Xeroderma Pigmentosa

Can medical cannabis help people with this condition? Find out more below. 

What is Xeroderma Pigmentosa?

Xeroderma Pigmentosum (XP) is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation from sunlight. Individuals with this condition have an increased risk of developing skin abnormalities, such as freckles, irregular pigmentation, premature aging, and skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The disorder may also affect the eyes, leading to photophobia (sensitivity to light), inflammation, and a higher risk of ocular cancer. 

Sometimes, XP can be accompanied by neurological complications, such as progressive hearing loss, poor coordination, and cognitive decline. These symptoms usually manifest during childhood, although the severity of the condition can vary significantly among affected individuals.

What causes it?

Xeroderma Pigmentosum is caused by mutations in one of at least eight genes (XPA to XPG and POLH) responsible for the nucleotide excision repair (NER) pathway, a vital cellular mechanism that detects and repairs DNA damage caused by UV radiation. In individuals with XP, the NER pathway is compromised, accumulating unrepaired DNA damage. This, in turn, increases the likelihood of errors during DNA replication, which can result in cell death or the development of cancerous cells. XP is inherited in an autosomal recessive manner, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

How common is it?

Xeroderma Pigmentosum is a rare genetic disorder with an estimated prevalence of 1 in 1 million people in the United States and Europe. However, the incidence may be higher in specific populations with a higher rate of consanguineous marriages, such as Japan, where the prevalence is estimated at around 1 in 22,000. Due to the condition’s rarity, accurate prevalence data may be difficult to obtain, and the actual frequency of XP might vary across different populations and regions. Nonetheless, it remains a rare disorder globally.

Are there types/stages?

Xeroderma Pigmentosum can be classified into different types or subgroups based on the gene affected. These types are XP complementation groups, designated by letters A through G and a variant form. Each complementation group corresponds to a mutation in a specific gene involved in the nucleotide excision repair (NER) pathway.

Although the underlying genetic defects differ among these complementation groups, the clinical manifestations are generally similar. However, the severity of symptoms and the likelihood of developing complications such as skin cancers or neurological problems can vary among the different types.

Xeroderma Pigmentosum does not follow a distinct staging system like some other diseases. Instead, the progression of the disorder is often described based on the severity and onset of symptoms, the extent of sun damage, and the development of complications such as skin cancers or neurological problems. Early detection and proper sun protection measures can help minimize the severity of the symptoms and reduce the risk of complications.

Signs & Symptoms

The signs and symptoms of Xeroderma Pigmentosum (XP) primarily involve increased sensitivity to ultraviolet (UV) radiation from sunlight. The severity and range of symptoms can vary significantly among individuals but generally include the following:

Skin symptoms:

1. Severe sunburn: Affected individuals may experience severe sunburn after only a short exposure to sunlight, often resulting in redness, blistering, and pain.
2. Freckling: Freckles may develop early, particularly on the sun-exposed face, arms, and hands.
3. Dry or rough skin: Areas exposed to the sun may become dry, rough, or scaly.
4. Irregular pigmentation: The skin may develop patches of hyperpigmentation (darkening) or hypopigmentation (lightening) due to UV damage.
5. Premature aging: The skin may show signs of premature aging, such as wrinkles, loss of elasticity, and thinning.
6. Skin cancers: Individuals with XP have an increased risk of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma, often at a young age.

Eye symptoms:

1. Photophobia: Sensitivity to light is common, causing discomfort or pain in bright light conditions.
2. Conjunctivitis: Inflammation of the membrane covering the white part of the eye (conjunctiva) may occur, leading to redness, itching, or discharge.
3. Keratitis: Inflammation or damage to the cornea may result in pain, tearing, or vision problems.
4. Cataracts: The development of cloudiness in the eye’s lens may cause blurred or hazy vision.
5. Ocular cancers: There is an increased risk of developing cancers in and around the eye, such as melanoma or squamous cell carcinoma.

Diagnosis & Treatment

Diagnosis of Xeroderma Pigmentosum (XP) involves a combination of clinical observation, patient history, and laboratory tests. The process typically includes the following steps:

1. Clinical observation
2. Patient history
3. Laboratory tests

Treatment for Xeroderma Pigmentosum primarily focuses on managing symptoms, preventing sun damage, and reducing the risk of skin cancers. There is currently no cure for XP. Some standard treatment and management approaches include:

1. Sun protection: Strict sun protection measures are crucial for individuals with XP. This includes wearing protective clothing, using broad-spectrum sunscreens with high SPF, and avoiding sun exposure during peak hours.
2. Regular skin exams: A dermatologist’s monitoring of the skin can help detect and treat skin cancers or precancerous lesions early.
3. Surgical intervention: Skin cancers or other abnormal skin growths may need to be surgically removed or treated using cryotherapy, laser therapy, or other methods.
4. Eye care: Regular eye exams, wearing UV-protective sunglasses, and managing eye-related symptoms such as dryness or inflammation are essential for maintaining eye health.
5. Neurological care: In cases with neurological symptoms, management may involve medications, physical therapy, or other supportive care.

Can medical cannabis help?

There is currently limited evidence of its effectiveness in treating the symptoms or complications of the disorder. While medical cannabis has been used for managing pain, inflammation, and certain neurological conditions, its role in XP management has not been well-established. 

Pain relief: THC, the primary psychoactive compound in cannabis, can bind to cannabinoid receptors in the brain and nervous system, exceptionally CB1 receptors. This interaction can modulate the perception of pain and provide relief. Medical marijuana has been used to manage pain in various conditions, such as chronic pain, neuropathic pain, cancer-related pain, and pain associated with multiple sclerosis.

Inflammation reduction: CBD, a non-psychoactive compound in cannabis, has been shown to have anti-inflammatory properties. It can interact with CB2 receptors, which are predominantly found in immune cells. By modulating the immune response and reducing the release of pro-inflammatory cytokines, CBD can help alleviate inflammation. Studies have suggested the potential benefits of CBD in managing inflammation in conditions like inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis.

It is essential to consult with a healthcare professional before considering any treatment, including medical cannabis, for a specific condition.