Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections

Hypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illus...

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Main Authors: Ramon Cohen, Viviana Ostrovsky, Lior Zornitzki, Daniel Elbirt, Taiba Zornitzki
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/4/773
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author Ramon Cohen
Viviana Ostrovsky
Lior Zornitzki
Daniel Elbirt
Taiba Zornitzki
author_facet Ramon Cohen
Viviana Ostrovsky
Lior Zornitzki
Daniel Elbirt
Taiba Zornitzki
author_sort Ramon Cohen
collection DOAJ
description Hypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illustrative case of <i>Mycobacterium simiae</i>. A meticulous literature search identified 24 cases relevant to this phenomenon (11 HIV-positive and 13 non-HIV), which were included in the analysis. Key clinical and laboratory findings reveal significant contrasts between HIV-positive and non-HIV patients. In the HIV-positive cohort, hypercalcemia is commonly developed after the initiation of highly active antiretroviral therapy (HAART) or treatment for NTM infections despite severe underlying immunosuppression. Conversely, in the non-HIV group, a spectrum of immunosuppressive conditions, including chronic renal failure and prolonged use of immunosuppressive drugs, was implicated in the pathogenesis of NTM infections with hypercalcemia. Two distinct mechanistic pathways likely underlie this association. In HIV-positive patients, immune restoration following HAART appears to drive granuloma formation and excessive 1,25-dihydroxyvitamin D production. In non-HIV individuals, prolonged immune suppression may facilitate macrophage activation associated with NTM infections, thereby contributing to hypercalcemia. Treatment strategies varied and included bisphosphonates, corticosteroids, and hemodialysis. Notably, bisphosphonates emerged as a safe and effective option in most cases. Antibiotic therapy was deemed unnecessary when hypercalcemia was the sole symptom of NTM infection. This review underscores the importance of recognizing hypercalcemia as a potential complication of NTM infections and tailoring management strategies to the patient’s underlying immunological status.
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spelling doaj-art-d1e22a95d9c44b31bbd00f42e4e5e8f22025-08-20T03:13:32ZengMDPI AGMicroorganisms2076-26072025-03-0113477310.3390/microorganisms13040773Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial InfectionsRamon Cohen0Viviana Ostrovsky1Lior Zornitzki2Daniel Elbirt3Taiba Zornitzki4Internal Medicine Department B, Kaplan Medical Center, Hebrew University Medical School, Rehovot 76100, IsraelDiabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School, Rehovot 76100, IsraelDivision of Cardiology, Tel-Aviv Sourasky Medical Center, School of Medicine, Tel-Aviv University, Tel-Aviv 46239, IsraelDepartment of Clinical Immunology, Allergy, and AIDS, Kaplan Medical Center, Hebrew University Medical School, Rehovot 76100, IsraelDiabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School, Rehovot 76100, IsraelHypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illustrative case of <i>Mycobacterium simiae</i>. A meticulous literature search identified 24 cases relevant to this phenomenon (11 HIV-positive and 13 non-HIV), which were included in the analysis. Key clinical and laboratory findings reveal significant contrasts between HIV-positive and non-HIV patients. In the HIV-positive cohort, hypercalcemia is commonly developed after the initiation of highly active antiretroviral therapy (HAART) or treatment for NTM infections despite severe underlying immunosuppression. Conversely, in the non-HIV group, a spectrum of immunosuppressive conditions, including chronic renal failure and prolonged use of immunosuppressive drugs, was implicated in the pathogenesis of NTM infections with hypercalcemia. Two distinct mechanistic pathways likely underlie this association. In HIV-positive patients, immune restoration following HAART appears to drive granuloma formation and excessive 1,25-dihydroxyvitamin D production. In non-HIV individuals, prolonged immune suppression may facilitate macrophage activation associated with NTM infections, thereby contributing to hypercalcemia. Treatment strategies varied and included bisphosphonates, corticosteroids, and hemodialysis. Notably, bisphosphonates emerged as a safe and effective option in most cases. Antibiotic therapy was deemed unnecessary when hypercalcemia was the sole symptom of NTM infection. This review underscores the importance of recognizing hypercalcemia as a potential complication of NTM infections and tailoring management strategies to the patient’s underlying immunological status.https://www.mdpi.com/2076-2607/13/4/773hypercalcemianontuberculous mycobacteriumHIVAIDS<i>Mycobacterium simiae</i>
spellingShingle Ramon Cohen
Viviana Ostrovsky
Lior Zornitzki
Daniel Elbirt
Taiba Zornitzki
Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
Microorganisms
hypercalcemia
nontuberculous mycobacterium
HIV
AIDS
<i>Mycobacterium simiae</i>
title Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
title_full Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
title_fullStr Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
title_full_unstemmed Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
title_short Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
title_sort exploring a rare association systematic review of hypercalcemia in nontuberculous mycobacterial infections
topic hypercalcemia
nontuberculous mycobacterium
HIV
AIDS
<i>Mycobacterium simiae</i>
url https://www.mdpi.com/2076-2607/13/4/773
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