Clinical Vignette “Joint Pain”

1. 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

2. 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.

3. 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

4. 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

5. Laboratory Assessment • ESR: 48 • Total CK: 78 • Alk phos: 97 • AST: 35 • ALT: 47 9 139 103 12.7 101 4.8 157 4.0 29 0.70 36.5

6. Plan: • Patient diagnosed with likely viral reactive arthritis • Treated with prednisone 40 mg daily for 6 days, and oxycodone for pain.

7. 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.

8. 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

9. 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.

10. 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 L5-S1 interspace • Limited neurologic exam secondary to patient’s extreme pain • No rash noted

11. Laboratory Results • ESR: 73 • CRP: 22.71 • CMP within normal limits • Blood cultures sent • Right knee aspirated 11.3 8.2 231 32.6

12. Differential Diagnosis?

13. 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 Polymyalgiarheumatica Spondyloarthropathy Crystal arthropathy Reactive arthritis

14. Data • MRI cervical spine: • Epidural and pre-vertebral abscess at C6-7 • MRI 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

15. MRI Lumbar Spine

16. MRI Cervical Spine

17. 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: IgG Ab positive, IgM Ab negative • Lyme disease Ab: IgG, IgM 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

18. 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?

19. 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)

20. 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

21. 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

22. Rat Bite Fever

23. 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

24. 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

25. Haverhill Fever • Streptobacillusmoniliformisinfection 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…

26. 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

27. 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

28. 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

29. 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

30. Clinical Manifestations • Symptoms start 3-7 days following exposure (can be up to 21 days) • Fever (intermittent) • Myalgias, arthralgias • Vomiting • Headache • Polyarthritis (can last years) • Sore throat • Serious complications • Meningitis • Endocarditis • Myocarditis • Pneumonia • Septic arthritis • Bacteremia • Multiple organ failure (Graves and Janda, 2001)

31. 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 (L4-S1) • 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 Streptobacillusmoniliformis. • Patient treated with 5 weeks IV ceftriaxone

32. 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

33. 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

34. 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

35. 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 L5 facet pending…

36. 5 Month MRI Lumbar Spine

37. 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

38. 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.