Patient with disseminated Mycobacterium avium-intracellulare complex involving the bone marrow, causing pancytopenia.
She reported no drug or alcohol abuse. She acquired HIV from unprotected heterosexual activity. She reported no exposure to tuberculosis and had started trimethoprim/sulfamethoxazole, azithromycin, and highly active antiretroviral therapy (HAART; lamivudine, zidovudine, and nelfinavir) in the preceding month.
She was thin and appeared to be her stated age. She was tachycardic, with clinical signs of dehydration. Abdominal examination showed bowel sounds with diffuse tenderness without peritoneal signs or organomegaly. Admission laboratory values included blood urea nitrogen, 29 mg/dL; creatinine, 1.7 mg/dL; and calcium, 15.2 mg/dL. Calcium was corrected to 16.2 mg/dL when albumin of 2.7 g/dL was taken into account. Ionized calcium was 1.91 (1.09 to 1.31). Fractional excretion of sodium was consistent with prerenal insufficiency. White blood count was 3,900/m[m.sup.3], hemoglobin was 7.3 g/d, and platelet count was 97,000/m[m.sup.3]. Reticulocyte count was 1.2%. Alkaline phosphatase was 183 U/L, with a normal aspartate aminotransferase, alanine aminotransferase, and [gamma]-glutamyl transpeptidase. Lipase was 1,047 U/L. Triglycerides were 354 mg/dL. Intact parathyroid hormone (PTH) was undetectable. A CD4 count was 89 cells/[micro]L. Chest radiography was normal. Electrocardiography showed sinus tachycardia with a QTc of 384.
The patient was admitted with a diagnosis of pancreatitis secondary to hypercalcemia, severe dehydration, and pancytopenia. The hypercalcemia resolved with administration of intravenous saline. After fluids were given, creatinine was 0.6 mg/dL. An ultrasound of her abdomen showed mild to moderately enlarged liver and spleen that were homogenous in appearance, sludge in the gallbladder, and a normal pancreas. A bone marrow biopsy showed a hypercellular bone marrow with trilinear hematopoiesis and normal maturation with multifocal granulomas that were positive for numerous acid-fast bacilli. Blood cultures and bone marrow culture grew Mycobacterium avium--intracellulare complex. 1,25-dihydroxyvitamin D level was 56.8 (normal range, 15.9 to 55.6). PTH intact (pg/mL) was 2.57 (normal range, 16 to 65). 25-hydroxyvitamin D level was 28.5 (normal range, 8.9 to 46.7). PTH-related peptide was not detectable.
The association of hypervitaminosis D is documented in many granulomatous diseases. These include sarcoidosis, Wegener disease, fungal infections, tuberculosis, and atypical mycobacteria. (1-4) The mechanism of hypercalcemia is unregulated, constitutive production of dihydroxyvitamin D by macrophages. Theoretically, any granulomatous disease may lead to the constitutive production of 1,25-vitamin D through dysregulation by cytokines. (5) Vitamin D increases the gut absorption of dietary calcium, and this suppresses the secretion of PTH.
This patient's pancytopenia and hypercalcemia resulted from M avium--intracellulare complex infiltrating her bone marrow. Hypercalcemia can cause pancreatitis and nephrogenic diabetes insipidus manifesting as polyuria.
The initiation of HAART probably precipitated an immune reconstitution syndrome. The increase in production of a cytokine such as [gamma]-interferon led to constitutive vitamin D production. We may well see more cases with initial HAART in severely immunocompromised HIV disease.
1. Playford EG, Bansal AS, Looke DF, et al. Hypercalcaemia and elevated 1,25(OH)(2)D(3) levels associated with disseminated Mycobacterium avium infection in AIDS. J Infect 2001;42:157-158.
2. Newell A, Nelson MR. Hypercalcaemia in a patient with AIDS and Mycobacterium avium intracellulare infection. Int J STD AIDS 1997;8:405.
3. Delahunt JW, Romeril KE. Hypercalcemia in a patient with the acquired immunodeficiency syndrome and Mycobacterium avium intracellulare infection. J Acquir Immune Defic Syndr 1994;7:871-872.
4. Aly ES, Baig M, Khanna D, et al. Hypercalcaemia: a clue to Mycobacterium avium intracellulare infection in a patient with AIDS. Int J Clin Pract 1999;53:227-228.
5. 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;82:2222-2232.
Carlos Palacio, MD
Shawn Wilker, MD
Sebastian Stanciu, MD
Department of Shands-Jacksonville
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|Publication:||Southern Medical Journal|
|Article Type:||Letter to the Editor|
|Date:||Jan 1, 2005|
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