Arthritis-Dermatitis Syndrome: a Case of Disseminated Gonococcal Infection with Petechial Skin Rash

Abstract

A previously healthy 36-year-old woman was admitted to the hospital with vaginal discharge, bilateral ankle pain, and a lower extremity skin rash, all of which developed after unprotected vaginal intercourse with a new male partner. On examination, there was a petechial and purpuric rash involving the lower extremities and bilateral tenosynovitis of the ankle dorsiflexor tendons. Urine NAAT was positive for Neisseria gonorrhea, confirming disseminated gonococcal infection (DGI). The patient was initially treated with oral azithromycin and intravenous ceftriaxone, but as a result of psychosocial circumstances, she was prematurely discharged on an oral cephalosporin agent. She represented with treatment-failure DGI and was treated with a 7-day course of intramuscular ceftriaxone. Repeat urine NAAT was negative for gonorrhea and the patient remained asymptomatic. This case features an atypical cutaneous manifestation of DGI, characterized by a painless petechial and purpuric skin rash rather than the tender papulo-pustular lesions that are typically seen. Additionally, it highlights the importance of DGI treatment with a 7-day parenteral cephalosporin therapy when antibiotic susceptibility is not available.

INTRODUCTION/BACKGROUND

Gonorrhea is caused by the diplococci organism, Neisseria gonorrhea, and it is the second most common notifiable disease, according to the Center of Disease Control and Prevention (CDC). The rates of reported infection in the USA have been steadily increasing with 110 cases per 100,000 people in 2014, and up to 179 cases per 100,000 people in 2018.^1,2 In addition, antibiotic resistance continues to be an increasing problem; as of 2018, half of all gonococcal infections demonstrate resistance to at least one antibiotic, posing an urgent threat to future treatment, and necessitating a recent 2020 update to treatment guidelines by the CDC.¹ In women, gonorrhea increases risk for pelvic inflammatory disease, which can result in infertility, chronic pelvic pain, and ectopic pregnancy. Additionally, gonococcal infection increases the risk of acquiring other sexually transmitted infections (STI), such as human immunodeficiency virus (HIV). In less than 3% of cases, gonorrhea develops into disseminated gonococcal infection (DGI), of which there are two main presentations: arthritis-dermatitis syndrome (polyarthralgia, tenosynovitis, and dermatitis) and purulent arthritis (mono- or oligoarticular arthritis without associated skin lesions).³ We present a case of arthritis-dermatitis syndrome featuring an atypical petechial skin rash rather than the pustular, hemorrhagic rash that is more characteristic of this condition. Understanding the spectrum of cutaneous manifestations associated with DGI can be important for establishing the diagnosis. This case also demonstrates the importance of parenteral therapy for patients with DGI, particularly when there are coexisting psychosocial factors that may complicate treatment.

CLINICAL CASE

A 36-year-old woman with a history of active intravenous drug use was admitted to the hospital with 6 weeks of vaginal discharge and dysuria and 3 days of acute bilateral ankle pain and non-painful lower extremity rash. Two months prior to symptom onset, the patient had unprotected vaginal intercourse with a new male partner with unknown STI history. The patient did not report fevers, chills, or neurologic symptoms. Two days prior to presentation, she received 250 mg intramuscular (IM) ceftriaxone and 1 g oral azithromycin at an urgent care clinic, but no STI testing was done. On examination, temperature was 36.8 °C, heart rate 101 beats/min, and blood pressure 140/96 mm Hg. There was a non-blanchable, non-palpable, and non-tender petechial and purpuric rash on the lower extremities extending to the mid-shins (Fig. 1). The patient had bilateral tenosynovitis of the ankle dorsiflexor tendons and mild bilateral ankle edema. There was no cervical motion tenderness. Laboratory evaluation was notable for a mildly elevated C-reactive protein at 11 mg/L but was otherwise unremarkable. Blood and urine cultures were negative. The presentation was most concerning for disseminated gonococcal infection (DGI) manifesting as the arthritis-dermatitis syndrome with an atypical rash.

Figure 1.

An atypical non-blanchable, non-palpable, and non-tender petechial and purpuric rash on the lower extremities extending to the mid-shins in a patient with disseminated gonococcal infection.

