l iver in fever

عبد الوهاب محمد السعدنى وحديثى. اطفال طب دكتوراه

الوالدة الطفوله. أمراض دكتوراهالخاصة االحتياجات وذوى

Fever is the most ancient landmark of Fever is the most ancient landmark of

disease. It is an increase in body disease. It is an increase in body

temperature above normal with it’s temperature above normal with it’s

circadian rhythm. It is the most common circadian rhythm. It is the most common

presenting symptom of the pediatric presenting symptom of the pediatric

emergencies department ,representing 15-emergencies department ,representing 15-

30 % of all cases30 % of all cases . .

Fever is an elevation of body temperature

that exceeds the normal daily variation,

in conjunction with an increase in

hypothalamic set point

Maximum normal oral temperature

At 6 AM: 37.2At 4 PM: 37.7

Pyrogens is any substance that causes fever

Exogenous pyrogens–Derived from outside the patient– Microbial products, toxins or

whole microorganisms

Endogenous pyrogens–Cytokines are small proteins that

regulate immune, inflammatory and hematopoietic processes.

– Cytokines that cause fever are called pyrogenic cytokines. Produced from

monocytes, neutrophils and lymphocytes.

–ILIL11, ILIL66, TNFTNF, Ciliary neurotropic factorCiliary neurotropic factor, and Interferon αInterferon α.

–Each cytokine is encoded by a specific gene

IN FEVER

Major causes of hepatitis are specific

hepatotropic hepatitis A,B,C and delta viruses.

Less common causes include other

viral infections (eg, infectious mononucleosis, yellow fever, cytomegalovirus infection).

Bacterial liver involvement with TB , Leptospirosis ,etc may result in granulomatous hepatitis..

VIRUSESVIRUSES BacterialBacterial

Q FeverQ Fever

LeptospirosisLeptospirosis

Relapsing Fever

SyphilisSyphilis

Typhoid feverTyphoid fever

BrucellosisBrucellosis

TuberculosisTuberculosis

LeprosyLeprosy

Yellow fever Yellow fever ADENOVIRUSEADENOVIRUSESSRift Valley Fever Rift Valley Fever virusvirusCytomegalovirusCytomegalovirusDengue feverDengue feverEpstein-Barr Epstein-Barr virusvirusCOXSACKIE COXSACKIE VIRUSESVIRUSESRUBELLA RUBELLA VIRUSVIRUSLassa feverLassa fever

CLINICAL SIGNS OF LIVER CLINICAL SIGNS OF LIVER DISEASEDISEASE

VIRUSES VIRUSES AFFECTING AFFECTING

LIVERLIVER

Yellow Yellow feverfever

is an acuteis an acute viral disease.It is an disease.It is an important cause important cause of of hemorrhagic illness in many illness in many African and African and South American South American countriescountries..

YellowYellow

fever (YF) fever (YF) is caused is caused by an by an arbovirus.arbovirus.

Yellow Yellow fever (YF) fever (YF) is is transmitttransmitted by the ed by the Aedes Aedes aegyptiaegypti mosquito.mosquito.

Yellow fever (YF) Yellow fever (YF) is transmitted is transmitted by the by the Aedes Aedes aegyptiaegypti mosquito from :mosquito from :

1-one 1-one humanhuman to to another (the another (the urban urban form of form of YF) or from:YF) or from:

2- 2- monkeysmonkeys to to humans (the humans (the jungle or sylvanjungle or sylvan form of YF).form of YF).

Pathogenesis of arbovirusesPathogenesis of arboviruses

Yellow fever After a After a 12-24 hour12-24 hour remission, remission,

there is an "intoxication" or there is an "intoxication" or hepatorenal stagehepatorenal stage that that features reemergence of features reemergence of generalized symptoms generalized symptoms including increased including increased temperature, temperature, jaundicejaundice, and , and prostration. prostration.

JaundiceJaundice usually appears on usually appears on the second or third day. After the second or third day. After the third day the symptoms the third day the symptoms recede, only to return with recede, only to return with increased severity in the final increased severity in the final stage.stage.

