Abstract
INTRODUCTION: Crystal arthropathies are well-known disease entities caused by the deposition of crystals within the articular surface, including monosodium urate, calcium pyrophosphate, basic calcium phosphate, oxalate, and cholesterol crystals. These crystals typically deposit in the joint space but can also affect other tissues, such as the renal tract and cardiopulmonary system. Here, we present a case of a Caucasian male who initially presented with dactylitis, presumed to be gout, despite a normal uric acid level. Later, he was diagnosed with 2,8-dihydroxyadenine crystalline (2,8 DHA) arthropathy and nephropathy. CASE DESCRIPTION: A 68-year-old Caucasian male initially presented with loin pain and hematuria, leading to a diagnosis of bilateral renal stones. A CT scan of the kidneys, ureters, and bladder revealed multiple high-density foci in the urinary bladder, with the largest stone measuring 6 mm. No hydronephrosis or perinephric fat stranding was noted. His CRP was 86gm/L, creatinine 193 µmol/L, and eGFR 30 mL/min. Eighteen months prior, he had been diagnosed with gout after presenting with dactylitis in both his hands and toes. X-rays of his hands demonstrated osteoarthritis changes at the proximal and distal interphalangeal joints of both hands and a chest x-ray was normal. He was started on allopurinol which was uptitrated to 300 mg and colchicine as and when required. His urate level at that time was 416 µmol/L, and subsequent measurements ranged from 246 to 338 µmol/L, with ongoing flare-ups. The patient had no children and one healthy sister. He was a non-smoker with occasional alcohol use, and had a history of scalp folliculitis treated with isotretinoin. Over the following 12 months, he continued to experience recurrent flares of dactylitis, often in an asymmetrical pattern affecting his hands. He also had recurring renal colic. Further investigations, including exclusion of seronegative inflammatory arthritis and atypical infections (e.g., tuberculosis), led to a renal biopsy, which revealed 2,8-dihydroxyadenine crystalline deposits. Genetic testing confirmed an APRT deficiency with a heterozygous mutation. The patient remains on allopurinol and has received lifestyle advice to increase fluid intake. He is being closely monitored by both rheumatology and renal services due to his risk of end-stage renal failure. DISCUSSION: 2,8-dihydroxyadenine crystalline nephropathy is a rare but preventable cause of end-stage renal failure. It is caused by adenine phosphoribosyltransferase (APRT) deficiency, an autosomal recessive disorder in purine metabolism, which can often mimic gout. Characteristic features include recurrent renal stones, dactylitis, and metatarsophalangeal (MTP) joint swelling. Diagnosis is confirmed through urine analysis, which reveals the presence of 2,8-DHA crystals, and joint aspiration, which typically shows birefringence and a distinctive Maltese cross appearance. APRT deficiency impairs the purine salvage pathway, leading to the accumulation of 2,8-DHA, similar to the pathophysiology of gout. Management includes allopurinol or febuxostat, although no “treat-to-target” approach has been established. In the absence of biomarkers, uric acid has been used as a surrogate marker, as it is a downstream product in this pathway. Case series have reported the accumulation of 2,8-DHA in various organ systems, including the liver, kidney, and lymph nodes, and post-transplant renal allografts. KEY LEARNING POINTS: 2,8 DHA crystalline arthropathy is a rare condition that can mimic gout occurring due to an APRT deficiency. Although primarily a renal disease it can cause joint involvement including dactylitis and MTP swelling. The true incidence of this crystal arthritis is unknown but should be considered in anyone with renal disease and a crystal arthritis. The diagnostic process simple, urine analysis will demonstrate the presence of 2,8 DHA crystals and joint aspiration will show a characteristic Maltese cross bifringence pattern. Confirmation can be sought with a renal biopsy and genetic testing. The management is generally supportive with allopurinol or febuxostat and hydration alongside monitoring Wednesday renal failure.