Infectious Arthritis

Contributor: Tara Rizvi, MD

CASE 1

A 26 year-old female is seen for evaluation of diffuse polyarthralgias that began one week ago. At the time, she developed a flu-like illness with joint pain and low grade fever. She noticed a skin rash over her face which resolved after 4 days. Her joints still continue to ache, particularly her fingers, wrists, and feet.

Past medical history and family history is unremarkable. She lives in Florida and has no travel history. She teaches third grade. She has never been sexually active, does not smoke, or use illicit drugs. She has received all recommended vaccinations.

Her vital signs are as follows: Temp – 98.8 degrees F, BP 110/60, P 84 RR 14. General physical examination was normal. Musculoskeletal examination is notable for tenderness of several MCP and PIP joints of the hands, mild synovitis and tenderness of the wrists and small bilateral knee effusions.

PARVOVIRUS ARTHRITIS

What is the differential diagnosis of the polyarthritis?

  • In this young woman, a one week duration of symptoms points towards infectious causes of polyarthritis, which would be at the top of our differential. Included in this list are parvovirus B19, hepatitis B and C virus, lyme disease, rubella virus or vaccine, alphaviruses, enterovirus, dengue, mumps, herpes or HIV virus infection.
  • Lyme disease, dengue and alphavirus infections are less likely given that she lives in non-endemic areas for these and has had no recent travel to an endemic area. There are no risk factors mentioned for Hepatitis B, C or HIV infection. Rubella arthritis is unlikely because of prior vaccination. Though joint symptoms can also develop about 2 weeks after rubella virus vaccination, she has no history of recent vaccinations reported. Parvovirus can cause arthritis in 60% of infected adults. The arthritis occurs more commonly in women. A rash may or may not be present. The typical pattern is acute onset symmetrical polyarthritis of the small joints of the hands. The patient also has an occupational risk for parvovirus exposure since she works with children.

An inflammatory arthritis associated with rheumatic disease could also be under consideration, such as a reactive arthritis, psoriatic arthritis or other spondyloarthropathies, rheumatoid arthritis, systemic lupus erythematosus and Sjogren’s syndrome, to name a few. However, the short duration of symptoms, accompanied by flu-like symptoms and rash make an infectious etiology more likely.

CASE 2

A 65 year-old male with past history of hypertension, obesity and benign prostatic hypertrophy is evaluated for a 2 day history of acute pain and swelling of his right knee. He has difficulty ambulating due to the pain and has been using a cane to walk. He has had a 5 year history of intermittent right knee pain due to osteoarthritis. He presents one week after vacationing in Greece, where he had been walking and climbing more than usual, and began to notice increased knee pain. The patient, along with other members of his family, had developed a watery diarrhea during his vacation, which resolved in 2 days with prescription medication from a local walk-in-clinic. He denies fevers or chills, but has had more fatigue lately, and difficulty sleeping due to the knee pain.

His vital signs are as follows: Temp – 100 F, BP- 144/79, P-80/min, RR-15/min. General physical exam is significant for obesity. Joint examination: Positive for heberdon’s and bouchard’s nodes at DIP’s and PIP’s bilaterally. The right knee is swollen, warm and painful with flexion and extension. Left knee reveals crepitus on extension, no effusion. Other joints are normal.

Laboratory studies:

  • WBC: 10,400/uL with 80% neutrophils
  • Hemoglobin: 14.5 g/dL
  • Platelets: 258,000/uL
  • ESR: 65mm/hr
  • Uric acid: 6.5

Synovial fluid analysis:

  • WBC 55,000/uL, with 92% neutrophils
  • Crystals: pending
  • Gram stain: pending

Right knee x-ray reveals osteoarthritic changes, chondrocalcinosis and a joint effusion.

What is the differential diagnosis of monoarthritis?

The differential diagnosis for a monoarthritis includes crystal arthropathy, reactive arthritis, rheumatoid arthritis or other connective tissue diseases. Viral arthritides, Lyme disease, or other fungal or mycobacterial infections may also be considered. In addition, hemarthrosis, tumors and other causes of intraarticular derangement such as meniscal tear and osteonecrosis can present as a monoarthritis. Arthrocentesis and synovial fluid evaluation is useful to differentiate between non-inflammatory and inflammatory causes.

