Introduction 

The pathogenesis of Degos disease remains quite elusive.¹ This is the mechanism of a disease, including how it develops, progresses, and either persists or is resolved. Degos disease is an extremely rare condition, with only 200 people affected worldwide, as reported in the literature.² The disease manifests as either cutaneous or systemic, with the latter having severe and complicated damage to several organ systems.² The systemic form is also likely to result in death, with 50% of patients with this form dying within 2-3 years of the initial onset.² Understanding the mechanism of Degos will allow scientists to develop drugs and targeted therapies for patients, also help reduce and manage symptoms better, and possibly develop a cure and reduce the mortality rate. 

This article covers Degos disease and its proposed theories of its mechanism. It also discusses the significance of knowing the mechanism and the impact it will have on future care for patients and the development of novel drugs. 

Background: what you need to know

Degos disease is an extremely rare condition that, according to literature, only 200 people worldwide have been affected by it.¹ It typically manifests in the fourth decade of adulthood, where males have a slight preponderance but also more severe malformations than females.³ However, a case where an infant as young as 3 weeks old has also been reported.¹  Degos is usually recognised and diagnosed by skin lesions; these appear with a white centre and are degenerative.¹ Moreover, Degos disease can occur in two unique forms: the cutaneous form or the systemic form. The cutaneous form is said to have a satisfying prognosis due to it only having skin-related malformations that commonly appear on the upper parts of the body.¹ Whereas the systemic form is aggressive, affecting other organs than just the skin, such as the gastrointestinal tract and the central nervous system. When several organs are involved, the disease usually causes death 2-3 years after the initial onset due to severe complications such as bowel perforations, strokes, and seizures.⁴

As Degos is a rare disease, the understanding of its mechanism remains undefined.¹ Scientists have theorised that it is a genetic condition that affects multiple generations, especially first-generation family members, which suggests an autosomal dominant inheritance.¹ However, it is also believed that Degos is sporadic. Degos is said to be an occlusive vasculopathy, which is where vessels become damaged and are unable to deliver essential nutrients and oxygen to different parts of the body. However, other hypotheses have been proposed, such as endothelial cell dysfunction.¹

The involvement of C5b-9 has also been suggested. It is found in large deposits in the skin, gastrointestinal tract, and parts of the brain in patients with the systemic form of Degos.⁵ C5b-9 is a protein complex which forms at the end of a complement system cascade, which is a part of the immune system.² This develops on cell membranes, triggering cell lysis.⁵

How degos disease may occur 

Endothelial cell dysfunction 

Endothelial cells are a flattened cell form that creates a covering lining all the blood vessels.² The layers of these cells are essential to the blood supply for tissues within the body.² Some scientists believe that Degos disease may arise from issues within endothelial cells.⁶ This would be as a result of the damage to the blood vessels, causing them to become narrow and swollen, increasing the risk of blood clots, which can result in a lack of blood flow to organs, and subsequently poor oxygen supply, causing organ failure (ischemia). Chronic ischemia will lead to systemic Degos, where organs such as the gastrointestinal tract and the central nervous system are commonly affected.¹ Moreover, this can result in bleeding in the gastrointestinal tract, strokes, and seizures, which are associated with high mortality.¹ Scientists also propose that endothelial cell dysfunction may be a result of an issue within the immune system. 

Blocked blood vessels

Vascular occlusion refers to blood vessels which are small to medium-sized and become obstructed by blood clots. This blockage results in a hindrance of blood flow to organs and tissue, causing damage.¹ This has the same impact on organs as endothelial cell dysfunction would and is also associated with the systemic form of Degos disease.

How do the damages and blockages work together? 

It is crucial to emphasise that the mechanism and exact process of Degos disease are not fully understood. But it is believed that the injury to the endothelial lining of vessels can form clots, which reduce the flow of blood and cause damage to tissues. 

Possible risk factors 

Rare inherited genetics

Although many cases of Degos disease have been reported as sporadic, an autosomal dominant pattern of inheritance has also been described in some families.¹

Immune system issues

Another popular theory is that the immune system accidentally targets the endothelium. For instance, the immune system might produce inflammatory molecules that can damage the endothelium.⁷ As this vessel lining is now impaired, the body proceeds to fix this by producing clots, but this obstructs the flow of blood instead.⁷ The reduced flow of blood causes damage to organs due to the lack of oxygen reaching them. In the case of degos, this leads to skin lesions and, in more severe systemic cases, to the central nervous system and the gastrointestinal system.⁷

Bacterial infection

Bacterial infection involvement in Degos disease is considered speculative. But some studies have highlighted the involvement of streptococcal infection in the diagnosis of Degos.⁸

Why do we need to understand the mechanism of degos? 

There are several important reasons to find and understand the mechanism of Degos, after all, it can cause death. 

Firstly, it is needed for early diagnosis and prognosis. As Degos disease usually starts with white atrophic skin lesions, doctors will know that this is associated with damage and occlusions to vessels and can aid in making early diagnoses before any systemic complications arise. Moreover, understanding its mechanism can help doctors identify which patients are likely to progress from the cutaneous form of the disease to the life-threatening systemic form of the disease.

Secondly, for the correct treatment approach. As of right now, there is no cure for Degos, and even treatments available, such as antiplatelets and anticoagulants, are not always effective.⁹ If immune system dysfunction truly drives Degos disease, then drugs that target the immune system could be beneficial. 

Lastly, understanding the pathogenesis of the disease will aid in the development of new research and targeted therapies. Once scientists have established and confirmed the role of endothelial cell dysfunction, immune system dysfunction, or vascular occlusion, it will allow for the clinical trials of drugs such as immunosuppressants or stronger anticoagulants. 

FAQ’s 

What is the underlying mechanism of degos disease? 

We don’t know. The mechanism is yet to be defined. It has been heavily suggested that endothelial cell dysfunction and vascular occlusion play a role in the onset of the disease.

What is the most common cause of mortality in degos disease? 

Uncontrollable sepsis, consistent bleeding in the gastrointestinal system, and a lesion in the brain are the most common causes of mortality in patients with systemic Degos disease. 

What does degos look like? 

Multiple red skin lesions with a white centre.

Is degos disease genetic or inherited? 

Most cases have been sporadic, but there have been cases in families that suggest an autosomal dominant pattern of inheritance.  

Summary

As previously mentioned, Degos is an extremely rare disease with only 200 people reported with this disease worldwide. This small pool of people proves challenging for scientists and doctors to understand the underlying mechanism of Degos. Although endothelial cell dysfunction and vascular occlusion may cause Degos, further research is paramount in fully establishing its cause, which will allow for much more efficient and accurate diagnoses. This may also provide hope for patients with the systemic form, as the risk of mortality may be reduced with the production of innovative therapies and treatments.