Clinical Vignette Joint Pain Kathryn Skelly MD MSc

Clinical Vignette “Joint Pain” Kathryn Skelly, MD, MSc Internal Medicine Resident , Maine Medical Center American College of Physicians Maine Chapter 2013 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 effusions No known tick exposure or rash Not sexually active. No penile discharge or dysuria No known family history of rheumatologic disease Uses 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 Exam VS: 37. 3; 137/89; 91; 18; 94% on room air General: Well-appearing HEENT: No lymphadenopathy Regular heart rhythm. No murmurs, rubs, or gallops Lungs clear to auscultation bilaterally Benign abdominal exam Musculoskeletal 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 4. 8 12. 7 36. 5 139 103 157 9 4. 0 0. 70 29 ESR: 48 Total CK: 78 Alk phos: 97 AST: 35 ALT: 47 101

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 prescribed Has been taking extra morphine, and reports that pain is still “ 16/10” Denied fevers Denied IV drug use or tick exposure.

Physical Exam VS: T 36. 8, P 89, BP 156/89, RR 18, 98% on RA Notable 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 Exam VS: 38. 3, BP: 141/76, P: 88, RR: 22, 96% on RA Warmth and effusions of both knees and right elbow tenderness and warmth over both AC joints with decreased range of motion of shoulders Tenderness along L 5 -S 1 interspace Limited neurologic exam secondary to patient’s extreme pain No rash noted

Laboratory Results 8. 2 11. 3 231 32. 6 ESR: 73 CRP: 22. 71 CMP within normal limits Blood cultures sent Right knee aspirated

Differential Diagnosis?

Our Differential Diagnosis Infection: Endocarditis Bacteremia and septic arthritis Osteomyelitis of the spine Disseminated gonococcal infection Tick-borne illness Viral Infection (parvovirus, hepatitis) Inflammatory Arthritis: Rheumatoid arthritis SLE Polymyalgia rheumatica Spondyloarthropathy Crystal arthropathy Reactive arthritis

Data MRI cervical spine: Epidural and pre-vertebral abscess at C 6 -7 MRI lumbar spine: Septic facet arthropathy at L 4 -5 with 9 X 17 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 seen Gram stain negative, culture no growth Hepatitis panel negative CCP Ab <6 (negative) RF 19 (0 -13) ANA <1: 80 Parvovirus: Ig. G Ab positive, Ig. M Ab negative Lyme disease Ab: Ig. G, Ig. M negative HIV negative ANCA negative Chlamydia, gonorrhea negative TEE: Structurally normal valves, with no evidence of vegetations Blood cultures negative at 48 hours, 2 sets

Hospital Course CRP 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 Course Blood cultures: Gram negative rods Suspected anaerobic activity Possible organisms: Salmonella Bacteroides Prevotella Fusobacterium Hospital Day #5 Patient 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 moniliformis Still awaiting final speciation Still on cefepime and metronidazole Likely septic polyarthritis (knees and AC joints) despite negative culture of aspirate Fastidious organism WBC in aspirate likely low due to initial course of prednisone Epidural 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 Q 4 hours HD #21: Patient discharged to rehab on IV penicillin therapy with weekly ID follow up

Rat Bite Fever

Rat Bite Fever Three 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 1914 Causal organism named Streptobacillus moniliformis in 1925

Streptobacillus Moniliformis Pleomorphic filamentous bacilli Characteristic bulbous swelling in chains and tangled clumps Fastidious Slow growing Must hold cultures at least 5 days Aerobic and facultatively anaerobic Torres et al. 2001

Haverhill Fever Streptobacillus moniliformis infection via ingestion of contaminated food Contamination with infected excreta or saliva Typical features: Absence of known rat exposure Large number of patients Common geographical and temporal exposure First described in 1926…

Outbreak in Haverhill, MA: 1926 86 patients developed symptoms over a 4 week period Symptoms: Abrupt, severe fever and chills Nausea, vomiting, headache Arthritis (>6 joints in 50% of patients) Relapsing and remitting rash Macular or papular, petechial; wrists, arms, feet, ankles Identified source of infection: raw milk 92% of patients had received raw milk from local bottling plant Suspected possible contamination from rat urine

Rat Bite Fever: Epidemiology 2 million animal bites per year in the U. S. 1% are rat bites Incidence likely very underestimated Rat bite fever is not a reportable disease Generally low clinical suspicion Difficult to culture Typical patient profile: Historically, children living in poverty Demographics 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=45 Rat 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) Presenting Symptoms Percentage of Myalgias, arthralgias Patients Vomiting Headache Fever 88 Polyarthritis (can last years) Arthritis/Arthralgia 73 Sore throat Rash 65 Serious complications Meningitis Endocarditis Myocarditis Pneumonia Septic arthritis Bacteremia Multiple organ failure 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 weakness MRI: Large epidural abscess (L 4 -S 1) Urgently went to OR Culture from abscess negative, but blood cultures grew gram negative rods: Patient treated empirically for Capnocytophaga spp. due to history of his dog licking a wound After 21 days, organism identified as Streptobacillus moniliformis. Patient treated with 5 weeks IV ceftriaxone

Diagnosis Consider in any patient with unexplained febrile illness, with rash and/or polyarthritis Particularly if rat or other rodent exposure Blood or synovial fluid Alert lab, so they can optimize media and culture Incubate cultures for 21 days Serologic testing not available

Treatment Mortality rate 13% without treatment Treatment of choice: IV penicillin 400, 000 -600, 000 IU (240 -360 mg) per day Add streptomycin or gentamicin for endocarditis Alternatives: Tetracycline, doxycycline, streptomycin Cephalosporins have been used successfully Duration of therapy is individualized

D. P. Clinical Course After 6 weeks: Still on IV Penicillin Continues to have severe back and knee pain CRP: 4. 95 Follow up MRI after 3 months: Epidural abscesses had resolved Multilevel osteomyelitis, discitis and inflammatory changes improving

D. P. Clinical Course After 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. 21 IR guided biopsy of L 5 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 areas Global poverty Lack of clean water supply, sanitary food Black market wildlife trade Exotic pets Animal parts Consumption

References Addidle 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.