Rigour after gonorrhea treatment in a 55-year-old man

Case

Visit 1. A 55-year-old man presented to the sexually transmitted infection (STI) clinic after a recent casual male partner informed him he had been diagnosed with gonorrhea. The patient engaged in condomless receptive and penetrative oral and anal sex with this man. Table 1 provides a summary of the patient’s case.

Review of systems: The patient was asymptomatic when he presented for care, but reported having had a painless genital lesion that was less than 1 cm² approximately 4 to 6 weeks earlier; it resolved spontaneously after 7 to 10 days. The patient suspected the lesion was an “ingrown hair.” He denied rashes, hair loss, and mucous lesions. He denied current or recent rigour, fatigue, weight loss, lymphadenopathy, myalgia, arthralgia, headaches, and vision or hearing changes.

Past medical history: The patient’s past medical history included insomnia, gastroesophageal reflux disease, and hypertension, for which he took trazodone, esomeprazole, and the telmisartan-amlodipine combination, respectively. He had been taking these drugs for longer than 12 months. He had started taking a fixed-dose combination of emtricitabine (200 mg) and tenofovir (300 mg) daily for HIV preexposure prophylaxis (PrEP) 5 months earlier.

The patient had similarly presented to the STI clinic 5 months previously as a contact of a gonorrhea case and was treated with 1 intramuscular dose of 250 mg of ceftriaxone (reconstituted with 0.9 mL of 1% lidocaine) plus 1 oral dose of 1 g of azithromycin.^1,2 This treatment was administered at the clinic. He experienced no reaction after treatment (both immediately after treatment and during the following day): no nausea, no emesis, no diarrhea, and no rigour. His test results at that time were negative for gonorrhea and chlamydia (urine nucleic acid amplification testing [NAAT], and pharyngeal and rectal cultures). He did not undergo serology testing at the clinic, but had documented negative HIV and syphilis test results from this time.

On examination: The patient was afebrile and had no perceptible rashes on his hands, feet, or trunk. His cervical nodes were not palpable or tender; he had no oral lesions or erythema. He had no palpable inguinal nodes or tenderness, and no lesions, erythema, or tenderness of his penis or genital area; no urethral discharge was present. He had no scrotal lesions or testicular tenderness. He had no external anal erythema, lesions, or discharge. Anoscopy was not performed.

Plan: The nurse practitioner who saw this patient at his initial visit collected pharyngeal and rectal swabs and urine for gonorrhea and chlamydia testing, as well as blood for HIV and syphilis testing. As the patient was a contact of a gonorrhea case, this same provider treated the patient in the clinic with 1 intramuscular dose of 250 mg of ceftriaxone (reconstituted with 0.9 mL of 1% lidocaine) plus 1 oral dose of 1 g of azithromycin.^1,2 The patient remained in the clinic after the injection without reaction.

A fourth-generation antigen-antibody combination assay was used for HIV testing.³ Syphilis testing was done using the reverse screening algorithm, starting with a chemiluminescent microparticle immunoassay (CMIA), followed by a rapid plasma reagin (RPR) test and a Treponema pallidum passive particle agglutination assay (TPPA) for samples with positive screening results.^4,5 Gonorrhea and chlamydia samples underwent NAAT.^6–8 Of note, between the patient’s previous and current presentation for care, in Ontario, NAAT for extragenital samples was validated by the Public Health Ontario laboratory. This occurred owing to a greater than 2-fold increase in sensitivity of NAAT compared with culture, and because the test swabs required were reduced from 2 swabs to 1. Moreover, extragenital testing is done with the same type of swab used for endocervical gonorrhea and chlamydia testing and is thus likely more readily available in many clinics.

Test results: The patient had negative results for HIV, pharyngeal and urine gonorrhea and chlamydia, and rectal chlamydia. His rectal gonorrhea test result was positive. For syphilis, the CMIA result was reactive, the RPR titre was 1:4, and the TPPA result was reactive. The STI clinic nurses contacted the patient and requested that he return to the clinic.

Visit 2. On returning to the clinic 8 days after the first visit, the patient was asymptomatic. To determine the need for gonorrhea re-treatment, I inquired if he had had issues with treatment. He denied nausea, emesis, and diarrhea, and he denied sexual contact with untreated partners. He reported rigour about 2 hours after receiving gonorrhea treatment; rigour lasted less than 12 hours and resolved spontaneously. He denied rashes, mucosal irritation and pain, myalgia, and arthralgia. He denied experiencing such symptoms when he was treated empirically for gonorrhea 5 months earlier.

I repeated the syphilis bloodwork, determined the patient’s stage of infectious syphilis (early latent phase owing to no symptoms, a confirmed negative result 5 months earlier, and no known contacts with any sexual partners recently diagnosed with infectious syphilis). I treated him with 1 intramuscular dose of 2.4 million units of benzathine penicillin G.^1,2 He tolerated the injection well and had no reactions during the 15 minutes he remained in the clinic. Interestingly, he reported a similar Jarisch-Herxheimer–like reaction after this treatment as well. Patients who receive more than 1 dose of antibiotics for syphilis typically only experience the Jarisch-Herxheimer reaction with the first treatment; it is possible that the second reaction occurred in this case because, in the first instance, the nurse practitioner had not actually treated him for syphilis. Instead, the nurse practitioner had treated him for gonorrhea, and potentially induced this reaction with a dose of medication that was appropriate for gonorrhea but subtherapeutic for syphilis. It is thus possible that he experienced the Jarisch-Herxheimer reaction twice.

Syphilis bloodwork from this second visit revealed reactive CMIA results, an RPR titre of 1:8, and reactive TPPA results, supporting the diagnosis of infectious syphilis. The change in syphilis titre might suggest the infection was primary (with a possible chancre in an undetected location such as the rectum); however, it might also be normal laboratory variation in the measurement of a serofast state.