- Case Report
- Open Access
Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report
© Sachdeva et al; licensee BioMed Central Ltd. 2008
- Received: 16 June 2008
- Accepted: 07 August 2008
- Published: 07 August 2008
Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10–20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden.
- Tuberculin Skin Testing
- Granulomatous Inflammation
- Radiotracer Uptake
If patients with chronic hyperuricemia are left untreated, gouty tophi can develop and usually deposit in subcutaneous tissues. Tophi have also been shown to occur within joints, as was the case in our patient, but have also been shown to deposit in various tissues such as kidney, breast and spinal cord . The histological hallmark of a gouty tophi is created when MSU crystals aggregate with intercrystalline matrix and induce surrounding granuloma formation . The MSU crystals serve as the inciting antigen which leads to an intense inflammatory reaction of macrophages, lymphocytes and large foreign body giant cells which may have completely or partially engulfed the mass of crystals .
Hypercalcemia has been described in patients with many types of granulomatous disorders such as tuberculosis, Wegener's granulomatosis, and Crohn's disease. By far the most widely evaluated and one of the more common causes of hypercalcemia due to granulomatous inflammation is sarcoidosis [4, 5]. The mechanism of hypercalcemia is PTH-independent extrarenal production of calcitriol from calcidiol by activated mononuclear cells within the granuloma. This leads to increased intestinal absorption of calcium, and to a lesser degree calcitriol-mediated increase in bone resorption . Lab parameters in our patient including elevated 1,25 dihydroxyvitamin D, ACE level, and suppressed iPTH support his granulomatous load as the cause of hypercalcemia . The synovial biopsy suggests that his gouty tophaceous burden is the underlying etiology of the granuloma formation. Furthermore long term use of immunosuppressants, in addition to aggressive uric acid lowering therapy with allopurinol, has maintained serum calcium, 1,25 dihydroxyvitamin D, and ACE levels within normal limits.
This case is unique in that although gouty tophi have been shown to prompt granuloma formation around the aggregation of MSU crystals, to our knowledge there is no literature describing the development of symptomatic hypercalcemia as is seen with a variety of other causes of granulomatous disorders. Obtaining a biopsy from another site which revealed increased radiotracer uptake per gallium-67 scan was contemplated. Showing gouty tophi with surrounding granuloma formation in these areas, as was seen in the synovial biopsy of the knee, would be even more suggestive of our theory but would also be highly unethical as he did very well with the above mentioned medical interventions.
Since gout is a common medical problem invariably seen by all rheumatologists as well as primary care physicians, this association should be taken into account especially if symptomatic hypercalcemia develops in the context of tophaceous gout. The list of antigens initiating granulomatous inflammation and hypercalcemia is a lengthy one, and based on our findings we feel MSU crystals should be added to this list.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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