onset of clinical
attack at a site different from attack,
or
In absence of Gd-enhancing lesions at 3 month scan, follow-up scan after an additional 3 months
showing Gd-lesion or new T2 lesion.

Steps in Making a Diagnosis of MS


Clinical Presentation Additional Data Needed
2 or more attacks (relapses) None; clinical evidence will suffice
(additional evidence desirable but must be consistent
2 or more objective clinical with MS)
lesions
2 or more attacks Dissemination in space, demonstrated by:
MRI
1 objective clinical lesion or a positive CSF and 2 or more MRI lesions
consistent with MS
or further clinical attack involving different site
1 attack Dissemination in time, demonstrated by:
MRI
2 or more objective clinical or second clinical attack
lesions
1 attack Dissemination in space, demonstrated by:
MRI
1 objective clinical lesion or positive CSF and 2 or more MRI lesions
(monosymptomatic consistent with MS
presentation)
and

Dissemination in time demonstrated by:


MRI
or second clinical attack
Insidious neurological Positive CSF
progression suggestive of MS
(primary progressive MS) and

Dissemination in space demonstrated by:


MRI evidence of 9 or more T2 brain lesions
or 2 or more spinal cord lesions
or 4-8 brain and 1 spinal cord lesion
or positive VEP with 4-8 MRI lesions
or positive VEP with <4 brain lesions plus 1 spinal
cord lesion

and

Dissemination in time demonstrated by:


MRI
or continued progression for 1 year
Diagnostic Criteria for Relapsing Polychondritis
Three or more clinical signs must be present:
1. Recurrent chondritis both auricles
2. Non-erosive inflammatory polyarthritis
3. Nasal chondritis
4. Ocular inflammation
5. Respiratory tract chondritis
6. Cochlear and, or, vestibular dysfunction
OR 1 or more signs with histologic confirmation
OR Chondritis in 2 or more separate sites AND response to steroids or immunosuppression
Differential diagnosis for these individual symptoms and signs includes most of the autoimmune
disorders and other infectious and non-infectious granulomatous disorders including Wegener's
granulomatosis, polyarteritis nodosa (PAN), Takayasu's arteritis, giant cell arteritis (GCA),
rheumatoid arthritis, Reiter's syndrome, rheumatic fever, polymorphic reticulosis, syphilis,
tuberculosis, histoplasmosis, leprosy, sarcoidosis, and malignancy.
Diagnostic Criteria for Kawasaki Disease
Presence of at least five of six conditions:
1. Fever for five days or more
2. Bilateral conjunctival injection without exudate
3. Polymorphous exanthem
4. Changes in lips and mouth:
• Reddened, dry, or cracked lips
• Strawberry tongue
• Diffuse redness of oral or pharyngeal mucosa
5. Changes in extremities:
• Reddening of palms or soles
• Indurative oedema of hands or feet
• Desquamation of skin of hands, feet, and groin (in convalescence)
6. Cervical lymphadenopathy:
• More than 15 mm in diameter, usually unilateral, single, non-purulent, and painful

Exclusion of diseases with similar presentation:


• Staphylococcal infection (such as scalded skin syndrome, toxic shock syndrome)
• Streptococcal infection (such as scarlet fever, toxic shock-like syndrome). Throat carriage
of group A streptococcus does not exclude the possibility of Kawasaki disease
• Measles and other viral exanthems
• Leptospirosis
• Rickettsial disease
• Stevens-Johnson syndrome
• Drug reaction
• Juvenile rheumatoid arthritis
Diagnostic Criteria for Mixed Connective Tissue Disease (MCTD)
Alarcon-Segovia Diagnostic Criteria for Mixed Connective Tissue Disease (MCTD)
1. Serological criteria: Positive anti U1 RNP at haemagglutination titer >1:1600
2. Clinical criteria:
a. Oedema of hands
b. Synovitis
c. Myositis
d. Raynaud´s
e. Acrosclerosis

Requirements:
a. Serological
b. At least 3 clinical features
c. Association of hand oedema, Raynaud´s and acrosclerosis requires at least one other
feature

Kusukawa Diagnostic Criteria for Mixed Connective Tissue Disease (MCTD)


