Introduction 

Imagine finding out that you have an extremely rare and often fatal condition that has no cure called Degos disease.¹ This has been the case for 200 individuals reported worldwide.² The small number of individuals affected by this condition means that its cause and development remain elusive. Despite Degos disease being commonly identified by skin lesions, it can also have a large effect on the central nervous system (CNS) as well as the gastrointestinal tract.^1,2. The neurological manifestations of Degos disease will be discussed in this article, including strokes, seizures, and encephalopathy.  

Understanding degos disease

Degos disease is an extremely rare genetic, multisystem condition that can often be fatal.¹ There are only 200 cases reported worldwide. ² Degos is commonly diagnosed by its characteristic skin lesions that appear with porcelain white atrophic centres and can affect several organs. The disease currently presents in two unique forms: a systemic threatening form or a benign form involving the skin (cutaneous). The former type is malignant, which can be fatal and is also known to have a poor prognosis due to its complications, such as bowel perforation and a massive intracerebral haemorrhage.³ The benign form tends to have a better prognosis as the lesions are on the skin and do not involve internal organs.³

The pathogenesis of Degos disease remains unknown. However, factors such as blood clotting defects, vessel inflammation, as well as endothelial cell dysfunction may be contributors to the onset of the disease.³

Usually, Degos disease manifests in the second to fifth decades of life.¹ Moreover, there is a minor predominance in those assigned female at birth (AFAB) but no sex-associated prognosis.¹ 

The neurological involvement in degos disease

In the malignant form of Degos disease, the CNS is one of the most commonly affected systems (64%).¹ Degos disease is fundamentally a disorder of the blood vessels. Scientists have suggested that the immune system targets the inner lining of arteries and arterioles. This causes swelling, narrowing of the vessels, and clot formation, which leads to restriction of blood flow.⁴ As the CNS is made up of the brain and the spinal cord, blocked blood vessels deprive both the brain and spinal cord of oxygen and nutrients, leading to ischaemia. This triggers major neurological conditions such as, stroke, seizures, and encephalopathy. Research highlights that 20-60% of patients with Degos disease have neurological complications.⁵

Stroke in degos disease

Degos disease can present with a variety of neurological complications, including ischaemic strokes and fatal haemorrhages (see Table 1).⁵ Research has highlighted that strokes occur in approximately 20% of patients with the systemic malignant form of Degos disease.⁷Neurological advancement has been associated with an increase in mortality, with an average of up to 2 years from the first appearance of skin lesions before death.⁷

Common symptoms of a stroke:⁶ 

• Sudden limb weakness
• Slurred speech
• Facial dropping

Less common stroke symptoms:⁶ 

• Vision issues
• Cognitive impairment 
• Dizziness spells

Table 1: Types of strokes associated with Degos disease. 

Seizures in degos disease

Abnormal activity in the brain, which can cause a disruption in the level of behaviour, memory, consciousness, or feelings, is referred to as a seizure.⁸ In Degos disease, the damage as a result of the occlusion of blood vessels in the outer layer of the brain, seizures can occur. The types of seizures commonly seen in Degos disease are highlighted in table 2. 

Table 2: Different types of seizures that can occur in degos disease. 

Controlling seizures is essential. Regular seizures can have a negative impact on the brain and body, causing long-term harm that occasionally may not be repairable.

Encephalopathy in degos disease

What is encephalopathy? 

The term "encephalopathy" refers to any disorder that alters the way the brain functions and impacts a person's perception or level of attentiveness.¹⁰ It usually causes global impairment, not just focal deficits as seen in strokes. Symptoms generally develop over time, following frequent vascular insults to the brain.¹⁰ At first, people with encephalopathy might have small changes in how they act or think. But as more harm happens, it exacerbates. This leads to significant changes in how they think and their ability to do things independently. In advanced stages, it can cause severe problems or even death if accompanied by other complications of Degos disease.

Symptoms of encephalopathy:¹⁰ 

• Confusion and amnesia 
• Problems with movement and coordination 
• Variations in personality 

Diagnosis and management of neurological malformations in degos disease

As degos disease is rare, it has proven difficult for scientists to understand the condition and find a cure. Therefore, management should focus on symptomatic control and providing care. Efficient and accurate diagnosis is also key in understanding if there are other organs involved. Hence, a multifaceted approach is needed here.

Steps of diagnosis 

1. Physical exam - The basis of diagnosis is made on the presence of the skin lesions and a tissue biopsy.^1-2 An assessment of any neurological symptoms should also occur
2. MRI/CT scan for imaging - Scans to detect different  areas of the brain that have reduced blood flow, dead tissue, and haemorrhages are used¹¹
3. EEG - This can confirm seizure activity 
4. Blood tests - There are no serum markers specific for the skin lesions, but many blood tests can be used to confirm defects in blood coagulation in patients¹
5. Multisystem evaluation - Degos disease can also affect the heart and gastrointestinal system. Elevations should also be conducted here

Management strategies

1. General actions: 

When doctors see genetic skin disorders, it is crucial to refer them to a dermatologist. They should also be referred to a neurologist who will aid patients in recognising symptoms such as weakness, confusion, and seizures. ¹ 

2. Medication: 
   • Antiplatelet agents such as Aspirin and clopidogrel are administered to decrease the risk of clot formation ² 
   • Anti-epileptic drugs (AEDs) such as levetiracetam are also used for managing seizures 

3. Neurological specific management: 
   • Strokes - supportive care, rehabilitation, physical therapy
   • Seizures - AEDs, emergency benzodiazepines for status epilepticus
   • Encephalopathy: psychological assistance, cognitive rehabilitation, and supportive care

4. Supportive care:

A multidisciplinary approach involving neurologists, dermatologists, immunologists, physiotherapists, and psychologists is important. Moreover, palliative care may be required in advanced systemic cases.

FAQs

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

Uncontrollable sepsis, consistent bleeding in the gastrointestinal tract, and damage to the vessels in the brain. 

What is the prognosis of degos disease? 

The systemic form of the disease often results in death 2-3 years from when the initial symptoms indicating systemic involvement first appear.  However, survival from the time of diagnosis can range from 1 year to over 12 years. 

Is degos disease genetic? 

Yes. It has an autosomal dominant pattern of inheritance. 

What age group is affected by degos disease? 

People aged 20-50 years old, but it can occur at any age. It is very uncommon in children. 

Is degos disease curable? 

No. However, symptoms can be controlled through various medications such as aspirin to reduce the risk of clot formation, to prevent blood clots and reduce the risk of stroke. 

Summary 

Degos disease is an intricate and rare condition which primarily affects the skin but can lead to complications in other surrounding organs. Neurological problems such as strokes, seizures, and encephalopathy can occur due to blocked vessels located in the brain. Due to the small number of cases recorded and their complex symptoms, it has been a challenge for scientists to find a cure and provide accurate diagnoses. This emphasises the need for further research to find and develop an efficient cure to help patients. Whilst there is no current cure, patients who present with neurological symptoms should be supported by health care professionals. They should receive regular check-ups to monitor the progression of symptoms and their disease. Quality of life should also be of key importance for doctors involved in the care of Degos disease patients, aiming to manage symptoms and reduce the risk of strokes, seizures, and encephalopathy. As our knowledge of the disease improves, our understanding of its effective management will too.