Sexually Transmissible Infections in Clinical Practice

24. A Young Man with a Painful Swollen Knee Joint

Alexander McMillan1, 2  


Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk


University of Edinburgh, Edinburgh, Uk

Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer



A 23-year-old man, William, who works as a waiter, presents to his General Practitioner with a 6-day history of having a painful swollen right knee joint. For the past 3 weeks he has also noticed some stinging when passing urine. His GP suspects that he may have acquired a sexually transmitted infection and refers him to a Sexual Health clinic.

A 23-year-old man, William, who works as a waiter, presents to his General Practitioner with a 6-day history of having a painful swollen right knee joint. For the past 3 weeks he has also noticed some stinging when passing urine. His GP suspects that he may have acquired a sexually transmitted infection and refers him to a Sexual Health clinic.

His GP has considered that the man may have urethritis, complicated by arthritis.

24.1 What Sexually Transmissible Infections May Be Associated with Arthritis?

Sexually transmissible infections associated with arthropathy include those shown in Table 24.1.

Table 24.1.

Sexually transmissible infections associated with arthropathy.

Chlamydia trachomatis

Neisseria gonorrhoeae

Treponema pallidum (secondary syphilis)

Mycoplasma genitalium

Ureaplasma urealyticum


Hepatitis B virus

Epstein–Barr virus

Shigella spp.

Campylobacter spp.

William attends the clinic 4 days later. He has now noticed pain and swelling of the left ankle joint, and he has developed a non-itchy, non-tender rash on his penis. He has also noticed that his eyes have become irritable. He has not had any recent episodes of diarrhea. There is no relevant past history, in particular he has had no previous joint or intestinal disorders, and he does not suffer from recurrent mouth ulcers. Although he plays football, he does not recall any recent significant injury. He lives in a large city in the United Kingdom and has not traveled into the countryside for more than 2 years. There is no family history of joint disease or of psoriasis. His only current medication is ibuprofen that was prescribed by his GP to control the joint pain. About 2 weeks before the onset of his urethral symptoms, he had unprotected vaginal intercourse with an unknown woman whom he had met at a party.

His temperature is 37.2°C, and his pulse 76 per minute. William has difficulty walking on account of pain in his right knee and left ankle joints, both of which are swollen and tender; the overlying skin is reddened. The left Achilles tendon is tender at its insertion into the calcaneum. Moist, glistening, red, sharply-defined macules with a polycyclic margin are found on the glans penis (circinate balanitis) (Fig. 24.1). Skin lesions elsewhere are not noted, and there are no oral lesions. The conjunctivae are reddened. There is a mucoid urethral discharge.


Figure 24.1.

Circinate balanitis.

24.2 What Diagnoses Would You Consider?

The clinical features strongly suggest a diagnosis of reactive arthritis, the salient features of which are shown in Table 24.2. Reactive arthritis is one of the spondyloarthropathies that include ankylosing spondylitis, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease and shares clinical features with these conditions. There is a strong association between these diseases and the major histocompatibility complex class I antigen HLA-B27: for example, the prevalence of HLA-B27 in patients with ankylosing spondylitis and reactive arthritis is between 85–95% and 30–80%, respectively.

Table 24.2.

Features of reactive arthritis.


• Asymmetrical oligoarthritis affecting principally the joints of the lower limbs

• Monoarthritis

• Sacroiliac joint involvement

• Enthesitis (inflammation of ligamentous and tendinous insertions)

• Dactylitis (inflammatory involvement of a whole digit with tendovaginitis and arthritis

Extra-articular features:

• Ocular features:

• Conjunctivitis

• Anterior uveitis

• Skin and mucosal lesions:

• Patchy loss of filiform papillae of the tongue

• Psoriatic lesions (circinate balanitis and keratoderma blennorrhagica [pustular psoriasis])

• Nail dystrophy

• Aortitis and cardiac conduction defects

Reactive arthritis may follow genital tract infection, particularly with Chlamydia trachomatis, and, less frequently N. gonorrhoeaeUreaplasma urealyticum, and Mycoplasma genitalium, and is often referred to as sexually acquired reactive arthritis (SARA). Sexually acquired reactive arthritis is a disorder of young adults, the age of onset usually being between 18 and 50 years. Males are affected some 50 times more frequently than females. Intestinal infections, particularly with Campylobacter spp., Shigella flexneriSalmonella spp., and Yersinia enterocolitica, can also trigger reactive arthritis.

The pre-patent period is variable, but the disease usually manifests itself 10–30 days after sexual intercourse or after an attack of dysentery or a dysentery-like illness. The mode of onset is variable, but commonly urethritis precedes the appearance of conjunctivitis, which is followed by arthritis. Any of the three features, however, may appear initially.

In this case there is oligoarthritis, enthesitis (inflammation of the insertion of the Achilles tendon), conjunctivitis, and circinate balanitis. Not all extra-articular manifestations of reactive arthritis need to be present to make the diagnosis. Other conditions, however, must be considered in the differential diagnosis (Table 24.3) and excluded by consideration of the clinical features and laboratory tests.

