Endgames Case Review

A limp with an unusual cause

BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1985 (Published 21 April 2015) Cite this as: BMJ 2015;350:h1985
  1. Rebecca Metcalfe, specialty trainee, genitourinary medicine1,
  2. Michael Reed, specialty trainee, rheumatology2,
  3. Andrew Winter, consultant, genitourinary medicine1
  1. 1Sandyford Sexual Health Service, Glasgow G3 7NB, UK
  2. 2Department of Rheumatology, Glasgow Royal Infirmary, Glasgow
  1. Correspondence to: R Metcalfe rebeccametcalfe{at}nhs.net

A 41 year old Ghanaian man resident in the United Kingdom presented with a five hour history of pain and swelling of the right ankle, left wrist, and right middle finger. He felt generally unwell but had no other specific symptoms on systemic inquiry. He had just returned from a two week visit to Ghana. There was no medical history of note, he was taking no regular drugs, and he had no known drug allergies. The appropriate travel prophylaxis had been adhered to. He had had unprotected intercourse with a new female partner about 10 days ago.

On examination, his temperature was 37.8°C. There was evidence of synovitis (joint swelling, redness, tenderness, and reduced range of movement) of the right ankle, left wrist, and the proximal interphalangeal joint of the middle finger of his right hand. Initial investigations confirmed that his neutrophil count, C reactive protein concentration, and erythrocyte sedimentation rate were raised. Radiographs of the affected joints showed soft tissue swelling but were otherwise normal.

The pain did not ease with oral non-steroidal anti-inflammatory drugs and he was admitted to hospital.

Questions

  • 1. What is the differential diagnosis?

  • 2. What is the most likely diagnosis and why?

  • 3. What further investigations are necessary?

  • 4. What are the treatment options?

Answers

1. What is the differential diagnosis?

Answer

The main differential diagnosis is between polyarticular septic arthritis and reactive arthritis. Other possibilities include seronegative inflammatory arthritis, connective tissue disorder, and polyarticular gout.

Discussion

Septic arthritis may be polyarticular, although this is less common than monoarticular septic presentations. Polyarticular septic arthritis is caused by the haematogenous spread of organisms to affected joints. Most cases are caused by Staphylococcus aureus or Streptococcus spp. Less common causes are Gram negative organisms such as Escherichia coli and Neisseria gonorrhoeae.1 2 Risk factors for septic arthritis include local factors such as pre-existing joint damage, recent joint surgery, joint prosthesis, and invasive procedures.2 3 Systemic risk factors include factors that predispose to bacteraemia, such as intravenous drug use or active infection elsewhere.2 3 Exposure to a source of infection may be through soft tissue injury or cellulitis, or through the gastrointestinal or genitourinary tracts.2 Certain bacteria, such as N gonorrhoeae, are particularly likely to infect a joint during a bacteraemic episode.4 Other risk factors include pre-existing rheumatoid arthritis, diabetes,3 HIV infection, and pharmacological immunosuppression.2

Sexually acquired infection with N gonorrhoeae can lead to disseminated gonoccocal infection and present as septic arthritis. It is an important cause of septic arthritis in young people.2 Presentation is typically subacute; joint involvement is usually monoarticular or oligoarticular and asymmetrical, and it may be migratory or additive.2

Reactive arthritis is a form of inflammatory arthritis that is a manifestation of an immune reaction to infection at a distant site. This results in a sterile inflammation of the synovial membrane, tendons, and fascia.5 Various infections can cause reactive arthritis, including bacterial infections of the genital tract, such as Chlamydia trachomatis, which result in sexually acquired reactive arthritis (SARA); gastrointestinal infections, including salmonella, shigella, and campylobacter; and viral infections, such as parvovirus, Epstein-Barr virus, coxsackie viruses, hepatitis B and C viruses, and acute HIV.6 Often the causative organism is not identified.6

Reactive arthritis is part of a group of inflammatory arthritides known as seronegative spondyloarthropathies. This group of conditions also includes ankylosing spondylitis, psoriatic arthritis, and inflammatory bowel disease related arthritis. All typically present with asymmetrical oligoarthritis.6 The axial skeletal may be affected, and extra-articular features such as inflammatory eye disease, tendinopathies, and rashes are often present.6 All of these conditions are associated with the HLA-B27 haplotype,6 and where these clinical features are seen in the context of recent infection, reactive arthritis should be suspected.

