Kathryn Skelly, MD, MScInternal Medicine Resident , Maine Medical

Center

American College of Physicians Maine Chapter2013 Annual Chapter Educational Meeting

September 28, 2013

D.P. : 44 year old male HPI:

Polyarthralgias for 1 day (shoulders, hands, knees)Fever to 100.9 and “flu-like symptoms”Acute on chronic bilateral knee effusionsNo known tick exposure or rashNot sexually active. No penile discharge or dysuriaNo known family history of rheumatologic diseaseUses medical marijuana but denied other drug use

ROS: Mild headache earlier in the week that had resolved Denied cough, sore throat, shortness of breath,

chest pain, abdominal pain, nausea, vomiting, diarrhea.

History Past Medical History:

Osteoarthritis (spine and knees) GERD

Medications: Morphine 30 mg QID (chronic back and knee pain) Pantoprazole 40 mg BID Medical marijuana

Allergies: Celebrex, nexium Social History:

Works as a landscaper. Single 4 drinks of alcohol daily. No tobacco Marijuana as above No recent travel outside Maine.

Family History: Patient unsure of family history

Physical ExamVS: 37.3; 137/89; 91; 18; 94% on room air

General: Well-appearingHEENT: No lymphadenopathyRegular heart rhythm. No murmurs, rubs, or gallopsLungs clear to auscultation bilaterallyBenign abdominal examMusculoskeletal and Neurologic exams:

Visible trapezius and rhomboid muscle spasms. No bony point tenderness to palpation along the spine. Pain with bilateral upper extremity abduction, but full

range of motion Strength 5/5 in upper and lower extremities No warmth or erythema of knees, but effusions present

Laboratory Assessment

ESR: 48Total CK: 78

Alk phos: 97AST: 35ALT: 47

139

4.0

103

29

9

0.70101

12.74.8

36.5

157

Plan:

Patient diagnosed with likely viral reactive arthritis

Treated with prednisone 40 mg daily for 6 days, and oxycodone for pain.

Second Presentation HPI:

Presents to ED with worsening bilateral shoulder pain, low back pain, and knee pain

He took prednisone as prescribedHas been taking extra morphine, and

reports that pain is still “16/10”Denied feversDenied IV drug use or tick exposure.

Physical ExamVS: T 36.8, P 89, BP 156/89, RR 18, 98%

on RANotable for hyperesthesia of skin over shoulders and trapezius muscles

Swelling and erythema over AC joints bilaterally, with “exquisite” tenderness to palpation.

Bilateral knee effusions noted. No rash.

Patient referred to rheumatology

Third Presentation HPI

Patient presents with worsening joint pain

Back pain and knee pain now so severe, patient can’t get out of bed or ambulate

Family called 911 because patient was having rigors at home.

Physical ExamVS: 38.3, BP: 141/76, P: 88, RR: 22,

96% on RAWarmth and effusions of both knees and

right elbowtenderness and warmth over both AC

joints with decreased range of motion of shoulders

Tenderness along L5-S1 interspaceLimited neurologic exam secondary to

patient’s extreme painNo rash noted

Laboratory Results

ESR: 73

CRP: 22.71

CMP within normal limitsBlood cultures sentRight knee aspirated

11.38.2

32.6

231

Differential Diagnosis?Differential Diagnosis?

Our Differential DiagnosisInfection:

EndocarditisBacteremia and septic arthritis

Osteomyelitis of the spineDisseminated gonococcal

infectionTick-borne illness

Viral Infection (parvovirus, hepatitis)

Inflammatory Arthritis:

Rheumatoid arthritisSLE

Polymyalgia rheumatica

SpondyloarthropathyCrystal arthropathyReactive arthritis

DataMRI cervical spine:

Epidural and pre-vertebral abscess at C6-7MRI lumbar spine:

Septic facet arthropathy at L4-5 with 9X17 mm abscess extending into the right subarticular recess and posterior paraspinal muscle

Patient started on vancomycin, ceftriaxone, metronidazole

Neurosurgery and infectious disease consults

MRI Lumbar Spine

MRI Cervical Spine

More Data:Right knee aspirate:

