pyrexia of unknown origin in children

7/30/2019 pyrexia of unknown origin in children

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PYREXIA OF UNKNOWN

ORIGIN


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FEVER WITHOUT A FOCUS Refers

to rectal temperature of 38C or higher

as the sole presenting feature.

fever without localizing signs and

fever of unknown origin aresubcategories of fever without a focus.

FEVER WITHOUT LOCALIZING SIGNS-Fever of acute onset, with duration of 38C Duration of >3 weeks

Evaluation- >2 outpatient visits or

1 wk in hospital.

Infection, malignancy, collagenvascular disease, undiagnosed,habitual hyperthermia.


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HEALTH CARE-ASSOCIATED

FUO

Temperature > 38C Duration > 1 week

Not present or incubating on admission

Health care associated infections

Post operative complications Drug fever


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IMMUNEDEFICIENT FUO

Temperature 38C in pt whoseneutrophil count is 1 week

Negative cultures after 48 hours

Majority due to infections but causedocumented in 40-60% cases.


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HIV RELATED FUO

Temperature 38C > 3 weeks for outpatient s

> 1 week for inpatients

HIV infection confirmed

HIV primary infection, typical and atypical

mycobacterial infections, CMV,toxoplasmosis, cryptococcosis, Immunereconstitution inflammatory syndrome.


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ETIOLOGYCommonest cause of FUO is a common disease

presenting in atypical way.

Rare causes are rare.1.Infections (most common cause)

account for > 1/3rd cases

Bacterial infections (imp ones being typhoid, tuberculosis,brucellosis) and infection syndromes like UTI, osteomyelitis arethe most common etiologies.

Among viral Infectious mononucleiosis is imp cause; parasaticinfections like malaria, leishmaniasis are imp causes.

Fungal causes rare

2.Collagen vascular ds. (2nd most common cause)

3. Neoplasms

4. Other causes :Hypersensitivity diseases

Granulomatous diseases

Familial hereditary diseases

Miscellaneous(factitious fever, drug fever)

Diagnosis could not be established in some cases.


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INFECTIONS: Most common

cause in children.

A)SPECIFIC INFECTION :-

BACTERIAL

SalmonellosisTuberculosisBrucellosisYersiniosisMeningococcemia

Actinomycocis

Mycoplasma pneumonia


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SPIROCHETES:

Leptospirosis

Lyme disease

Relapsing fever

Rat bite fever Syphilis

CHLAMYDIA: Lymphogranuloma venerum

Psittacosis


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RICKETTSIA:

Q fever Rocky Mountain Spotted fever

Tick borne typhus

FUNGAL DISEASES:

Blastomycossis

Coccidiodomycosis

Histoplasmosis


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PARASITIC DISEASES

Malaria

Leishmaniasis

Amebiasis

Giardiasis Toxoplasmosis


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B )LOCALISED INFECTIONS:

Abscesses (Intraabdominal/retroperitoneal) ,hepatic,pelvic, perinephric, rectal, & subphrenic.

Osteomyelitis

Pyelonephritis Brain abscess

Cholangitis

Infective Endocarditis Mastoiditis

Odontogenic infection

Sinusitis


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COLLAGEN VASCULAR DISEASES:

Juvenile rheumatoid arthritis

Systemic lupus erythematous Behcet disease

Jvenile dermatomyositis

NEOPLASMS:

Leukemia

Hodgkin disease Neuroblastoma

Wilms tumur


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HYPERSENSITIVITY DISEASES:

Drug fever Hypersensitivity pneumonitis

Serum sickness

GRANULOMATOUS DISEASES:

Crohn disease

Sarcoidosis

Granulomatous hepatitis


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FAMILIAL HEREDITARY DISEASES:

Sickle cell anemia

Anhidrotic ectodermal dysplasia

Familial dysautonomia

Fabry disease

Familial mediterranean fever


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MISCELLANEOUS:

Chronic active hepatitis

Kawasaki disease

Inflammatory bowel disease

Pancreatitis Factitious fever

Pulmonary embolism

Thrombophlebitis Thyrotoxicosis


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DIAGNOSTIC APPROACH TO

FUO

Exclude:1. Protracted but waning symptoms from acute

RTI

2. Repeated but unrelated episodes of fever with

identifiable causes

Remember the cause is mostly a common diseasewithout classical presentation or with atypicalpresentation.

Reassess history and physical examination

Potentially diagnostic clues which guideinvestigations.