Rheumatoid arthritis typically presents with a symmetrical pattern of joint involvement, usually with sparing of the distal interphalangeal joints. Connective tissue disorders may present with arthralgia as a predominant feature. Other features of connective tissue disorders including a history of Raynaud’s phenomenon, photosensitivity, rashes, renal or haematological disease, or the presence of antinuclear antibodies are important clues when considering this diagnosis. Gout can affect multiple joints simultaneously. This is less common than the typical monoarticular form of the disease, which most often affects the metatarsophalangeal joint of the great toe.

2. What is the most likely diagnosis and why?

Answer

Septic arthritis as a result of disseminated N gonorrhoeae infection is the most likely diagnosis because of the abrupt onset of arthritis and systemic illness shortly after sexual intercourse with a new partner.

Discussion

The most likely diagnosis is septic arthritis caused by disseminated N gonorrhoeae infection.

Patients who present with a short history of a hot, swollen, and tender joint (or joints) with restricted movement should be regarded as having septic arthritis until proved otherwise.7 The explosive onset of synovitis of multiple joints, with symptoms of systemic illness, suggests a diagnosis of septic arthritis.

In young adults, gonoccocal septic arthritis should be considered in the differential diagnosis of any new presentation of arthritis, especially given the recent history of a new sexual partner.8 It should be suspected if there are no risk factors for non-gonoccocal septic arthritis, such as pre-existing joint disease, prosthetic joints, or a history of intravenous drug use. It is common for patients with disseminated gonoccocal infection to have no genital symptoms.8

Polyarticular reactive arthritis should also be considered. Recent exposure to a new sexual partner is a risk factor for SARA. However, this is usually characterised by monoarticular or oligoarticular joint involvement of gradual onset, which is often migratory or additive.5 6 Furthermore, tenosynovitis is often present and there is often a history of symptoms consistent with recent infection; 80% of men with SARA have a recent history of urethral discharge or dysuria.5

N gonorrhoeae is a Gram negative, non-motile, non-spore forming bacterium that characteristically grows in pairs (diplococci). It is the second most common sexually transmitted bacterial infection in the United Kingdom, with 29 291 cases diagnosed in England in 2013—a 15% increase from 2012.9 The UK currently has the highest rates in Europe, at more than 45 reported cases per 100 000 population.10

N gonorrhoeae enters the body through the mucosal surfaces of the urethra, cervix, pharynx, and rectum. Although infection of the male urethra is usually symptomatic, cervical, pharyngeal, and rectal infection may be silent, or the symptoms may not be recognised as being caused by a sexually acquired infection.1 For this reason, it can go untreated and infected patients will occasionally develop disseminated gonoccocal infection through haematogenous spread from infected mucous membranes.

The prevalence of gonoccocal arthritis has fallen in recent decades and has been reported to cause 0.06% of all cases of septic arthritis in the UK.1 This figure is higher in developing countries, especially those with poor public health.