13,200 leukocytes 88% PMN 12% lymphocytes

No crystals seenGram stain negative, culture no growth

Hepatitis panel negativeCCP Ab <6 (negative)RF 19 (0-13)ANA <1:80Parvovirus: IgG Ab positive, IgM Ab negativeLyme disease Ab: IgG, IgM negativeHIV negativeANCA negativeChlamydia, gonorrhea negativeTEE: Structurally normal valves, with no evidence of vegetationsBlood cultures negative at 48 hours, 2 sets

Hospital CourseCRP up to 29.35 (from 22.7 )

Hospital day #3:Blood cultures from admission now positive

for gram negative rods (2/2)Patient changed to cefepime (still on

vancomycin and metronidazole)

Patient reveals more history:Pets: iguanas and snakes at home

What are you thinking now?

Hospital CourseBlood cultures:

Gram negative rodsSuspected anaerobic activityPossible organisms:

SalmonellaBacteroidesPrevotellaFusobacterium

Hospital Day #5Patient reports that several days before

symptoms started, he was bitten by a live rat while feeding it to his pet snake (hospital admission was about 11 days after the bite)

Working Diagnosis“Rat bite fever”

Organism on gram stain resembles Streptobacillus moniliformisStill awaiting final speciation Still on cefepime and metronidazole

Likely septic polyarthritis (knees and AC joints) despite negative culture of aspirateFastidious organismWBC in aspirate likely low due to initial course of

prednisoneEpidural abscesses

Followed by neurosurgery No surgical intervention

Final Diagnosis:“Rat bite fever”, with cervical and lumbar

epidural abscesses, osteomyelitis, and septic polyarthritis

Hospital Day #16, final speciation on blood cultures:Streptobacillus moniliformis Identified in collaboration

between MMC and Mayo Clinic

Patient changed to IV penicillin G Q4 hours

HD #21: Patient discharged to rehab on IV penicillin therapy with weekly ID follow up

Rat Bite Fever

Rat Bite FeverThree Clinical Syndromes:

Streptobacillus moniliformis infection Accounts for most cases in the United States

Spirillum minus (sodoku) Mostly in Asia, but found worldwide

Haverhill Fever

First reported in the U.S. in 1914Causal organism named Streptobacillus

moniliformis in 1925

Streptobacillus MoniliformisPleomorphic filamentous

bacilliCharacteristic bulbous

swelling in chains and tangled clumps

FastidiousSlow growing

Must hold cultures at least 5 days

Aerobic and facultatively anaerobic

Torres et al. 2001

Haverhill FeverStreptobacillus moniliformis infection via

ingestion of contaminated foodContamination with infected excreta or

salivaTypical features:

Absence of known rat exposureLarge number of patients

Common geographical and temporal exposure

First described in 1926…

Outbreak in Haverhill, MA: 192686 patients developed symptoms over a 4 week periodSymptoms:

Abrupt, severe fever and chillsNausea, vomiting, headacheArthritis (>6 joints in 50% of patients)Relapsing and remitting rash

Macular or papular, petechial; wrists, arms, feet, ankles

Identified source of infection: raw milk92% of patients had received raw milk from local

bottling plantSuspected possible contamination from rat urine

Rat Bite Fever: Epidemiology2 million animal bites per year in the U.S.

1% are rat bites

Incidence likely very underestimatedRat bite fever is not a reportable diseaseGenerally low clinical suspicionDifficult to culture

Typical patient profile:Historically, children living in povertyDemographics changing

Children (pet rat), pet store workers, animal lab personnel

Disease Transmission Found predominantly in nasal and oropharyngeal flora of rats

10-100% of domesticated and lab rats 50-100% wild rats

Infection and colonization documented in other species: Guinea pigs, gerbils, ferrets, cats, dogs, mice

Infection resulting from: Rat bite Rat scratch Handling infected rat (can be transmitted via infected saliva) Ingesting food/water contaminated with infected rat feces Exposure in cases of infection can be unknown

