Algorithms

Acromegaly TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGSuspected growth hormone excess

Patient presents with enlarged feet and head, headache

ORDERIGF-1 (Insulin-Like Growth Factor 1)

ANDGrowth Hormone (GH)

normal or elevated

MRI to evaluate pituitary gland and consider evaluation of other pituitary functions

Acromegaly confirmed

Oral glucose tolerance test (OGTT) with 75 gm loadAND

Measure growth hormone level 2 hour post OGTT with Growth Hormone test

Suppression of GH Failure of suppression of GH (GH >0.25 ng/mL)

Acromegaly excluded

2006 ARUP Laboratories. All Rights Reserved. Revised 9/26/11 www.arupconsult.com

INDICATIONS FOR TESTINGSuspected Cushing Syndrome

(central obesity, muscle weakness, refractory hypertension)

Adrenal Hyperfunction (Cushing Syndrome) TestingClick here for topics associated with this algorithm

ORDERCortisol Urine Free

by LC-MS/MS

ORDERCortisol, Saliva (between

11 pm and midnight)

OR

0.112 g/dL 60 g/day male>45 g/day female yesno

normalRepeat

Cortisol, Saliva (tested at midnight)

0.112 g/dL normal

Cushing Syndrome unlikely; no further

testing

normalRepeat

Cortisol Urine Free by LC-MS/MS test

>60 g/day male>45 g/day female normal

Cushing Syndrome

likely

Low dose dexamethasone suppression test (DST) protocol: 1 mg dexamethasone PO (taken between 11 pm and midnight)

Then measure at 8 am the following morning:Cortisol, Serum or Plasma

(or Cortisol Urine Free by LC-MS/MS)

Cushing Syndrome unlikely; no further

testing

Urine cortisol

INDICATIONS FOR TESTINGSuspected adrenal insufficiency, small cardiac size, Na+5 mEq/L, dehydration, cold intolerance, orthostatic hypotension

Adrenal Insufficiency TestingClick here for topics associated with this algorithm


ORDERCortisol by LC-MS/MS,

Serum or Plasma

300 pg/mL

ACTH 1:2 ratio and 11-Deoxycortisol >7 g/dL

Adrenal failure

unlikely

MRI/CT of adrenal glands

CRH stimulation

test

ORDERAdrenocorticotropic

Hormone

INDICATIONS FOR TESTINGFatigue, weakness, pallor, dizziness, fainting

Anemia TestingClick here for topics associated with this algorithm

Anemia present on CBC (males Hgb

INDICATIONS FOR TESTINGVascular thrombosis

One or more clinical episodes of arterial, venous, or small vessel thrombosisUnexplained pregnancy loss defined as:

One or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestationOne or more premature births of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe preeclampsia or recognized features of placental insufficiencyThree or more unexplained, consecutive, spontaneous abortions before the 10th week of gestation, and with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded

Additional indications for testing may also include the presence of endocarditis, stroke, heart attack, livedo reticularis, thrombocytopenia, hemolytic anemia, thrombotic microangiopathy and bone marrow necrosis

Strong suspicion of APS still present

Possible APSRepeat testing in 12 weeks


No further testingNon-criteria APS antibodies identified

Consider repeat testing in 12 weeks to demonstrate persistenceConsider referral to a specialist

APS confirmed

Antiphospholipid Syndrome TestingClick here for topics associated with this algorithm

ORDERCardiolipin Antibody, IgABeta-2 Glycoprotein 1 Antibody, IgAPhosphatidylserine Antibodies, IgG, IgM, and IgAProthrombin Antibody, IgGProthrombin Antibody, IgM

ORDERLupus Anticoagulant Reflexive PanelCardiolipin Antibodies, IgG and IgMBeta-2 Glycoprotein 1 Antibodies, IgG & IgM

All negative At least 1 test positive

At least 1 test positiveand at least 1 clinical

criterion metAll negative

All negative At least 1 test positive

C1-INH Deficiency Testing AlgorithmClick here for topics associated with this algorithm

2006 ARUP Laboratories. All Rights Reserved. 08/28/12 www.arupconsult.com

INDICATIONS FOR TESTINGRecurrent angioedema (without urticaria)Recurrent episodes of abdominal pain and vomittingLaryngeal edemaPositive family history for angioedema

Consider angioedema types other than HAE types I and II

Medications (eg, ACE inhibitors)Estrogen-relatedFactor XII relatedOther

Hereditary Angioedema Acquired Angioedema

ORDERC-1-Esterase Inhibitor Panel (includes

complement component 4)

C4, C1-INH protein quantities normal C4 and C1-INH protein quantities decreasedC4 quantity low but C1-INH protein

normal or elevated

Determine C1-INH function

Measure C1Q and consider age of onset of symptoms

Later age of onset and/or low C1Q

Earlier age of onset and/or C1Q normal

C1-INH function normal

C1-INH function

decreased

Diagnosis:Angioedema due to C1-INH

deficiency

Confirm by second measurement of C4 and C1-INH quantity and function

No family history of angioedema

Family history of angioedema

Confirm C4, C1-INH normal during attack

Clostridium difficile-Associated Disease (CDAD) TestingClick here for topics associated with this algorithm

General Testing Recommendations1

Detection of C. difficile toxins by EIA is not recommended as a stand-alone test.Only test diarrheal (ie, unformed) stool (3 loose stools/day for 1-2 days).Non-diarrheal stool should only be tested with suspected ileus due to C. difficile.Testing of asymptomatic patients and test of cure is not clinically useful.Repeat testing during the same episode of diarrhea is not recommended.

1 Modified from Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by SHEA and IDSA and A practical guidance document for C. difficile toxin laboratory testing (ASM, 8/24/2010)


The following testing may be considered when high level of clinical suspicion:

Clostridium difficile toxin B gene (tcdB) by PCR

Clostridium difficile Culture with Reflex to Cytotoxin Cell Assay

Endoscopy

Determine toxin status

ORDERClostridium difficile toxin B gene

(tcdB) by PCR

OR


ORDERGlutamate Dehydrogenase

Antigen (EIA)

Detects toxigenic and non-toxigenic C. difficile

RECOMMENDED ALTERNATIVETURNAROUND TIME DEPENDS

ON RESULT

RECOMMENDED SINGLE TESTTURNAROUND TIME 24 HRS

REFERENCE METHODTURNAROUND TIME 96 HRS

ORDERClostridium difficile Culture with Reflex to Cytotoxin Cell Assay

ORDERClostridium difficile toxin B gene (tcdB) by PCR

(nucleic acid amplification test)

negative



Endoscopy

OR OR


Clostridium difficile toxin B gene (tcdB) by PCR

Endoscopy

Consider Other Causes of DiarrheaBacterial, fungal, viral infections; parasitic infections with recent travel to endemic areasHyperosmolar states (eg, tube feeding), medication, other

Toxigenic C. difficile detected


positive

Toxigenic C. difficile not

detected

Toxigenic C. difficile

not detected


Toxigenic C. difficile

not detected

C. difficile antigen not

detected

negativepositive

negativepositive negativepositive

Celiac Disease Testing for Symptomatic Individuals Click here for topics associated with this algorithm

ORDER Immunoglobulin A

IgA level 7.0 mg/dL but below age-matched

range

Perform biopsy

Marsh 2Marsh 0-1

EMA and/or DGP negativeHLA positive

EMA andDGP negative and

HLA negative

EMA and/or DGP positiveHLA positive

Celiac disease

confirmed

Celiac disease

confirmed

INDICATIONS FOR TESTINGNonspecific symptoms (anemia, failure to thrive, fever, skin rash and weight loss)Diarrhea >4 weeks duration

Likely false-positive anti-tTG

test

Consider early phase disease follow-up testing on normal dietConsider false-positive results

Selective IgA deficiency (

Central Diabetes Insipidus (Posterior Pituitary) TestingClick here for topics associated with this algorithm


INDICATIONS FOR TESTINGSuspected central diabetes insipidus

Symptoms: polydipsia, polyuria, nocturia

ORDEROsmolality, Urine

AND/OROsmolality, Serum or Plasma

AND Sodium, Plasma or Serum

UO 50% increased UO

Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children TestingClick here for topics associated with this algorithm

Adult or older childRecurrent upper and lower respiratory tract infections

AND/ORDiarrhea, abscesses, sepsis, meningitis

Rule out:1. Physical/anatomic lesions such as foreign body (bronchial), eustachian tube dysfunction, indwelling catheter or other anatomic abnormalities 2. Cancer3. Connective tissues diseases 4. Diabetes5. Renal disease

Then perform the following testing:1. Comprehensive Metabolic Panel (general health screening for immunodeficiency)2. CBC with Platelet Count (general health screening for immunodeficiency)3. Human Immunodeficiency Virus Type 1 and 2 (HIV-1, HIV-2) Antibody with Reflex to Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Confirmation by Western Blot4. Protein Electrophoresis with Reflex to Immunofixation Electrophoresis Monoclonal Protein Detection, Quantitation & Characterization, IgA, IgG & IgM, Serum AND Bence Jones proteins (Bence Jones Protein, Quantitative Free Kappa and Lambda Light Chains, Urine) OR Monoclonal Protein Detection Quantitation & Characterization, SPEP, IFE, IgA, IgG, IgM, Serum5. Sweat Chloride (at accredited cystic fibrosis center)6. If only recurrent sinopulmonary disease - pneumococcal antibody IgG titers pre and post vaccine (1 month), Streptococcus pneumoniae Antibodies, IgG (14 serotypes)

sweat chloride abnormal HIV +

No pneumococcal antibodies

immunoglobulin evaluation abnormal

Abscesses, pneumonia, recurrent respiratory infections with or without diarrhea all testing normal

Cystic fibrosis confirmed

ORDERCystic Fibrosis (CFTR)

32 Mutations with Reflex to Sequencing

Follow HIV Algorithm

Specific antibody

deficiency

low IgG or IgM Hypogammaglobulinemia

low complement Complement defect

abnormal DHR

Chronic granulomatous disease

Genetic testingdecreased CD11b/CD

18

Leukocyte adhesion deficiency, type 1

increased IgE

Possible Hyper IgE syndrome

(Job syndrome)

