Introduction

Chediak-Higashi Syndrome (CHS) is a rare inherited disorder which affects various parts of the body, particularly the immune system. The disease is caused by mutations in a gene called CHS1 (also known as the LYST gene). The CHS1/LYST gene is responsible for the production of lysosomes, which are small structures within cells that act as their own personal recycling unit. Lysosomes contain various chemicals which break down waste in cells, particularly white blood cells, platelets, and other immune cells.  They help protect the body against bacteria and other foreign materials that may cause us harm. In a healthy immune system, white blood cells trap germs and destroy them using enzymes and toxic chemicals. In CHS, the white blood cells are unable to trap and therefore destroy the germs, which causes frequent bacterial infections that can cause life-threatening illnesses.¹ 

Common infection risks in CHS include:² 

• Skin abscesses. 
• Respiratory infections, e.g., pneumonia.
• Oral infections, e.g., gum disease and mouth ulcers.
• Blood infections (sepsis).

CHS is an autosomal recessive disease, meaning both parents must be carriers of the faulty CHS1 gene, which is why the disease is so rare!¹ The disease often arises in childhood and can manifest as frequent and severe infections, easy bruising, albinism (due to defective platelets), visual impairments and nerve issues, so early intervention is key.

The immune system is the body’s defence system against diseases, responsible for fighting against infection, so those with CHS have persistent infections, which can be very dangerous and life-threatening. The persistent infections can lead to an overreaction of the immune system, meaning the body attacks itself. This leads to what is known as the ‘accelerated phase’ of CHS, which affects roughly 85% of CHS patients and is life-threatening without adequate treatment.¹ 

Symptoms of the accelerated phase may present as:² 

• Persistent fever
• Enlarged liver and spleen
• Low white cell counts
• Bleeding problems may appear as being easily bruised
• Neurological impairments

Luckily, there are various supportive treatments and infection control strategies for CHS, including supportive treatments for symptom relief and improving quality of life, infection control strategies, and curative treatment via hematopoietic stem cell transplantation (HSCT). 

Chediak-Higashi Syndrome (CHS) management/treatment

The goals of supportive care for CHS are to improve patients’ quality of life, reduce symptoms, and help increase the body’s immune system so it can effectively fight infections.

The main goals of supportive care for Chediak-Higashi Syndrome are to improve patients' quality of life, manage or reduce symptoms, and increase the body’s immune system so it can effectively fight infections. Whilst supportive care does not provide a cure for CHS, it is important in ensuring people feel better, have a better quality of life, and prevent complications. This may include treatments to reduce bleeding risk, various therapies to improve physical movement and learning, medicines to control infections, and practical steps such as sun protection and good dental hygiene.³  

Examples of supportive treatments that are commonly used in CHS are: 

• Antibiotics: due to the impaired immune system
• Blood and platelet transfusions: this helps when patients experience bleeding problems, such as bruising easily, by increasing the overall blood count
• Corrective lenses and sun protection: CHS often causes sun sensitivity, albinism, and impaired vision⁹
• Vitamin C supplements: High doses of vitamin C have been shown to help children in the stable phase of CHS¹⁰

Faulty immune response management/treatment

Chediak-Higashi Syndrome management adopts a multidisciplinary approach and focuses on two main goals: preventing and combating infections, in addition to supporting the immune system. The disease weakens the body’s defence system (the immune system), meaning those with CHS are more vulnerable to bacterial, viral, and fungal infections. However, the only known cure is an allogeneic hematopoietic stem cell transplantation (HSCT).² HSCT is a medical procedure which replaces a patient’s faulty immune system with healthy immune stem cells from a donor. This means an individual with CHS can fight infections more effectively, preventing the life-threatening ‘accelerated phase’.The additional administration of antibiotics, antivirals, antifungal medications, and blood transfusions is also effective at managing the impaired immune response demonstrated in the disease. Whilst HSCT is the only known cure for the disease, it only addresses the immune aspect of the disease and not all symptoms, such as nerve damage and albinism. 

