Patient with disseminated Mycobacterium avium-intracellulare complex involving the bone marrow, causing pancytopenia.
To the Editor: We report the case of a 35-year-old female who presented to the emergency department with a recent diagnosis of acquired immunodeficiency syndrome acquired immunodeficiency syndrome, see AIDS. (AIDS) 1 month prior while undergoing a workup for a 35-pound weight loss. She had a CD4 count of 25 and a high viral load. She reported nausea and vomiting Nausea and Vomiting Definition
Nausea is the sensation of being about to vomit. Vomiting, or emesis, is the expelling of undigested food through the mouth. for 2 days and a constant sharp pain under her diaphragm that was pleuritic pleu·rit·ic
Of or relating to pleurisy.
pertaining to or emanating from pleurisy. See also pleural.
pleuritic ridge in nature. It radiated to her back and decreased with lying on her right side. She reported constipation and a feeling of fullness in her abdomen for 2 days, with fever of 102.9[degrees]F.
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 nelfinavir /nel·fin·a·vir/ (nel-fin´ah-vir) an HIV protease inhibitor that causes formation of immature, noninfectious viral particles; used as the mesylate salt in the treatment of HIV infection. ) 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 peritoneal /peri·to·ne·al/ (per?i-to-ne´al) pertaining to the peritoneum.
pertaining to the peritoneum. signs or organomegaly. Admission laboratory values included blood urea nitrogen blood urea nitrogen
n. Abbr. BUN
Nitrogen in the form of urea in the blood or serum, used as a indicator of kidney function.
Blood urea nitrogen (BUN) , 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 electrocardiography (ĭlĕk'trōkärdēŏg`rəfē), science of recording and interpreting the electrical activity that precedes and is a measure of the action of heart muscles. showed sinus tachycardia with a QTc of 384.
The patient was admitted with a diagnosis of pancreatitis secondary to hypercalcemia Hypercalcemia Definition
Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood. , severe dehydration, and pancytopenia pancytopenia /pan·cy·to·pe·nia/ (-sit-ah-pe´ne-ah) abnormal depression of all the cellular elements of the blood.
n. . 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 Bone marrow biopsy
A procedure in which cellular material is removed from the pelvis or breastbone and examined under a microscope to look for the presence of abnormal blood cells characteristic of specific forms of leukemia and lymphoma. showed a hypercellular bone marrow with trilinear hematopoiesis Hematopoiesis
The process by which the cellular elements of the blood are formed. The three main types of cells are the red cells (erythrocytes), which serve to carry oxygen, the white cells (leukocytes), which function in the prevention of and recovery from 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 nephrogenic diabetes insipidus
Diabetes insipidus caused by an inability of the kidney tubules to respond to antidiuretic hormone and reabsorb water. manifesting as polyuria polyuria /poly·uria/ (-ur´e-ah) excessive secretion of urine.
Excessive passage of urine, as in diabetes. Also called hydruria. .
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