Abstract
INTRODUCTION: This case presents a diagnostically challenging journey of a young female with intermittent joint pain and swelling, initially suspected to be related to hypermobility syndrome, ultimately diagnosed as gout. Her diagnosis was complicated by rarity of gout in young females, normal inflammatory indices, and normal joint ultrasound on most occasions. The diagnosis was confirmed through joint aspiration revealing monosodium urate crystals and raised uric acid levels. The case is significant due to the rarity of gout in premenopausal women. It highlights the importance of thorough clinical reassessment. CASE DESCRIPTION: A 40-year-old female with a background of asthma, arrhythmia (with loop recorder in situ), childhood joint dislocations, two miscarriages, and a son with reflux nephropathy and autism, presented with a complex history of intermittent joint pain and swelling since 2020. She is a social smoker and has reported low alcohol intake at presentation. Her symptoms began in February 2020 with left ankle pain and swelling. Ultrasound demonstrated inflammatory changes, but serological markers (ANA, RF, CCP) were negative and inflammatory markers were normal. Initial management included steroid injection with partial relief. By October 2020, she reported intermittent polyarticular joint pain and swelling (MCP, shoulder, wrists, knees, and ankle) with systemic symptoms such as fatigue and weight loss. Despite this, no objective inflammation was noted on examination or ultrasound. She was managed symptomatically with analgesics. In November 2020, hypermobility syndrome was diagnosed based on clinical features and Beighton score, without any evidence of synovitis on ultrasound. However, symptoms escalated, particularly affecting the left ankle. By April 2021, joint aspiration of the left ankle revealed monosodium urate crystals, confirming gout. Uric acid was elevated at 0.75 mmol/L. She was started on prednisolone and allopurinol. After discussion with genetic experts, genetic testing for inherited causes (Bartter’s, Gitelman’s, ADPKD) was not performed due to unlikeliness and the identification of under-excretion of uric acid on 24 hour urine test. Despite escalation of allopurinol dose to 400 mg OD, she continued to have flares through 2022, with persistently elevated uric acid levels. In November 2023, a further ankle flare led to aspiration confirming abundant urate crystals. She was subsequently switched from allopurinol to febuxostat. This case illustrates a diagnostic challenge in a young female with crystal arthropathy, complicated by hypermobility. DISCUSSION: This case is clinically intriguing due to the patient’s atypical presentation of gout in a young, premenopausal woman, compounded by a background of joint hypermobility. Initial clinical decisions focused on joint hypermobility as the main cause of joint pain. This decision was emphasised by negative autoimmune serologies (ANA, RF, CCP), low inflammatory markers, and joint ultrasound which did not persistently show active synovitis, directing us toward a non-inflammatory or mechanical aetiology. The turning point came when aspiration of a swollen ankle revealed monosodium urate crystals, confirming a diagnosis of gout. Although this is an uncommon diagnosis in women of her demographic, the discovery prompted further investigation into potential secondary causes. Discussion with genetic experts excluded inherited metabolic conditions, and it was ultimately determined that her hyperuricaemia resulted from under-excretion of uric acid. Escalation of urate-lowering therapy from allopurinol to febuxostat was warranted due to persistent flares and elevated uric acid levels, despite increasing allopurinol doses. This case raises this key question: • Should young women with atypical joint pain and negative autoimmune work-up be screened earlier for crystal arthropathy? Ultimately, this case has highlighted the importance of reassessment, keeping an open differential, and not dismissing gout purely based on age or gender. It reinforces the value of diagnostic joint aspiration and tailoring management to the individual’s unique social and clinical context. KEY LEARNING POINTS: 1. Atypical presentation of gout in young women: Although gout is more common in older men, it can occur in young, premenopausal women and should be considered in the differential diagnosis of unexplained joint pain and swelling. 2. Challenges in diagnosing gout with coexisting hypermobility: Joint hypermobility can mimic or mask inflammatory joint symptoms, complicating clinical assessment and potentially delaying diagnosis. 3. Importance of joint aspiration for definitive diagnosis: Identification of monosodium urate crystals through joint aspiration remains the gold standard for confirming gout, especially when clinical and serological findings are inconclusive. 4. Negative autoimmune serologies do not exclude inflammatory joint disease: Normal ANA, RF, and CCP, along with absent synovitis on imaging, do not rule out crystal arthropathies or other inflammatory conditions.