Livedo Reticularis is a common dermatological finding characterized by a reversible, mottled, purplish, or bluish net-like pattern on the skin. At Protheragen, we are focused on understanding the vascular dysregulation underlying Livedo Reticularis and developing tailored preclinical approaches. We provide comprehensive, end-to-end preclinical drug and therapy development services.
Introduction to Livedo Reticularis
Livedo Reticularis (LR) is a vascular dermatosis characterized by persistent, net-like mottled discoloration resulting from impaired cutaneous microcirculation. Often secondary to autoimmune disorders (e.g., SLE, antiphospholipid syndrome) or cryoglobulinemia, LR affects 1-5% of rheumatology patients with significant diagnostic overlap with livedo racemosa.
Fig.1 Congested and ectatic vessels in the superficial dermis. (Paudyal
et al., 2022)
Pathogenesis of Livedo Reticularis
The pathogenesis of Livedo Reticularis fundamentally involves vasoconstriction of small dermal arterioles, leading to a characteristic pattern of blood flow.
- Arteriolar Vasoconstriction: The core mechanism involves a reduction in the diameter of small arteries and arterioles in the dermis, particularly in response to cold or other stimuli. This reduces blood flow to the skin, causing a mottled appearance.
- Deoxygenated Blood in Venules: As oxygenated blood flow is diminished, the blood within the interconnected venules becomes deoxygenated, resulting in the visible bluish or purplish net-like pattern. When the vasoconstriction resolves (e.g., with warming), blood flow normalizes, and the pattern fades.
- Physiological vs. Pathological: In its physiological form, this is a normal vascular response to temperature changes. However, in pathological Livedo Reticularis, the vasoconstrictive response can be exaggerated or triggered by systemic factors such as immune complex deposition, vascular inflammation, or hyperviscosity syndromes, which compromise microcirculation.
- Endothelial Dysfunction: In cases associated with systemic diseases, underlying endothelial dysfunction or subtle microvascular damage can contribute to the impaired regulation of blood flow, making the skin more susceptible to this pattern.
Therapeutics Development for Livedo Reticularis
| Therapeutic Strategy |
Target / Intervention |
Mechanistic Validation/Model Data |
Development Stage |
| Tacrolimus 0.1% ointment |
Local T-cell suppression |
Inhibits IL-17+T-cell infiltration in dermal biopsies |
Clinical use |
| Iloprost |
Prostacyclin analog (vasodilation) |
Restores capillary perfusion in cold-challenge organoids |
Phase II |
| Imsidolimab |
IL-36R antagonism |
Suppresses IL-36-driven neutrophil extracellular traps (NETs) in vasculitis models |
Phase II |
| Anifrolumab |
IFNAR blockade |
Abolishes type I IFN signature in SLE-associated LR endothelial cells |
Phase I |
| ADSCs |
VEGF/TSG-6-mediated endothelial repair |
Reverses cholesterol emboli-induced vaso-occlusion in xenografts |
Phase I/II |
| Nano-delivered Protein C |
Targeted anticoagulant delivery |
Localized thrombus resolution in microfluidic platforms |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers comprehensive services to advance therapeutics for Livedo Reticularis. Our team of expert scientists, dermatologists, and geneticists integrates specialized knowledge with advanced technologies to support your project through tailored therapeutic development and disease model development.
Therapeutic Development Platforms for Livedo Reticularis
Protheragen delivers integrated end-to-end solutions across small molecule, gene therapy, cell therapy, and biologic platforms. These target ABHD5-driven lipid metabolic dysfunction underlying Livedo Reticularis for broad therapeutic applications.
Disease Models Development for Livedo Reticularis
Protheragen provides a comprehensive suite of preclinical models to accelerate Livedo Reticularis research, including cutting-edge 2D cell models, 3D skin models, and animal models customized to replicate disease pathology and evaluate therapeutics.
| 2D Cell Models & 3D Skin Models |
| Protheragen's preclinical models research services for Livedo Reticularis are built-designed as a solid foundation for the development effective therapies. We perform in vitro studies using 2D cell models and 3D skin models to detect and study the molecular mechanisms of Livedo Reticularis. |
| Optional Models |
- Human Endothelial Cell Lines
- Vascular Smooth Muscle Cell Models
|
- Co-culture Models of Endothelial Cells with Immune Cells
- 3D Skin Models with Embedded Microvessels
|
| Animal models |
| In vivo preclinical studies are also a meaningful part of our services. We will use, such as genetically engineering models, to test the safety and efficacy of proposed therapeutics. These animal models are carefully selected based on their ability to mimic the human condition of Livedo Reticularis. |
| Optional Models |
- Vasculitis-Induced Mouse Models
- Antiphospholipid Syndrome (APS) Mouse Models
|
- Cold-Induced Vasoconstriction Models in Rodents
- Drug-Induced Vasculopathy Models
|
| Optional Species |
Mice, Rats, Non-human primates, Others |
As a one-stop preclinical research services provider, Protheragen supports the development of therapies for rare conditions affecting skin, such as Livedo Reticularis. We offer end-to-end solutions through our team of scientists ranging from target discovery, disease modeling, through drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Paudyal, A., et al. "Livedo Reticularis and Flagellate Erythema in Adult Dermatomyositis: A Rare Cutaneous Presentation." Rheumatology (Oxford) 61.3 (2022): e62-e63.
- Srichawla, B. S. "Susac Syndrome with Livedo Reticularis: Pathogenesis and Literature Review." Cureus 14.7 (2022): e27352.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
