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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 4  |  Page : 993-996
Hypercalcemic crisis as a prodromal feature of Pneumcystis jirovecii pneumonia

1 Department of Medicine, Faculty of Medicine, Kuwait University, Safat, Kuwait
2 Department of Medicine, Al-Amiri Hospital, Ministry of Health, Kuwait City, Kuwait

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Date of Submission04-Apr-2017
Date of Decision29-May-2017
Date of Acceptance03-Jun-2017
Date of Web Publication28-Aug-2018


We describe a patient who had developed hypercalcemic crisis, with altered mental status and renal failure, one year following aggressive corticosteroid-therapy for lupus nephritis. Her disease relapsed after successful live-related kidney transplantation 11 years ago. She had normal parathyroid hormone and 25-hydroxyvitamin D yet high 1,25 dihydroxyvitamin D. Four weeks later, she developed severe dyspnea and hypoxia with a reticulonodular pattern on chest computed tomography. Bacteriological and serological tests were negative for pathogens. However, bronchoalveolar lavage established the diagnosis of Pneumocystis jiroviceii pneumonia (PJP). Her pneumonia and hypercalcemia improved with Co-trimoxazole. The case indicates that severe hypercalcemia can herald PJP.

How to cite this article:
El-Reshaid K, Al-Bader S. Hypercalcemic crisis as a prodromal feature of Pneumcystis jirovecii pneumonia. Saudi J Kidney Dis Transpl 2018;29:993-6

How to cite this URL:
El-Reshaid K, Al-Bader S. Hypercalcemic crisis as a prodromal feature of Pneumcystis jirovecii pneumonia. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Aug 8];29:993-6. Available from: https://www.sjkdt.org/text.asp?2018/29/4/993/239630

   Introduction Top

Pneumocystis jiroviceii pneumonia (PJP) is a serious and common complication of immuno-suppressive therapy. The disease was identified >100 years ago as a protozoan then was reclassified as a fungus in 1988.[1] Its main manifestations are progressive dyspnea and hypoxia with an almost clear chest X-ray. Few cases reports described mild hypercalcemia in association with PJP following kidney transplantation, leukemia, and AIDS.[2],[3],[4],[5],[6] However, hypercalcemic crisis, due to PJP, following immunosuppressive treatment for lupus nephritis (LN) is rare.

   Case Report Top

The patient was a 34-year-old girl with live-related kidney transplantation for 11 years. Her underlying kidney disease was LN. One year ago, she had a fever, symmetrical polyarthritis, pericarditis, ascites, and progressive proteinuria. Kidney biopsy of the transplanted kidney showed diffuse proliferative glome-rulonephritis with full-house immunoglobulin and C3 deposition. Diagnosis of a flare of her LN was established, and she was treated with multiple courses of high-dose corticosteroids in addition to mycophenolate mofetil, tacrolimus, and rituximab. One year later, she presented with altered mental status. Laboratory tests showed severe anemia (hemoglobin: 80 g/L) with normal transferrin saturation% and Vitamin B12 and significant hypercalcemia (corrected serum calcium: 3.3 mmol/L) despite discontinuation of her oral calcium and one alpha therapy two weeks ago. Moreover, she had progressive worsening of her serum creatinine from baseline 150 mmol/L to 320 mmol/ L. Intact parathyroid hormone and 25-vitamin D were normal at 38 pmol/L and 4 pmol/L, respectively. However, 1,25-dihydroxyvitamin D was high at 480 pmol/L (normal range 50150 pmol/L). Brucella antibodies were negative by ELISA testing as well as Quantiferon T-test for tuberculosis. Anti-ds DNA and serum complements 3 and 4 were normal. Serum angiotensin-converting enzyme was normal. Serum protein electrophoresis showed polyclonal gammopathy. Viral screen by polymerase chain reaction did not show any significant existence of cytomegalovirus and BK virus. Her initial chest X-ray was normal. She was treated empirically with biphos-phonate (pamidronate: 90 mg infusion over 4 h); yet failed to lower her serum calcium. Aggressive hydration and corticosteroids mildly improved her hypercalcemic state. Four weeks later, she developed a low-grade fever, cough as well as progressive dyspnea and hypoxia. She was supported with oxygen to keep her O2 saturation >92%, yet her mental status remained altered. At that stage, her chest X-ray showed linear atelectasis in the right lung base with middle lobe consolidation, collapse and elevated right copula of the diaphragm [Figure 1]. Moreover, high-resolution computed tomography of her chest showed multiple consolidation patches and right posterior lung segmental/subsegmental atelectasis [Figure 2]. Bronchoscopy was done, and her bronchiolo-alveolar lavage established the diagnosis of PJP [Figure 3]. After confirming that, she was G6PD-negative, she was treated with 21-days of Co-trimoxazole and short-course of prednisone. Over the following month, her hypercalcemia resolved and 1,25 dihydroxy-vitamin D return to normal level. Moreover, serum creatinine decreased to 148 umol/L.

Figure 1: Chest X-ray showing linear atelectasis in the right lung base with middle lobe consolidation, collapse and elevated right copula of the diaphragm.

