case report rat bite fever resembling rheumatoid...

Case ReportRat Bite Fever Resembling Rheumatoid Arthritis

Ripa Akter,1 Paul Boland,1 Peter Daley,2 Proton Rahman,3 and Nayef Al Ghanim4

1Department of Internal Medicine, Memorial University, St. John’s, NL, Canada A1B 3V62Disciplines of Medicine and Laboratory Medicine, Memorial University, St. John’s, NL, Canada A1B 3V63Department of Medicine, Memorial University, St. John’s, NL, Canada A1B 3V64Eastern Health, St. John’s, NL, Canada A1C 5B8

Correspondence should be addressed to Proton Rahman; [email protected]

Received 12 September 2015; Accepted 30 March 2016

Academic Editor: Alice Tseng

Copyright © 2016 Ripa Akter et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a historyof rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistakenfor rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever andpolyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation.We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, allof which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but canhave a lethal course if left untreated.

1. Introduction

Rat bite fever (RBF) is a systemic febrile illness causedby either Streptobacillus moniliformis, common in Westerncountries, or Spirillum minus, which is the most prevalentpathogen in Asia [1, 2]. It is transmitted to humans by bites orscratches from infected rats. Classic clinical features includefever, rash, and polyarthritis [1]. When RBF presents withsymmetrical polyarticular synovitis, rheumatoid arthritismay initially be diagnosed incorrectly, leading to delay inappropriate therapy [3–7]. Complications of RBF includeseptic arthritis, endocarditis, and rarely discitis, as in ourpatient. The mortality rate of untreated cases ranges from 7%to 13% and for cases complicated by endocarditis it can be upto 53% [1, 2].

2. Case Report

A 46-year-old female was admitted with a one-week historyof fever and symmetric polyarthritis of the distal upper andlower extremities, with thirty minutes of morning stiffness. Afew days prior to her admission, she had a one-day history ofnausea, vomiting, and diarrhea. She denied recent travel orillicit drug use. Her previous medical history was significant

for a seizure disorder, irritable bowel syndrome, chronicmechanical back pain, and iron deficiency anemia.Her familyhistory was unremarkable for any rheumatological illness.

On examination, she was febrile (38∘C), tachycardic(130 beats per minute), and hypotensive (96/64mmHg).The most prominent physical finding was effusions in herwrists, ankles, and selected metatarsophalangeal joints. Hercardiopulmonary, abdominal, and dermatological examina-tions were otherwise unremarkable. Erythrocyte sedimen-tation rate was 76mm/hr (normal: 0–12mm/hr) and C-reactive protein was 149mg/L (normal: 0–8mg/L). Therewas a mild leukocytosis of 11.1 × 109/L (normal: 4.8–10.8 ×109/L). Initial blood culture and serological tests includinghepatitis B and hepatitis C, parvovirus B19, HIV, Lymedisease,Chlamydia trachomatis, andNeisseria gonorrheawerenegative. Rheumatological workup including rheumatoidfactor, anti-nuclear antibody, anti-cyclic citrullinated pep-tide antibody, anti-neutrophil cytoplasmic antibodies, anti-dsDNA antibody, and complement levels was all withinnormal limits. Chikungunya virus serology was not orderedas this diagnosis was unlikely given she had not travelled. Apresumptive diagnosis of seronegative rheumatoid arthritiswas made, based on the clinical presentation of symmetrical

Hindawi Publishing CorporationCanadian Journal of Infectious Diseases and Medical MicrobiologyVolume 2016, Article ID 7270413, 7 pageshttp://dx.doi.org/10.1155/2016/7270413

2 Canadian Journal of Infectious Diseases and Medical Microbiology

(a) (b) (c)

Figure 1: Sagittal MRI pulse sequences of lumbosacral spine at presentation. (a) (T1-weighted) shows markedly reduced signal at the L5-S1level while (b) (T2-weighted) shows increased T2 signal both in keeping with edema. (c) shows enhancement of the vertebral end plates. Allfindings are in keeping with discitis.

inflammatory polyarthritis and negative infectious workup.She was started on a trial of oral prednisone. She experiencedmild improvement in her synovitis. She was discharged homeon triple therapy for rheumatoid arthritis which includedmethotrexate, sulfasalazine, and hydroxychloroquine.