Candida specific IgE neutrophil

chemotaxis

low neutrophil

count

Hematology consultMay need bone marrow

exam

Neutrophil antibody positive

Autoimmune neutropenia

ORDERImmunoglobulins (IgA,IgG, IgM), QuantitativeImmunoglobulin EComplement Activity Enzyme Immunoassay, TotalCBC with Platelet Count and Automated DifferentialNeutrophil Oxidative Burst Assay (DHR)Leukocyte Adhesion Deficiency PanelMyeloperoxidase Stain

monoclonal proteinpresent

Consider monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma or Waldenstrm macroglobulinemia

Follow Plasma Cell Dyscrasia

Algorithm

Hypogammaglobulinemia secondary to malignancy1. Chronic lymphocytic

leukemia2. Lymphoma

possiblesecondary

hypogammaglobulinemias

Loss secondary to disease1. Chronic renal disease2. Nephrotic syndrome 3. Protein-losing enteropathy4. Intestinal lymphangiectasia

Drug induced1. Steroids2. Anti-rheumatic drugs3. Phenytoin4. Carbamazepine

ORDERLymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45ROLymphocyte Subset Panel 7 - Congenital Immunodeficiencies

ORDERLymphocyte Antigen

and Mitogen Proliferation Panel with Cytokine Response to

Mitogens, 12 Cytokines testing

Consider true T-cell deficiency, HIV, CD4 deficiency, adenosine deaminase deficiency, nucleoside phosphorylase deficiency, chronic mucocutaneous candidiasis (may also consider Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response to Mitogens, 12 Cytokines)

Contact immunology consultant or medical

director

abnormal

ORDERLymphocyte Antigen

and Mitogen Proliferation Panel

Possible complement deficiency

Individual complement testing based on results of CH50,

AH50

If all normal, contact immunology director for

further evaluation

abnormal complement activity

ORDERComplement Activity

Enzyme Immunoassay, Total and AH50

Rule out immunoglobulin abnormality or absent

spleen

Recurrent severe viral infections, candidiasis,

herpes, etc.

Recurrent severe sepsis,Neisseria spp, S.

pneumoniae, infections


ORDERInterleukin-1-Receptor-Associated Kinase-4 (IRAK-4) Deficiency ScreenToll-Like Receptor Function

Innate immune deficiency

abnormal

absence of myeloperoxidase

Myeloperoxidase deficiency

low IgG, IgM, IgA

ORpoor

antibody response

ORDERB-Cell

Immunodeficiency Profile

B-cells present

Common variable immune deficiency

(CVID) or other immune deficiency

Immunology consult

May need immunoglobulin

replacement

IgA low

ORDERImmunoglobulin G Subclasses

(1, 2, 3, 4)

Absent IgALow IgG 2, 4Pneumococcal vaccine response low

Immunology consult May need

immunoglobulin replacement with low

IgA containing preparation

IgA absent

Warn of possible reaction to IgA-containing blood

products

Symptomatic treatment

high IgMlow IgG, IgA

Perform CD 40 Ligand testing

PossibleHyper IgM Syndrome

ORDERB-Cell


normal IgM cells, low IgG and IgA

decreased CD15

Leukocyte adhesion deficiency, type 2

Mutation present

Immunodeficiency Evaluation for Chronic Infections in Infants and Children TestingClick here for topics associated with this algorithm

Recurrent respiratory infections with or without chronic diarrhea Severe viral infections; Candida or other fungal infections; recurrent sinopulmonary infectionsAbscesses, pneumonia, delayed separation of umbilical cord;

recurrent respiratory infections with or without diarrhea

CONSIDERImmunoglobulins (IgA, IgG, IgM), QuantitativeLymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45RO or Lymphocyte Subset Panel 7 Congenital ImmunodeficienciesResponse to polyvalent pneumococcal vaccine if >2 years Response to DT vaccineSweat Chloride testing (at accredited cystic fibrosis center)

low IgG, IgM, IgAORpoor

antibody response to vaccination

ORDERB-Cell


no B-cells present

Bruton X-linked agammaglobulinemia

high IgMlow IgG, IgA

B-cells present

Common variable immune deficiency

(CVID) or other immune deficiency

CD 40 Ligand testing

PossibleHyper IgM

Syndrome

Immunology consult May need

immunoglobulin replacement

positive sweat

chlorideCystic fibrosis

low IgA

ORDERImmunoglobulin G Subclasses

(1, 2, 3, 4)

IgA absentLow IgG 2,4Poor pneumococcal vaccine response

Immunology consult May need immunoglobulin replacement with low IgA

containing preparation

IgA absentNormal IgG subclasses

Warn of possible reaction to IgA- containing blood

products

Symptomatic treatment

Test of choice in children 18 months is HIV PCR (antibodies do not work in infants)

ORDERCD4+ T-Cell Recent Thymic Emigrants (RTEs)Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45RO or Lymphocyte Subset Panel 7 Congenital ImmunodeficienciesLymphocyte Antigen and Mitogen Proliferation Panel

low T-celllow LAMabnormal

RTEsabnormal

facies hypocalcemia

Possible severe combined

immunodeficiency

ORDERAdenosine Deaminase, RBCPurine Nucleoside Phosphorylase Toll-Like Receptor Function

Also consider IL-2R gamma chain defect or other related diseases

low T-celllow LAMabnormal

RTEs

DiGeorge syndrome

HIV positive See HIV algorithms

Decreased response to

Candida

ORDERToll-Like Receptor Function Assay

Possiblechronic

mucocutaneous candidiasis

ORDERImmunoglobulins (IgA, IgG, IgM), QuantitativeComplement Activity Enzyme Immunoassay, Total and AH50CBC with Platelet Count and Automated DifferentialNeutrophil Oxidative Burst Assay (DHR)Leukocyte Adhesion Deficiency PanelMyeloperoxidase StainLymphocyte Subset Panel 7 Congenital Immunodeficiencies

low IgG or IgM Hypogammaglobulinemia

abnormal complement

activity

Possible complement deficiency

Genetic testing

increased IgE

Possible Hyper IgE syndrome

(Job syndrome)

Candida specific IgE neutrophil

chemotaxis

low neutrophil

count

Kostmann agranulocytosis

Hematology consultMay need

granulocyte colony stimulating factor

Neutrophil antibody positive

Autoimmune neutropenia


ORDERChromosome

FISH, Metaphase

(specify 22q11 deletion)

positive for

deletionORDERB-Cell


normal IgM cells, low IgG and IgA

all normalInnate immune deficiency

absence of myeloperoxidase

Myeloperoxidase deficiency

ORDERIndividual complement

testing based on results of CH50, AH50

If all normal, contact

immunology director for

further evaluation

T-cell disorder evaluationImmunoglobulin disorder evaluation

IgA lowNormal IgG subclasses

Consider celiac testing

abnormal DHR

Chronic granulomatous

disease

decreased CD11b/CD

18

Leukocyte adhesion

deficiency, type 1

decreased CD15

Leukocyte adhesion

deficiency, type 2ORDERGenetic testing

ORDER IRAK-4 and toll receptor

abnormal

Complement Deficiency TestingClick here for topics associated with this algorithm

Indications for testingComplement deficiency suspected

(recurrent bacterial infections, especially S.pneumoniae, Neisseria spp; autoimmune disorders)


Lectin pathway component deficiency

Low or absent CH50 Normal AH50

Low or absent MBL

Normal CH50Low or absent AH50

Low or absentCH50 and AH50

Classical pathway component deficiency

Alternate pathway component deficiency

Terminal pathway component deficiency

Consider any or all of the following:C3, C5, C6, C7, C8, C9 levels or function testingFactor H, I levels

Consider any or all of the following:C1, C2, C4 levels or function testing C1 esterase testing if angioedema present

Consider any or all of the following:Properdin levels or function testingFactor B, D, levels

Multiple components abnormal

Consider genetic testing if hereditary deficiency suspected

Suggests disorder associated with complement consumption

no yes

Normal CH50 and AH50AND

High suspicion for Complement deficiency

Mannose Binding Lectin (MBL)

Total Complement Activity (CH50) and AH50

Also consider evaluation for immunoglobulin disorders

Disease legendCREST CREST syndrome (calcinosis, Raynaud phenomenon,

esophageal dysmotility, sclerodactyly and telangiectasia)DIL Drug-induced lupus erythematosus dcSSc Diffuse cutaneous sclerodermalcSSc Limited cutaneous sclerodermaMCTD/UCTD Mixed connective tissue disease/Undifferentiated

connective tissue diseasePM/DM Polymyositis/DermatomyositisSjS Sjgren syndromeSLE Systemic lupus erythematosusSSc Scleroderma (systemic sclerosis)

Antibody Key

RNP RNP (U1) (Ribonucleic Protein) (ENA) Antibody, IgG

Scl-70 Scleroderma (Scl-70) (ENA) Antibody, IgGSm Smith (ENA) Antibody, IgGSS-A SSA (Ro) (ENA) Antibody, IgGSS-B SSB (La) (ENA) Antibody, IgG

Anti-Nuclear Antibodies (ANA), IgG by ELISA with

Reflex to ANA, IgG by IFA*

Centromere pattern

Cytoplasmic pattern

Speckled pattern

Peripheral/rim/homogenous pattern

Nucleolar pattern

lcSSc, CREST

PM/DM, SLE, SSc

SLE, SSc, PM/DM

Sm+ SS-A /SS-B+ U1RNP+ Scl-70+ No specificity**

SLE, SjS MCTD/UCTD

* ELISA screen detects antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Sm, RNP, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells** Unidentified specificities or markers of low prevalence in CTDNote: Overlap may occur among the antibodies and disesases. Associations between ANA IFA pattern and disorders such as autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are not indicated

INDICATIONS FOR TESTINGPatient with systemic symptoms

(arthritis, arthralgias, skin rashes, anemia, renal dysfunction, pleuritis, pericarditis)

SLE dcSSc


Connective Tissue Disease TestingClick here for topics associated with this algorithm

False-positive results may be induced by age, certain infections, cancers, and drugsANA may be positive in inflammatory diseases such as autoimmune liver diseases

positivenegative

Possible scenariosNo connective tissue disease (CTD)False-negative result consider SSc, PM/DM or inactive SLEIf suspicion for CTD is strong, consider testing for disease-specific antibody tests or panels

