(Chest. 2005;128:1878-1881.)
© 2005
American College of Chest Physicians
Persistent Radiographic Infiltrates in a Patient With Chronic Cough*
William J. Janssen, MD and
Jeffrey M. Sippel, MD
* From the Department of Medicine (Dr. Janssen), Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver; and the Department of Medicine (Dr. Sippel), Saint Anthony Medical Center, Denver, CO.
Correspondence to: William J. Janssen, MD, University of Colorado Health Sciences Center, 4200 East Ninth Ave, Box C-272, Denver, CO 80262; e-mail: William.Janssen{at}uchsc.edu
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Introduction
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A 47-year-old man with chronic renal failure was evaluated for 3 months of nonproductive cough. He also complained of mild breathlessness with exertion, but otherwise felt well. He denied fevers, chills, weight loss, and hemoptysis. He had no symptoms of sinus disease, asthma, or gastroesophageal reflux. A tuberculin skin test was nonreactive.
The patient’s medical history included chronic renal failure caused by hypertension. He had been hemodialysis dependent for 4 years, and had been hospitalized twice for hypervolemia and hyperkalemia. His medications included minoxidil, labetalol, calcium acetate, and vitamins. Prior to the development of renal failure, the patient worked in construction. He denied use of tobacco, alcohol, and illicit drugs, and had no recent travel.
On physical examination, the patient had an oxygen saturation of 94%. His lungs were clear, and his cardiac exam was normal. He had no lymphadenopathy, normal jugular venous pulsation, and no peripheral edema.
Laboratory examination revealed a serum calcium of 9.5 mg/dL, a phosphorus of 5.2 mg/dL, and a hematocrit of 44%. A chest radiograph demonstrated bilateral patchy infiltrates (Fig 1
). CT results corroborated these findings (Fig 2, 3
).
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What is the most likely diagnosis?
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Answer: Metastatic calcification secondary to chronic renal failure
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The term calcification refers to the deposition of calcium salts in the soft tissues. Dystrophic calcification occurs in previously damaged tissue, whereas metastatic calcification occurs in normal, uninjured tissue. In the lungs, dystrophic calcification is seen in granulomatous disorders such as tuberculosis, histoplasmosis, coccidiomycosis, and sarcoidosis, following infections such as pneumocystis and varicella, and with occupational lung diseases including silicosis and coal worker’s pneumoconiosis.123 Metastatic calcification is seen following orthotopic liver transplantation and in hypercalcemic states such as hyperparathyroidism, vitamin D toxicity, milk-alkali syndrome, and malignancy.123 Sixty to 75% of chronic hemodialysis patients will have some degree of pulmonary calcification at autopsy.24 This is the largest patient population affected by metastatic pulmonary calcification.
The pathogenesis of metastatic pulmonary calcification is poorly understood. In chronic renal failure, elevated serum phosphorus and calcium levels are common, but they correlate poorly with the development of pulmonary calcification.24 An alkaline pH favors precipitation of calcium phosphate in tissues, and it is possible that the intermittent alkalosis that follows bicarbonate hemodialysis is a precipitating factor.3 Parathyroid hormone may also play a role. Removal of parathyroid glands from laboratory animals with chronic renal failure prevents pulmonary calcinosis, and leads to disease regression in those with preexisting lung calcification.5
Histologically, metastatic pulmonary calcification is characterized by linear calcific deposits in the alveolar septal walls, and a secondary fibroproliferative response.46 There is also calcification of the elastic lamina in small and medium-sized pulmonary vessels, and within the bronchial basement membrane.4
Chest radiographs are rarely helpful in the diagnosis and management of metastatic pulmonary calcification.37 Radiographs are unable to detect small amounts of calcium; when compared to autopsy results, they demonstrate parenchymal calcification in < 15% of patients.4 In cases where radiographs are abnormal, the findings are nonspecific. Abnormalities include ill-defined nodules, interstitial infiltrates, and airspace disease. These nonspecific findings may be mistaken for pulmonary edema, hemorrhage, pneumonia, infarct, and malignancy.37 Furthermore, there is no correlation between the degree of radiographic involvement and clinical status. Patients with markedly abnormal radiographic findings may be asymptomatic, while others with benign findings may have significant functional limitation.2
CT provides a more reliable method for detecting metastatic pulmonary calcification. Standard 7- or 10-mm-thick images may fail to detect microscopic calcification due to signal averaging from normal adjacent tissue. Therefore high-resolution images should be obtained.8 Three parenchymal patterns are common: (1) diffuse or patchy ground-glass opacification, (2) dense consolidation, often in a lobar distribution, and (3) multiple nodules in a diffuse or localized distribution.378 These patterns are not mutually exclusive, and a combination of several patterns may exist. Calcium is common in the vessels of the chest wall, and the combination of parenchymal nodules and vascular calcification is highly suggestive of metastatic pulmonary calcification.7 Calcium also deposits in the myocardium, tracheobronchial tree, and the segmental pulmonary arteries.78
An alternative to CT is 99mTc methylene diphosphate bone scintigraphy. This modality is highly specific, and is useful for sorting out equivocal cases in which infiltrates have the appearance of pneumonia or pulmonary edema.39 Bone scintigraphy provides an added benefit in that other organs such as the stomach and kidneys can be evaluated for metastatic pulmonary calcification.