The patient returned to the hospital next day withworsening synovitis, fever (39∘C), and new onset of back painlocalized to the lumbar spine. Sulfasalazine andmethotrexatewere discontinued because of a new transaminitis (aspar-tate aminotransferase 105U/L (normal: 0–37U/L); alanineaminotransferase 114U/L (normal: 0–55U/L)). The ESR waselevated at 124MM/HR and C-reactive protein at 170mg/L.Right ankle aspiration was performed followed by methyl-prednisolone injection due to ongoing severe pain. The syn-ovial fluid samplewas inadequate for gram stain; however, theculture was negative. She then received intravenous methyl-prednisolone, 250mg every 24 hours for 2 days withoutimprovement. Repeated blood culture grew Streptobacillusmoniliformis in the anaerobic flask. MRI revealed L5-S1discitis (Figure 1) and transthoracic echocardiogram showedno evidence of endocarditis. On further questioning, thepatient admitted to having a pet rat and a pet cat, both ofwhich had died of an unknown illness in the week prior tothe initial presentation to hospital. The patient was told by alocal veterinarian that the rat was “in kidney failure” thoughfurther details are unavailable. The patient spent the nightprior to the death of the rat comforting the ailing animal inher arms. During this time, she received a scratch to her chest.

A diagnosis of RBF was made. The patient thenwas treated with intravenous ceftriaxone with discontinua-tion of steroids and hydroxychloroquine with symptomaticimprovement. She was discharged home with a 3-monthcourse of intravenous ceftriaxone on the advice of infectiousdisease and neurosurgery specialists to ensure resolutionof her discitis. Three months after discharge, the patientwas well with complete resolution of her arthritis, marked

improvement in the lower back pain, and normal inflamma-tory markers. A repeat MRI showed resolution of the discitis.

3. Discussion

Streptobacillus moniliformis is not routinely reported to pub-lic health authorities in most jurisdictions, and hence thetrue incidence rate is unknown. We report a challengingcase of RBF with discitis involving L5-S1, which was initiallypresumed to be rheumatoid arthritis. RBF with discitis isextremely rare. To our knowledge, this is the third reportedcase of discitis associated with rat bite fever. Dubois et al.reported a case of RBF with spondylodiscitis involving T5-T6 and L2-L3 [12]. Nei et al. described another case of discitisinvolving L3-L4 [13].

Apart from direct rat bite or scratch, infection can alsospread to humans by bites or scratches from animals that preyon rodents, such as cats, dogs, and pigs [8]. Streptobacillusmoniliformis is part of the normal nasopharyngeal floraof rats. Other rodents such as mice, guinea pigs, ferrets,squirrels, and gerbils also colonize this bacteria [7]. Ingestingcontaminated food products can also cause RBF, as describedin Haverhill, Massachusetts, in 1926 [8]. RBF in farmersdue to ingestion of unpasteurized milk has been reported[8]. Pet owners, children, and those working in pet shopsand animal research laboratories are at an elevated risk ofcontracting this infection [14]. Ninety percent of patientsdevelop fever within 3–10 days of exposure, which can followa relapsing pattern [2]. Typically a maculopapular, petechial,or purpuric rash is seen in the extremities and biopsy isconsistent with a leukocytoclastic vasculitis [2, 15, 16]. Othersymptoms include vomiting and headache [14]. A migratorypolyarthritis is seen commonly affecting the hands, wrists,elbows, knees, and, rarely, the sternoclavicular and sacroil-iac joints [2, 3, 17, 18]. Streptobacillus moniliformis septicmonoarthritis is described, in some cases requiring surgical

Canadian Journal of Infectious Diseases and Medical Microbiology 3

Table1:Re

ported

Caseso

fRatbitefeverw

ithinitialpresum

eddiagno

sisof

rheumatologicaldisorders.

Stud

y/year/

[reference]

Age/sex

Rat

bite/scratch

Occup

ation

Family

histo

ryof

rheumato-

logical

disorders

Clinical

features

Affected

joints

Jointaspira

teanalysis

Jointaspira

tecultu

re

Identifi

catio

nmetho

dof

Streptobacil-

lus

moniliform

is

Bloo

dcultu

reRh

eumatological

worku

pJoint

erosion

Initial

presum

eddiagno

sisTreatm

ent

Outcome

Legout

etal./2

005

[3]

60/fe

male

Ratb

itePetsho

pem

ployee

Father-

seropo

si-tiv

erheuma-

toid

arthritis

Fevera

ndpo

lyarthritis

Symmetric

alaffectin

gsm

alljoints

ofbo

thhand

sand

ankles

and

right

knee

Rightk

nee

syno

vialflu

id:

leuk

ocytosis(40

×109/L)w

ith90%

neutroph

ils

GNB

PCR

amplificatio

nof

partof

16S

RNAgene

Negative

RF,A

NA,

ANCA

s,specific

anti-filaggrin

antib

ody,and

cryoglob

ulin

weren

egative

Noerosion

Rheumatoid

arthritis

Initial:N

SAID

sand

IVmethylpredn

isolone

500m

g/dayfor3

days,

noim

provem

ent

Postc

ulture:arthrotom

yof

right

knee

and4

weeks

ofantib

iotic

swhich

inclu

dedIV

penicillinfollo

wed

byoralrifam

pinand

clind

amycin

Successfu

llytre

ated

Dendlee

tal./2

006

[4]