Table 24.3.

Differential diagnosis of reactive arthritis.

Gonococcal arthritis

Acute septic arthritis (excluding gonococcal arthritis)

Post-infectious arthritis:

• Post-streptococcal infection

• Lyme disease

• Viral arthritis, including rubella, Epstein–Barr virus, HIV, hepatitis B, and erythrovirus 19 (parvovirus)

Gout and pseudogout



Ankylosing spondylitis, ulcerative colitis and Crohn’s disease

Behçet’s disease



Gonococcal arthritis is the disease with which SARA is most often confused. Both conditions have urethritis and arthritis in common. Patients with disseminated gonococcal infection (DGI) often present with fever, migratory arthralgia, tenosynovitis, and skin lesions (painful, asymmetrically distributed hemorrhagic, or vesiculopustular lesions on an erythematous base [Fig. 24.2] that should not be confused with the psoriatic lesions found in reactive arthritis [Fig. 24.3]). Other individuals present with a septic joint, with or without skin lesions. Note: Although DGI is most often associated with a septic joint, reactive arthritis is found in up to 20% of patients with gonorrhoea and arthritis.


Figure 24.2.

Skin lesions of disseminated gonococcal infection.


Figure 24.3.

Pustular psoriasis (keratoderma blenorrhagica) of sole of foot.

Other than gonococcal arthritis, acute septic arthritis may be caused by numerous organisms, e.g., Staphylococcus aureus, Streptococcus pyogenes, Neisseria meningitidis, Salmonella spp., and Streptococcus pneumoniae. Any joint may become inflamed, but most often the knee, wrist, and elbow are affected.

In post-streptococcal infection, the onset of arthritis, which is usually polyarticular, is acute, when large joints are chiefly affected.

Borrelia burgdorferi is transmitted by the bite of an infected tick. Arthritis, which is usually episodic, develops weeks to months later, and principally affects the large joints. In this case, there is no history of exposure to ticks.

Acute episodes of gout usually affect a single peripheral joint, especially the first metatarsophalangeal joint. Pseudogout, acute synovitis associated with the deposition of calcium pyrophosphate crystals in articular cartilage, may resemble septic arthritis with fever. It is a condition found in the elderly and is an unlikely diagnosis here.

Acute arthritis may be the presenting feature of ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, Behçet’s disease, but there are usually additional features of these conditions which are absent in this case.

Acute arthritis, often associated with erythema nodosum, may also be a feature of sarcoidosis.

A Gram-stained smear of urethral exudate shows about 20 polymorphonuclear leucocytes per ×1,000 microscopical field; Gram-negative diplococci are not seen. A urine sample contains large numbers of polymorphonuclear leucocytes but protein and red cells are absent. Urethral and pharyngeal material (taken as described in Case 1) is sent to the laboratory for culture for N. gonorrhoeae, and a first-voided specimen of urine is obtained for the detection of C. trachomatis by a nucleic acid amplification assay. A sample of synovial fluid, aspirated under aseptic conditions, appears yellow and turbid. Many polymorphonuclear leucocytes are seen on a Gram-stained smear of the aspirate, but neither Gram-positive nor Gram-negative bacteria are identified. Urate or pyrophosphate crystals are not seen in a sample examined by polarized light microscopy. An aliquot of fluid is sent for bacterial culture. The peripheral blood total white cell count is 14 × 109 /L (normal range: 4.0–11.0 × 10 9 /L), with a neutrophil leucocytosis; other hematological parameters are within normal limits. The erythrocyte sedimentation rate (ESR) is 75 mm/h (normally 0–10 mm/h), and the C-reactive protein concentration is 62 mg/L (normally <5 mg/L). Serum urate, calcium, and angiotensin-converting enzyme estimations are requested. Serum samples are also sent for the determination of anti-streptolysin O (ASO) and for rheumatoid factor. Serological tests for syphilis, Lyme disease, HIV, hepatitis B virus, Epstein–Barr virus, and erythrovirus 19 (parvovirus) are undertaken.

24.3 How Do You Interpret These Laboratory Findings?

Although the leucocytosis, elevated ESR, and C-reactive protein indicate an acute inflammatory response, these changes are not specific.

The absence of Gram-negative diplococci in the urethral smear makes urethral gonorrhoea with dissemination an unlikely diagnosis. Culture from possibly infected anatomical sites (in this case, urethra and pharynx), as was performed in this case, however, is the investigation of choice for gonococcal arthritis. It should be noted that, as organisms are seldom visualized, failure to identify Gram-negative diplococci in synovial fluid does not exclude the diagnosis.

Gram-smear microscopy of synovial fluid may aid in the diagnosis of non-gonococcal septic arthritis. Bacteria, however, are only visualized in about 50% of cases, but when detected Gram-positive and Gram-negative organisms can be differentiated, facilitating choice of initial antimicrobial therapy.

Failure to identify crystals in the synovial fluid makes a crystal arthropathy an unlikely diagnosis.