SLE, DIL

Nuclear Antibody (ANA) by IFA, IgG

RISK FACTORSFamily history of genetic disorders/IDNeurocognitive dysfunctionCerebral palsy and static encephalopathyHypotoniaSeizure disorderBirth defects (eg, cardiac defect, cleft palate, club feet)Growth abnormalitiesNonfamilial dysmorphic featuresFamily history of recurrent miscarriages

OrderMRI/CT

Presence ofMicrocephalyMacrocephalyFocal findings on neurologic examCerebral palsyHypotoniaSeizuresAutism/ASD

Developmental Delay (DD) or Intellectual Disability (ID) Testing

Family history of metabolic disorder

Cytogenomic SNP Microarray or Cytogenomic SNP Microarray Buccal Swab first line testing for most developmental delay syndromes

ORCytogenomic SNP Microarray with Five-Cell Chromosome Study, Peripheral Blood useful if chromosome and array tests would

otherwise have been ordered concurrently

OTHER AVAILABLE TESTINGX Chromosome Ultra-High Density Microarray (consider this test if FMR1 testing is negative)Chromosome Analysis, Peripheral BloodChromosome FISH, MetaphaseFragile X (FMR1) with Reflex to Methylation AnalysisRett Syndrome (MECP2), Sequencing and Deletion/DuplicationRett Syndrome (MECP2), Full Gene SequencingRett Syndrome (MECP2), Deletion and DuplicationAngelman Syndrome and Prader-Willi Syndrome by Methylation Angelman Syndrome (UBE3A) SequencingCDKL5-Related Disorders (CDKL5) Sequencing and Deletion/DuplicationCDKL5-Related Disorders (CDKL5) SequencingCDKL5-Related Disorders (CDKL5) Deletion/DuplicationPTEN-Related Disorders (PTEN) Sequencing and Deletion/DuplicationX-Linked Intellectual Disability Panel, Sequencing, 76 Genes


Evaluation for DD/IDIdentify family history of risk factors

Genetics consultationTreat symptomatically

Metabolic testingRefer for metabolic consult

IF male with neurocognitive dysfunctionORDER

Fragile X (FMR1) with Reflex to Methylation Analysis

Note: test more likely to be positive in the following cases:

Physical features characteristic of Fragile XFamily history supportive of X-linked IDMaternal family history of premature ovarian failure, ataxia and/or tumor

Sufficient minor or major dysmorphic (atypical) features Episodic deterioration

May want to consider Cytogenetic and/or molecular testing based on clinical presentationGenetics consultation

yes no

negative

noyes

yes no

abnormal

Click here for topics associated with this algorithm

Refer for genetics

consultation


Diarrhea, Acute TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGAcute diarrhea

(3 days)

Supportive careif diarrhea

persists >3 days

Not improved 3-5 days

Supportive careConsider empiric antibiotics

pending culture results

Consider repeat stool exam; colonoscopy (+)

biopsy

Diarrhea >3 days

Supportive care

Bloody diarrhea (suggests bacterial etiology), residence or travel in endemic

areas, or immunocompromised

patientsSee Clostridium difficile-Associated Disease (CDAD)

Algorithm

If appropriate clinical setting, consider

Norovirus Group 1 and 2 Detection by RT-PCRRotavirus Antigen by EIARotavirus and Adenovirus 40-41 Antigens

ORStool Culture and E. coli Shiga-like Toxin by EIAGiardia Antigen by EIAOva and Parasite Exam, Fecal (Immunocompromised or Travel History)

If appropriate clinical setting, considerCampylobacterMicrosporidiumCryptosporidiumCyclospora


If appropriate clinical setting, considerNorovirus Group 1 and 2 Detection by RT-PCRRotavirus Antigen by EIARotavirus and Adenovirus 40-41 Antigens


yes no

yes noORDER

CBC with Platelet Count and Automated Differential to aid in determining etiology

yesno

HIV, Immunocompromised

yesno

Add on testing for Microsporidium, Cryptosporidium and Cyclospora

Zollinger-Ellison Syndrome TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGRecurrent ulcers, diarrhea, gastroesophageal reflux disease (GERD)

ORDERGastrinAND

Gastric Analysis (for pH)(if on proton pump inhibitor, must

stop for 2 weeks)

>500 pg/mLgastric pH

ORDERHepatitis B Virus Surface Antigen with Reflex to ConfirmationHepatitis B Virus Core Antibodies (Total)Hepatitis B Virus Surface Antibody

ANDHepatitis C Virus Antibody by CIA

ORDERHepatitis Panel, Acute with Reflex to HBsAg Confirmation (includes the following):Hepatitis A Virus Antibody, IgMHepatitis B Virus Surface Antigen with Reflex to ConfirmationHepatitis B Virus Core Antibody, IgMHepatitis C Virus Antibody by CIA

HBV surface antigen +HBV core IgM abs +

HBV surface antigen +HBV core IgM abs -

HBV surface antigen -HBV core IgM abs +

HBV surface antigen -

HBV core IgM abs -

Acute HBVFollow to determine resolution

Possibly chronic HBV or contamination of specimen

HBV infection probably resolving

HBV surface antigen -HBV core abs +

HBV surface abs -

HBV surface antigen +HBV core abs +

HBV surface abs -

HBV surface antigen -HBV core abs +

HBV surface abs +

Chronic HBV likely

False + anti-HBc or chronic infection Consider HBV DNA testing and/or HBV

vaccine followed by repeat HBV serology

HBV surface antigen -HBV core abs -

HBV surface abs +

Expected serology response from HBV vaccine

Recovered from HBV infection

INDICATIONS FOR TESTINGAcute onset

JaundiceViral illness

INDICATIONS FOR TESTINGChronic

Moderately elevated transaminases(Possible past history of hepatitis)

Repeat test 4-6 wks

Repeat test in 4-6 wks

Repeat test in 4-6 wks

To monitor therapy, use HBV DNA, HBsAg, HBsAb, HBeAg, HBeAbHepatitis B Virus DNA Quantitative Real-Time PCR

Repeat test in 4-6 wksTo monitor therapy, use HBV DNA, HBsAg, HBsAb, HBeAg and HBeAb

Hepatitis B Virus TestingClick here for topics associated with this algorithm

Consider other etiologiesViral

Cytomegalovirus Epstein-Barr virus Herpes simplex virus Varicella-zoster virusHepatitis A, C, D or E

Toxin exposureAlcoholTetrachloride

Nonalcoholic acute steatohepatitisDrug-induced hepatitis

Acetaminophen Antiseizure medications Isoniazid (Nydrazid) Oral contraceptives Rifampin (Rifadin) Sulfonamides

AutoimmuneSystemic lupus erythematosusPrimary biliary cirrhosisSclerosing cholangitisAutoimmune hepatitis

BacterialLeptospira sppCoxiella burnetii (Q-fever)Rickettsia rickettsii (Rocky Mountain spotted fever) Treponema pallidum (Secondary syphilis) Sepsis Rickettsia typhi (typhus fever)

Granulomatous M. tuberculosisSarcoidosis

Hereditary Wilson diseaseHemochromatosis Alpha-1-antitrypsin deficiency

IschemiaParasitic

Liver trematodesToxocara spp


Test KeyHBV DNA - Hepatitis B Virus DNA Quantitative Real-Time PCRHBeAg Hepatitis Be Virus AntigenHBeAb Hepatitis Be Virus AntibodyHBsAb Hepatitis B Virus Surface AntibodyHBsAg Hepatitis B Virus Surface Antigen with Reflex to Confirmation

Please see Hepatitis C Virus Testing Algorithm

HCV positive

If testing confirms

HBV, consider

Hepatitis B Virus

Genotyping testing

ORDERHepatitis C Virus RNA

Quantitative, Real-Time PCR

Currently infected

negative positive

Not currently infected

Either previously infected and recovered

OR false-positive anti-HCV

screen

INDICATIONS FOR TESTINGHigh/low anti-HCV by CIA or ELISA

Chronic HCV

ORDERHepatitis C Virus Genotype by Sequencing

(consider liver biopsy)

Monitor treatmentHepatitis C Virus RNA Quantitative, Real-Time PCR

Genotype 1

End of treatmentHepatitis C Virus RNA Quantitative, Real-Time PCR


Hepatitis C Virus TestingClick here for topics associated with this algorithm

no

ORDERInterleukin 28 B (IL28B)-

Associated Variants, 2 SNPs

Treatment decision

yes

Minimal or no symptoms

Acutely symptomatic(Follow up in 3-6 months to assess for resolution)

Hepatitis B confirmed by testing

ORDERHepatitis Delta Virus Antibody

Strong suspicion of HDV

ORDERHepatitis Delta Antigen by ELISA

ANDHepatitis Delta Virus (HDV), IgM Antibody, EIA

Also consider Hepatitis B Virus Surface Antigen with Reflex to Confirmation and

Hepatitis B Virus Core Antibody, IgM testing to rule out chronic HBV versus coinfection with

HBV

Acute infection

Chronic infection

Acute infection, probably

recovering

Recovered HDV infection

Ag +IgM +

Ag +IgM -

Ag -IgM +

Ag -IgM -

INDICATIONS FOR TESTINGPatient with signs and symptoms of acute hepatitis (abrupt

onset of nausea, anorexia or jaundice) or confirmed chronic hepatitis B with worsening liver disease


Cytomegalovirus Epstein-Barr virus Herpes simplex virus Varicella-zoster virusHepatitis A, B, C or E




AutoimmuneSystemic lupus erythematosusPrimary biliary cirrhosisSclerosing cholangitisAutoimmune hepatitis

BacterialLeptospira sppCoxiella burnetii (Q-fever)Rickettsia rickettsii (Rocky Mountain spotted fever)Treponema pallidum (Secondary syphilis) Sepsis Rickettsia typhi (typhus fever)


Hereditary Wilson diseaseHemochromatosis Alpha-1-antitrypsin deficiency

IschemiaParasitic



Hepatitis Delta Virus (HDV) TestingClick here for topics associated with this algorithm

positive negative

Helicobacter pylori TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGPersistent dyspepsia, abdominal pain

Obvious causeNonsteroidal anti-inflammatory drug (NSAID) useKnown gastroesophageal reflux disease (GERD)