Sometimes wait for diagnostic clues to appear.


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Comprehensive History

Physical Examination

Lab Investigations


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HISTORY AgeRespiratory, genitourinary tract

infection, localized infection, JIA are morecommon in children >6 year.

- Adolescent patients are more likely tohave tuberculosis, inflammatory bowel

disease, lymphoma.

Sex chronic granulomatous diseaseBoys.

Pelvic inflammatory disease, UTI girls

Residence Leptospirosis Gujarat,Kerela, Maharashtra, Andaman & Nicobar

Leishmaniasis

Bihar & Uttar Pradesh


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FEVER

Duration, height, and pattern?

How was the fever assessed?

-By touch, forehead strip, or measured with athermometer, if measured with a thermometer, whichtype was used.

Was the fever confirmed by someone otherthan the caregiver?

Are there specific circumstances that

precede the temperature elevation?-temperature elevations after exercise or late in the

afternoon

Does the child appear ill or develop any

signs or symptoms during the febrile

R t t id l ti


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Response to nonsteroidal-anti-

inflammatory antipyretics?-Lack of response may indicate a noninflammatory

condition as the cause of FUO (eg, dysautonomia ,ectodermal dysplasia, hypothalamic dysfunction,

diabetes insipidus)

Is there associated sweating?

- Patients with fever, sweating, and heat intolerance mayhave hyperthyroidism, whereas those with fever, heat

intolerance, and absence of sweating may have

ectodermal dysplasia.


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FEVER PATTERN

a) & b)Continuousfever

c) Remittent fever

d) Intermittent fever

e) Undulant fever

f) Relapsing fever


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Associated complaints

It is important to ask, and ask again, about

past or current abnormalities orcomplaints.

Red eyes that resolved spontaneously

may suggest Kawasaki disease.Nasal discharge may suggest sinusitis.

Recurrent pharyngitis with ulcerationsmay suggest the periodic fever withaphthous stomatitis, pharyngitis, andadenitis syndrome (PFAPA).

Limb or bone pain may suggest leukemia,

osteomyelitis, or infantile cortical

G t i t ti l l i t t


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Gastrointestinal complaints may suggest

Salmonellosis, an intraabdominal

abscess,hepatosplenic cat scratch, or

inflammatory bowel disease.

Urinary complaints

Poor growth, poor appetite, and weight

loss.


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Exposure history :-Contact with infected or otherwise ill

persons. Tuberculosis

Exposure to animals: including household

pets, domestic animals in the community,and wild animals.


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Zoonoses Exposure history

Leptospirosis Exposure to contaminated water/soil; endemicareas

Brucellosis Consumption of unpasteurized dairy productsfrom an infected cow, sheep, goat or Through

contact with infected farm animals.

Toxoplasmosis Contact with cats or history of pica

Tularemia Hand contact with infected animals or theirconsumption (unusual meats like rabbit/squirrel)

Psittacosis Contact with parrots or other birds


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Travel history:

Travel history (including place of residence)

extending back to birth.

The travel history should include : The site(s) oftravel, Prophylactic medications and immunizations

before travel. Measures taken to prevent exposureto contaminated food and water.

Whether artifacts, rocks, or soil from other

geographic areas were brought into the home.

Exposure to other persons with a recent history of

travel.


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Diet History:

Consumption of raw meat, or raw shellfishmay be a clue to brucellosis, toxoplasmosis,tularemia or hepatitis.

Consumption ofunpasteurized dairy products -Brucellosis , Q fever.

A history of pica, specifically eating dirt,may be associated with diseases such as

visceral larva migrans and toxoplasmosis.

Ingestion ofcontaminated food/water:Typhoid fever


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Past medical and surgical history

- h/o Blood transfusion

- Abdominal surgery- Head trauma

Existing disease

- Congenital or acquired heart disease

- Sickle cell anemia

- Cancer

- HIV

IMMUNIZATION HISTORY


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Drug historyMany drug causes fever including

topical agents. - fever as an allergic reaction - impair sweating (phenothiazines,

anticholinergics) - fever may be associated with drug

related serum-sickness like reactions,erythema multiforme

Resolution of fever occurs within 48 hrsor 3 to 5 drug half lives after thediscontinuation of the drug

Reoccurence of fever within few hrs ifdrug is restarted.


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Psychosocial history:-

Social history should ascertain familydynamics and raise any suspicion of

neglect, abuse, or starvation.