Nearly 90% patients with chronic renal failure have abnormal pulmonary function test results.10 The most common abnormalities are impaired diffusion capacity and reduced vital capacity. Pulmonary calcinosis may contribute to these abnormalities by increasing vascular permeability and inducing interstitial fibrosis. Tissue calcium content from biopsy specimens correlates strongly with reductions in PaO2, vital capacity, and diffusion.4
There are little data regarding the natural history of metastatic pulmonary calcification. The majority of patients are asymptomatic, while others have dyspnea and cough as the primary manifestation. Progressive disease with pulmonary fibrosis, cor pulmonale, and respiratory failure develops in a minority of patients. Therapeutic options are limited and are aimed at correcting hypercalcemia and hyperphosphatemia. Patients should be evaluated for hyperparathyroidism, and parathyroidectomy should be considered in recalcitrant cases. Renal transplantation may lead to disease remission in some patients,11 while disease in others may progress despite the presence of a normal functioning allograft.12
Received for publication October 12, 2004.
Accepted for publication November 22, 2004.
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References
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- Brown, K, Mund, DF, Aberle, DR, et al (1994) Intrathoracic calcifications: radiographic features and differential diagnoses. Radiographics 14,1247-1261[Abstract]
- Bendayan, D, Barziv, Y, Kramer, MR Pulmonary calcifications: a review. Respir Med 2000;94,190-193[CrossRef][ISI][Medline]
- Chan, ED, Morales, DV, Welsh, CH, et al Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med 2002;165,1654-1669[Abstract/Free Full Text]
- Conger, JD, Hammond, WS, Alfrey, AC, et al Pulmonary calcification in chronic dialysis patients: clinical and pathologic studies. Ann Intern Med 1975;83,330-336[ISI][Medline]
- Akmal, M, Barndt, RR, Ansari, AN, et al Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy. Kidney Int 1995;47,158-163[ISI][Medline]
- Murris-Espin, M, Lacassagne, L, Didier, A, et al Metastatic pulmonary calcification after renal transplantation. Eur Respir J 1997;10,1925-1927[Abstract]
- Hartman, TE, Muller, NL, Primack, SL, et al Metastatic pulmonary calcification in patients with hypercalcemia: findings on chest radiographs and CT scans. AJR Am J Roentgenol 1994;162,799-802[Abstract/Free Full Text]
- Greenberg, S, Suster, B Metastatic pulmonary calcification: appearance on high resolution CT. J Comput Assist Tomogr 1994;18,497-499[ISI][Medline]
- Faubert, PF, Shapiro, WB, Porush, JG, et al Pulmonary calcification in hemodialyzed patients detected by technetium-99m diphosphonate scanning. Kidney Int 1980;18,95-102[ISI][Medline]
- Bush, A, Gabriel, R Pulmonary function in chronic renal failure: effects of dialysis and transplantation. Thorax 1991;46,424-428[Abstract]
- Fulladosa, X, Gonzalez, MT, Cruzado, JM, et al Metastatic pulmonary calcifications in severe secondary hyperparathyroidism: evolution after renal transplantation. Transplant Proc 1995;27,2272-2276[ISI][Medline]
- Breitz, HB, Sirotta, PS, Nelp, WB, et al Progressive pulmonary calcification complicating successful renal transplantation. Am Rev Respir Dis 1987;136,1480-1482[ISI][Medline]
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