>55 yearsOR

Alarm symptomsGastrointestinal bleedingUnexplained iron deficiency anemiaEarly satietyUnexplained weight lossProgressive dysphagiaOdynophagiaRecurrent vomiting Family history of upper gastrointestinal cancer Previous esophogastric malignancy

Remove cause if possible OR

Treat based on etiology

no yes

Esophagogastroduodenoscopy (EGD)

ORDERHelicobacter pylori Breath Test

ORHelicobacter pylori Antigen, Fecal by

EIA

negative positive

Treat to eradicate H. pylori

Empiric trial of proton pump inhibitor for 4-6 weeks

symptoms still present

no symptoms present

Consider EGD

Consider repeat H. pylori testing

during EGD

No further therapy required


Reevaluate after completion of therapy or

symptom resolution

Hemochromatosis TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGSuspicion of hemochromatosis (family history, compatible symptoms)

ORDERIron and Iron Binding Capacity

Note: Test includes serum transferrin saturation (STS)AND

Ferritin (SF)

No further testing at this point

Repeat STS and SF tests

Repeat STS and SF tests at 2-year intervals

Secondary iron

overloadIf both elevated, do liver biopsy

FOR ADULTS, ORDERHemochromatosis (HFE) 3

Mutations(accounts for >90% of mutations in

Caucasians)

C282Y/C282Y C282Y/ H63DC282Y/S65CC282Y/wtH63D/H63DH63D/S65C

Ferritin 90% of cases)

CONSIDERHAMP (HEPC) gene

sequencing(accounts for

INDICATIONS FOR TESTINGPatient with anemia and evidence of hemolysis

Hemolytic Anemias TestingClick here for topics associated with this algorithm

ORDERCBC with Platelet Count and Automated DifferentialReticulocytes, Percent & NumberLactate Dehydrogenase, Serum or Plasma HaptoglobinBilirubin, Total, Serum or Plasma

Heinz bodies


Presence of the following may provide clues to the etiology of the anemia Increased reticulocyte countAbnormal peripheral smear

Polychromasia, spherocytes, schistocytes, sickle cells, stomatocytes, Heinz bodies, basophilic stippling, unusual red cell inclusions, and agglutination

Note: lack of any of the above does not rule out hemolytic anemia

Consider environmental factors, mechanical cardiac valve,

vasculitis, malignant hypertension Proceed based on above findings

Schistocytes

Spherocytes, pyropoikilocytes,

elliptocytes or acanthocytes

decreased platelets

yes

no

ConsiderDICTTPHELLPHUS

increased D Dimer

decreased fibrinogen

DIC

ADAMTS13 activityTTP

Osmotic Fragility,

Erythrocyte (usually positive)

acquired

noConsider molecular

testing

Direct Coombs (Anti-Human

Globulin)

IgG+

Autoimmune hemolytic anemia (consider drug induced, hemolytic disease of the newborn, autoimmune disease)

Consider one or more of the following tests

Isopropanol heat stability testingGlucose-6-Phosphate Dehydrogenase (G6PD) 2 MutationsEnzymes of glutathione cycle

Polychromasia without other reproducible

morphologic abnormality

Consider one or more of the following tests

Pyruvate kinase HexokinaseGlucose phosphate isomerase

Sickle cells

Basophilic stippling acquired

no

Serum lead level

Congenital 5' nucleotidase

deficiency

Consider lead

poisoning

5' nucleotidase testing

Polychromasia only with or

without platelet decrease

Consider PNH

Paroxysmal Nocturnal Hemoglobinuria Panel, RBC and WBC

Agglutination

Consider cold

agglutinins disease

Direct Coombs (Anti-Human

Globulin)

+ for complement

Cold agglutinins disease

Cold agglutinins

testing

Unusual red cell inclusions

Considermalaria,

bartonella (oroya fever), babesia

yes

Recluse spider venom, clostridium sepsis

+C3

Cold agglutinins disease,

paroxysmal cold hemoglobinuria

(PCH)

yes

yesno

Confirm PCH with Donath Landsteiner testing

Suggestsmicroangiopathic RBC destruction

ConsiderRBC membrane

disorder (hereditary

spherocytosis, hereditary

elliptocytosis, autoimmune hemolysis)

Consider Sickle cell disease diverse genotypes: SS, SC,

SE, S thalassemia, S Lepore

HPLC

ConsiderPyruvate kinase deficiencyHexokinase deficiencyOther enzyme defects

ConsiderGlucose-6-Phosphate dehydrogenase deficiencyUnstable hemoglobin defectsGlutathione metabolism defectsHemoglobin H disease

For hemoglobin disorders, consider HPLC, genetic testing

Acute hepatitis A Acute hepatitis BSee HBV Testing

algorithm

Hepatitis C

No known prior history of hepatitis

Known prior hepatitis B infection

ORDERHepatitis Panel, Acute with Reflex to HbsAg Confirmation (includes the following):

Hepatitis A Virus Antibody, IgM Hepatitis B Virus Core Antibody, IgMHepatitis B Virus Surface Antigen with Reflex to ConfirmationHepatitis C Virus Antibody by CIA

INDICATIONS FOR TESTINGNew onset of symptoms (nausea, jaundice, fever, anorexia,

dark urine)


Hepatitis Virus ScreeningClick here for topics associated with this algorithm

See HDV Testing algorithm

Consider coinfection with hepatitis delta

virus (HDV)


Cytomegalovirus Epstein-Barr virus Herpes simplex virus Varicella-zoster virus




Autoimmune Systemic lupus erythematosusPrimary biliary cirrhosisSclerosing cholangitisAutoimmune hepatitis

Bacterial Leptospira spp Coxiella burnetii (Q-Fever) Rickettsia rickettsii (Rocky Mountain spotted fever) Treponema pallidum (Secondary syphilis) Sepsis Rickettsia typhi (typhus fever)


HereditaryWilson diseaseHemochromatosis Alpha-1-antitrypsin deficiency

IschemiaParasitic


HAV Abs + HBV core IgM Abs +HBV surface antigen + HCV Abs +Negative hepatitis results

OFFER SCREENING TO ALL ADULTS AND CHILDREN >13 YEARS (CDC, 2010)High-risk patients: previous blood product recipient, intravenous drug abuse, multiple sexual encounters, chronic hepatitis, organ donors, recurrent pneumonia, and tuberculosis

Human Immunodeficiency Virus in Adults TestingClick here for topics associated with this algorithm


4th Generation Ag/AbCombo test

ORDERHuman Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/O/2) by ELISA, with Reflex to HIV-1/HIV-2 Antibody Differentiation

by Multispot

negative

repeatedly reactive

indeterminateOR

negative

positive

Confirmation by Multispot

(Combo test reflexes to Multispot)

HIV confirmedDetermine therapy (draw a new sample)

ORDERLymphocyte Subset Panel 1 - CD4 Absolute Count Only

ANDHuman Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR

ORDER NAAT testing

Point-of Care Rapid Test(eg, HIV 1/2 STAT-PAK, Multispot HIV-1/HIV-2,

OraQuick ADVANCE, Reveal G3, Clearview Complete HIV 1/2, Unigold Recombigen)

negative

preliminary positive

Confirmation by Western Blot

Human Immunodeficiency Virus Type 1 (HIV-1)

Antibody Confirmation by Western Blot

(3rd generation assay reflexes to Western Blot)

3rd Generation Antibody Only Immunoassay

ORDERHuman Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies by CIA with Reflex to HIV-1 Antibody Confirmation by Western Blot

ORHuman Immunodeficiency Virus Type 1 (HIV-1) Antibody by CIA with Reflex to HIV-1 Antibody

Confirmation by Western Blotnegative

repeatedly reactive

*indeterminate

positive

HIV confirmedDetermine therapy

ORDER(draw a new sample)

Lymphocyte Subset Panel 1 - CD4 Absolute Count OnlyAND

Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR

Repeat testing4 weeks

Consider retesting in high-risk patients, if clinically indicated



Notes:Preferred test if acute HIV is suspected. Antigen/antibody combination reduces diagnostic window by 5-7 days when compared to antibody only assay.

positive

negative

Acute HIV-1

ORDER(draw a new sample)

Lymphocyte Subset Panel 1 -CD4 Absolute Count Only

positive

negative

HIV-1 confirmed

*negative

indeterminate 3 indeterminates over 6 months is negative

*Consider HIV-2 testing if clinically indicated

Human Immunodeficiency Virus in Infants TestingClick here for topics associated with this algorithm

SCREENINFANTS

Of HIV Positive Mothers

ORDERHuman Immunodeficiency Virus 1, PCR, Qualitative

Do not use cord bloodRepeat test at 1-2 months and 3-6 months of age

ORHuman Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR

More sensitive testDo not use cord bloodRepeat test at 1-2 months and 3-6 months of age

SCREENINFANTS of HIV-positive mothers


Primary HSV infection

HSV Infection During Pregnancy TestingClick here for topics associated with this algorithm


Acquired in first 2 trimesters

yes

2 negative cultures and no active lesions

Sequential viral cultures from 32nd week

Vaginal delivery C-section

Vaginal delivery in progress

Maternal and neonatal acyclovir

treatment

Recommend C-section

Recurrent HSV infection

Genital lesions during first 2 trimesters

C-section recommended if

prodromal syndromes or lesions active at

time of delivery

Antiviral treatment in last 4 weeks of pregnancy

Sequential viral cultures on cervical vaginal secretions starting 36th week

Positive cultures

C-section

C-section Vaginal delivery

Active genital lesions

no

yes no

yes no

yes no

yes no

yes no

Note: If there is rupture of membranes for either primary or recurrent HSV and fetal lungs are mature, C-section should occur within 4-6 hours of membrane rupture.

If fetal lungs are immature, no guidelines exist; however, antivirals are recommended until delivery.