Two forms of disseminated gonoccocal infection have been described: a bacteraemic form and a suppurative one. However, these are probably two stages of the same condition and features of both may coexist.1 The more common suppurative form presents with arthritis as the primary feature. Septic arthritis is found in 50% of cases and is usually monoarticular. Various joints can be affected, most commonly the knees, wrists, ankles, and interphalangeal joints of the fingers. The bacteraemic form typically presents as a characteristic triad of migratory polyarthralgia, skin lesions, and tenosynovitis, together with systemic upset. Joint involvement is typically asymmetrical and migratory or additive. Skin involvement comprises a dermatitis, characterised by papules on the trunk and limbs, progressing to vesicular or pustular lesions.1 2 These lesions are usually small and erythematous and may be missed on dark skin.2 Tenosynovitis affects multiple sites simultaneously, particularly wrists, fingers, ankles, and toes.2

Risk factors are female sex (female:male ratio 4:1), immunodeficiency including HIV infection, and complement deficiency. Exposure to N gonorrhoeae through sexual contacts is the main risk factor,2 and a recent new sexual contact should raise suspicion.

3. What further investigations are necessary?

Answer

Initial investigations include blood tests (white blood cell count, C reactive protein, erythrocyte sedimentation rate, blood cultures), radiography of the affected joints, and aspiration of synovial fluid from the affected joints for analysis (Gram stain, microscopy, and culture). Nucleic acid amplification tests should be performed on genital, pharyngeal, or rectal samples (guided by sexual history) to look for gonoccocal and chlamydial DNA.

Discussion

Because a hot swollen joint is a medical emergency, unless there is a definitive alternative diagnosis, all cases should be referred for urgent specialist assessment.7 Blood cultures should always be taken (even in the absence of a fever) to identify bacteraemia and isolate a potential causative organism. The patient’s systemic response should be assessed by assessing the white blood cell count, C reactive protein, erythrocyte sedimentation rate, and inflammatory markers. Liver function and renal function should be assessed because end organ damage may affect the choice of treatment.7

Most importantly, synovial fluid must be aspirated from any affected joints before starting antibiotics.7 A Gram stain can give an early indication of the causative organism and culture should also be carried out. In the case of N gonorrhoeae, intracellular Gram negative diplococci may be seen on a Gram stain alongside leucocytosis.

For septic arthritis caused by Gram positive organisms such as S aureus, synovial fluid cultures are positive in most cases,1 but it can be more difficult to make a diagnosis of disseminated gonoccocal infection. Cultures of synovial fluid are positive in less than 50% of cases of gonoccocal septic arthritis and the Gram stain is positive (Gram negative bacteria are seen) in less than 50% of culture positive samples.2 7 Therefore, a negative Gram stain (no bacteria seen) or culture result does not exclude the diagnosis. Purulent synovial fluid is more likely to yield organisms,6 and the samples should be sent fresh to the laboratory. Prior warning to laboratory staff will help ensure that the sample is plated on a modified New York or chocolate agar in a timely manner.

If these cultures are negative, the diagnosis is made on the basis of the typical clinical syndrome and gonococci isolated from blood cultures or another site,6 11 so it is important to look elsewhere for organisms.

Any skin lesions should be cultured and a sexual health screen obtained, with samples from any exposed sites. About half of patients with gonoccocal arthritis have positive cultures on swabs from one of three sites (cervical, urethral, or rectal).12

Molecular amplification is significantly more sensitive than culture and the best way to exclude gonorrhoea in both genital and extragenital anatomical sites.11 Most laboratories offer a commercial dual nucleic acid amplification test (NAAT) for C trachomatis and N gonorrhoea. Samples for NAAT should be taken from all exposed anatomical sites as guided by the patient’s sexual history. First pass urine samples in men and vaginal swabs (which can be self taken) in women are adequate to exclude genital gonorrhoea by NAAT testing. Pharyngeal and rectal swabs are usually taken by clinicians. These tests do not provide antibiotic sensitivities, so additional swabs should be taken for culture (endocervical by pelvic examination, urethral, rectal, and pharyngeal) if possible, but treatment of suspected disseminated gonoccocal infection should not be delayed to arrange this. NAATs are not approved by the manufacturer for use on skin lesions or joint aspirate from patients with suspected disseminated gonoccocal infection, but it is worth discussing suspected cases with the local laboratory because the test may be beneficial in difficult cases.