Rift Valley Rift Valley FeverFever

Rift Valley FeverRift Valley Fever

Rift Valley Fever is an Rift Valley Fever is an infectious infectious zoonoticzoonotic disease affecting sheep, disease affecting sheep, goats, and cattle.goats, and cattle.

The disease is The disease is caused bycaused by the Rift Valley Fever the Rift Valley Fever (RVF) virus, a member of (RVF) virus, a member of the genus Phlebovirus.the genus Phlebovirus.

The disease is The disease is transmittedtransmitted by by Aedes Aedes aegyptiaegypti mosquitoes. mosquitoes.

In severe cases,In severe cases, the disease becomes serious . the disease becomes serious . Symptoms include fever, myalgias, and Symptoms include fever, myalgias, and encephalitis, including headache, coma, and encephalitis, including headache, coma, and seizuresseizures

Rift Valley FeverRift Valley Fever Severe cases of RVF fall Severe cases of RVF fall

into into three three categories:categories:

11•• Liver necrosisLiver necrosis (focal or (focal or

diffuse ) diffuse ) with with hemorrhaging.hemorrhaging.

22 • • Retinitis with Retinitis with visualvisual impairment.impairment. 33•• MeningoMeningoencephalitisencephalitis

19771977 outbreak in Egypt: outbreak in Egypt: petechial haemorrhages petechial haemorrhages

and hyphema in a womanand hyphema in a woman’’s s faceface

MODE OF TRANSMISSIONMODE OF TRANSMISSION

Dengue hemorrhagic Dengue hemorrhagic feverfever

Dengue fever(West Nile fever), Dengue fever(West Nile fever), is the world's most important is the world's most important viral hemorrhagic fever viral hemorrhagic fever diseasedisease; it is the most ; it is the most geographically wide-spread of geographically wide-spread of the the arthropod-bornarthropod-born viruses, viruses, especially in the especially in the Americas, the Americas, the Pacific islands and on Pacific islands and on continental Asiacontinental Asia. .


Dengue virus infection can present Dengue virus infection can present a diverse a diverse clinical spectrum,clinical spectrum, ranging ranging from asymptomatic illness to from asymptomatic illness to dengue shock syndrome, as well as dengue shock syndrome, as well as unusual manifestations, such as unusual manifestations, such as hepatitis,hepatitis, encephalitis, myocarditis, encephalitis, myocarditis, Reye's syndrome, hemolytic Reye's syndrome, hemolytic uremic syndrome. uremic syndrome.


Liver injuryLiver injury due to dengue due to dengue infection is not uncommon and infection is not uncommon and has been described since 1970 .has been described since 1970 .

Painful hepatomegalyPainful hepatomegaly, the main , the main clinical symptom observed, is clinical symptom observed, is seen in up to 30% of patients.seen in up to 30% of patients.

Epstein-Barr virusEpstein-Barr virus

Synonyms and related keywordsSynonyms and related keywords: : glandular feverglandular fever, , infectious mono, infectious mono, infectious mononucleosisinfectious mononucleosis, , Epstein-Barr virus, EBV, feverEpstein-Barr virus, EBV, fever . .

Infectious Mononucleosis Infectious Mononucleosis PathophysiologyPathophysiology

EBV is EBV is transmittedtransmitted via intimate via intimate contact with body secretions, contact with body secretions, primarily oropharyngeal secretions. primarily oropharyngeal secretions. EBV infects the EBV infects the B cellsB cells in the in the oropharyngeal epithelium.oropharyngeal epithelium.

Circulating B cellsCirculating B cells spread the spread the infection throughout the entire infection throughout the entire reticular endothelial system (RES), ie, reticular endothelial system (RES), ie, liver, spleen, and peripheral lymph liver, spleen, and peripheral lymph nodes.nodes.

Infectious MononucleosisInfectious Mononucleosis

Infectious Mononucleosis Infectious Mononucleosis MOUTHMOUTH

Later physical Later physical findingsfindings include include hepatomegaly, hepatomegaly, palatal petechiae, palatal petechiae, jaundice( jaundice( less than less than 10%)10%),, uvular edema, uvular edema, splenomegaly, and, splenomegaly, and, rarely, (1-2%) rarely, (1-2%) findings associated findings associated with with splenic splenic rupture. rupture.

