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
4 Canadian Journal of Infectious Diseases and Medical Microbiology
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
Canadian Journal of Infectious Diseases and Medical Microbiology 5
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.
6 Canadian Journal of Infectious Diseases and Medical Microbiology
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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