Urine polymerase chain reaction (PCR) was positive for Neisseria gonorrhea, confirming the diagnosis of DGI. Arthrocentesis of the right ankle joint revealed a white blood cell count of 300/hpf, but no organisms were identified by Gram stain or culture. Rapid plasma reagin screening was non-reactive and urine PCR was negative for Chlamydia trachomatis. Magnetic resonance imaging of the right ankle was negative for osteomyelitis. Both urine and blood cultures were negative for bacterial growth so antibiotic susceptibilities were not done. The patient was started on 1 g of IV ceftriaxone daily with improvement in the tenosynovitis and rash. On day 4 of treatment, citing a family emergency, the patient left the hospital against medical advice. Instead of receiving the recommended full course of parenteral therapy, she was discharged on an oral regimen consisting of cefpodoxime 400 mg twice daily and azithromycin 500 mg daily, both for 3 days, amounting to a total of 7 days of antibiotic therapy. The patient was also advised to notify recent sexual partners to get tested for possible gonorrhea infection.

Within 4 days of discharge, the patient was re-hospitalized with recurrent symptoms. The patient reported taking the antibiotics as prescribed although there was concern for nonadherence as there appeared to be extra pills in the patient’s possession that could not be accounted for. On examination, vital signs were unremarkable, but there was increased tenosynovitis and bilateral ankle edema compared to recent discharge. Repeat blood cultures were negative. Intravenous ceftriaxone was restarted, resulting in symptom improvement. The patient was discharged on three additional days of intramuscular ceftriaxone (administered at an outpatient primary care clinic) for a total of 7 days of antibiotic therapy. A month after therapy was completed, repeat urine nucleic acid amplification test (NAAT) was negative for gonorrhea and at a 4-month follow-up visit, the patient remained symptom free.

DISCUSSION

This case highlights two important concepts in relation to disseminated gonococcal infection: dermatologic manifestations of arthritis-dermatitis syndrome can be atypical and parenteral therapy is necessary when antibiotic susceptibilities are unknown. There were 583,405 reported cases of gonorrhea in the USA in 2018, a 5.0% increase from 2017 and an 82.6% increase from 2009.¹ Like most STIs, gonorrhea infections are likely underreported, with the CDC estimating approximately 1,140,000 new cases a year.⁴ In concert with the increasing prevalence of gonorrhea, drug-resistant strains are on the rise, making prompt diagnosis and treatment necessary. The highest rates of gonorrhea infection occur among teenagers and young adults, with increasing rates of diagnosis in men compared to women.¹ Infected subjects are often asymptomatic; as a result, United States Preventative Services Task Force (USPSTF) recommends routine screening for Neisseria gonorrhea via NAAT in sexually active females less than 24 years old, while risk-based screening is recommended in females above 24 years old; there is insufficient evidence currently to determine the benefit of screening in men.^5,6 When symptomatic, women typically present with cervicitis or pelvic inflammatory disease, while men present with urethritis and epididymitis; however, other presentations such as conjunctivitis or pharyngitis can occur. DGI is rare, accounting for 0.5–3% of gonorrhea infections.³ Systemic invasion of bacteria leading to DGI is thought to be more common during menstruation, pregnancy, and the use of intra-uterine devices.⁶