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Figure 2: Axial projection of a computed tomography scan of the chest, showing multiple consolidation patches and right posterior lung segmental/subsegmental atelectasis.

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Figure 3: Photomicrograph of a bronchioloalveolar lavage showing the characteristic aggregates of crushed ping-pong balls (cysts) of pneumocystis jiroviceii (Immunofluorescent stains x400).

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   Discussion Top

In healthy individuals, primary hyperpara-thyroidism is the most common cause while in immunocompromized hosts, lymphoma, and tuberculosis are the leading etiologies.[6] Our patient had end-stage kidney disease due to LN. She had stable kidney transplantation for 11 years. Unfortunately, her LN relapsed one year ago and she had to be treated aggressively with multiple courses of high-dose cortico-steroids, MP and even rituximab. Though her kidney function was stable for months; yet she started to deteriorate in association with progressive hypercalcemia. Her oral intake of calcium and 1 hydroxyvitamin D were discontinued, yet her hypercalcemia continues to progress for weeks later. Hyperparathyroi-dism, exogenous hypervitaminosis D, immobilization, and malignancy were excluded by clinical, radiological, laboratory, and serological assessment. The persistently high 1,25 dihydroxyvitamin D was suggestive of an intrinsic ectopic focus yet overt clinical manifestations of a granulomatous disease were lacking. Ultimately, she developed hyper-calcemic crisis as manifested with progressive deterioration of her mental and renal functions. She improved partially with hydration and corticosteroids yet all her abnormalities had resolved permanently after treatment of her PJP indicating a cause and effect phenomenon. Interestingly, PJP manifestations were overt only four weeks after the development of her hypercalcemia. The latter phenomenon was reported only once before.[3]

Hypercalcemia in association with granulomatous disease is mediated by an extra-renal increase of 1,25 dihydroxyvitamin D production since elevated levels were found in a patient with sarcoidosis and bilateral nephrectomy.[7] Peripheral blood monocytes and pulmonary alveolar macrophages normally produce 1,25 dihydroxyvitamin D yet are suppressed by 1 a-hydroxylase in a negative feedback pattern.[8] In granulomatous disease, inflammatory cytokines such as gamma interferon activate the later enzyme leading to progressive hypercalcemia.[9] In severe cases of PJP, pulmonary alveolar macrophages proliferate in their attempt to clear infection leading to inflammatory exudates, edema, interstitial fibrosis, alveolar cell erosions, and even granuloma formation with subsequent hypercalcemia.[10]

In conclusion, hypercalcemia and even crisis can herald overt PJP in patients receiving long-term immunosuppressive therapy. Co-trimoxazole is essential, cost-effective prophylaxis of PJP in the setting of prolonged immunosuppression and should be considered not only in patients with solid-organ or lymphoproliferative transplantation but also in those with refractory autoimmune diseases.

Conflict of interest: None declared.

   References Top

Thomas CF Jr., Limper AH. Pneumocystis pneumonia. N Engl J Med 2004;350:2487-98.  Back to cited text no. 1
Aguirre AR, Balbo BE, Ianhez LE, da Costa MC, Andrade L. Hypercalcemia and suppressed PTH levels in a renal transplant patient infected with Pneumocystis carinii. Ren Fail 2007;29:513-6.  Back to cited text no. 2
Bency R, Roger SD, Elder GJ. Hypercalcaemia as a prodromal feature of indolent Pneumocystis jirovecii after renal transplantation. Nephrol Dial Transplant 2011;26:1740-2.  Back to cited text no. 3
Chatzikyrkou C, Clajus C, Haubitz M, Hafer C. Hypercalcemia and pneumocystis pneumonia after kidney transplantation: Report of an exceptional case and literature review. Transpl Infect Dis 2011;13:496-500.  Back to cited text no. 4
Mills AK, Wright SJ, Taylor KM, McCormack JG. Hypercalcaemia caused by Pneumocystis carinii pneumonia while in leukaemic remission. Aust N Z J Med 1999;29:102-3.  Back to cited text no. 5
Ahmed B, Jaspan JB. Case report: Hypercalcemia in a patient with AIDS and Pneumocystis carinii pneumonia. Am J Med Sci 1993;306:313-6.  Back to cited text no. 6
Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician 2003;67: 1959-66.  Back to cited text no. 7
Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL. Hypercalcemia in an anephric patient with sarcoidosis: Evidence for extra-renal generation of 1,25-dihydroxyvitamin D. N Engl J Med 1981;305:440-3.  Back to cited text no. 8
Dusso AS, Kamimura S, Gallieni M, et al. Gamma-interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: A mechanism for the hypercalcemia of various granulomatoses. J Clin Endocrinol Metab 1997;82:2222-32.  Back to cited text no. 9
Hartel PH, Shilo K, Klassen-Fischer M, et al. Granulomatous reaction to Pneumocystis jirovecii: Clinicopathologic review of 20 cases. Am J Surg Pathol 2010;34:730-4.  Back to cited text no. 10

Correspondence Address:
Prof. Kamel El-Reshaid
Department of Medicine, Faculty of Medicine, Kuwait University, P. O. Box 24923, 13110 Safat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.239630

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  [Figure 1], [Figure 2], [Figure 3]


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