Splenic tendernessSplenic tenderness may be present in may be present in patients with patients with splenomegaly.splenomegaly.

Mononucleosis hepatitisMononucleosis hepatitis is is characterized by peculiar characterized by peculiar necroinflammatory changesnecroinflammatory changes which, at the difference of which, at the difference of classical viral hepatitides consist classical viral hepatitides consist of of more inflammation and less more inflammation and less necrosisnecrosis. .

The The sinusoidssinusoids are filled and are filled and distended with distended with mononuclearmononuclear cells cells which are large and sometimes which are large and sometimes clustered to resemble clustered to resemble granulomasgranulomas sometimes similar to sarcoidosissometimes similar to sarcoidosis. .

Infectious mononucleosis Infectious mononucleosis hepatitishepatitis:Marked :Marked mononuclear mononuclear cell infiltration of the sinusoidscell infiltration of the sinusoids

without significant necrosiswithout significant necrosis

Mononucleosis Mononucleosis hepatitishepatitis

Another peculiar feature is Another peculiar feature is the presence of a the presence of a marked marked regenerative activity of regenerative activity of hepatocyteshepatocytes with presence with presence of increased number of of increased number of binucleate cells, polyploid binucleate cells, polyploid nuclei and mitotic figures. nuclei and mitotic figures.

Infectious mononucleosis Infectious mononucleosis heapatitis:heapatitis:High power of High power of

previous illustration showing the previous illustration showing the signs of high regenerative activitysigns of high regenerative activity

ATYPICAL LYMPHOCYTEATYPICAL LYMPHOCYTE

Infectious MononucleosisInfectious Mononucleosis

Liver function testsLiver function tests show show elevation of liver elevation of liver enzyme enzyme levels in nearlylevels in nearly 90% of 90% of people with glandular people with glandular fever.fever.

An early, transient,An early, transient, mild mild

increase in serum increase in serum transaminases is transaminases is characteristic of EBV characteristic of EBV infectious mononucleosisinfectious mononucleosis..

CytomegalovirusCytomegalovirus

CytomegalovirusCytomegalovirus Cytomegalovirus Cytomegalovirus

an encapsulated an encapsulated DNADNA virus, Is a virus, Is a member of the member of the herpesviridae herpesviridae family ,is found family ,is found worldwide, worldwide, though it is though it is more common more common in developing in developing nations.nations.

CytomegalovirusCytomegalovirus Only occasionally will the virus induce Only occasionally will the virus induce

mononucleosis-like syndrome, mononucleosis-like syndrome, prolonged fever, and or mild hepatitisprolonged fever, and or mild hepatitis. . Otherwise, once the individual is Otherwise, once the individual is infected, the virus will remain dormant, infected, the virus will remain dormant, and for most people, recurrent and for most people, recurrent infections will not develop.infections will not develop.

For For immunocompromised immunocompromised individuals, individuals, the virus is able to reactivate, which can the virus is able to reactivate, which can lead to diseases such as CMV retinitis. lead to diseases such as CMV retinitis.

CytomegalovirusCytomegalovirus

CMV inclusion body: CMV inclusion body: Hepatocyte Hepatocyte with a large intranuclear with a large intranuclear inclusion body. Surrounded by a clear inclusion body. Surrounded by a clear halo. Dark punctiform inclusions are halo. Dark punctiform inclusions are

seen also in the cytoplasm. seen also in the cytoplasm.

Epstein-Epstein-Barr Barr VirusVirus

CytomeCytomegalovirgalovirusus

ToxoplaToxoplasmosismosiss

Viral Viral HepatitisHepatitis

FatigueFatigue ++++-/+-/+ + +

MalaiseMalaise++++-- + +

Mild sore Mild sore throatthroat

++++-/+-/+ -/+ -/+

Early Early maculopapulamaculopapular rashr rash

++---- -/+ -/+

Early Early bilateral bilateral upper eyelid upper eyelid edemaedema

++---- - -

Unilateral Unilateral localized localized adenopathyadenopathy

----++ - -

Epstein-Epstein-Barr Barr

VirusVirus

CytomegaloCytomegalovirusvirus

ToxoplToxoplasmosasmos

iiss

Viral Viral hepatitishepatitis

BilateralBilateral

posterior posterior cervical cervical adenopathyadenopathy

++++-- -/+ -/+

Tender Tender hepatomegahepatomegalyly

-/+-/+-/+-/+-- + +

SplenomegaSplenomega

lyly ++-/+-/+-/+-/+ - -

WBC countWBC count NN-/-/NN-/-/NN - -

Elevated Elevated SGOTSGOT†/SGPT†/SGPT‡‡

++++++-/+-/+ +++ +++

Atypical Atypical lymphocytes lymphocytes (>10%)(>10%)