An inconsistent history - suspicion of a

factitious fever orMunchausensyndrome by proxy.

SEXUAL HISTORY

EXAMINATION


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EXAMINATION

The patient with FUO should beevaluated while febrile. This isnecessary to assess:

- Temperature.- How ill the patient appears.- To determine the effect of fever on

sweating and the heart and respiratoryrates.

- Document any accompanyingsymptoms (eg, malaise or myalgias)Or signs (The rash of JIA is

characteristically evanescent and maybe present only during fever)

VITALS


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VITALS

Temperature - documentation andpattern during hospitalization. (fever

pattern) Pulse rate:- relative bradycardia (Typhoid,

weils dis)

Respiration : Tachypnoea may be seen

with pneumonia or with multisystemdisorders with lung involvement.

Blood Pressure : Hypertension is presentin chronic pyelonephritis ,inflammatory/vasculitic disorders, SLE.

WEIGHT- weight loss , chronic diseases,

such as inflammatory bowel disease (IBD),


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GENERAL EXAMINATION:

Pallor - Malaria, kala azar, most chronic

bacterial infections, SABE; leukemia,lymphoma; inflammatory/vasculitic

illnesses.

Icterus liver abscess, viral hepatitis;IMN, malaria; weils disease (icteric

leptospirosis)

Clubbing- lung abscess, liver abscess,bronchiectiasis, SABE, inflammatory

bowel ds.


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Lymph nodesExamine for Lymphadenopathy Localized Cervical Lymphadenopathy:

1. Tuberculosis2. Lymphadenitis (bacterial)

3. Cat scratch disease4. Glandular fever (Tularemia)

5. Kawasaki ds

Generalised Lymphadenopathy:indicates significant systemic disease.

1. Tuberculosis

2. Infectious Mononucleiosis, CMV, Toxoplasmosis

3. Hodgkins ds

4. ALL Painful gland:

- Inflammatory process or suppuration +++

- Hemorrhage into the necrotic center of a malignant node.


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Consistency Soft & fluctuant infection

Stony hard node Cancer & usually metastasis

Firm & rubbery Lymphoma

Matting

-Benign: Tuberculosis/Sarcoid-Malignant: Metastatic Carcinoma/Lymphoma


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Joints: swelling may be seen inseptic arthritis

JIA, SLE, Rheumatic fever

Serum sicknessLeukemia, lymphoma.

Others:osler nodes bacterial endocarditis

subcutaneous nodules rheumaticfever


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Skin findings:

Rose spots typhoidPetechial lesions IE, Bacteremia;

Some viral infections

Rickettsial infections

leukemia

Erythema nodosum TB, sarcoidosis

Macular Salmon pink rash JIA

Malar rash (butterfly) SLE

Janeway lesion (palmar erythema) Bacterial endocarditis

Erythema marginatum Rheumatic fever

Eschar Tularemia

Eyes


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EyesBulbar conjuctivitis Leptospirosis, Kawasaki ds

Palpebral conjuctivitis IM, coxsackie virus; TB

Phylectenular conjunctivitis (small white elevated lesions) TB

Petechial conjunctival hge Infective endocarditis

Uveitis JIA, SLE, Behcets, vasculitis,

sarcoidosis, Kawasaki ds

Proptosis Orbital infection,

orbital tumor, orbital mets

(neuroblastoma)

Wegners granulomatosis, thyrotoxicosis

Absent tears n corneal

reflexes

Familial dysautonomia

FUNDUS EXAMINATION

Choroid tubercles TB

Chorioretinitis CMV, toxoplasmosis


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EAR, NOSE AND THROAT Ear examination by otoscope.

Nose and Paranasal sinuses:

DNS, nasal discharge s/o sinusitisSinuses should be palpated for tenderness

Throat:

Tonsils, e/o Abscesses, Post pharyngeal wall forcongestion.

Pharyngeal hyperemia without exudate can be the onlysign of IM.

Dental abscess

Gingival hypertrophy or inflammation withloosening of teeth:leukemia

Langerhans cell histiocytosis

Reccurent oral thrush : immunocompromised patients

Chest


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Examination of the chest may reveal findingsconsistent with pneumonia, tuberculosis.

Pleuritisinflammatory/vasculitic disorders andmalignancy.

The presence of a cardiac murmur, especiallyone of new onset, may suggest infectiveendocarditis.