There are two main presentations of DGI: arthritis-dermatitis syndrome and purulent arthritis syndrome. Arthritis-dermatitis syndrome manifests as constitutional symptoms (during the acute phase), migrating polyarthralgia, tenosynovitis, and cutaneous lesions. The lesions most often involve the posterior distal extremities and are characterized by hemorrhagic papulo-pustules, vesicles, or bullae. They often only last for 3 to 4 days and resolve without systemic antibiotic treatment.^7,8 The cause of these typical skin findings is thought to be due to microabscess formation after bacterial embolization to the skin.⁷ Atypical cutaneous manifestations, including petechiae, purpura, urticaria, erythema multiforme, erythema nodosum, abscesses, cellulitis, vasculitis, and necrotizing fasciitis, are rare and have only been described in case reports; the cause for these differing presentations is unknown.^7,9 Other conditions that may present with a petechial/purpuric rash and multi-system involvement include sepsis/purpura fulminans, meningococcemia, rickettsial disease, Henoch-Schönlein purpura, other vasculitides, systemic lupus erythematosus, thrombocytopenia, drug rash, and Haverhill fever. This case describes a unique and atypical presentation of the arthritis-dermatitis syndrome, characterized by a petechial/purpuric rash involving the skin around the ankle joints and the shins. Clinicians should be aware of the different cutaneous manifestations of DGI, especially since patients may be reticent to disclose their behavior or symptoms surrounding STI risk out of fear of stigmatization. In this case, if the patient had not reported recent unprotected sex or the genitourinary symptoms, the diagnosis of DGI would likely have been delayed. Awareness that the cutaneous manifestations of DGI are not always typical is important for prompt diagnosis and treatment and avoidance of long-term sequela and emerging antibiotic resistance.

The diagnosis of gonorrhea can be made with NAAT, which has been cleared by U.S. Food and Drug Administration (FDA) for urogenital sites, including male and female urine, as well as endocervical, vaginal, and male urethral samples when collected by a clinician.^5,10 NAAT, however, is not FDA-approved for detection of rectal, oropharyngeal, and conjunctival gonococcal infection—all of which require culture for diagnosis.⁸ Culture remains the gold standard diagnostic test, though sensitivity is low. Culture may be helpful when antibiotic susceptibility testing is needed in cases of suspected treatment failure or testing in patients with DGI.

Treatment of gonococcal infection has evolved over the years in response to the emergence of drug-resistant strains of N. gonorrhea. According to the CDC 2019 report on antibiotic resistance threats in the USA, there has been a 124% increase in drug-resistant N. gonorrhea since the 2013 report.⁴ In 2007, due to increasing prevalence of fluoroquinolone-resistant strains, the CDC recommended cephalosporins-ceftriaxone-or cefixime- as the primary group of antibiotics for treatment. However, increasing rates of treatment failure with cefixime occurred between 2006 and 2011, prompting the CDC to no longer recommend cefixime as a first-line agent, leaving ceftriaxone as the only primary treatment.¹⁰ There is, however, growing concern for emerging resistance to ceftriaxone, noting that, in 2018, 0.2% of isolates had elevated ceftriaxone minimum inhibitory concentrations.¹ In a 2020 update for uncomplicated gonorrhea infection of the cervix, urethra, or rectum, the CDC recommends treatment with ceftriaxone 500 mg intramuscular once for patients weighing less than 150 kg.² When co-infection with C. trachomatis cannot be excluded, non-pregnant patients should be treated with doxycycline 100 mg twice daily for 7 days.² It should be noted that these recommendations are different from previous guidelines, reflecting better understanding of the optimal ceftriaxone dosing for treatment of gonorrhea as well as the increasing resistance to azithromycin seen in N. gonorrhea and other organisms and increased understanding of the impact on the gut microbiome.²

For DGI, the recommended treatment regimen remains unchanged from the treatment guidelines set forth by the CDC in 2015 and includes 1 g ceftriaxone intramuscular or intravenous for 7 days and a single dose of 1 g oral azithromycin.¹⁰ Patients may be switched to an oral regimen guided by antibiotic susceptibility if and when available and after 24–48 h of significant clinical improvement, for a total of 7 days of antibiotic therapy. In this case, during her initial hospitalization, this patient was unable to complete the recommended antibiotic regimen of parenteral ceftriaxone and had to be prematurely transitioned to an oral cephalosporin without known antibiotic susceptibility, eventually experiencing treatment failure. As antibiotic susceptibilities were not available in this case, it is unknown if the cause of the treatment failure was due to the premature transition to oral antibiotics (and possible nonadherence) or if this was a case of antibiotic resistance. Repeat treatment with a total of 7 days of IM ceftriaxone therapy in coordination with close outpatient follow-up was successful. This case highlights an atypical cutaneous manifestation of DGI and the importance of not only accurate diagnosis, but also the nuances of treatment and risk for treatment failure when parenteral therapy is not available.

Declarations

Conflict of Interest

The authors declare that they do not have a conflict of interest.