Common Symptoms
1. Reynaud´s Phenomenon
2. Swollen fingers or hands
Presence of Anti U1 RNP
Mixed findings
A. Systemic lupus erythematosus (SLE) like
• Polyarthritis
• Pericarditis/pleuritis
• Lymphadenopathy
• Facial erithema
• Leucopenia/thrombocytopenia
B. Scleroderma like
• Sclerodactyly
• Pulmonary fibrosis
• Esophageal dysmotility
C. Polymyositis like
• Muscle weakness
• High creatine phosphokinase (CPK)
• Myophatic electromyogram (EMG)
Requirement for diagnosis: At least one common symptom, with positive U1 RNP antibodies and
one or more findings in at least two of the three categories A, B, and C.
Diagnostic Criteria for Tuberous Sclerosis Complex (TSC)
The diagnostic criteria for tuberous sclerosis complex (TSC) were revised at the Tuberous
Sclerosis Complex Consensus Conference, July 1998.
Definite TSC: Two major features or one major feature plus two minor features
Probable TSC: One major feature plus one minor feature
Possible TSC: One major feature or two or more minor features
Major Features
• Facial angiofibromas or forehead plaque
• Nontraumatic ungual or periungual fibromas
• Hypomelanotic macules (three or more)
• Shagreen patch (connective tissue nevus)
• Multiple retinal nodular hamartomas
• Cortical tuber 1
• Subependymal nodule
• Subependymal giant cell astrocytoma
• Cardiac rhabdomyoma, single or multiple
• Lymphangiomyomatosis 2
• Renal angiomyolipoma 2
Minor Features
• Multiple randomly-distributed pits in dental enamel
• Hamartomatous rectal polyps
• Bone cysts
• Cerebral white matter radial migration lines 1,3
• Gingival fibromas
• Nonrenal hamartoma
• Retinal achromic patch
• "Confetti" skin lesions
• Multiple renal cysts

1. Cerebral cortical dysplasia and cerebral white matter migration tracts occurring together are
counted as one rather than two features of TSC.
2. When both lymphangiomyomatosis and renal angiomyolipomas are present, other features of
tuberous sclerosis must be present before TSC is diagnosed.
3. White matter migration lines and focal cortical dysplasia are often seen in individuals with
TSC; however, because these lesions can be seen independently and are relatively nonspecific,
they are considered a minor diagnostic criteria for TSC.
NIH Diagnostic Criteria for Neurofibromatosis
Diagnosis of Neurofibromatosis Type 1 (NF1)
1. Six or more café au lait macules over 5 mm in greatest diameter in prepubertal
individuals and over 15 mm in greatest diameter in postpubertal individuals
2. Two or more neurofibromas of any type or one plexiform neurofibroma
3. Freckling in the axillary or inguinal regions (Crowe´s sign)
4. Optic glioma
5. Two or more Lisch nodules (iris harmartomas)
6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex
with or without pseudoarthrosis
7. A first-degree relative (parent, sibling, or offspring) with NF1 by the above criteria
The criteria are met in an individual if two or more of the features listed are present.

Diagnosis of Neurofibromatosis Type 2 (NF2)


1. Bilateral masses of the eighth cranial nerve seen with appropriate imaging techniques
(e.g., CT or MRI)
2. A first-degree with NF2 and either:
a) Unilaterial mass of the eighth cranial nerve, or
b) Two of the following:
• Neurofibroma
• Meningioma
• Glioma
• Schwannoma
• Juvenile posterior subcapsular lenticular opacity
The criteria are met by an individual who satisfies condition 1 or 2.
Criteria for the Classification of the Antiphospholipid Syndrome (APS)
Clinical Criteria
Vascular thrombosis
• One or more clinical episodes of arterial, venous, or small-vessel thrombosis, occurring
within any tissue or organ
Complications of pregnancy
• One or more unexplained deaths of morphologically normal fetuses at or after the 10th
week of gestation; or
• One or more premature births of morphologically normal neonates at or before the 34th
week of gestation; or
• Three or more unexplained consecutive spontaneous abortions before the 10th week of
gestation
Laboratory Criteria
Anticardiolipin antibodies
• Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on
two or more occasions at least six weeks apart
Lupus anticoagulant antibodies
• Lupus anticoagulant antibodies detected in the blood on two or more occasions at least
six weeks apart, according to the guidelines of the International Society on Thrombosis
and Hemostasis
A diagnosis of definite antiphospholipid syndrome requires the presence of at least one of the
clinical criteria and at least one of the laboratory criteria. No limits are placed on the interval
between the clinical event and the positive laboratory findings.
The following antiphospholipid antibodies are currently not included in the laboratory criteria:
anticardiolipin IgA antibodies, anti-B2-glycoprotein I antibodies, and antiphospholipid
antibodies directed against phospholipids other than cardiolipin (e.g., phosphatidylserine and
phosphatidylethanolamine) or against phospholipid-binding proteins other than cardiolipin-
bound B2-glycoprotein I (e.g., prothrombin, annexin V, protein C, or protein S).