Abdomen

Hepatic or splenic enlargement is common ininfections of the reticulo endothelial system(salmonellosis, brucellosis, etc.), cat scratchdisease, infective endocarditis, malaria, and manyothers.

Tenderness on palpation of the liver edge may be

Musculoskeletal


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MusculoskeletalThe bones and muscles should be palpated

for tenderness.

Tenderness over a bone - osteomyelitis,malignant invasion of the bone marrow or

infantile cortical hyperostosis.

Muscle tenderness

Characteristic of leptospirosis, various

arboviral infections or dermatomyositis.

Tenderness over the trapezius muscle may

indicate subdiaphragmatic abscess.

G it i


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Genitourinary

Patients with FUO should have a careful

rectal, external genitalia, and pelvicexamination (for sexually active femaleadolescents).

The rectal examination is performed toevaluate the patient forper rectaltenderness or a mass, which can

indicate a pelvic abscess or tumor.

Stool should be examined for occultblood.

Lab Investigations


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Lab Investigations

Preliminary investigation, which should

be done in all patients of PUO include,1) Complete blood counts

2) Peripheral smear

3)

Malarial parasite4) ESR&CRP

5) WIDAL test

6) Blood culture

7) Urinalysis and culture

8) Tuberculin test

9) Chest x-ray & abdominal ultrasound.

1)Complete blood counts with a


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1)Complete blood counts with adifferential absolute neutrophil count< 5000/l-against indolent bacterial

infection except typhoid.absolute neutrophil count > 10,000/l a

severe bacterial infection highly likely.

2)Peripheral smear can reveal organismsof malaria, toxoplasma, relapsing fever.

3) ESR, CRP


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) ,

Non specific markers for inflammationn infection

ESR > 30mm/hr indicates inflammation nneed for evaluation of cause.

ESR > 100mm/hr suggests tuberculosis,malignancy, autoimmune ds or Kawasaki

ds.

CRP Becomes elevated and returns to

normal more rapidly than ESR.CRP is elevated in:1. Bacterial Infection

2. Neoplasm

3. Immunological-mediated inflammatory states

5)Blood cultures


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5)Blood cultures

Should be obtained aerobically

Multiple or repeated blood culturesmaybe needed to detect bacteremia asso

with IE, osteomyelitis, or deep seated

abscesses.

Isolation of leptospires, Fransciella, or

Yersinia require special media.

6)Urine analysis & Cultures

7)Tuberculin Skin Test

8) WIDAL TEST

9)Xrays:


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) y Chest xray

Miliary shadows Disseminated tuberculosis

Mediastinal mass Lymphoma, sarcoid,

malignancy Fluffy shadows Pneumocytis jiroveci

Sinuses, mastoids or GI tract as indicatedby specific historical or physical findings.

Ultrasound abdomen: For imaging almost allthe abdominal and pelvic viscera.

Ultrasonography of Abdomen: intrabdominalabscesses of liver, subphrenic spaces, pelvisor spleen.

USG of Kidney, Ureter, Urinary bladder (KUB) In all cases of FEBRILE UTI

Second line investigation


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Second line investigation

Bone marrow examination- leukemia, metastatic

neoplasm, fungal or parasitic disease, histiocytosis,hemophagocytosis or storage disease.

Serologic testsSerology for HIV

Anti-nuclear Antibodies autoimmune disorders like SLE Rheumatoid Factor juvenile rheumatoid arthritis

IgM Antibody -- CMV

Heterophile Antibody Test Ebstein barr virus

Cold-agglutinin -- Mycoplasma pneumoniae

Reagin antibody -- Treponema pallidum

Serum agglutination test Brucella

The reliability and sensitivity and specificity of

these tests vary.

Radionuclide scans


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Bone Tc scan osteomyelitis

Gallium scan occult inflammation

Indium labelled WBC scan occult abscesses

Total body CT or MRI:

Total body CT or MRI (both with contrast)permits detection of neoplasms andcollections of purulent material without theuse of surgical exploration or radioisotopes

CT or ultrasound-guided aspiration orbiopsy of suspicious lesions has reducedthe need for exploratory laparotomy or

thoracotomy.

MRI is particularly useful for detecting


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MRI is particularly useful for detecting

osteomyelitis if there is concern about a

specific limb.

BIOPSY

Biopsy is occasionally helpful in

establishing a diagnosis of FUO.

Bronchoscopy, laparoscopy,

mediastinoscopy, and GI endoscopy can

provide direct visualization and biopsymaterial when organ-specific

manifestations are present.