24.4 What Is the Most Likely Diagnosis and What Is the Initial Management?

The presumptive diagnosis is sexually acquired reactive arthritis (SARA), complicating probable urethral chlamydial infection. There is no history suggestive of intestinal infection, although some such infections are symptomless and difficult to detect by the time of development of arthritis.

Treatment is not curative but is aimed at relieving symptoms. When the patient first attends, the course of the disease should be fully explained to him. He should be told particularly that the acute episode may last for at least 6 weeks, but that sometimes it may last for much longer. The management of the features of SARA are as follows:

·               The management of non-gonococcal urethritis has already been discussed (see Case 5). The presence of the complication of SARA does not alter the general approach. Treatment of the genital tract inflammation does not appear to alter the course of the disease.

·               Conjunctivitis is a self-limiting condition, generally resolving within a few weeks of its onset. As anterior uveitis is a recognized complication of reactive arthritis, and may be difficult to recognize, referral to an ophthalmologist is recommended.

·               During the acute stage of the illness, when the joints are markedly inflamed, bed rest is advisable. It is of great importance to ensure that the correct posture is assumed during this period of rest to reduce the risk of development of flexion deformities. A physiotherapist can help with the patient’s management. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are usually effective in the management of the arthritis of SARA. The aspiration of a tense effusion in the knee joint followed immediately by the instillation of a corticosteroid may be useful in alleviating joint symptoms.

·               In the management of enthesitis, rest, physiotherapy, and ultrasound therapy are often helpful, but NSAIDs are also required. Local injection of a corticosteroid can give rapid relief of symptoms, but repeated injections may be necessary.

·               Circinate balanitis (psoriasis of the penis) usually resolves spontaneously within a few weeks of its onset, but healing may be facilitated by the use of a topical steroid preparation, combined with an antimicrobial agent. When there is secondary bacterial infection, the use of local saline lavages, and dressings soaked in normal saline applied to the glans, are of value.

Five days after his clinic attendance, the laboratory test results are available. Chlamydia trachomatis DNA was detected in the first-voided urine specimen, but N. gonorrhoeae was not isolated from the urethra or pharynx. Neither bacteria nor fungi were cultured from the synovial fluid. Serum urate, calcium, and angiotensin-converting enzyme concentrations were within normal limits, and serological tests for syphilis, Lyme disease, and the viral infections noted above were negative. The ASO titer was low.

24.5 Have These Further Results Aided in the Diagnosis?

The detection of C. trachomatis in the urethra is further supporting evidence for a diagnosis of SARA. Negative urethral and pharyngeal cultures for N. gonorrhoeae effectively exclude a diagnosis of gonococcal arthritis. Note: Culture of joint aspirate for N. gonorrhoeae is positive in fewer than 50% of cases of gonococcal arthritis. Nevertheless, it is good practice to perform gonococcal culture on synovial fluid when the diagnosis of this condition is suspected.

As bacterial culture of synovial aspirate is positive in over 90% of cases of non-gonococcal septic arthritis, this diagnosis is very unlikely.

A normal serum urate concentration does not exclude gout, but the absence of urate crystals in the synovial fluid makes the diagnosis less likely.

In acute sarcoidosis, the serum calcium concentration is often, but not invariably elevated, as is that of angiotensin-converting enzyme. Normal concentrations in this case, and the absence of other clinical features such as erythema nodosum, make sarcoidosis an unlikely diagnosis.

The low concentration of anti-streptolysin O excludes a diagnosis of post-streptococcal infection, and the negative serological tests exclude Lyme disease, syphilis, and the viral infections associated with post-infectious arthritis.

The absence of associated features makes the diagnosis of ankylosing spondylitis, psoriatic arthritis, the arthritis associated with inflammatory bowel disease, and Behçet’s disease less likely.

24.6 What Is the Course of SARA?

Sexually acquired reactive arthritis is a self-limiting condition. The duration of the first episode of SARA varies between 2 weeks and several years. In general (more than 70%) first episodes resolve within 12 weeks. At least half of patients develop recurrences, the interval between the initial episode and the recurrence varying between 3 months and up to 36 years. Although recurrence may be precipitated by urethritis or dysentery, other factors have been identified and include surgical operations on the urinary tract.

Following the acute arthritis of the initial episode, there may be no clinical evidence of joint damage. In some cases, with each recurrent episode of arthritis, permanent damage is done to the joint that may ultimately show the features of chronic arthritis. Uncommonly, in less than 5% of cases, following the initial episode of arthritis, resolution of the inflammatory process is incomplete and chronic arthritis rapidly develops in the affected joints. The patient complains of pain, stiffness, and swelling of the joint, the severity of symptoms being subject to exacerbations and remissions; deformity is the ultimate fate of joints affected in this way. Most frequently it is the joints of the lower limbs and the sacroiliac joints which bear the brunt of chronic arthritis in this disease. Generally, as chronic arthritis develops, other manifestations of the disease become less obvious, with the possible exception of anterior uveitis.

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