ORDERHuman T-Lymphotropic Virus Types I/II Antibodies with Reflex to HTLV I/II Confirmation

CONFIRMATIONORDER

Human T-Lymphotropic Virus Types I/II Antibodies, Western Blot(This test is also part of reflex from Human T-Lymphotropic Virus Types

I/II Antibodies with Reflex to HTLV I/II Confirmation but can be ordered separately)

negative rgp 46-1, p19 & GD21rgp 46-11,

p24 & GD21rgp 46-1, rgp 26-11, p24, p19 & GD21

At least 2 of p23, GD21, p19 in combination with any other

viral bands, but not rgp 46-1 or rgp 46-11

Any combination of bands (including rgp 46-1 and/or rgp 46-11) but only one of p24,

GD21 or p19

HTLV I/II confirmed

See above bands for typing

ORDERHuman T-Lymphotropic Virus Types I/II Antibodies, Western Blot repeat 2 weeks after initial testing to

reassure patient and/or 3 months after initial testing to meet CDC requirements

Human T-Lymphotropic Virus Types I and II TestingClick here for topics associated with this algorithm

No HTLV I or II

No HTLV I or II:

likely false-positive

HTLV I HTLV II HTLV I/HTLV II Untypable

Two indeterminates =

negative

False-positiveNo HTLV I or II

INDICATIONS FOR TESTING

Patient with risk factorsIV drug useResidence in endemic areaMultiple sexual partnersBlood transfusion history

Patient symptomaticDisease processes:

Adult T-cell leukemia or lymphomaParaparesis (and from at-risk country of origin)Undiagnosed myopathy

negative positive


negative positive

indeterminate

indeterminate

INDICATIONS FOR TESTINGSuspicion of primary aldosteronism

Manifestations: hypertension, hypokalemia, metabolic alkalosis

Hyperaldosteronism TestingClick here for topics associated with this algorithm


ORDERAldosterone/Renin Activity Ratio

ORAldosterone & Renin, Direct with Ratio

(both are best assessed in the morning)

Plasma aldosterone (ALDO)/renin activity (PRA) ratio 10 ng/dL

Urine aldosterone 14 g/24 hr OR

Plasma aldosterone 10 ng/dL

Primary aldosteronism

Essential hypertension likely

Adrenal CT scan (MRI does not add to sensitivity)

equivocal

Serum sodium normal or moderately elevated

Plasma aldosterone 5-10 ng/dL

Repeat testing in 3 months

APA or PAH: Unilateral

laparoscopic adrenalectomy

yesBilateral AVS no

Normal, micronodularity or bilateral masses

Unilateral hypodense nodule >1 cm but 40 years

Lateralization

yesno

positive

yesno

IHA GRA

Abbreviation Key

APA aldosterone-producing adenomaAVS adrenal venous samplingCT computed tomographyGRA glucocorticoid-remediable aldosteronismIHA idiopathic hyperaldosteronismMRI magnetic resonance imagingPAH primary adrenal hyperplasia

Consider genetic testing for GRA

Confirm sodium loading with Urine, 24 Hr

Na+ >200 mmol

INDICATIONS FOR TESTINGHypercalcemia

(defined as serum calcium 10.3 mg/dL)

Hypercalcemia TestingClick here for topics associated with this algorithm

ORDERParathyroid Hormone,

Intact

low high

Primary hyperparathyroidism

Vitamin D excessCancers

Milk-alkali SyndromeHyperthyroidism

ORDERParathyroid Hormone-

Related Peptide (PTHrP)

low or normal high

Cancer ORDERVitamin D, 1, 25-Dihydroxy

low high

Cancer Lymphoma or granulomatous

disease (sarcoidosis)


Confirm hypercalcemiaORDER

Calcium, Serum or Plasma(add Albumin by Nephelometry on LTD, if not

previously tested)OR

Calcium, Ionized, Serum

Hypercalcemia confirmedClinical evaluation to rule out other causes, such as metastatic disease

ORDERCalcium, Urine

high (>100)

low(

Hypocalcemia Testing


INDICATIONS FOR TESTINGSuspect hypocalcemia

Symptoms: muscle cramping, tetany, tingling

ORDERCalcium, Serum or PlasmaAlso order:

Phosphorus, Inorganic, Plasma or SerumAlbumin, Serum by SpectrophotometryMagnesium, Plasma or SerumCreatinine, Serum or Plasma

ORDERParathyroid Hormone,

Intact

Renal disease or

Pseudohypoparathyroidism

ORDERVitamin D, 25-

Hydroxy

Magnesium deficiency Hypoparathyroidism

Hypoalbuminemia(Pseudohypocalcemia) Vitamin D deficiency

LOW CORRECTED CALCIUMCorrected calcium = measured total calcium +0.8 (4.0 - serum

albumin)

normal

Magnesium low

Magnesium normal

Albumin low

low

highlow

Creatinine high Phosphorus

normal or high Magnesium

normal

Creatinine normal Phosphorus low or

normal Magnesium normal

Creatinine normal Phosphorus

normal or high

Creatinine normal Phosphorus

normal or low Magnesium

normal


INDICATIONS FOR TESTINGPre-pubertal/pubertal small testes, eunuchoidal body habitus, lack of

secondary sexual characteristics, gynecomastiaPost-pubertal impotence, gynecomastia, weakness, depression,

decreased libido

Hypogonadism TestingClick here for topics associated with this algorithm

low testosteronenormal or low LH

normal or low FSH

ORDERTestosterone, Adult Male (or perform mass spectometry if pre-pubertal)

ANDLuteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)

normal testosteronenormal LH

normal FSH

normal testosteronenormal LH

elevated FSH

low testosteroneelevated LH

elevated FSH

Secondary or tertiary

hypogonadism

Normal - consider other etiologies

Seminiferous tubule disease

Primary hypogonadism


If testosterone levels are:< 200 ng/dL repeat testing with Testosterone, Adult Male200-400 ng/dL test free testosterone with Testosterone Free, Adult Male or bioavailable testosterone with Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Adult Male> 400 ng/dL normal testosterone

Hypopituitarism (Anterior Pituitary) TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGSuspected hypopituitarism (anterior pituitary)

Symptoms: fatigue, depression and other endocrine dysfunction

Baseline morning levels based on clinical presentation

ORDERThyroid Stimulating

Hormone with Reflex to Free

Thyroxine

ORDERAdrenocorticotropic

HormoneAND

Cortisol, Serum or Plasma

PERFORM Metyrapone

testing or insulin-induced

hypoglycemia with repeat ACTH

and 11-Deoxycortisol

Quantitative by HPLC-MS/MS,

Serum or Plasma

low 11-deoxycortisol

low ACTH

low 11-deoxycortisolhigh ACTH

Pituitary adrenocorticotropic hormone deficiency

Adrenal etiology

normal or low TSH low free T4

high TSH low free T4

Thyroid-stimulating hormone deficiency

Primary hypothyroidism

ORDERLuteinizing Hormone and

Follicle Stimulating HormoneAND

Testosterone, Free & Total (Includes Sex Hormone

Binding Globulin), Adult MaleOR

Estrogens, Fractionated by Tandem Mass Spectrometry

low LH/FSHlow testosterone or estrogen and high suspicion

ORDERProlactin

high low

Prolactin-induced

hypogonadism

Follicle-stimulating hormone deficiency

ORDERIGF-1 (Insulin-Like Growth Factor I)

ANDIGF Binding Protein-3

low

Insulin-induced

hypoglycemiatesting with

serial growth hormone

(GH) measurement

GH

*Immunobullous Skin Diseases TestingINDICATIONS FOR TESTING

Symptomatic adults

Paraneoplastic Pemphigus

Screen for immunobullous

diseases

Screen for immunobullous

diseases

Pemphigoid (Herpes) GestationisWill usually resolve post pregnancy if occured during pregnancyLikely to recur with subsequent pregnanciesMay also recur with other hormonal changes, including contraception

ORDERPerilesional skin biopsy for Cutaneous Direct Immunofluorescence, Biopsy

AND Paraneoplastic Pemphigus Antibody Screen

Presence of neoplastic disease

negative


Monitor for developing immunobullous disease

Consider porphyria or pseudoporphyria(perilesional skin biopsy is not specific but will not be consistent with immunobullous disease)

Repeat screening:In 3-6 months for persistent unexplained diseaseIn 6-12 weeks for rapidly evolving disease


IgA endomysial antibodies*

Cutaneous DIF skin biopsy for granular and/or fibrillar IgA

Repeat DIF skin biopsy

Dermatitis herpetiformis

Monitor treatment response withIgA endomysial* and Tissue Transglutaminase

(tTG) Antibody, IgA(or if IgA deficient Tissue Transglutaminase

Antibody, IgG)

positive

IgA basement membrane zone epidermal, dermal or

combined epidermal/dermal pattern antibodies

Linear IgA disease

Monitor treatment response with

Epithelial Basement Membrane Zone IgA

Antibodies OR

Epithelial Skin Antibody

IgG basement membrane zone antibodies

Pemphigoid

Monitor treatment response with Pemphigoid Panel - Epithelial

Basement Membrane Zone IgG & IgA, BP180 & BP230 IgG Antibodies

Epidermolysis bullosa acquisita

Monitor treatment response with

Epithelial Basement Membrane Zone IgG

AntibodiesOR

Epithelial Skin Antibody

ORDERBullous Pemphigoid (180 kDa and 230 kDa) Antigens, IgG

(BP180, BP230 antibodies)

(Note: Necessary if pemphigoid panel

testing was not ordered)

Epidermal pattern

Dermal pattern

Combined epidermal/dermal

IgG cell surface antibodies

Pemphigus

P. foliaceus(most common)

ORP. erythematosus

P. vulgaris (most common)

ORP. vegetans

Monitor treatment response withPemphigus Panel - IgG Epithelial Cell Surface

Antibodies and Levels of IgG Desmoglein 1 andDesmoglein 3 Antibodies, Serum

IgA Pemphigus

Monitor treatment

response withPemphigus IgA

Antibodies

positivenegative

negative

Desmoglein 3 increased

Desmoglein 1 increased

Screen for Immunobullous Diseases (pemphigus, pemphigoid, epidermolysisbullosa acquisita, linear IgA disease, or dermatitis herpetiformis)

HistologyPerilesional skin biopsyCutaneous Direct Immunofluorescence, BiopsySerology

Pemphigus Panel IgG Epithelial Cell Surface Antibodies and Levels of IgG Desmoglein 1 and Desmoglein 3 Antibodies, SerumPemphigoid Panel Epithelial Basement Membrane Zone IgG & IgA, BP180 & BP230 IgG AntibodiesTissue Transglutaminase (tTG) Antibody, IgA with Reflex to Endomysial Antibody, IgA by IFA (alternative test: Celiac Disease Dual Antigen Screen with Reflex)