++++++ - -

Epstein-Epstein-Barr Barr

VirusVirus

CytomegCytomegalovirusalovirus

ToxoplasToxoplasmosimosiss

Viral Viral hepatitishepatitis

ThrombocytThrombocyt

openiaopenia -/+-/+-/+-/+-- -/+ -/+

Elevated IgMElevated IgM§ § CMV titerCMV titer --++-- - -Elevated IgM Elevated IgM EBV VCAII EBV VCAII titertiter

++---- - -

Elevated IgM Elevated IgM toxoplasmosis toxoplasmosis titertiter

----++ - -

Elevated Elevated hepatitis (eg, hepatitis (eg, A, B, D) IgM A, B, D) IgM

titertiter

------ + +

OTHER VIRUSES RARELY AFFECTING

THE LIVER

ADENOVIRUSESADENOVIRUSES :Severe and fatal :Severe and fatal hepatitis with severe respiratory hepatitis with severe respiratory infection may develop in these infection may develop in these individuals. Intranuclear viral antigen individuals. Intranuclear viral antigen has been detected in cases of hepatitis .has been detected in cases of hepatitis .

COXSACKIE VIRUSESCOXSACKIE VIRUSES :Hepatitis is :Hepatitis is

frequently associated with myocarditis frequently associated with myocarditis and consists of necroinflammatory and consists of necroinflammatory changes involving lobules and porta changes involving lobules and porta tracts, to be distinguished from tracts, to be distinguished from congestive changes due to heart failure. congestive changes due to heart failure.

RUBELLA VIRUSRUBELLA VIRUS : :The liver may The liver may be involved with variable degree be involved with variable degree of acute hepatitis, biliary of acute hepatitis, biliary obstruction and destruction. obstruction and destruction.

Lassa feverLassa fever :There is marked :There is marked hepatocyte damage in the liver hepatocyte damage in the liver consisting in eosinophilic consisting in eosinophilic necrosis of individual cells but necrosis of individual cells but jaundice is rare.jaundice is rare.

Bacterial infectionsBacterial infections

Q FeverQ Fever

Q FeverQ Fever

Q fever is Q fever is caused by a caused by a microbe called microbe called ""Coxiella Coxiella burnetiiburnetii””, , Gram-negative Gram-negative obligate obligate organisms.organisms.

AnimalsAnimals such as such as cattle, sheep, and cattle, sheep, and goats can carry goats can carry the the Q fever microbeQ fever microbe in in tissues involved in tissues involved in birth--birth--the uterus, the uterus, placenta, and birth placenta, and birth fluids. fluids.

Infected animals Infected animals also release the also release the microbe in microbe in milk and milk and manuremanure..

Q FeverQ Fever

People acquire the infection byPeople acquire the infection by inhalinginhaling infectious aerosols and infectious aerosols and contaminated dusts generated by contaminated dusts generated by animals or animal products.animals or animal products.

People can also get Q fever by People can also get Q fever by drinking drinking infected milk, but most infected milk, but most infections are spread through the infections are spread through the air. air.

Q feverQ fever PATHOGENESISPATHOGENESIS

Q Fever: signs and Q Fever: signs and symptomssymptoms

A small percentage of patients develop hepatitis and jaundice.

Other rare clinical syndromes including endocarditis, have been reported.

Hepato/splenomegaly and endocarditis are also common in chronic Q fever.