Radiography should be carried out, although the results are usually normal in septic arthritis.1 However, occasionally pre-existing joint damage can be found. Baseline radiographs are important for assessing any joint damage from septic arthritis on later imaging. The presence of radiographic erosions in this context would suggest underlying inflammatory arthritis.

HIV testing and syphilis serology are recommended in all patients with an acute sexually transmitted infection,13 as performed routinely in all sexual health clinics. Screening for blood borne viruses should include hepatitis B and C testing if there is any identified risk. All patients with unexplained arthralgia should be tested for HIV.

4. What are the treatment options?

Answer

Gonoccocal septic arthritis is treated with a seven day course of antibiotics. Current UK guidelines recommend an intravenous third generation cephalosporin (such as ceftriaxone), with a switch to oral therapy once there is clinical improvement and organism sensitivities are known. Sexual contacts should be sought and tested (partner notification).

Discussion

Septic arthritis is a medical emergency. Inadequate or delayed treatment results in joint destruction. Mortality is 0-11%, rising to 50% in patients with polyarticular disease.1 3

Until about 20 years ago gonoccocal strains reported in disseminated gonoccocal infection were mostly penicillin sensitive, but more recently N gonorrhoeae has developed multiple antibiotic resistance,4 so local and national guidelines must be followed.

In the UK, antibiotic resistance is monitored by reference laboratories and reported by the Health Protection Agency and Health Protection Scotland in England and Wales and Scotland, respectively.14 15 The British Association of Sexual Health and HIV (BASHH), which is advised by these organisations, updates current recommendations and treatment guidelines accordingly.13 The emergence of multidrug resistant gonorrhoea is of global concern,4 so adherence to guidelines is key.

Current UK recommendations for disseminated gonoccocal infection are treatment with a third generation cephalosporin (such as ceftriaxone 1 g), intramuscularly or intravenously every 24 hours.13 16 In patients with true cephalosporin allergy or severe penicillin allergy, spectinomycin 2 g intramuscularly every 12 hours can be used or, if the organism is quinolone sensitive, ciprofloxacin 500 mg intravenously every 12 hours.

Once sensitivities are known and the clinical condition is improving, the antibiotic can be switched to an appropriate oral agent to complete a total of seven days of treatment.

If symptoms persist at 72 hours, culture is repeated to exclude resistant organisms. A “test of cure” NAAT should be performed at any positive genital or extragenital site three weeks after treatment. C trachomatis coinfection requires assessment and appropriate treatment.

Gonoccocal arthritis is typically less inflammatory and causes less joint damage than other forms of bacterial septic arthritis, most notably arthritis associated with Staphylococcus or Streptococcus spp.2 Surgical intervention is not usually needed. However, purulent joint effusions should be aspirated, with repeat aspirations as necessary. Surgical lavage or debridement is rarely necessary.

The identification and testing of sexual contacts are a vital part of management that help avoid reinfection and reduce ongoing transmission.13 Specialist sexual health advisers can help with this.

Patient outcome

Our patient was initially treated with non-steroidal anti-inflammatory drugs. However, when symptoms worsened, he was started on broad spectrum intravenous flucloxacillin and gentamicin. Culture of synovial fluid aspirated from the left wrist joint yielded N gonorrhoeae and the treatment was changed to intravenous ceftriaxone. A urinary NAAT test for N gonorrhoeae taken a week after presentation was negative; however, the likely site of infection was the urethra, given the sexual history of unprotected vaginal intercourse.

He recovered well, with no residual joint discomfort or malformation. He tested negative for HIV and hepatitis B carriage. He informed his two recent sexual partners so that they could access testing and epidemiological treatment as contacts of gonorrhoea.

Notes

Cite this as: BMJ 2015;350:h1985

Footnotes

  • Competing interests: We have read and understood BMJ Group policy on declaration of interests and declare no competing interests.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References

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