OREpithelial Skin Antibody AND Tissue Transglutaminase (tTG) Antibody, IgA with Reflex to Endomysial Antibody, IgA by IFA

positive, titer >1:10

negative positive

ORDERIgG Desmoglein 1 &

Desmoglein 3(Note: Necessary if

pemphigus panel testing was not ordered)

positive

IgA cell surface antibodies

ORDERPemphigus IgA

Antibodies as additional or separate test for

suspected IgA pemphigus

ORDERPerilesional skin biopsy for Cutaneous Direct Immunofluorescence, Biopsy

ANDHerpes Gestationis Factor (IgG Complement-Fixing Basement Membrane Zone Antibodies) and IgG BP180 antibody level

Pregnant female, typically 2nd or 3rd trimester

For Endomysial Antibodies, a screening IgA tissue transglutaminase assay (ELISA) can be ordered OR request Endomysial Antibody test by indirect immunofluorescence (IgA and/or IgG) with or without accompanying IgA and/or IgG tissue transglutaminase assay through the Immunodermatology Laboratory.

negative positive

Jewish Genetic Diseases Carrier Screening AlgorithmClick here for topics associated with this algorithm

Test partner for Sandhoff carrier status

INDICATIONS FOR TESTINGFrench Canadian ancestryLouisiana Cajun ancestryPositive family history for Tay-Sachs diseasePartner is a confirmed carrier of Tay-Sachs disease

INDICATION FOR TESTINGAshkenazi Jewish ancestry

INDICATIONS FOR TESTINGFamily history of a Jewish genetic disorder other than Tay-Sachs Partner is a carrier of a Jewish genetic disorder other than Tay-Sachs

Offer DNA testing to assess carrier status for the familial

disorder or for the disorder for which the partner is a carrier

ORDERTay-Sachs (HEXA) 7

Mutations

noyes

ORDERAshkenazi Jewish Diseases (BLM, ASPA, IKBKAP,

FANCC, GBA, MCOLN1, SMPD1, HEXA) AND

Cystic Fibrosis (CFTR) 32 Mutations

Targeted molecular analysis for 9 disorders common in individuals of Ashkenazi Jewish descent

Canavan diseaseCystic fibrosisFamilial dysautonomiaTay-Sachs diseaseBloom syndromeFanconi anemia type CMucolipidosis IVNiemann-Pick disease type AGaucher disease

ORDERHexosaminidase A Percent and Total Hexosaminidase, Plasma or Serum (for

males, non-pregnant women and women not taking oral contraceptives)OR

Hexosaminidase A Percent and Total Hexosaminidase in Leukocytes (for pregnant women or women taking oral contraceptives)

Comprehensive Ashkenazi Jewish carrier testing desired

Screening for Tay-Sachs disease only

Hexosaminidase A enzyme quantitation indicates noncarrier

Hexosaminidase A enzyme quantitation is inconclusive or

indicates carrier

Hexosaminidase A & total enzyme quantitation indicates possible

Sandhoff carrier

No mutation detected

Mutation detected (carrier)

Pseudo-deficiency mutation detected (noncarrier)

CONSIDERHEXA gene sequencingTest partner


Test partner ORDER

Hexosaminidase A Percent and Total Hexosaminidase, Plasma or Serum (for males, non-pregnant women and women not taking oral contraceptives)

ORHexosaminidase A Percent and Total Hexosaminidase in Leukocytes (for

pregnant women or women taking oral contraceptives)

INDICATIONS FOR TESTINGLiver disease of unknown etiology (all viral serologies negative,

elevated transaminases)

ANA and/or F-actin/SMA + LKM-1 +

M2 +(Note: ANA may be positive in some individuals who test

positive for the anti-mitochondrial antibody)

AIH-1PSC is also a

possibilityAIH-2 PBC

ORDERAnti-Neutrophil Cytoplasmic Antibody, IgGSoluble Liver Antigen Antibody, IgG

pANCA + (Atypical)

SLA -

SLA +ANCA -

AIHPSCUC

AIH-1AIH-3

CCHAIC

Disease key

AIC Autoimmune cholangitisAIH Autoimmune hepatitisCCH Cryptogenic chronic hepatitisPBC Primary biliary cirrhosisPSC Primary sclerosing cholangitisUC Ulcerative colitis

Test key

ANA Anti-nuclear antibodyLKM-1 Liver-kidney microsome 1 (cytochrome P450 2D6)M2 Mitochondrial antigen 2 (PDH-E2)pANCA Perinuclear antineutrophil cytoplasmic antibodySLA Soluble liver antigenSMA Smooth muscle antibody

Liver Disease or Hepatitis of Unknown Etiology TestingClick here for topics associated with this algorithm

ORDERAutoimmune Liver Disease Evaluation with Reflex to Smooth Muscle Antibody (SMA), IgG by IFA

OR Individual tests:

F-Actin (Smooth Muscle) Antibody, IgG by ELISA with Reflex to Smooth Muscle Antibody, IgG TiterAnti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA

Liver-Kidney Microsome-1 Antibody, IgGMitochondrial M2 Antibody, IgG (ELISA)


negative

positive negative

positive

ORDERAnti-Neutrophil Cytoplasmic

Antibody, IgG,if PSC suspected

Suggests PSC

Perform cholangiography

positive

If PSC suspected perform

cholangiography

pANCA + (atypical)

INDICATIONS FOR TESTINGHistology positive for lung cancer

Lung Cancer Molecular TestingClick here for topics associated with this algorithm


Non-small cell lung cancer (NSCLC)

(testing most useful in adenocarcinoma subtypes)

Small cell lung cancer (SCLC)

Do not perform molecular testing

no

ORDERKRAS Mutation Detection

ORDER

ALK (D5F3) with interpretation by Immunohistochemistry

ANDROS1 with Interpretation by Immunohistochemistry

with Reflex to FISH if Equivocal

Wild-type EGFR Nonresponsive to TKIs

Nonresponsive to ALK-inhibitorsResponsive to ALK-inhibitors

yes no

Yes* no

ALK or ROS1 expression positive

Mutation positive

* Tumor with ALK rearrangement is generally mutually exclusive for EGFR or KRAS mutations

ORDEREGFR Mutation Detection by

Pyrosequencing

Yes*

Mutation positive

Nonresponsive to EGFR TKIs

EGFR TKI responsiveness likely

4 weeks after onset of disease

ORDERFull meningitis workup (CSF studies)

ANDBorrelia burgdorferi Antibodies, Total by ELISA (CSF)

OR CONSIDERBorrelia burgdorferi C6 Peptide Antibodies, Total by ELISA (CSF)

ANDBorrelia burgdorferi Antibodies, IgG and IgM by Western Blot (CSF)Consider Borrelia Species by PCR (Lyme Disease)


IgG -IgM +

CNS disease confirmed

No further testing on initial specimen

Test convalescent sample

No further testing on initial specimen

Test convalescent sample

negative

negative

Lyme disease

IgG - IgG +

positive

positive or indeterminate

chronic acute

positivenegative

Lyme disease

Lyme disease highly unlikely; if high suspicion, consider

referral to infectious disease specialist

Follow-up IgG Western Blot (within 30 days) recommended to help confirm Lyme disease/rule out false positive IgM Western Blot

IgG +IgM -

Lyme disease

INDICATIONS FOR TESTINGElevated white blood cell count and lymphocytes

ORAbnormal manual differential results

Absolute lymphocytosis >4,000/L or abnormal morphology

B-cell lymphoproliferative

disorderT-cell LGLL

NK-cell LGLL

Consider the following: Follicular lymphoma Burkitt lymphomaSome diffuse large B-cell lymphomas

Hairy cell leukemia

CLL/SLL Mantle cell lymphoma

CONSIDERIGH-CCND1 Fusion, t(11;14) by FISH IGH-CCND1 (BCL-1/JH) Translocation, t(11;14) by PCRChromosome FISH, Interphase on fresh tissue

Large granular lymphocytic leukemia

(LGLL)

ORDER

Leukemia/Lymphoma Phenotyping by Flow Cytometry

CONSIDERIGHV Mutation Analysis by Sequencing ZAP-70 Analysis by Flow CytometryChromosome FISH, CLL Panel


Apparent reactive cause(infection, post-splenectomy)

Considerreactive lymphocytosis positive findings

Consider Szary syndrome

Consider anaplastic large-cell lymphoma

Consider peripheral T-cell lymphoma NOS

Angioimmunoblastic T-cell lymphoma

CD10+ CD4+

CD4+CD7-CD26-

CD4+/-CD8+/-

CD30+

Aberrant T-cell or NK-cell phenotype

Manage cause and recheck

white blood cell count

Unexplained persistence

CD19+ and/or CD20+ Light chain restriction

CD57-, CD56-, and CD16-

At least 1 positive: CD56, CD57, or CD16

no

Consider other etiologies:Viral (Epstein Barr virus, cytomegalovirus, HIV, HTLV, hepatitis, HHV8) Other (tuberculosis, Rickettsia, brucella, toxoplasmosis, syphilis, Babesia)

Infectious cause

Manage and recheck white blood

cell count

No infectious causeObserveConsider drug-induced hyperthyroidism, autoimmune thyroid disease, thymoma

CD3+CD3-

Follow-up T-cell clonality testing:T-Cell Clonality Screening by Next Generation SequencingT-Cell Clonality by Flow Cytometry Analysis of TCR V-BetaT-Cell Clonality Screening by PCR

CONSIDERIGH-BCL2 (BCL-2/JH) Translocation, t(14;18) by PCRChromosome FISH, InterphaseIGH-BCL2 Fusion, t(14;18) by FISHIGH/MYC t(8;14) by FISHMYC (8q24) Gene Rearrangement by FISHLymphoma (Aggressive) Panel by FISHBCL6 (3q27) Gene Rearrangement by FISH

CD5-CD10+

CD5-CD10-

CD11c+ CD25+CD103+

In immunocompromised patients (eg, post-transplant), consider EBV testing

Epstein-Barr Virus by PCREpstein-Barr Virus (EBV) By in situ Hybridization, Paraffin

Lymphoma Leukemia Phenotyping TestingClick here for topics associated with this algorithm