Neurological symptoms management 

The neurological symptoms of CHG may appear later in life and may present as tremors, learning difficulties, and overall motor weakness.⁴ While there is no cure for the neurological symptoms, as HSCT cannot effectively treat the neurological decline evident in CHS, supportive care and treatments are available to improve the quality of life. A care plan may include physical therapy, which focuses on maintaining muscle strength, in addition to occupational therapy, aiming to make everyday tasks such as eating, drinking, and dressing easier. Medications can also be prescribed to reduce muscle stiffness and spasms, for example, clonazepam.⁵ 

Managing the accelerated phase of Chediak-Higashi Syndrome

The accelerated phase is the most serious stage of Chediak-Higashi Syndrome and can be life-threatening if not treated quickly. The accelerated phase is often triggered by an infection. During this phase, the immune system, which is weakened in those with CHS, becomes overactive and begins to attack the body’s own tissues and organs - this reaction is called ‘hemophagocytic lymphohistiocytosis (HLH)’.⁶ The phase must be treated immediately and is done so through a combination of medications such as those used in chemotherapy and steroids to suppress the immune system. With the eventual plan of performing hematopoietic stem cell transplantation.¹ 

Living with Chediak-Higashi Syndrome

CHS affects each person and their family differently, often resulting in a stressful and isolating time. However, there are several approaches which may alleviate this for many individuals.

• Genetic counselling: due to the genetic nature of the disease, genetic counselling can help families learn about the risk for developing or passing on a genetic condition
• Support networks: these can make it easier to connect with others with CHS, helping families cope, share advice, and stay informed regarding treatments

Infection control strategies

As mentioned throughout the article, even a simple infection can prove to be fatal for someone living with CHS. This is why infection control is vital in the management of CHS, protecting patients from becoming dangerously sick. 

Key strategies used to reduce infection risk in people with CHS involve: 

• Good hygiene practices: such as frequent handwashing, good oral hygiene
• Avoiding exposure to illness: those with CHS should reduce their contact with individuals who are sick, especially during high-infection seasons such as cold and flu season
• Vaccinations: they protect against certain diseases; however, it is essential that the vaccination is not live, meaning the virus is still active and not dead (such as the MMR vaccine) and must be inactivated due to the patient’s compromised immune status
• Early identification and aggressive treatment
• Preventative medicines: such as daily preventive antibiotics to reduce infection risk
• Drugs that boost the immune system
  • Interferon-gamma: a drug that helps white blood cells work better⁷ 
  • G-CSF (Granulocyte-Colony Stimulating Factor): This boosts the number of infection-fighting neutrophils in the blood⁸

Summary 

Chediak-Higashi Syndrome has a profound impact on the immune system and overall health, impacting patients’ quality of life. While there is no simple cure, supportive treatments and infection control strategies are available, providing those with CHS longer, healthier lives. The most effective long-term solution is a stem cell transplant, which can strengthen the immune system, preventing life-threatening infections - though this cannot resolve all symptoms,  such as the problems with skin pigmentation (presented as albinism) or long-term neurological damage, highlighting the importance of a multidisciplinary treatment approach in improving overall outcomes. By adopting an approach which combines infection prevention, supportive care, and advanced treatments such as stem cell transplantation, patients with CHS have a better chance at managing the condition, reducing the potential complications, and improving their overall outcomes. 

FAQs

What is Chediak-Higashi Syndrome (CHS)?

A very rare genetic condition that affects the immune system, nervous system, skin, and eyes. Those with CHS also often present with albinism.

Why are those with CHS more susceptible to infections? 

The immune system does not work properly, and the white blood cells, which usually destroy bacteria and viruses, are faulty. 

What is a stem cell transplant, and why is it important? 

A stem cell transplant replaces the faulty immune system with healthy donor cells from a matched donor, helping the body fight infections. 

Can CHS be cured without a transplant? 

No, whilst supportive treatments can help manage symptoms, the impaired immune response still remains - this can be particularly dangerous in the ‘accelerated phase of CHG’ 

Does CHS affect learning or development?

Yes. Some children with CHS may experience developmental delays, spasms, and/or trouble with coordination.