What are the typical clinical manifestations of septic arthritis?

Septic joint due to bacterial infection is a destructive form of arthritis. A septic joint should be suspected in any patient presenting with an acutely swollen, warm and painful joint restricting movement. Erythema may or may not be present. The joint effusion may be moderate, or scant. Usually there is a significant degree of pain associated with active and passive movement of the joint. Patients are commonly febrile, though chills and spiking fevers are not as common. There may be a history of recent skin, urinary, respiratory or gastrointestinal infection.

80% of joint infections are monoarticular; most commonly involving the knee (in 50% cases) but may involve other joints such as wrists, ankles, hips, shoulders or small joints of the hands and feet. The remaining septic arthritis presentations may be oligoarticular or polyarticular, which are more likely to occur in patients with sepsis, or with rheumatoid arthritis or other systemic connective tissue diseases.

What is the next best course of action for this patient?

This patient has a known history of osteoarthritis and has evidence of chondrocalcinosis on xray, raising the possibility of mechanical causes and of pseudogout as a cause of his joint swelling. However, based upon his presentation of an acutely swollen joint, history of a recent infection, current fever and neutrophilia, a septic joint is very likely and must be ruled out. Crystal arthropathy and other causes of monoarthritis can occur along with a septic joint infection. Arthrocentesis is key if an infected joint is suspected. In his case, he has a synovial fluid WBC of more than 50,000u/L with predominately PMN’s, which should raise our suspicion for a joint infection even further.

Thus the next best course of action would be to begin treatment with parenteral antibiotics and to perform initial joint drainage by arthroscopy or open drainage. Choice of antibiotic is directed based upon gram stain result: Vancomycin for gram + cocci and/or a third generation cephasporin for gram – bacilli. Recommended duration of parenteral treatment may be based on the organism, but typically 2 weeks of parenteral antibiotics are given followed by another 2 weeks of oral antibiotic therapy.

Of note, the sensitivity of the gram stain for non-gonococcal bacterial arthritis is around 60%, so patients with a negative gram stain who have a high enough pretest probability for bacterial arthritis need to be treated with appropriate parenteral antibiotic coverage at least until culture results are back.

Patient Care

  1. Recognize the clinical presentations and treatment of bacterial, viral (hepatitis B and C, HIV, Parvovirus B19), Lyme and mycobacterial arthritis.
  2. Describe the steps in performing arthrocentesis of the joints.
  3. Recognize how to interpret results of synovial fluid analysis.
  4. Describe cultures useful in diagnosing gonococcal and non-gonococcal arthritis.
  5. Describe the clinical management of bacterial septic arthritis, including initial antibiotic therapy and joint drainage.
  6. Identify the serologic tests useful in diagnosing viral and Lyme arthritis.
  7. Identify radiographic changes suggestive of septic arthritis ( 1, 2, 3, 4, 5).
  8. Identify the skin changes seen in disseminated gonococcal infection ( 1, 2) and Lyme’s disease ( 1, 2, 3).
  9. Identify physical exam, radiographic findings and pathology seen in mycobacterial arthritis ( 1, 2, 3, 4).

Medical Knowledge

  1. Identify the role that infection plays in triggering arthritis.
  2. List the most common bacterial organisms causing arthritis in children, adults, IV drug users, and patients with prosthetic joints.
  3. Define factors that predispose to bacterial septic arthritis.
  4. Describe the sensitivity of synovial fluid stains and cultures for bacterial, gonococcal and mycobacterial arthritis.
  5. Understand the poor outcomes related to septic joints and the overall prognosis and thus the importance of early treatment.
  6. Relate the epidemiology of Lyme disease.

Interpersonal And Communication Skills

  1. Explain the evaluation, diagnosis, treatment and prognosis clearly to patient and family, using a patient-centered approach.
  2. Establish a relationship with the patient and discuss the need for appropriate follow up and monitoring with the patient.
  3. Demonstrate the ability to communicate and interact with the primary team, consultants (orthopedics, infectious disease) and allied health professionals (physical and occupational therapy) in the management of a patient with a septic joint.

Professionalism

  1. Recognize the importance of patient confidentiality and privacy.
  2. Demonstrate integrity and honesty in interactions with others.
  3. Serve as an advocate for your patient, showing sensitivity to their individual needs.
  4. Understand the need to provide ongoing supportive care to the patient.