49/fe

male

Ratb

iteNot

repo

rted

Not

repo

rted

Polyarthritis,

fever,rash,

pneumon

ia,

andhepatitis

MCP

,wris

ts,kn

ees,rig

htelb

ow,and

right

ankle

Rightelbow

:nu

merou

sPMN

Noform

alanalysis-sample

clotte

d

Pleomorph

icGNB

16SrRNA

gene

sequ

encing

Negative

ANAandRF

complim

ent

levelswere

norm

al

Noerosion

Rheumatoid

arthritisor

Still’sdisease

Initial:oralpredn

isone

25mgdaily

with

worsening

syno

vitis

Postc

ulture:doxycyclin

e100m

gtwiced

ailyfor6

weeks

Successfu

llytre

ated

Stehleet

al./2

003

[5]

72/m

ale

Ratb

iteNot

repo

rted

Not

repo

rted

Polyarthritis

Both

knees,

elbow

s,and

left3rdMCP

RightK

nee:

leuk

ocytosis

(aroun

d50×

109/L)w

ith83%

neutroph

ilsRe

arthrocentesis

ofbo

thkn

ees,

right

elbow

,and

left3rdMCP

:analysisno

trepo

rted

Streptobacillus

moniliform

isgrew

onrepeat

syno

vialflu

idcultu

re

16SrRNA

gene

sequ

encing

Negative

Not

repo

rted

Noerosion

Atypical

rheumatoid

arthritis

Outpatient:N

SAID

and

deflazacortfora

lmost1

mon

th,no

improvem

ent

Posta

dmission:bo

luso

fIV

steroids,minim

alim

provem

ent

Postc

ulture:broad

spectrum

antib

iotic

s

Successfu

llytre

ated

Holroyd

etal./1988

[6]

59/m

ale

No

Not

repo

rted

Not

repo

rted

Fevera

ndpo

lyarthritis

PIP,MCP

,wris

tand

knees,

ankles,

elbow

s,and

shou

lders

bilaterally

Leftkn

ee:

leuk

ocyte

3,700/mm3with

80%

PMN

Leftwris

t:57,000/m

m3

and90%

PMN

Leftwris

t:pleomorph

icGNBwith

bullo

ussw

ellin

g

Gas

chro-

matograph

yof

thec

ellular

fatty

acid

oforganism

Streptobacillus

moniliform

is

NegativeR

Fand

weaklypo

sitive

ANA1:40

Not

repo

rted

Rheumatoid

arthritis

Outpatient:patient

took

NSA

IDsfor

1day

priortoadmission

Postc

ulture:ticarcillin

andgentam

icin;

penicillinGfortotal10

days

Successfu

llytre

ated


Table1:Con

tinued.

Stud

y/year/

[reference]

Age/sex

Rat

bite/scratch

Occup

ation

Family

histo

ryof

rheumato-

logical

disorders

Clinical

features

Affected

joints

Jointaspira

teanalysis

Jointaspira

tecultu

re

Identifi

catio

nmetho

dof

Streptobacil-

lus

moniliform

is

Bloo

dcultu

reRh

eumatological

worku

pJoint

erosion

Initial

presum

eddiagno

sisTreatm

ent

Outcome

Kanechorn

and

Niumpradit/

2005

[7]

61/fe

male

Rodent

bite

Retired

nurse

Not

repo

rted

Fever,

petechialrash,

myalgia,and

symmetric

alpo

lyarthritis

Fingers,

wris

ts,

knees,and

ankles

Siteof

joint

aspiratio

nno

trepo

rted.