Q fever-focal hepatic Q fever-focal hepatic granulomagranuloma ((intra- acinar granuloma with a central fat intra- acinar granuloma with a central fat vacule surrounded by fibrin ring and vacule surrounded by fibrin ring and

macrophagesmacrophages))


Leptospirosis CAUSED BY Leptospirosis CAUSED BY Leptospira interrogans Leptospira interrogans ((Leptospira Leptospira icterohaemorrhagiaeicterohaemorrhagiae ) : ) : a flexible, spiral-a flexible, spiral-shaped, Gram-negative shaped, Gram-negative spirochete with internal spirochete with internal flagellaflagella . .

Transmission occurs by Transmission occurs by contamination of water, soil, or contamination of water, soil, or vegetation by urinevegetation by urine excreted from excreted from infected animalsinfected animals..

HumansHumans are consideredare considered incidental hostsincidental hosts

to the disease (to the disease (Leptospirosis)Leptospirosis) because because transmission of the disease between people is transmission of the disease between people is

rare, at bestrare, at best . .

Interesting FactInteresting Fact:: Brown ratsBrown rats carry diseases, including carry diseases, including Weil's Weil's disease, Viral hemorrhagic fever disease, Viral hemorrhagic fever (VHF), Q fever(VHF), Q fever.. They can also act They can also act as reservoirs of as reservoirs of bubonic plague.bubonic plague.

Leptospirosis:PATHOGENESLeptospirosis:PATHOGENESISIS

Icteric Icteric leptospirosis or leptospirosis or Weil's syndromeWeil's syndrome is the more is the more severe form and severe form and is characterized is characterized by deep by deep jaundicejaundice(blilirub(blilirubin in

May exceed May exceed 30mg/dl)30mg/dl)


Liver Liver involvement is marked by involvement is marked by centrilobular centrilobular necrosis and Kupffer cellnecrosis and Kupffer cell proliferation, with hepatocellular proliferation, with hepatocellular dysfunction.dysfunction.

Abdominal examination can reveal Abdominal examination can reveal liver liver enlargement and tendernessenlargement and tenderness from from hepatitis. A positive Murphy sign can hepatitis. A positive Murphy sign can be observed in patients who develop be observed in patients who develop acalculous cholecystitisacalculous cholecystitis. .

Relapsing Fever

Relapsing fever is Relapsing fever is transmitted transmitted to to humans by 2 vectors, humans by 2 vectors, ticks and lice. ticks and lice.

Relapsing Fever

RFs are spirochetal infections with Borrelia sp)gram negative helical bacteria).

Relapsing Fever-transmission

Relapsing Fever-pathogenesis

Relapsing Fever

HepatosplenomegalyHepatosplenomegaly is common. is common. Conjunctival injection, epistaxis, cough, Conjunctival injection, epistaxis, cough, and slight hemoptysis may also occur.and slight hemoptysis may also occur.

Symptoms last for 3-10 days, when Symptoms last for 3-10 days, when there is a crisis (>fever and severity of there is a crisis (>fever and severity of other symptoms), followed by other symptoms), followed by recovery recovery and relapseand relapse in about 7-14 days . in about 7-14 days .

Petechial or maculopapular rash. Petechial or maculopapular rash. Rales , Rhonchi .Rales , Rhonchi . Nuchal rigidity& Lymphadenopathy.Nuchal rigidity& Lymphadenopathy. Iritis and iridocyclitis .Iritis and iridocyclitis .

Relapsing Fever-CLINICAL

Jaundice in Jaundice in Relapsing Fever

The The liver liver shows shows necroinflammatory necroinflammatory changes with changes with elevation of serum elevation of serum transaminasestransaminases and and serumserum bilirubin bilirubin up up to 15mg/100mlto 15mg/100ml

SyphilisSyphilis

SyphilisSyphilis

This historical disease used This historical disease used to produce the "to produce the "hepar hepar lobatumlobatum" in its congenital form " in its congenital form due to dissecting fibrosis due to dissecting fibrosis produced by granulation tissue produced by granulation tissue containing spirochetae pallidae containing spirochetae pallidae and hepatic granulomas in any and hepatic granulomas in any form. form.

Typhoid and Typhoid and paratyphoid feverparatyphoid fever

Typhoid Typhoid andand paratyphoid paratyphoid feverfever

Typhoid feverTyphoid fever is is an acute systemic an acute systemic febrile illness febrile illness caused by caused by Salmonella typhiSalmonella typhi . .