Dim CD20CD23+

Low light chain intensity

Bright CD20CD23-

High light chain intensity

CD5+CD10-

yes

Lynch Syndrome Testing(HNPCC)


INDICATIONS FOR TESTINGTumors from individuals should be tested for microsatellite instability in the following situations (based on Revised Bethesda Guidelines for testing colorectal tumors for microsatellite instability):Colorectal cancer diagnosed in an individual


Food intoleranceSubstance tolerance test (eg, Lactose Tolerance

test)abnormal

Carbohydrate malabsorption tolerance

test; (14C)-D-xylose breath test

Measurement of 7 alpha-hydroxy-4-cholesten-3;

SeHCAT test

CONSIDERCeliac Disease Reflexive Cascade

ORImmunoglobulin ATissue Transglutaminase Antibody, IgGTissue Transglutaminase (tTG) Antibody, IgA

abnormal

abnormal

Bacterial fermentation

disorder

Ileal diseaseOR

Bile acid malabsorption

Celiac disease

CONSIDERPancreatic Elastase,

Fecalabnormal Pancreatic insufficiency

Other potential testing: Fat, Fecal Quantitative, Homogenized AliquotXylose Absorption Test (Adult 5 g dose)Xylose Absorption Test (Adult 25 g dose)Xylose Absorption Test (Child)

Biopsy of intestinepositive

positive

Possible Disorders:Gallbladder diseaseLiver diseasePancreatic diseaseAbdominal adenopathyGynecologic cancer (eg, ovarian)

Abdominal ultrasound or CT scan

Possible Disorders:Pancreatic diseaseBiliary disease

Lower bowel endoscopy and biopsy

Secretory function and endoscopic retrograde

pancreatography (ERCP)

normal

normal

Possible Disorders:Celiac diseaseTropical sprueCollagenous sprueWhipple diseaseInflammatory bowel diseaseParasites (eg, giardia)Eosinophilic enteritisPrimary intestinal lymphomaPrimary intestinal lymphangiectasisImmunodeficiency syndromeA-b-lipoproteinemia

Follow up in 6 weeks

normal

abnormal

abnormal

INDICATIONS FOR TESTINGChronic diarrhea

Steatorrhea

ORDERScreening blood tests:

CBC with Platelet CountElectrolyte PanelSedimentation Rate, Westergren (ESR)Liver enzymes including albumin (Alanine Aminotransferase, Serum or Plasma; Aspartate Aminotransferase, Serum or Plasma; Albumin, Serum by Nephelometry)Thyroid Stimulating Hormone with Reflex to Free Thyroxine

In addition, include:Fecal tests:

Occult Blood, Fecal by ImmunoassayFecal Leukocytes (Lactoferrin, Fecal by ELISA)Fat, Fecal QualitativeClostridium difficile toxin B gene (tcdB) by PCR (if risk factors present)Ova and Parasite Exam, Fecal (Immunocompromised or Travel History)

Consider celiac serologies (see below)

abnormal

Proceed using best judgment based on clinical presentation

Consider tests below

normal

Malabsorption TestingClick here for topics associated with this algorithm

negative

negative

Consider rebiopsy or another disease

process

CONSIDERDisaccharidase, Tissue abnormal

Disaccharidase deficiency

abnormal

Megaloblastic Anemia TestingClick here for topics associated with this algorithm

Occasionally, clinician may find normal levels of B12 in symptomatic patients (usually neurologic symptoms)

MMA and homocysteine may be appropriate to confirm B12 deficiency, as homocysteine may have a role in detecting folate or B12 deficiency

INDICATIONS FOR TESTINGPatient presents with megaloblastic anemia and/or neurologic symptoms

ORDERVitamin B12 & Folate

ORDERMethylmalonic Acid, Serum

or Plasma (Vitamin B12 Deficiency)

ORDERIntrinsic Factor Blocking Antibody

ORDERGastric Parietal Cell

Antibody, IgG

ORDERGastrin

Folate deficiency


Optional antibody testing when MMA >0.4 mol/L (MMA >0.4 mol/L confirms B12 deficiency )

Vitamin B12 >400 pg/mL Vitamin B12 100-400 pg/mL Low folate levels only

Not pernicious

anemia

Pernicious anemia

Pernicious anemia

Not pernicious anemia

Pernicious anemia(indirect confirmation)

positive

100 pg/mL

negative

Nofolate deficiency

Low or normal folate levels and high suspicion

for deficiency

ORDERFolate, RBC

ORDERMethylmalonic Acid, Serum or Plasma (Vitamin B12 Deficiency)Homocysteine, Total

0.4 mol/L

Low

Normal

Vitamin B12

Nephrolithiasis TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGFlank pain, nausea/emesis, symptoms of a stone

ORDERUrinalysis, Complete

yes

Consider CT scan, however may

consider treatment with close

observation


Hematuria

no

High suspicion of stone Fever

yesno

CT scan to rule out obstruction

yesno

Nephrolithiasis likely

ORDERCBC with Platelet Count

and Automated Differential

Leukocytosis and leukocytes on urinalysis

yesno

Pyelonephritis less likely; obstruction possible

Suspect pyelonephritis or concomittant infection

Perform other testing Helical CT scan

If confirmation required, do CT scan; otherwise, treat symptomatically

Strain urine for stone; send for stone

analysis

positivenegative

Strain urine for stone; send for Calculi (Stone)

Analysis; consider 24 hour urine analysis,

particularly if not first stone

For first stone, usually no

workup initially necessary

If acute HIV-1 or HIV-2 is suspected ORDER

Human Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/0/2) by ELISA, with Reflex to HIV-1/HIV-2

Antibody Differentiation by Multispot

Negative for HIV-1 and HIV-2 antibodies and p24 Ag

New CDC Proposed HIV Diagnostic AlgorithmClick here for topics associated with this algorithm


repeatedly reactive

HIV-1/HIV-2 antibody differentiation immunoassay(Multispot)

(Combo assay reflexes to differentiation test)

HIV-1 (+)HIV-2 (-)

(-)

Note: New HIV diagnostic algorithm was proposed by the CDC in 2010 and officially published in the CLSI (Clinical and Laboratory Standards Institute) document - M-53A: Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection: Approved Guideline in 2011.

HIV-1 (-)HIV-2 (+)

HIV-1 (+)HIV-2 (+)

HIV-1 (-)HIV-2 (-)

Consider HIV-2 NAAT testing for

resolution

Reported as positive; cannot

differentiateHIV-1 from HIV-2

Reported as positive for

HIV-1

Reported as positive for

HIV-2

HIV-1 (indeterminate)HIV-2 (-)

Reported as indeterminate for

HIV-1

Acute HIV-1 infection

Redraw the sample

ORDERHIV-1 NAAT testing

Negative for HIV-1

(+) (-)

Reported as indeterminate for

HIV-1

Pheochromocytoma TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGPatient with:

New onset hypertensionDiaphoresisAdrenal abnormalityTachycardia

INDICATIONS FOR TESTINGPatient with:

Family history of MEN2von Hippel-Lindau syndromeFamilial paraganglioma syndrome Neurofibromatosis type 1

ORDERMetanephrines, Plasma (Free)

ORMetanephrines Fractionated by

HPLC-MS/MS, Urine

ORDERMetanephrines, Plasma (Free)


HPLC-MS/MS, Urine

moderate to very elevated concentrations

Proceed with CT/MRI of abdomen and pelvis

mildly elevated or indeterminate

High suspicion for pheochromocytoma

tumor visualized

Metaiodobenzylguanidine scan (MIBG)

ORPET using 18F-FDG or

18F-DOPA

not elevated

not elevated

Repeat testing: Metanephrines, Plasma (Free)


HPLC-MS/MS, Urine

Pheochromocytoma unlikely; if high

suspicion exists, repeat testing in 3-6

months


elevated

Consider genetic testing; refer to Paraganglioma/Pheochromocytoma Molecular Testing Algorithm

no yes

Evaluate potential false positives (influence of diet, medications, inappropriate

sampling conditions)

If suspicion still exists for pheochromocytoma, consider additional

evaluation

Pheochromocytoma unlikely; if high

suspicion exists, repeat testing in 6-

12 months

Pheochromocytoma likely

Paraganglioma Pheochromocytoma Molecular TestingClick here for topics associated with this algorithm

Recommendations for genetic testing for paraganglioma/pheochromocytomaGenes in the boxes are most likely to account for the clinical picture, but clinical presentation for hereditary paraganglioma-pheochromocytoma syndromes can be highly variable and a genetics consultation is recommended

Clinical evaluation

Syndromic (personal or

family history of below findings)


Family history consistent with a parent-of-origin effect--predisposition to paraganglioma/pheochromocytoma

only with paternal transmission

Multiple paraganglioma

Single paraganglioma

SDHB immunohistochemistry

SDHB*, SDHC*, SDHD*, SDHA, SDHAF2

SDHD* MAX** SDHAF2**

NF1Neurofibromas, optic glioma,

Lisch nodules, caf au lait spots

Medullary thyroid cancer, parathyroid hyperplasia/

adenoma

Renal cysts/carcinoma,hemangioblastoma,

endolymphatic sac tumor

Parathyroid, pituitary, and/or gastro-entero-pancreatic

tumors; facial angiofibromas, collagenomas

Erythrocytosis

RET

VHL

EGLN1

MEN1

SDHB*, SDHD, SDHC, MAX, RET, TMEM127, VHLMalignant

Extra-adrenal sympathetic

Extra-adrenal abdominal

Pheochromocytoma

Head or neck

SDHB*, SDHD, VHL,

SDHB*, TMEM127

SDHD*, SDHC*, SDHAF2, SDHA, SDHB, TMEM127

SDHB*, SDHD*, TMEM127, VHL

Absent expression

Malignant

Bilateral pheochromocytoma

Head and/or neck

SDHB*, SDHD, SDHC, MAX, TMEM127

SDHD*, SDHB, SDHC, SDHAF2, TMEM127, SDHA

TMEM127

Increased epinephrine

Increased norepinephrine VHL

RET

References:1. Opocher G and Schiavi F. Genetics of pheochromocytomas and paragangliomas. Best Pract Res Clin Endocrinol Metab 2010 Dec;24(6):943-56.2. Mannelli M et al. Clinically guided genetic screening in a large cohort of Italian Patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. J Clin Endocrinol Metab 2009 May;94(5):1541-7.3. Baysal BE. Clinical and molecular progress in hereditary paraganglioma. J Med Genet 2008 Nov;45(11):689-94.4. Karasek D, Frysak Z, and Pacak K. Genetic testing for pheochromocytoma. Curr Hypertens Rep 2010 Dec;12(6):456-64.5. Burnichon N et al. The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 2009 Aug;94(8):2817-27. Comino-Mendez et al. Exome sequencing identifies MAX mutations as a cause of hereditary

pheochromocytoma. Nature Genetics 2011 July; 43(7): 663-669.6. Welander J, Soderkvist P, and Gimm O. Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocrin-Related Cancer 2011 Dec;18(6):R253-76.