Problem-Based Learning

  1. Identify knowledge deficits regarding infectious arthritis and set goals to formulate a learning plan.
  2. Develop a willingness to recognize mistakes and learn from them.
  3. Demonstrate the ability to review and interpret literature relevant to the care of patients with arthritis secondary to infection.
  4. Recognize the similarities between a septic joint and acute gouty arthritis, and that they can occur concomitantly (1).
  5. Understand the impact on health and the adverse outcomes for the patient if a septic joint is diagnosis is missed.

System Based Practice

  1. Effectively engage all medical providers and incorporate different facets of the health system in managing infectious arthritis.
  2. Identify barriers to the delivery of optimal patient care for patients with infectious arthritis.

References

Questions

(Answer questions 1-6 on a piece a paper. Find Answer Key at the bottom on the page.)

CASE 1

A 23-year-old woman is evaluated in the emergency room for fever, malaise and joint pain. Symptoms began 5 days ago, when she had right wrist pain which resolved spontaneously. She subsequently developed pain in the left wrist and left knee associated with mild swelling. On exam today, she has joint swelling over the left wrist and a small left knee effusion. She is sexually active and reports a mild vaginal discharge in the last couple of weeks.

Physical examination reveals a temperature of 101.1 degrees F, pulse 90 bpm, blood pressure 134/72. General physical exam is normal except for 4 small vesiculo-pustular erythematous lesions noted on her left hand. Musculoskeletal exam reveals tenosynovitis and tenderness of the left wrist, and a small left knee effusion. Other joints are normal.

Laboratory data:

White blood cell count 15,000/cu mm
Polymorphonuclear leukocyte (PMN): 75%
ESR: 63 mm/hr
CMP: normal
HIV: negative
Hepatitis serologies: negative
Arthrocentesis of the left knee is performed and synovial fluid results are as follows:
White blood cell count: 38,000
Polymorphonuclear leukocyte (PMN): 85%
Crystals and gram stain: negative

1) What is the next step for diagnosis:

  1. Repeat arthrocentesis
  2. Send cervical, urethral and rectal cultures
  3. X-ray the left knee
  4. Order ANA, RF and CCP Ab
  5. Steroid injection to left knee.

2) What is the most appropriate treatment for this patient?

  1. Amoxicillin PO
  2. Doxycycline PO
  3. Cefixime PO
  4. Ceftriaxone IV
  5. Ciprofloxacin IV

 

CASE 2

A 59-year-old Army Veteran is evaluated for swelling and pain of the right elbow. He has a long standing history of rheumatoid arthritis and is wheelchair bound. He has had several episodes of right olecranon bursitis over the last few years, attributed to the friction of his elbows on the arm of his wheelchair. The last episode one year ago responded well to corticosteroid injection. During the past few days, he has noticed redness, warmth, and pain over the elbow.

The patient’s temperature is 100.0F, pulse is 100 bpm, pulse 78, blood pressure is 125/70. On joint exam, there is obvious swelling and tenderness and warmth of the right olecranon bursa. There is pain with both palpation and with extension of the elbow. The patient is holding his elbow in a flexed position. The hands show ulnar deviation at the MCP joints with synovitis.

3) What is the most appropriate next step to confirm a diagnosis?

  1. X-ray of the right elbow
  2. Aspiration of the olecranon bursa
  3. Steroid injection of the olecranon bursa
  4. Surgical referral for surgical removal for recurrent bursitis
  5. Begin Cefazolin PO

Needle aspiration of the right olecranon bursa yields 10 mL of cloudy . WBC: 60,000/mm3. No crystals seen. Gram stain reveals gram-positive cocci in clusters.

4) Which of the following antibiotics should be administered to this patient?

  1. Doxycycline
  2. Trimethoprin – sulphamethoxazole
  3. Cefotaxime
  4. Linezolid
  5. Vancomycin

References and further reading:

  1. Mathews CJ1, Weston VC et al. Bacterial Septic Arthritis in Adults; Lancet. 2010 Mar 6;375(9717):846-55
  2. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/rheumatology/septic-arthritis/

CASE 3

A 38 year old pregnant female is referred to you for management. She is currently 26 weeks pregnant. She frequently visits her family in upstate New York. 8 weeks ago she developed a swollen and painful left knee. There was no history of rash, tick bite, cardiac, respiratory or neurologic symptoms. The left knee was aspirated and synovial fluid was slightly cloudy, with a WBC of 18,500, and 82% PMN’s. Gram stain and cultures were found to be negative. She had a positive Lyme titer by ELISA, and Western blot assay had shown 9 bands. (normal is less than five.)

