Prurigo nodularis (PN) — also known as nodular prurigo — is an inflammatory skin disease. PN causes bumpy nodules and pruritus (intense itchiness). Researchers aren’t sure what causes the condition, but they believe it may be due to issues with the immune system and nerves in the skin.

PN is linked to several risk factors, both inherited and environmental. Inherited risk factors are passed down from parents to their children in their DNA. These risk factors can’t be controlled. Environmental risk factors include exposure to certain medications, age, or other ongoing health conditions. Keep reading to learn more about the inherited and environmental risk factors and other potential causes of prurigo nodularis.

The Skin and Prurigo Nodularis

PN makes the skin extremely itchy. This often leads people to scratch or pick at their skin. All that scratching can cause the skin to thicken, resulting in raised bumps that continue to itch. An itch-scratch cycle can develop, which can be difficult to break — even with anti-itch creams and pills.

The Role of the Nervous System

Skin studies of people living with PN have helped uncover why some people develop the condition.

It helps to first understand the three layers that make up the skin:

• Epidermis — This thin, outer layer of skin protects the body from outside elements.
• Dermis — The middle layer of tissue contains blood capillaries, nerve endings, sweat glands, and hair follicles.
• Hypodermis — The bottom layer of skin tissue serves several functions. It stores fat energy, provides insulation and padding, and attaches the skin to bones and muscle.

Research has shown that people with PN have more nerve fibers in the dermis and fewer in the epidermis, compared to those who don’t have PN. The excess nerve fibers may make people feel more itchiness, which leads to PN symptoms. The exact way this works isn’t clear, but scratching may contribute to it.

The Role of the Immune System

People with PN also have different skin makeup compared to those who don’t have the condition. Studies have found that there are more inflammatory immune cells in people with PN, such as mast cells. Mast cells cause allergy symptoms when they release histamine, a chemical that causes allergic reactions. When histamine is released, it often causes itchy skin and hives. Mast cells are also associated with eczema. Other immune cells help draw in inflammatory cells by releasing special chemical signals known as cytokines.

The combination of increased nerves and inflammation is likely to blame for the intense itchiness associated with PN.

Inherited Risk Factors

Inherited factors are passed down from parent to child. Often, these are seen as mutations (changes) in genes. These mutations can increase the chances of developing a condition or disease. However, researchers haven’t found an exact gene linked to developing PN.

Race and ethnicity may affect a person’s chance of developing PN. A study of 909 people with PN found that African American participants were 3.4 times as likely to have the condition as white participants. However, race and ethnicity often tie into environmental risk factors that complicate these associations.

Environmental Risk Factors

Cleveland Clinic notes that environmental factors can increase a person’s risk of developing PN. These include:

• Age and sex
• Exposure to certain cancer medications
• Underlying health conditions
• Certain infections

An overactive immune system is part of many of these factors, adding to the inflammation linked to PN.

Age and Sex

Age and sex play a large role in who develops PN. According to the American Academy of Dermatology, people over 50 are more likely to develop the condition. In particular, PN tends to affect middle-aged people between the ages of 51 and 65 more often. Women are also more likely to have PN than men. According to the National Organization for Rare Diseases (NORD), women account for 54.2 percent of cases.

Most cases of PN appear in older individuals, but younger people can also develop the condition. However, younger people with PN usually have other inflammatory or allergic conditions, such as atopic dermatitis (the most common subtype of eczema).

Medication

Almost all medications come with side effects, and this is especially true for cancer treatments. Researchers believe that some people may develop PN after having certain cancer treatments due to how they activate the immune system to help fight off the cancer. Medications that may cause PN include the chemotherapy drugs carboplatin and paclitaxel, as well as some immunotherapy drugs like pembrolizumab.

Related Conditions

PN may develop on its own or along with other skin conditions, infections, or diseases. Treatments for other conditions may also increase the risk of developing PN.

Other Skin Disorders

People with PN have more inflammatory immune cells in their skin. It’s also common for them to have other skin disorders, such as:

• Cutaneous T-cell lymphoma — A type of cancer that involves immune cells in the skin
• Bullous pemphigoid — A skin condition that causes fluid-filled blisters
• Atopic dermatitis
• Chronic dry skin
• Psoriasis
• Keratoacanthoma — A type of skin cancer

• Lichen planus — A condition that causes inflammation of the mucous membranes along with itchy skin

Infections

During an infection, your immune system switches on to fight off harmful germs. Infections caused by bacteria, viruses, or parasites can also result in PN flaring up. PN likely develops because the immune system is in overdrive, fighting the infection.

Some causes of PN include:

• Certain bacteria, such as Mucogenicum and Helicobacter pylori
• Tuberculosis
• Hepatitis C
• HIV
• Herpes zoster, or shingles, resulting in itchy skin lesions

Systemic Diseases

Systemic (whole-body) diseases that can cause the skin to itch are also linked to an increased risk of PN. In some cases, treating the underlying disease helps treat PN, but this isn’t always true. Conditions that may give you a higher risk of developing PN include:

• Cancer (such as lymphoma and bladder cancer)
• Diabetes
• Anemia caused by low iron levels
• Liver disease
• Thyroid disease and related problems
• Kidney disease
• Celiac disease
• Gout
• Polycythemia vera (a blood disorder in which bone marrow makes too many blood cells)
• Skin cancer

Mental Health Conditions

Mental health is also associated with PN. People living with depression or anxiety may develop what’s called psychogenic itch. This type of itch isn’t caused by a skin condition, but enough picking and scratching at the skin can trigger PN to develop.

Can Prurigo Nodularis Be Prevented?

Unfortunately, PN can’t be prevented. If another health condition is contributing, treating it may ease PN symptoms, but it may not fully resolve them.

If you notice symptoms of PN, talk to your healthcare provider about ways to manage them. Managing prurigo nodularis can help prevent flares and break the itch-scratch cycle. Treatment options may include:

• Topical corticosteroids — Creams or ointments that reduce inflammation
• Phototherapy — Controlled doses of light that calm the skin
• Antihistamines — Medicines that ease itching by blocking the effects of histamine
• Biologics — Newer medicines made from living cells that target specific parts of the immune system

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