Causes of Pallor in Tuberculosis
Pallor in tuberculosis is primarily caused by anemia of chronic disease (ACD), which results from systemic inflammation affecting iron homeostasis during active TB infection. 1, 2
Mechanisms of Anemia in Tuberculosis
Anemia of chronic disease (ACD) is the predominant form of anemia in TB patients, affecting approximately 60% of cases compared to only 26% in healthy controls 2
The chronic inflammatory state in TB leads to increased production of hepcidin, a key iron regulatory hormone, which impairs iron absorption from the gut and prevents iron release from macrophages 2, 3
Elevated hepcidin levels correlate with TB severity, with median levels of 63.7 ng/mL in TB cases versus 14.2 ng/mL in controls without TB 2
Hepcidin levels are associated with more severe TB symptoms and higher mycobacterial load, indicating a direct relationship between disease activity and anemia 2
Types of Anemia in Tuberculosis
While ACD is most common in TB (59.8% of cases), iron deficiency anemia (IDA) can coexist, creating a multifactorial anemia picture 2, 3
Pure iron deficiency anemia is less common in TB patients (only about 1%) compared to controls without TB (10%) 2
The anemia profile changes during TB treatment, with ACD declining from 36% at diagnosis to 8% after 6 months of treatment 3
Even after successful TB treatment, anemia with iron-responsive components (IDA or mixed IDA+ACD) may persist, requiring specific interventions 3
Biomarkers and Diagnosis
Elevated serum ferritin with low transferrin saturation is characteristic of ACD in TB patients 3, 4
Hepcidin is a particularly sensitive biomarker that decreases significantly from a median of 84.0 ng/mL at diagnosis to 9.7 ng/mL after just 2 months of TB treatment 3
Serum iron levels correlate with TB severity, with lower levels associated with more severe lung symptoms and lesions 5
Traditional hematological indices (hemoglobin, MCV, PCV) may not reliably distinguish between ACD and IDA in TB patients 4
Treatment Implications
TB treatment itself significantly improves anemia parameters, particularly ACD, even without specific iron supplementation 3, 4
Iron supplementation in TB patients with mild to moderate anemia accelerates improvement in hematological parameters in the initial phase (first month) but shows no advantage over placebo by 6 months 4
The window for iron-based interventions opens approximately 2 months into TB treatment, when hepcidin levels have decreased significantly 3
Indiscriminate iron supplementation in all TB patients is not recommended, as it may not benefit those with pure ACD and could potentially support mycobacterial growth 1, 3
Immunological Impact
Iron deficiency in TB patients is associated with altered T cell subsets, including decreased MAIT, Vδ2+, and Treg cell percentages 5
These immunological changes may contribute to more severe lung lesions and disease progression 5
Cytokine profiles are affected by iron status, with increased levels of interleukin-1β (IL-1β) and IL-7 observed in iron-deficient TB patients 5
In conclusion, pallor in TB primarily results from anemia of chronic disease due to inflammation-induced dysregulation of iron metabolism, with hepcidin playing a central role. Effective TB treatment is the primary intervention for resolving this anemia, with iron supplementation potentially beneficial only after the initial phase of treatment when hepcidin levels have normalized.