She was treated with ceftriaxone 2g intravenously daily for 30 days. She returns today feeling better but still has mild arthralgias and myalgias, in addition to symptoms of fatigue. A physical examination is unremarkable except for her pregnant state. The joint exam is largely normal, with complete resolution of the knee effusion. Repeat Western blot assay shows seven bands (normal <5.)

5) Which treatment option is most appropriate at this point?

  1. Begin amoxicillin 2 g daily, to be continued for 3 months
  2. Begin ceftriaxone 2 g IV daily for an additional 30 days
  3. Begin hydroxychloroquin 400 mg daily
  4. Reorder Western blot assay
  5. Reassure the patient that no further treatment is needed

CASE 4

A 50 year old man is sent for evaluation for polyarthralgias. He does not complain of joint swelling today, but relates having had two episodes of wrist and knee swelling in the last year, which resolved after arthrocentesis and steroid injection. He has been told he may have crystal arthropathy, but lab review shows negative crystals in both synovial fluid specimens sent in the last year. He also has pain in the joints of his hands, ankles and feet, and morning stiffness that lasts 15-20 minutes. Review of systems is positive for fatigue for six months and a skin rash over his legs noticed six weeks ago. He denies fever or chills.

Past medical is unremarkable. He has had no surgeries. He denies recent travel, tobacco or recreational drug use.

Joint exam reveals tenderness over the PIP’s, MCP’s, wrists, knees and feet bilaterally. There is no joint swelling present. He has palpable purpura over the skin of the lower extremities.

INFECTIOUS ARTHRITIS

Laboratory studies:

CBC: normal
Cr: 1.4
AST: 92 IU/L
AST: 101 IU/L
ANA: 1:40 speckled
ESR: 45mm/hr
RF: >250 IU/mL
CCP Ab: negative
C3: 50mg/dL
C4: 12 mg/dL

Further blood tests and x-rays of the joints are ordered and a dermatology consult is requested.

6) What is the most likely diagnosis:

  1. Systemic lupus erythematosus
  2. Reactive arthritis
  3. Hepatitis C
  4. Rheumatoid arthritis
  5. HIV arthropathy

Answer Key

CASE 1

1) The correct answer is B.

This patient has disseminated gonococcal infection (DGI) with classic symptoms of tenosynovitis, characteristic skin lesions and a migratory polyarthritis. DGI can occur as one of 2 syndromes: A triad of tenosynovitis, dermatitis and migratory polyarthralgias , or a purulent arthritis without skin lesions. There is a degree of overlap between the two presentations.

In case of this more common presentation of the classic triad with DGI, synovial fluid cultures may often be negative. Patients suspected of DGI should also have urethral, cervical and/or rectal cultures submitted to increase the yield of isolating Neisseria gonorrhoea. Approximately 50% of patients who have gonococcal arthritis have positive cultures from one of the above three mucosal sites. The culture for N gonorrhoeae is almost always negative in skin lesions, is positive in less than 50% of synovial fluid cultures and less than one third of blood cultures.

2) The correct answer is D.

Therapy of disseminated gonococcal infection usually consists of a third generation cephalosporin given parenterally for the first few doses. Other choices would include IV cefotaxime and IV ceftazadime . An update to the 2010 CDC guidelines was issued in 2012, stating that oral cephalosporins are no longer a recommended treatment for gonococcal arthritis. Thus PO amoxicillin or doxycycline use would be incorrect. Due to evidence of declining cefixime susceptibility, the CDC no longer recommends cefixime (choice C) at any dose as a first-line regimen for treatment of gonococcal infections. Quinolones are not recommended for empiric therapy even for mild non-disseminated gonococcal infections, so D is incorrect.

All DGI cases should receive the first dose of antibiotics parenterally if treated outpatient. In a patient who appears toxic as above, IV therapy with a third generation cephalosporin should be initiated and continued after hospital admission. Patients should also receive 1 gram of oral azithromycin, or doxycycline 100 mg twice a day for seven days to cover potential Chlamydia. trachomatis co-infection. Treatment of sexual partners is also recommended.