Note:* Gene(s) most likely to account for phenotype** Supporting literature is limited

AND

Plasma Cell DyscrasiasClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGBone pain, recurrent infections, anemia,

lytic lesions on plain film

Perform baseline testing1. CBC with Platelet Count and Automated Differential2. Metabolic profile, which should include

A. Calcium, Serum or PlasmaB. BUN/creatinine, Serum or PlasmaC. Protein, Total, Serum or PlasmaD. Albumin, Serum or Plasma by Spectrophotometry

3. Lactate Dehydrogenase, Serum or Plasma

Rule out1. Chronic infections such as HIV2. Immunoglobulin deficiencies such as CVID3. Chronic inflammatory processes such as

systemic lupus erythematous, liver disease4. Other malignancies

If all negative

ORDERProtein Electrophoresis with Reflex to Immunofixation Electrophoresis Monoclonal Protein Detection, Quantitation & Characterization, IgA, IgG, & IgM, Serum24 hr urine protein electrophoresis

ORMonoclonal Protein Detection Quantitation & Characterization, SPEP, IFE, IgA, IgG, IgM, Serum (Protein electrophoresis with reflex testing may occasionally miss IgA MGUS or multiple myeloma)Urine immunofixation electrophoresis

Serum M protein

Normal baseline testing

Abnormal baseline testing

ORDERSerum free light chain ratio (Kappa/Lambda Quantitative Free Light Chains with Ratio,

Serum) to diagnose oligosecretory myeloma and non-secretory myeloma

Normal FLC ratio

Abnormal FLC ratio

Monoclonal gammopathy

of undetermined significance

(MGUS)

Repeat evaluation in 3-6 months

ORDERBone marrow biopsy

Skeletal survey

Paraneoplastic Neurological Syndromes Testing

INDICATIONS FOR TESTINGPatient presenting with symptoms that are suspicious for

paraneoplastic neurological syndromes (PNS)

Known malignancy

no

PNSconfirmed

Test for antibodies suggested by clinical symptoms

yes

PNS confirmedEvaluate for most common tumors

associated with the syndrome based on

age, sex


yes

Test for antibodies that support clinical symptoms and type of

tumor present

Well characterized onconeuronal antibodies

presentAntibodies

present

nono yes

Evaluate for other possible complications

related to cancer Consider CSF and electrolyte testing,

EMG, muscle biopsy, MRI/PET

PNS possible but evaluate for other

disorders associated with neurologic

symptoms (eg, chronic infections, metabolic

encephalopathy)

none

Evaluate with other neurologic testing (EMG, muscle biopsy, CT,

MRI) to look for tumor and/or neurologic diagnosis

positivenegative

Reevaluate in 6 months or sooner

depending on symptoms

PNS probably present, antibody negative

syndrome

Antibody Testing AvailableParaneoplastic Antibodies (PCCA/ANNA) by IFA with Reflex to Titer and Immunoblot*

Panel includes the followingPurkinje Cell/Neuronal Nuclear IgG ScreenNeuronal Nuclear Antibody (ANNA) IFA Titer, IgG Purkinje Cell Antibody, Titer Neuronal Nuclear (Hu, Ri, and Yo) Antibodies IgG by Western Blot*

Neuronal Nuclear (Hu, Ri, and Yo) Antibodies IgG by Western Blot*Amphiphysin Antibody, IgGVoltage-Gated Calcium Channel (VGCC) AntibodyVoltage-Gated Potassium Channel (VGKC) Antibody

* Well-characterized antibodies


Porphyrias TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGClinical suspicion of porphyrias

Symptoms:Cutaneous photosensitivityCutaneous bilsters

Consider PCT

Consider EPP

ConsiderCEP

ORDERErythrocyte

Porphyrin, (EP) Whole Blood

ORDERPorphyrins &

Porphobilinogen (PBG), Urine

Consider acute porphyriaAIPHCPVP

ORDERPorphobilinogen (PBG),

Urine

negative positive

Repeat testing when symptoms are present

ORDERPorphyrins, Fecal

AIP

Adult

strong suspicion

Consider ADP (rare)

AbbreviationsDisordersADP Aminolevulinic acid

dehydratase deficiency porphyria

AIP Acute intermittent porphyriaCEP Congenital erythropoietic

porphyriaEPP Erythropoietic protoporphyria HCP Hereditary coproporphyria PCT Porphyria cutanea tarda VP Variegate porphyria

ORDERAminolevulinic Acid

(ALA), Urine

positive

ADPprobable

negative

Other testingPorphyrins, Fecal

May considerErythrocyte Porphyrin (EP) Whole BloodZinc Protoporphyrin (ZPP), Whole Blood


Symptoms:Neurological Abdominal

ANDCutaneous photosensitivity

Symptoms:Neurological Abdominal

Consider HCPVP

Child

Other suggested testingZinc Protoporphyrin (ZPP) Whole BloodEnzymatic and mutation analysis

Confirmatory testing Porphobilinogen (PBG) Deaminase, ErythrocyteMutation analysis

positive*

HCP or VP

Porphyrins, Total, Plasma

or Serum

HCP

positive urine porphyrins,*

negative PBG

PCT

Porphyrins, Total, Plasma or Serum

*Interpretation by medical expert necessary to distinguish the overproduction in the heme pathway

positivepositive*

CEPEPP

Pseudoporphyria, immunobullous disease

or connective tissue disease possible

CONSIDERSkin biopsy for direct immunofluorescence and serum for indirect immunofluorescenceConnective tissue disease workup

negative

Repeat testing when

active symptoms are present

positive*

VP

Monitor disease Porphyrins, Total, Plasma or Serum

Other testingPorphyrins, Fecal

Patient presents in 1st trimester Patient presents in 2nd trimester

Sequential Screen, Specimen #1First Trimester Screen

Note: Regardless of screen results, 2nd trimester AFP (Only) should be offered

low riskhigh risk

Low risk pending 2nd specimen

Low risk for DS or T18

Genetic counseling with NIPT or amniocentesis/CVS

Integrated Screen, Specimen #1

Quad Screen

low risk

Low risk for DS, T18, and ONTD; no further testing

recommended

Sequential Screen, Specimen #2

low riskhigh risk

Level II US to confirm dating and presence of twins and/or fetal/placental abnormalities

If EDD changes by 10 or more days based on US (Quad and Serum

Integrated only) recalculate

Integrated Screen, Specimen #2

high risk

Genetic counseling with NIPT or amniocentesis

EDD is correct within 10 days

SECOND TRIMESTER:

FIRST TRIMESTER:


AFP Alpha Fetoprotein, CRL Crown Rump Length, CVS Chorionic Villus Sampling, DIA Dimeric Inhibin A, DR Detection Rate, DS Down Syndrome, hCG Human Chorionic Gonadotropin, NIPT Non-Invasive Prenatal Testing, NT Nuchal Translucency, ONTD Open Neural Tube Defect, PAPP-A Pregnancy-Associated Placental Protein A, Pt Patient, SPR Screen Positive Rate, T18 Trisomy 18, uE3 Unconjugated Estriol

Prenatal Screening and Diagnosis(Based on ACOG screening recommendations, 2007;ACOG Committee Opinions Recommendations, 2012)


LOW RISKPt 3.5mm and aneuploidy screens are negative, offer patient genetic counseling with NIPT or amniocentesis/CVS; targeted US or fetal echo or both

Pretest counseling/assess patient risk for fetal aneuploidy

Primary Amenorrhea TestingClick here for topics associated with this algorithm

INDICATIONS FOR TESTINGLack of menstrual flow by age 14 and absence of secondary sexual characteristics

or lack of menstrual flow by age 16 and presence of secondary sexual characteristics

Physical and pelvic examination May also consider pelvic ultrasound if unable to confirm presence of uterus

2006 ARUP Laboratories. All rights reserved. Revised 03/27/2014 www.arupconsult.com

Transverse vaginal septumImperforate hymenAbnormal cervical os Other vaginal abnormality (5%)

anatomic abnormality

normal

ORDERThyroid Stimulating Hormone with Reflex to Free ThyroxineProlactinLutenizing Hormone, Folicle Stimulating Hormone

TSH, prolactin

Uterus presentUterus absent

ORDERTestosterone, Free and Total

(Includes Sex Hormone Binding Globulin), Females or Children

normalelevated

normalhigh

Androgen insensitivity

46,XY 46,XX 45, X and variants

5 alpha reductase deficiency

Rokitansky Kster

syndrome

Ulrich Turner

syndrome

Primary ovarian failure

X-chromosome abnormality Turner syndromeFSH receptor deficiencyAutoimmune gonadal destruction

Functional hypothalamic amenorrhea

Eating disorder, exercise, weight lossStress, chronic illnessDelayed puberty (20%)Gonadotropin releasing hormone (GNRH) deficiency (20%) consider MRI Pituitary disorders (2%) consider MRIMedication-induced (chemotherapy, oral contraceptives, antidepressants, antipsychotics)

hypertension

Consider 17-hydroxylase deficiency

Androgen-secreting tumor

ORDERDehydroepiandrosterone

Sulfate, SerumDHEAS elevated

ORDERChromosome Analysis

ORDERBeta-hCG, Urine Qualitative or

Beta-hCG, Serum Qualitative to exclude pregnancy

Positive

Pregnant

Negative

Elevated prolactin

Perform an MRI on the head

Abnormal TSH

Thyroid Disease

ORDERTestosterone, Free and Total

(Includes Sex Hormone Binding Globulin), Females or Children

elevatedNot elevated

Consider PCOS

Are one of the following symptoms present?

vi

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