Analysis:

leuk

ocyte

coun

tsof

over

64,000

cells/m

m3and

alln

eutro

phils

Negative

Not

repo

rted

Negative

ANAandRF

negativ

eNot

repo

rted

Septic

arthritisand

rheumatoid

arthritis

Initial:erythromycin,

Ibup

rofenas

wellas

rabies

vaccinationand

tetanu

stoxoidpriorto

admission

Posta

dmission:

dexamethasone

4mg

every6ho

urs,

amoxicillin/clavu

lanic

acid

plus

doxycycline,

noim

provem

ent

Afterjointa

nalys

is:ceftriaxone

and

penicillinGfor4

weeks,arthrotom

yand

debridem

ento

fjoints,

unrepo

rted

sites

ofjoints

Successfu

llytre

ated

Abdu

lazize

tal./2

006

[8]

68/m

ale

Rat

expo

sure,

nobite

Dairy

farm

erNot

repo

rted

Symmetric

alpo

lyarthritis,

rash,fever,

myalgias,and

headache

PIP’s,

MCP

’s,wris

ts,

ankles,and

knees

Leftkn

ee:w

hite

bloo

dcellcoun

tof

19,250/m

m3,

84%

PMN

leuk

ocytes,and

CPPD

crystals

Negative

Not

repo

rted

Pleomorph

icgram

negativ

ebacilli

Not

repo

rted

Noerosion

Acutep

ol-

yarticular

pseudo

gout

Initial:ibu

profen

and

NSA

IDs

Postc

ulture:p

enicillin

Gfor14days

successfu

llytre

ated

Successfu

llytre

ated

Tatte

rsalland

Bourne/2003

[9]

56/m

ale

Ratb

iteNot

repo

rted

Not

repo

rted

Fever,rash,

asym

metric

polyarthritis,

hand

ischemia,

sore

throat,

andloose

stools

Rightelbow

,wris

t,shou

lder,left

thum

bMCP

joint,bo

thmidtarsal

joints,

and

right

ankle

Leftthum

bMCP

:analysis

notreported

Leftankle:urate

crystals

Gram

negativ

epleomorph

iccoccob

acillus

Streptobacillus

moniliform

is

DNA

sequ

encing

Negative

Autoantib

odies

andANCA

sweren

egative

Not

repo

rted

Vasculitis

orreactiv

earthritis

Initial:IV

methylpredn

isolone

andcyclo

phosph

amide

forfew

days

with

minim

alim

provem

ent

Postc

ulture:oral

doxycycline

for6

weeks

Successfu

llytre

ated

Dworkinet

al./2

010

[10]

59/m

ale

Rat

expo

sure,

nobite

Not

repo

rted

Not

repo

rted

Polyarthritis,

diarrhea,

malaise,and

presum

edendo

carditis

knees,

ankles,

wris

ts,right

elbow

Leftkn

ee:

analysisno

trepo

rted

Pleomorph

icGNB

16SrRNA

gene

sequ

encing

Negative

ANAele

vated

1:160and

norm

alcomplim

ent,RF

and,ANCA

levels

Not

repo

rted

Polyarthritis

ofinfectious

orcollagen

vascular

disease

etiology

Initial:N

SAID

sand

steroids

Postc

ulture:penicillin,

doxycycline,and

gentam

ycin

for6

weeks

Successfu

llytre

ated


Table1:Con

tinued.

Stud

y/year/

[reference]

Age/sex

Rat

bite/scratch

Occup

ation

Family

histo

ryof

rheumato-

logical

disorders

Clinical

features

Affected

joints

Jointaspira

teanalysis

Jointaspira

tecultu

re

Identifi

catio

nmetho

dof

Streptobacil-

lus

moniliform

is

Bloo

dcultu

reRh

eumatological

worku

pJoint

erosion

Initial

presum

eddiagno

sisTreatm

ent

Outcome

Budairet

al./2

014

[11]

29/m

ale

Rat

expo

sure

Manual

labo

rerina

warehou

se

Not

repo

rted

Malaise,fever,

sore

throat,

rash,and

polyarthralgia

Right

second

MCP

,right

elbow

,right

knee

and

both

ankles

Rightank

leaspiratio

n:yello

wclo

udy

fluid

Analysis

not

repo

rted

Cultu

renegativ

e

16SrRNA

PCR

identifi

edorganism

Negative

ANA,dou

ble

strandedDNA

antib

ody,

glom

erular

basement

mem

brane

antib

ody,

myeloperoxidase

antib

odyand

proteinase-3

antib

odies,RF

,and

immun

oglobu

-lin

swerea

llno

rmal

Not

repo

rted

Vasculitis

Posto

rganism

identifi

catio

n:intravenou

sbenzylpenicillinand3

weeks

oforal

amoxicillin

Successfu

llytre

ated

GNB:

gram

negativ

ebacilli;P

IP:P

roximalInterphalangeal;MCP

:metacarpo

phalangeal;R

F:rheumatoidfactor,A

NA:anti-n

uclear

antib

ody,ANCA

:anti-n

eutro

philcytoplasmicantib

ody;NSA

ID:n

onste

roidal

anti-inflammatorydrug;IV:

Intravenou

s;PC

R:po

lymerasec

hain

reactio

n;PM

N:Polym

orph

onuclear;C

PPD:calcium

pyroph

osph

ated

ihydrate.


debridement [19, 20]. Additional complications includeosteomyelitis, pericardial effusion, endocarditis, pneumonia,meningitis, and multiorgan failure [1, 2, 14, 20].

