Acute seronegative polyarthritis associated with lymphogranuloma venereum infection in a patient with prevalent HIV infection

INTRODUCTION

Sexually acquired reactive arthritis (SARA) is a systemic inflammatory disorder characterized by an acute aseptic peripheral arthritis within one month of primary infection. The most common pathogen is Chlamydia trachomatis (serovars D-K) but Neisseria gonorrhoeae, Mycoplasma fermentans, Mycoplasma genitalium and Ureaplasma urealyticum have also been implicated. Enteric infections can also trigger SARA, including Shigella flexneri, Salmonella enteritidis, Salmonella typhimurium, Yersinia enterocolitica, Yersinia pseudotuberculosis and Campylobacter jejuni. ¹ We present a case of SARA secondary to lymphogranuloma venereum (LGV).

CASE REPORT

A 44-year-old man who has sex with men presented to the rheumatology outpatient department with a three-month history of oligoarthritis. He had experienced a gradual onset of pain, morning stiffness and swelling in his left foot and ankle followed by pain in his left wrist, shoulder and hand. He had no history of skin or mucosal lesions and had never suffered with psoriasis. He was a firefighter but had been reassigned to desk duties.

On examination, the left wrist was tender but not swollen. He had clinical swelling and inflammation of the left middle metacarpophalangeal (MCP) joint, foot and ankle, with focally increased tenderness in the mid-tarsal region. A clinical diagnosis of possible rheumatoid arthritis was considered. The left wrist and left middle MCP joint were injected with intra-articular glucocorticoids.

Initial investigations revealed a mild lymphopaenia and raised inflammatory markers (C-reactive protein 34 mg/L, erythroyte sedimentation rate 83 mm/hour) together with a polyclonal hypergammaglobulinaemia. Antinuclear antibodies were negative, rheumatoid factor low-grade positive (66 IU/mL) but anticyclic citrullinated peptide antibodies were negative. Parvovirus serology confirmed past, but not recent, exposure. Hepatitis A, B and C and syphilis serologies were negative (on 2 occasions, at baseline and 6 months later) but his fourth-generation HIV-1 test (Abbott) was positive. Incident testing (STARHS) suggested that this was not a recent infection. His baseline CD4 count was 352 cells/mm³ (33%) and viral load 5181 copies/mL.

Three months later, there was improvement in the foot/ankle pain but persistent swelling in the left wrist, left shoulder and now right knee. Due to his positive HIV antibody test, he was seen in the genitourinary clinic and here he acknowledged a six-month history of intermittent right-groin pain and passing mucus per rectum, which actually preceded his joint symptoms. Despite the mucus, there were no other symptoms suggestive of enterocolitis, specifically no diarrhoea or loose stools, no rectal bleeding and no change in bowel habit. His sexual history included two UK male partners in the three months prior to the onset of all symptoms and no intercourse since then. He reported oral and receptive anal sex as well as receptive fisting with both partners. On examination, there were enlarged inguinal lymph nodes on the right side and proctoscopy revealed an inflamed rectal mucosa with purulent discharge. Microscopy and culture were negative for gonorrhoea (from throat, urethra and rectum); however, polymerase chain reaction-based testing was positive for rectal C. trachomatis. Subsequently, the Sexually Transmitted Bacteria Reference Laboratory (Health Protection Agency, Colindale, UK) performed LGV-specific DNA testing and confirmed that this was positive (serovar L2). He was treated with a three-week course of doxycycline, 100 mg twice daily, and test-of-cure was negative six weeks after completion of antibiotics, utilizing the same assay technique.

After the doxycycline, his polyarthritis improved dramatically with complete resolution of his arthritis and inflammatory markers within four to six weeks. The patient resumed full active duties in the fire service.

DISCUSSION

In view of the pattern of asymmetrical polyarthropathy and the dramatic response to treatment, the most likely diagnosis was LGV-associated SARA. Although he had a borderline-positive rheumatoid factor, this is common in the context of HIV infection.

LGV is caused by the L1–3 serovars of C. trachomatis. It is endemic in east and west Africa, India, parts of south east Asia and the Caribbean; however, since 2003 outbreaks have been reported in developed countries, predominantly in HIV-infected men who have sex with men (MSM). In the UK, most cases have involved symptomatic proctitis and less commonly inguino-genital manifestations. ² Non-LGV proctitis can be effectively eradicated by seven days of doxycycline but LGV proctitis requires prolonged treatment ³ (current UK recommendation: doxycycline for 21 days ⁴ ).

In the differential diagnosis, we considered that this might have been SARA secondary to HIV infection. Arthralgia is a recognized feature of acute seroconversion but seroconversion illness is usually short-lived (<10 weeks) and arthritis with true inflammatory synovitis is not a recognized feature. HIV-associated arthritis was originally described in 1988 among four patients with a subacute oligoarthritis predominantly in the knee and ankle. ⁵ Since then the existence of HIV-associated arthritis has been controversial with no clear evidence found. ^6–8 The results of a Spanish case-control study suggested that the type of arthritis seen among HIV-infected patients related more to the risk factors associated with acquisition than the virus (e.g. seronegative arthropathy were more likely among HIV-infected MSM than those infected by other modes of transmission). ⁹

In this case, we believe that the most convincing evidence of LGV causation is the dramatic clinical improvement and resolution of the polyarthritis after effective eradication of the infection. It is noteworthy that Keat et al. reviewed the literature on chlamydia and arthritis in 1983. In this review, arthritis was reported as a feature of LGV with cases reported in 1939 and 1942. Keat et al. ¹⁰ estimated an incidence of 5% of ‘aseptic arthritis’ associated with LGV and described an asymmetrical oligo- or polyarthritis without evidence of sacroiliitis or spondylitis. He reflected that LGV was ‘now seen rarely in Europe’. To our knowledge, this case with features exactly like those described in the earlier literature is only the second reported case of reactive arthritis associated with the recent outbreaks of LGV. ¹¹