OA08 Florid early-onset polyarticular calcium pyrophosphate deposition disease: when it’s not all crystal-clear

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Abstract Introduction Calcium pyrophosphate deposition disease (CPPD) arises from deposition of calcium pyrophosphate crystals within articular and periarticular tissues. Although CPPD is most commonly associated with ageing and osteoarthritis, a severe polyarticular pattern in younger patients warrants investigation for underlying causes. Gitelman syndrome, an inherited renal tubulopathy, is a recognised but underdiagnosed contributor, which drives CPPD primarily by its associated hypomagnesaemia. Its early symptoms such as myalgia, muscle cramps, fatigue and/or dizziness are often non-specific, leading to diagnostic delay. Timely recognition allows referral for renal input and appropriate correction of biochemical abnormalities, improving clinical outcomes and avoiding inappropriate long-term treatments. Case description A 57-year-old male baker was referred to Rheumatology with longstanding, progressive polyarthritis affecting multiple joints. He had been treated in the community for presumed gout for over two decades, initially presenting in his 30s with episodic oligoarthritis, which gradually evolved into symmetrical polyarthritis. Despite being on long-term allopurinol (200 mg daily), his serum urate levels remained between 230–390 µmol/L, and flares persisted. His comorbidities included type 2 diabetes mellitus (HbA1c 49–60 mmol/mol), chronic kidney disease stage G3aA1, bilateral keratoconus, and mixed anxiety and depression. He had a normal BMI of 23, minimal alcohol intake, and no family history of renal or inflammatory joint disease. At initial rheumatology review, he reported constant generalised joint pain with intermittent severe attacks occurring up to three times per year. Examination revealed synovitis in multiple joints, including MCPs, first CMCs, wrists, elbows (with fixed flexion deformities), shoulders, knees, and ankles, without tophi. Rheumatoid factor, anti-CCP, ANA, and HLA-B27 were negative. Plain radiographs of the symptomatic sites demonstrated florid chondrocalcinosis, erosions, exuberant periarticular calcifications, and secondary osteoarthritic changes. Intra-articular steroids were ineffective, and tapering prednisolone below 25 mg/day resulted in significant functional impairment. NSAIDs were discontinued due to worsening renal function. Hydroxychloroquine and colchicine were both poorly tolerated due to gastrointestinal side effects. Methotrexate was considered but not initiated. Biochemistry revealed persistently low serum magnesium (∼0.38 mmol/L), intermittent hypokalaemia, and metabolic alkalosis (serum bicarbonate ∼30 mmol/L). The patient described longstanding fatigue, muscle cramps, salt craving, dry mouth, nausea, and dizziness, previously attributed to fibromyalgia. Renal ultrasound excluded nephrocalcinosis. Referral to Metabolic Medicine and Renal Services led to a diagnosis of Gitelman syndrome. Genetic testing confirmed compound heterozygous mutations in the SLC12A3 gene. He was started on lifelong high-dose oral magnesium replacement with renal follow-up. Discussion This case exemplifies the critical need to reassess long-standing rheumatological diagnoses when clinical features fail to align with expected disease patterns. When patients show persistent symptoms despite standard treatment for gout, and especially when urate levels are consistently low, alternative diagnoses must be explored. CPPD typically presents in older adults or in association with osteoarthritis, and its polyarticular, erosive form is uncommon in individuals under 60. One under-recognised metabolic cause of CPPD is hypomagnesaemia, which disrupts crystal homeostasis through inhibition of pyrophosphatase activity, resulting in elevated extracellular pyrophosphate and subsequent calcium pyrophosphate crystal formation. Gitelman syndrome, a rare autosomal recessive tubulopathy caused by mutations in SLC12A3, leads to chronic renal wasting of magnesium and potassium, alongside metabolic alkalosis. Although usually diagnosed in adolescence or early adulthood, its variable expression and subtle, non-specific symptoms often delay recognition well into adulthood. Our patient experienced two decades of unexplained polyarthritis, managed presumptively as gout despite consistently normal urate levels and no evidence of tophi or urate crystals. The combination of florid chondrocalcinosis on imaging and persistent biochemical abnormalities ultimately pointed towards Gitelman syndrome, a diagnosis confirmed through genetic testing. Crucially, the clinical picture, previously seen as refractory gout and/or fibromyalgia, shifted towards a systemic metabolic disease with an identifiable and potentially modifiable cause. This case highlights how integration of rheumatology, metabolic, and renal expertise can redirect clinical thinking and patient outcomes. It challenges clinicians to think beyond inflammatory or autoimmune paradigms, particularly in patients with poor treatment response and systemic symptoms. Importantly, identifying Gitelman syndrome has major therapeutic implications, enabling targeted electrolyte correction, improved symptom control, and prevention of further crystal damage. Key learning points This case demonstrates that early-onset, severe, or refractory CPPD should prompt thorough evaluation for secondary metabolic causes, even in patients with long-standing presumed diagnoses. Florid polyarticular chondrocalcinosis should raise clinical suspicion for CPPD driven by systemic factors. Among these, persistent hypomagnesaemia is a key contributor to crystal formation and must not be overlooked. Gitelman syndrome, while rare, is an important inherited renal tubulopathy that exemplifies the connection between systemic electrolyte disturbances and musculoskeletal manifestations. Chronic hypomagnesaemia impairs enzymatic degradation of pyrophosphate, leading to pathological crystal accumulation. However, Gitelman syndrome often presents with non-specific symptoms, such as fatigue, salt craving, dizziness, and/or muscle cramps, that are easily misattributed to chronic pain or fibromyalgia. This can result in years of misdiagnosis, as seen in this case. A structured diagnostic approach, including extended biochemical profiling, is vital in atypical or treatment-resistant arthropathies. Ultimately, this case reinforces the importance of a holistic, multidisciplinary approach to complex rheumatological presentations. Collaboration across rheumatology, renal, and metabolic services can help uncover rare but clinically significant disorders such as Gitelman syndrome. Early diagnosis not only improves symptom control but may slow or prevent disease progression. Clinicians should maintain a high index of suspicion in patients with unexplained joint disease and abnormal electrolytes, recognising that common symptoms may have uncommon, treatable causes.

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