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Innovative Medicines & Omics Vitamin D deficiency and cherry angiomas

A B inflammatory cytokines such as interleukin-6 and tumor
necrosis factor-alpha, both of which are implicated in
vascular inflammation and remodeling. A deficiency
10
in this anti-inflammatory regulation may further
predispose dermal vasculature to aberrant growth and
lesion formation.
The dermal microenvironment is also influenced by
matrix metalloproteinases (MMPs), enzymes involved
in extracellular matrix remodeling and angiogenesis.
11
Studies have shown that Vitamin D deficiency leads to an
upregulation of MMP activity, contributing to vascular
instability and hyperproliferation. This interplay between
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MMPs, VEGF, and oxidative stress, in the absence of
sufficient Vitamin D, could synergistically drive the
formation of cherry angiomas. 13
Figure 1. Cherry angiomas present as well-demarcated, erythematous,
dome-shaped papules on the skin. (A) A lesion localized to the neck In the context of this patient, the severe Vitamin D
region; (B) A lesion on the left breast. Both lesions are small, measuring deficiency (serum level: 3 ng/mL) likely represents a
approximately 2 – 5 mm in diameter, and exhibit the characteristic red profound disruption in these regulatory mechanisms. The
coloration typical of cherry angiomas.
sudden appearance of cherry angiomas localized to the
3. Discussion breast and neck regions may reflect heightened vascular
vulnerability in these areas, potentially attributed to
Cherry angiomas are benign vascular lesions with an hormonal or mechanical factors. While the exact molecular
unclear pathogenesis. While factors such as aging, triggers remain to be fully elucidated, this case highlights
hormonal changes, and oxidative stress have been a plausible mechanistic link between Vitamin D deficiency
implicated, this case introduces a novel hypothesis linking and cherry angiomas, warranting further investigation.
severe Vitamin D deficiency to the development of cherry This hypothesis aligns with emerging evidence
angiomas. Vitamin D is essential for vascular health, and suggesting that Vitamin D deficiency is not only a marker
its deficiency can lead to endothelial dysfunction and of systemic health but also a driver of localized vascular
dysregulated angiogenesis, both of which could drive the pathologies. Given the potential reversibility of vascular
formation of these vascular lesions. abnormalities associated with Vitamin D deficiency, it is
Vitamin D exerts its biological effects through plausible that cherry angiomas, particularly those arising
calcitriol, the active metabolite, which binds to the VDR in the context of severe deficiency, could regress with
expressed in endothelial and vascular smooth muscle adequate Vitamin D supplementation. Emerging evidence
cells. Through VDR signaling, Vitamin D regulates the suggests that vitamin D repletion can restore endothelial
expression of angiogenesis-related genes, including those function and modulate pro-angiogenic pathways,
that are involved in the inhibition of pro-angiogenic including VEGF suppression and oxidative stress
pathways. A well-documented target of Vitamin D is reduction. Although no direct studies have investigated the
VEGF, a key driver of capillary proliferation and dilation. effects of Vitamin D supplementation on cherry angiomas,
Under normal conditions, Vitamin D suppresses VEGF clinical observations in related vascular conditions provide
expression, thereby preserving vascular integrity. In a rationale for exploring this therapeutic avenue. Future
states of severe Vitamin D deficiency, VEGF activity studies should aim to evaluate whether normalizing serum
may become upregulated, leading to abnormal capillary Vitamin D levels through supplementation can mitigate
proliferation and angiogenesis. These mechanisms the progression or potentially reverse the development of
could explain the sudden onset of cherry angiomas cherry angiomas in susceptible individuals.
observed in this case. In addition, Vitamin D deficiency
is associated with increased oxidative stress and the 4. Conclusion
accumulation of reactive oxygen species (ROS), which This case highlights a novel and plausible link between
exacerbate endothelial damage. ROS disrupts vascular severe Vitamin D deficiency and the development of cherry
endothelial cell junctions and promotes capillary leakage, angiomas, potentially mediated by mechanisms involving
potentially contributing to the pathophysiology of cherry endothelial dysfunction, oxidative stress, and dysregulated
angiomas. Moreover, Vitamin D is known to inhibit pro- angiogenesis. The patient’s profound deficiency in
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Volume 2 Issue 2 (2025) 115 doi: 10.36922/imo.8087