COMPLICATIONS OF ANGIOKERATOMAS

Caraffa A. Complications of angiokeratomas. International Journal of Infection. 2025;9(1):11-13

A. Caraffa^*

School of Pharmacy, University of Camerino, Camerino, Italy.

*Correspondence to:
Dr. Alessandro Caraffa,
School of Pharmacy,
University of Camerino,
62032 Camerino, Italy.
e-mail: alecaraffa@libero.it

Received: 20 January, 2025 Accepted: 03 April, 2025

ISSN 1972-6945 [online] Copyright 2025 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

KEYWORDS: Angiokeratoma, angiogenesis, infection, skin, bacteria

INTRODUCTION

Angiogenesis is a normal physiological process of new blood vessel formation which is essential for growth and diverse functions of the body, including wound healing and embryogenesis. Angiogenesis plays a crucial role in tissue development, function, and repair (1,2). During embryonic development, angiogenesis provides cells with adequate oxygen and nutrients for proper growth. In pathological conditions, angiogenesis helps to restore blood supply and aid recovery, and in malignant tumors, such as glioblastomas, angiogenesis sustains rapid growth. Targeting excessive blood vessel growth in tumors limits their progression.

Angiogenesis is a key physiological process in tissue growth, wound healing, and immune responses. The development of angiogenesis can be significantly influenced by infections through various biological and biochemical mechanisms involving pathogen-derived signals, immune responses, oxidative stress, and endothelial cell remodeling (3). Pathogens, immune responses, and host factors interact to regulate vascular growth, sometimes promoting and sometimes inhibiting angiogenesis.

Angiogenesis can sometimes alter the dilation of blood vessels in the papillary dermis, which contributes to the formation of lesions called angiokeratomas. Angiokeratomas are benign vascular lesions of the superficial dermal blood vessels. They are often associated with hyperkeratosis and form dilations of the superficial blood vessels, causing thickening of the skin with spots (4). They can appear as solitary lesions with a diameter that usually ranges from 1 to 3 mm or multiple lesions and vary in color from dark red to brown. Angiokeratomas have been associated with some genetic conditions, such as Fabry disease.

Angiokeratomas are small blood-filled vesicles that are not infectious, but they can be susceptible to secondary infections. Hyperkeratosis and vascular abnormalities can create an environment where microorganisms can easily proliferate (5). Staphylococcus aureus and Streptococcus pyogenes contribute to bleeding during infections through various mechanisms (hemolysins, coagulases, proteases, and inflammatory mechanisms) that disrupt vascular integrity.

DISCUSSION

Angiokeratomas are normally benign but they may be prone to secondary infections. Fabry disease-related angiokeratoses results in an accumulation of phospholipids or deficient α-Galactosidase A with the accumulation of globotriaosylceramide (Gb3) in multiple cell types, particularly in the vasculature, which can lead to end organ failure. This disease is caused by mutations in the GLA gene which encodes the enzyme a-Galactosidase that is responsible for catalyzation in many processes, including the cleavage of glycoproteins, glycolipids, and polysaccharides. Angiokeratomas of Fordyce affect the scrotum or vulva and may be caused by increased local venous pressure.

There is an increase in oxidative stress and abnormalities of the vascular system caused by the endothelial dysfunction in angiokeratomas. This leads to an inflammatory response with activation of the NF-κB pathway and the release of cytokines. In addition, there is an increase in vascular endothelial growth factor (VEGF) that promotes vascular ectasia, and activation of transforming growth factor-beta (TGF-β) that contributes to fibrosis and the formation of lesions (6). Dysregulation of nitric oxide (NO) can also occur with the formation of microvascular and endothelial abnormalities.

In angiokeratomas, hyperproliferation and differentiation of keratinocytes and mTOR and activation of the PI3K/AKT pathways results in the increased proliferation of keratinocytes and hyperkeratosis. Furthermore, dysregulation of the Wnt/β-catenin pathway contributes to epidermal thickening. Microtrauma can cause lesions and/or ulcerations of the vesicles with subsequent bleeding and bacterial infection, most commonly from S. aureus or S. pyogenes.

S. aureus is a human pathogenic bacterium that is responsible for many infections and can cause life-threatening systemic infections and/or superficial skin diseases. Infections caused by S. aureus can be complicated by hemorrhages due to tissue damage, as occurs in angiokeratomas. S. aureus has several virulence factors that contribute to tissue damage, inflammation, and disruption of hemostasis, leading to hemorrhages (7).

S. aureus utilizes diverse biological mechanisms to evade immune responses, which contribute to inflammation and bleeding. Immune evasion occurs through the binding of protein A to the Fc region of IgG which prevents opsonization and phagocytosis, while superantigens, such as toxic shock syndrome toxin-1, cause excessive immune activation, leading to systemic inflammation and capillary leakage. Lipoteichoic acid and peptidoglycan inactivate pro-inflammatory cytokines IL-1, IL-6, and TNF, increasing vascular permeability and bleeding. The hemolysins A, B, and G form pores in host cell membranes to cause endothelial damage and red blood cell lysis. Targeted treatments could certainly ameliorate the infection and prevent excessive bleeding.

S. pyogenes is a Gram-positive, facultative anaerobic bacterium which is capable of forming colonies of 1-2 mm with β-type hemolysis after 24 hours when grown in vitro. This bacterium is capsulated, non-motile, and asporogenous, with homolactic metabolism and negative catalase. It is a highly virulent bacterial pathogen that is responsible for a variety of infections, ranging from pharyngitis to life-threatening sepsis. One of the main pathological effects of pyogenic bacterial infections is bleeding, which can occur due to vascular damage, intravascular coagulation, and disruption of endothelial integrity.

Vascular damage is caused by hemolysins or streptolysins O and S. Streptolysin O is a cytotoxin that causes cell lysis and increased vascular permeability by targeting endothelial cells and immune cells; streptolysin S is responsible for β-hemolysis on blood agar, contributing to erythrocyte lysis and tissue damage. S. pyogenes alters the balance between coagulation and fibrinolysis through streptokinase, promoting fibrin degradation and increasing the risk of bleeding.

CONCLUSIONS

Angiokeratomas are benign skin vesicles, but their potential complications (infection, bleeding) and their complex biochemical mechanisms require special attention. Angiokeratomas do not usually require treatment, although in some cases of frequent bleeding, they can be removed by laser or cryotherapy. In subjects with these vascular lesions, there is often psychological damage as well.

The presence of angiokeratomas, especially in the genital area, can cause discomfort and embarrassment and fear of malignancy or social stigma often contributes to emotional distress. Misinterpretation of the lesions as serious conditions such as melanoma can result in excessive medical consultations and anxiety.

Conflict of interest

The author declares that they have no conflict of interest.

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