A Rare Case of Calcitriol-mediated Hypercalcemia in a Patient with Pneumocystis Jiroveci Pneumonia and the Role of Steroids in its Management

Introduction:
Calcitriol-mediated hypercalcemia is an uncommon complication of Pneumocystis jiroveci pneumonia (PJP). Some cases of PJP have been reported in patients with solid organ transplants and AIDS. Here we present a case of calcitriol-mediated hypercalcemia due to granulomatous Pneumocystis jiroveci pneumonia in a patient with a history of multiple sclerosis.

Case Description:
A 45-year-old man with a medical history of multiple sclerosis, spondyloarthritis, smoking, and bipolar disorder was admitted for the evaluation of fever, fatigue, constipation, confusion, and weight loss of 10 Lbs over three months. His medications include rituximab, methotrexate, vitamin D-4000 IU, lithium, and calcium carbonate-600 mg. Laboratory evaluation showed elevated serum calcium (15 mg/dl) with a suppressed parathyroid hormone (9 pg/mL). Other pertinent findings include mildly elevated 25-hydroxyvitamin D (87 ng/ml), significantly elevated 1,25-dihydroxyvitamin D (381 pg/ml), and normal PTHrP ( <2 pmol/L), vitamin A (0.82 mg/L) and TSH (1.31 mU/L). Extensive workup including AFB smear for tuberculosis, ACE level for sarcoidosis, SPEP for multiple myeloma, leukemia-lymphoma flow cytometry, and CT chest and PET-CT for malignancy were unremarkable. Treatment with large-volume intravenous fluids, calcitonin, and zoledronic acid followed by denosumab showed a transient reduction in serum calcium level to 10.5 mg/dl in 2 days and a rebound to a peak of 15.4 mg/dl in a week. Bronchoscopy with bronchoalveolar lavage which was done for persistent fever and new onset hypoxia revealed PJP confirmed by PCR. With this new finding, the diagnosis of PJP-induced calcitriol-mediated hypercalcemia was considered. He was then treated with Bactrim and prednisone 60 mg daily. Due to the severity of hypercalcemia, he required a hemodialysis session while waiting for the medications to take effect. His calcium normalized a week after the initiation of steroids and antibiotics and he was discharged on a slow prednisone taper. Clinic follow-up 4 weeks after discharge showed normal calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels. Discontinuation of prednisone was attempted but resulted in rebound elevation of 1,25-dihydroxyvitamin D requiring continuation of low-dose prednisone 5 mg.

Discussion:
Our immunocompromised patient developed hypercalcemia induced by PJP infection due to granulomatous production of 1α-hydroxylase resulting in increased calcitriol formation. Steroids unsurprisingly appear to have the best impact on PJP-induced hypercalcemia because of their anti-inflammatory property. In this clinical entity, it inhibits inflammation and granuloma formation leading to a reduction in the release of 1 α-hydroxylase and 1,25-dihydroxyvitamin D levels.

It is essential to consider PJP as an etiology of hypercalcemia, especially in immunosuppressed patients. Steroid appears to be effective medical therapy in this setting. The timing and duration of treatment, and the efficacy of bisphosphonates and denosumab, require further studies.