References:

  1. 1.P.A. Rice, Gonococcal arthritis (Disseminated gonococcal infection) Infect Dis Clin North Am 19 (2005), pp. 853–861
  2. http://www.cdc.gov/std/Gonorrhea

3) The correct answer is B.

Any unexplained joint or bursal fluid in a febrile patient must be aspirated to assess for infection. Even though this patient has a prior history of chronic arthritis and similar episodes in the past, aspiration is key to rule out infection. Having underlying joint disease and an immunosuppressed status due to RA medications are both predisposing factors for infection in a joint.

4) The correct answer is E.

The olecranon bursa is a superficially located bursa over the olecranon surface that can become inflamed in rheumatic conditions such as gout and rheumatoid arthritis, and also in cases of trauma and infection. The most common organism implicated in septic bursitis is Staphylococcus aureus, but there is an emerging role of methicillin-resistant S. Aureus (MRSA) infections even in the community setting. The antibiotic of choice for treatment of gram positive cocci on gram stain is IV vancomycin.

5) The correct answer is E.

This woman was appropriately treated with IV ceftriaxone for an adequate period of time. The presence of refractory or partially treated disease should have been considered if the patient continued to have signs of arthritis or if she developed features of Lyme carditis or neurologic disease. However, she continues to feel well; fatigue and mild aches and pains are non-specific and may be attributed to pregnancy. Thus she can be reassured that her Lyme disease has been treated effectively and no further therapy is indicated.

Serologic tests may remain positive for years after Lyme disease treatment, despite the infection having resolved. Follow up serologic testing is generally not helpful if the patient is doing well clinically, and may confound the picture. Since antibiotic therapy does not immediately halt the immune response, it is not unusual for follow up western blot assays to show persistence of bands.

Follow up serologic testing may be of significance if the patient is not clinically improving, or worsening, in which case a persistent infection may be present. However, despite this, there is no evidence that even chronic lyme arthritis can be prevented or treated with greater than 1 month of antibiotic course. Intravenous treatment for two weeks to one month is the CDC’s recommended treatment duration

References and further reading:

  1. Eugene D. Shapiro, M.D. Lyme Disease; N Engl J Med 2014; 370:1724-1731
  2. http://www.cdc.gov/lyme

6) The correct answer is C.

The presentation of polyarthralgias, palpable purpura, elevated liver tests and a positive rheumatoid factor (with negative CCP Ab) is suggestive of chronic Hepatitis C virus infection. Hepatitis C infection can result in formation of circulating immune complexes which may deposit in tissues to produce clinical manifestations of mixed essential cryoglobulinemia. These may include arthritis, glomerulonephritis, and vasculitis.

A substantial number of patients with hepatitis C infection have musculoskeletal complaints such as arthralgias and myalgias. Hepatitis C arthropathy may be present in 2 to 20 percent of patients with HCV. It generally presents as a rheumatoid-like arthritis, or as an oligoarthritis.

Hepatitis C infected hepatic lymphocytes may secrete molecules with rheumatoid factor positivity. HCV infection is associated with a positive RF in 54 to 82 percent of cases, more commonly in patients with mixed cryoglobulinemia.

SLE can present with similar arthralgias and rash, however, an ANA titer of 1:40 is considered negative, and the positive RF and elevated liver tests do not go along with the diagnosis. Likewise, reactive arthritis can present with arthropathy, a similar rash, conjunctivitis and/or urethritis. However, the patient currently is presenting with arthralgias without frank arthritis.. Rheumatoid arthritis and reactive arthritis do not typically go together with the elevated liver tests, negative CCP Ab and low complements on blood tests. Lastly, though HIV arthropathy can present similarly, again the constellation of laboratory tests are most suggestive of diagnosis of Hepatitis C.

References and further reading:

  1. Zeynel A. Sayiner, Uzma Haque et al. Hepatitis C Virus Infection and It’s Rheumatologic Implications. Gastroenterology and Hepatology Volume 10 Issue 5, May 2014.
  2. Rosner I1, Rozenbaum M, et al. The Case for Hepatitis C arthritis. Semin Arthritis Rheum;2004 Jun;33(6):375-87.

Last updated February 2015.