S. ParatyphiS. Paratyphi causes the less causes the less severe severe paratyphoid paratyphoid feverfever..

Typhoid is Typhoid is usually usually spread spread byby feces- feces-contaminated contaminated food or water.food or water.

IncubationIncubation is is highly highly variable, variable, ranging from ranging from 3-60 days.3-60 days.


The The liver is enlarged liver is enlarged AND TENDERAND TENDER

Infarction Infarction abscessesabscesses and acute yellow and acute yellow atrophy occur in rare atrophy occur in rare instances.instances.

Moderate elevation in Moderate elevation in serum serum transaminasestransaminases and serumand serum bilirubinbilirubin

SalmonellosisSalmonellosis may infect the may infect the liver where they produce liver where they produce histiocytic histiocytic granulomas. granulomas. Typhoid noduleTyphoid nodule consists consists of an intra parenchymal focus of of an intra parenchymal focus of necrosis with histiocytes, some necrosis with histiocytes, some neutrophils an will contain the gram neutrophils an will contain the gram

negative organisms.negative organisms.

Typhoid fever-focal hepatic Typhoid fever-focal hepatic necrosisnecrosis

Typhoid and Hepatitis ATyphoid and Hepatitis A

Brucellosis or undulant Brucellosis or undulant feverfever: : Brucellosis is Brucellosis is

causedcaused by gram by gram negative negative coccobacilli coccobacilli ((Brucella abortusBrucella abortus and other and other B.B. biovars) biovars)

transmitted transmitted through through contaminated contaminated milk, and animal milk, and animal products.products.

Sources of Brucella infectionSources of Brucella infection

Portals of entry for Brucella Portals of entry for Brucella speciesspecies

Spread of Brucella in the Spread of Brucella in the bodybody

Brucellosis or undulant Brucellosis or undulant feverfever

Fever, chills, sweats, aches, fatigue, Fever, chills, sweats, aches, fatigue, and joint pain are the most common and joint pain are the most common manifestationsmanifestations..

The most commonly affected The most commonly affected systemssystems (with a variety of (with a variety of manifestations) are cardiac, manifestations) are cardiac, respiratory, respiratory, gastrointestinalgastrointestinal, , genitourinary, and central nervous genitourinary, and central nervous system. system.

BrucellosisBrucellosis in the in the chronicchronic form will cause LIVER form will cause LIVER noncaseating noncaseating granuloma granuloma lesionslesions, sometimes with , sometimes with atypical nuclei of their atypical nuclei of their histiocytes as to histiocytes as to mimic mimic HodgkinHodgkin’’s granulomass granulomas..

HEPATIC TuberculosisHEPATIC Tuberculosis

HEPATIC TuberculosisHEPATIC Tuberculosis It involves the liver most frequently It involves the liver most frequently

in in miliary tuberculosismiliary tuberculosis where it where it forms multiple granulomas with or forms multiple granulomas with or without giant cells or caseation without giant cells or caseation necrosis.necrosis.

If the granulomas are numerous, the If the granulomas are numerous, the only only functional changefunctional change may be may be elevation of serum alkaline elevation of serum alkaline phosphatase due to the local phosphatase due to the local compression of the liver parenchyma compression of the liver parenchyma around each single granulomaaround each single granuloma..

HEPATIC TuberculosisHEPATIC Tuberculosis TB TB granulomasgranulomas in the liver may in the liver may

be very similar to those of be very similar to those of sarcoidosissarcoidosis because caseation because caseation necrosis is often absent. necrosis is often absent.

Because the Because the organismsorganisms are are rarely seen in TB granulomas of rarely seen in TB granulomas of the liver, the histological the liver, the histological differential diagnosis with differential diagnosis with sarcoidosis may be difficultsarcoidosis may be difficult. .

Same TB granuloma of the Same TB granuloma of the liverliver

LeprosyLeprosy Liver Liver granulomas granulomas are observed are observed

in the lepromatous form of the in the lepromatous form of the disease. They contain acid-fast disease. They contain acid-fast bacilli and the bacilli and the "lepra histiocyte"lepra histiocyte" " which are large histiocyte with which are large histiocyte with clear cytoplasm.clear cytoplasm.