The pathogenesis of arthritis in RBF is multifactorial.Systemic symptoms, such as fever and rash, may occur witha sterile synovial fluid culture, suggesting a reactive phe-nomenondue to an immunemediated process. In other cases,synovial fluid cultures are positivewith orwithout bacteremiasuggesting a direct infectious process [4, 21, 22]. Featuresthat suggest an immune mediated phenomenon may includevasculitic rash, hypocomplementemia, and cryoglobulinemia[23]. Wang and Wong suggest that septic arthritis caused byStreptobacillusmoniliformis detected in synovial fluidwithoutbacteremia is a separate entity with distinct clinical featuresin which fever and rash are uncommon [21].

The diagnosis of RBF can be challenging as blood culturesare usually negative [14]. Streptobacillus moniliformis is afacultatively anaerobic, highly pleomorphic gram negativebacillus [21]. Bacteria can vary in length from two to fifteen𝜇m. Its growth can be inhibited by sodium polyanetholsulfonate, an anticoagulant found on most aerobic culturebottles [21]. Therefore, this organism is more likely to growin anaerobic cultures [3]. Positive blood, synovial fluid, orrarely skin lesion culture followed by identification usinggas chromatography or sequencing of 16 s rRNA genes canconfirm the diagnosis [3–6, 16]. Up to 25%of affected patientsmay have a false positive serology test for syphilis [23].

Although this infection is difficult to diagnose, its prog-nosis is favorable.The standard treatment of RBF is penicillinor, in the case of penicillin allergy, tetracycline [21]. Strep-tobacillus moniliformis is also susceptible to cephalosporins,carbapenems, erythromycin, and clindamycin [21].

Table 1 summarizes nine cases of RBF mimicking arheumatological disorder. Six out of the nine cases receivedsteroid therapy (Table 1). In a case described by Tattersalland Bourne, a patient received cyclophosphamide wheninflammatory vasculitis was suspected (Table 1). These caseshighlight the importance of maintaining a broad differen-tial that includes RBF when assessing potential cases ofrheumatoid arthritis. The positive blood culture was themain clue to the diagnosis in our case. This case report alsohighlights the potential hazard ofmisdiagnosis and treatmentwith immunosuppressive agents. Infectious etiology is alwayson the differential, such that a zoonotic exposure historyand blood cultures should be obtained when assessing apatient with fever and arthritis. Also occupational, travel, andrecreational history should be sought for potential rodentexposure in suspected cases.

Additional Points

(i) Rat bite fever is uncommon and very difficult todiagnose.

(ii) A history of zoonotic exposure is key to diagnosis.

(iii) Clinicians should include rat bite fever in the dif-ferential diagnosis of symmetrical inflammatory pol-yarthritis.

(iv) Prognosis is good when treated appropriately butpotentially lethal if left untreated.

(v) Repeating joint aspiration and blood cultures couldincrease the likelihood of a positive identification ofpathogens associated with RBF.

Ethical Approval

No ethical approval was required for this case report.

Consent

Patient consent was obtained.

Competing Interests

All authors have no competing interests to declare.

Acknowledgments

Theauthors would like to thank theDepartment of Radiologyfor providing MRI images.

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[20] D. D. Flannery, I. Akinboyo, J. M. Ty, L. W. Averill, and A.Freedman, “Septic arthritis and concern for osteomyelitis in achild with rat bite fever,” Journal of Clinical Microbiology, vol.51, no. 6, pp. 1987–1989, 2013.

[21] T. K. F. Wang and S. S. Y. Wong, “Streptobacillus moniliformisseptic arthritis: a clinical entity distinct from rat-bite fever?”BMC Infectious Diseases, vol. 7, article 56, 2007.

[22] R. L. Rumley, N. A. Patrone, and L. White, “Rat-bite fever asa cause of septic arthritis: a diagnostic dilemma,” Annals of theRheumatic Diseases, vol. 46, no. 10, pp. 793–795, 1987.

[23] D. R. Mandel, “Streptobacillary fever. An unusual cause ofinfectious arthritis,” Cleveland Clinic Journal of Medicine, vol.52, no. 2, pp. 203–205, 1985.

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