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Echocardiography:This technique is highly sensitive indiagnosing endocarditis, particularly whentransesophageal echocardiography is

available.

Venous doppler study: For venousthrombosis


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TREATMENTAntimicrobial agents should not be used as

antipyretics. An exception may be the use of

antituberculous treatment in critically illchildren with suspected disseminatedtuberculosis.

Empirical trials of other antimicrobialagents may be dangerous and can obscure

the diagnosis.After a complete evaluation, antipyretics

may be indicated to control fever andrelieve symptoms.

OG OS S


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PROGNOSIS

Children with FUO have a better

prognosis than do adults.

In many cases, no diagnosis can be

established and fever abatesspontaneously.

In as many as 25% of cases in whomfever persists, the cause of the fever

remains unclear, even after thorough

evaluation.

FEVER OF UNKNOWN ORIGIN


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PERFORM HISTORY AND

EXAMINATION

TRAVEL , OTHER EXPOSURES OR

PE FINDING SUGGESTIVE OF

SPECIFIC DISORDERS

PERFORM PRELIMMINARY LAB

EVALUATION

& CONSIDER SEROLOGY FOR

EBV,CMV,BRUCELLA, S.

TYPHI,LEPTOSPIROSIS

NEXT SLIDE

YES NO


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ABNORMAL RESULT

ABNORMAL WBCABNORMAL SMEAR

MALIGNANCY

MALARIA

SCA

THRMBOCYTOPENIA

ANAEMIA

POSITIVE

URINE

CULTURE

ABNORMAL

CXR

POSITIVE

BLOOD

CULTURE

ABNOMAL

SEROLOGY

BACTEREMIA

EMV

CMV

TYPHOID FEVER

LEPTOSPIROSIS

BRUCELLOSIS

TBMALIGNANCY

MALARIA

MALIGNANCY

SLE

UTI

PERFORM PRELIMMINARY LABEVALUATION



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EBV,CMV,BRUCELLA, S.TYPHI,LEPTOSPIROSIS

ELEVATED ESR

OBTAIN ANA &

RHEUMATOID

FACTOR

ABNORMAL

RESULT

JRA

COLLAGEN

VASCULAR

DIS

NORMALRESULT

OBTAIN Tc WBC

SCAN,CT ABDOMEN /

PELVIS BONE SCAN

ABNORMAL

RESULT

OSTEOMYELITISABSCESS

(INTRAABDOMINAL, PELVIC)

IBD MALIGNANCY

NORNAL

RESULT

BONE

MARROW

MALIGNANCY

NFECTION

ABNORMAL

TRAVEL , OTHER EXPOSURESOR PE FINDING SUGGESTIVE


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EXPOSURE TO WILD OR

DOMIESTICATED

ANIMAL

RASH OR PATECHIAE TRAVEL OR EXPOSURE

TO PERSONS RECENTLY

TRAVELED

Zoonoses (brucellosis,

Leptospirosis, Tularemia

etc)

JIA, Ac Rheumatic Fever,

Endocarditis, SLE,

Tularemia

Malaria, Leishmaniasis,

Rickettsial ds

MILD UPPER

RESPIRATORY

SYMPTOMS

INGESTION OF

CONTAMINATED FOOD

OR MILK OR WATER OR

H/O PICA

WEIGHT LOSS OR

IMPAIRED LINEAR

GROWTH, VAGUE

ABDOMINAL

COMPLAINTS

Sinusitis, Pulmonary ds

(pneumonia, TB,

abscess)

Wegners granulomatosis

Malignancy

Typhoid, Brucellosis,

Toxoplasmosis, Visceral

larva migrans

Inflammatory Bowel ds

Intra abdominal abscess

Malignancy

OR PE FINDING SUGGESTIVE

OF SPECIFIC DISORDERS


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BONE, JOINT OR

MUSCLE PAIN ORTENDERNESS

ABNORMAL

CARDIAC EXAM

OTHER PHYSICAL

ABNORMALITIES(NEUROLOGIC,

CUTANEOUS,

DENTAL)

Osteomyelitis,

malignancy

Dermatomyositis,

arboviral infections

Carditis (rheumatic

fever)

Endocarditis

Viral

peri/myocarditis

SLE

Ectodermal

dysplasia

CNS/hypothalamic

disorders

Infantile cortical

hyperostosis


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pyrexia of unknown origin in children