Hepatic granulomas may be the Hepatic granulomas may be the cause of cause of relapserelapse after an after an apparent successful therapy. apparent successful therapy.

Liver Lepromatous Liver Lepromatous granuloma with H&E stain.granuloma with H&E stain.

Liver Lepromatous Liver Lepromatous granulomagranuloma

RICKETTSIAL INFECTIONSRICKETTSIAL INFECTIONS

*Rocky Mountain Spotted Fever :*Rocky Mountain Spotted Fever : It is due to a rickettsia transmitted by It is due to a rickettsia transmitted by

ticksticks. The organisms after infection . The organisms after infection proliferate in endothelial cells of proliferate in endothelial cells of various organs. various organs.

The clinical syndrome 2 to 14 days The clinical syndrome 2 to 14 days after the tick bite starts with after the tick bite starts with fever,fever, malaise, vomiting. On the third day a malaise, vomiting. On the third day a skin rashskin rash appears on the limbs. Later appears on the limbs. Later the rash disappears leaving the rash disappears leaving hemorrhagic spots. hemorrhagic spots.

JaundiceJaundice is present in 1/3 of the cases is present in 1/3 of the cases with portal inflammation and presence with portal inflammation and presence of rickettsiae in the portal spaces. of rickettsiae in the portal spaces.

Causes of Hepatic Causes of Hepatic Granulomas Granulomas

Bacterial InfectionsBacterial Infections: brucellosis, : brucellosis, cat-scratch fever, syphilis, TB*, cat-scratch fever, syphilis, TB*, other mycobacterial infections, other mycobacterial infections, LeprosyLeprosy , , tularemia, Q fever, tularemia, Q fever, Rickettsia, Actinomycosis and Rickettsia, Actinomycosis and Typhoid fever. Typhoid fever.

Viral infectionsViral infections, which are less , which are less common (eg, infectious common (eg, infectious mononucleosis, cytomegalovirus mononucleosis, cytomegalovirus and Coxsackieand Coxsackie) .) .

Hepatic GranulomasHepatic Granulomas

Hepatic granulomas are usually Hepatic granulomas are usually asymptomaticasymptomatic. However, the . However, the underlying disorder underlying disorder may causemay cause extrahepatic manifestations, extrahepatic manifestations, hepatic inflammation, fibrosis, hepatic inflammation, fibrosis, portal hypertension, or a portal hypertension, or a combination. combination.

The The liver liver may enlarge slightly, may enlarge slightly, and mild jaundice may develop. and mild jaundice may develop.

Hepatic granulomasHepatic granulomas DiagnosisDiagnosis is based on Liver function tests is based on Liver function tests

&Imaging, but &Imaging, but biopsybiopsy is necessary only if a is necessary only if a treatable underlying disorder (eg, treatable underlying disorder (eg, infection) is suspected or if other liver infection) is suspected or if other liver disorders need to be ruled out. disorders need to be ruled out.

liver function testliver function test results are only mildly results are only mildly deranged, usually with a disproportionate deranged, usually with a disproportionate elevation of elevation of alkalinealkaline phosphatase. phosphatase. Bilirubin Bilirubin levelslevels are typically normal or only mildly are typically normal or only mildly elevated, unless concomitant elevated, unless concomitant hepatocellular injury coexists. hepatocellular injury coexists. EnzymeEnzyme values may simulate viral hepatitis if values may simulate viral hepatitis if extensive hepatocellular necrosis is extensive hepatocellular necrosis is present (eg, in infectious mononucleosis). present (eg, in infectious mononucleosis).

ConclusionConclusion * A large number of * A large number of viral and bacterialviral and bacterial

organisms can involve the liver .organisms can involve the liver .

* These systemic infections * These systemic infections can causecan cause hepatic derangements, ranging from hepatic derangements, ranging from mild liver function tests abnormalities to mild liver function tests abnormalities to frank jaundice and, rarely, hepatic frank jaundice and, rarely, hepatic failure.failure.

* They should be put in mind in * They should be put in mind in differential diagnosisdifferential diagnosis of abnorml liver of abnorml liver function tests. function tests.

l iver in fever

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