Possible infection from dog bite after dog had contact with rat: (Wouters et al 2008): 3/18 dogs who had proven contact with

rats were found to have Streptobacillus moniliformis in their mouth

Graves and Janda (2001) Microbial Diseases

Laboratory, State of California:Documented cases of

human infection with Streptobacillus moniliformis from 1970-1998

N=45Rat exposure:

Bite, scratch, kiss, other rat association

Animal Exposure Percentage of Patients

Pet rat 54

School rat 14

Other rat exposure

11

Wild rat 9

Mouse 3

Squirrel 3

Exposure not known

6

Clinical Manifestations Symptoms start 3-7 days following exposure (can be up to 21 days)

Fever (intermittent)Myalgias, arthralgiasVomitingHeadachePolyarthritis (can last years)Sore throat

Serious complicationsMeningitisEndocarditisMyocarditisPneumoniaSeptic arthritisBacteremiaMultiple organ failure

Presenting Symptoms

Percentage of Patients

Fever 88

Arthritis/Arthralgia 73

Rash 65

Fatigue/Malaise 20

Headache 18

Chills 15(Graves and Janda, 2001)

Epidural Abscess and Streptobacillus moniliformis: One Case Report in the Literature (Addidle et al., 2012)58 year old male presented with 2 weeks back

pain, fevers, lower extremity weaknessMRI: Large epidural abscess (L4-S1)Urgently went to ORCulture from abscess negative, but blood cultures

grew gram negative rods:Patient treated empirically for Capnocytophaga

spp. due to history of his dog licking a woundAfter 21 days, organism identified as

Streptobacillus moniliformis.Patient treated with 5 weeks IV ceftriaxone

DiagnosisConsider in any patient with unexplained

febrile illness, with rash and/or polyarthritisParticularly if rat or other rodent

exposureBlood or synovial fluid

Alert lab, so they can optimize media and culture

Incubate cultures for 21 daysSerologic testing not available

TreatmentMortality rate 13% without treatmentTreatment of choice:

IV penicillin 400,000-600,000 IU (240-360 mg) per dayAdd streptomycin or gentamicin for

endocarditisAlternatives: Tetracycline, doxycycline,

streptomycinCephalosporins have been used

successfullyDuration of therapy is individualized

D.P. Clinical CourseAfter 6 weeks:

Still on IV PenicillinContinues to have severe back and

knee painCRP: 4.95Follow up MRI after 3 months:

Epidural abscesses had resolvedMultilevel osteomyelitis, discitis

and inflammatory changes improving

D.P. Clinical CourseAfter 5 months:

On oral Penicillin (500 mg QID)MRI shows stable disease in cervical spine, but progression of osteomyelitis in the lumbar spine

CRP 0.21IR guided biopsy of L5 facet pending…

5 Month MRI Lumbar Spine

Considerations for the Future:Zoonoses on the Rise?Changing planet:

Human wildlife conflict Habitat loss, dissolving boundaries Commercial bushmeat hunting worldwide

Urbanization of previously rural areasGlobal poverty

Lack of clean water supply, sanitary foodBlack market wildlife trade

Exotic pets Animal parts Consumption

ReferencesAddidle et al. 2012. Epidural Abscess Caused by

Streptobacillus moniliformis. Journal of Clinical Microbiology; 50(9): 3122-3124.

Elliot, S. 2007. Rat Bite Fever and Streptobacillus moniliformis. Clinical Microbiology Reviews. P. 13-22.

Graves and Janda, 2001. Rat-Bite Fever (Streptobacillus moniliformis): A Potential Emerging Disease. Int J Infect Dis; 5:151-154.

Wouters et al, 2008. Dogs as Vectors of Streptobacillus moniliformis infection? Vet Microbiol; 128(3-4): 419-22.

Torres et al, 2001. Remitting Seronegative Symmetrical Synovitis with Pitting Edema Associated with Subcutaneous Streptobacillus moniliformis Abscess. Journal of Rheumatology 2001; 28: 1696-8.