Does Prurigo Nodularis Ever Go Away?

Prurigo nodularis (PN) is a rare skin condition with no known cause, although it appears to be an autoimmune disease. Some believe that it arises due to immune dysregulation between the immune system and receptors present in the skin. 

PN leads to the development of cutaneous nodules that can cause extreme skin irritation. These itchy bumps can create a cycle of itching and scratching, which leads to more nodules and even more inflamed skin. Constant scratching prevents the nodules from healing and can result in scarring. Itching can be so severe that people scratch themselves to the point of bleeding or discomfort.

Signs and symptoms of prurigo nodularis (PN) include:

• The primary symptom of PN is the appearance of hard, irritating nodules on the skin of the arms, legs, stomach, neck, and/or upper and lower back, although other areas may be affected as well.
• Difficult-to-reach areas such as the upper section of the middle back are usually spared, and nodules do not typically develop on the face, palms, or soles of the feet.
• Multiple nodular skin lesions may manifest as tiny red lumps. Because the nodules are symmetrically distributed, they may produce constant or intermittent episodes of acute itching.
• Nodules can range in size from a few millimeters to more than 3 centimeters (approximately 0.2 inches to over 1.2 inches).
• Crusting and scaling can be noticed on freshly scratched lesions, which then darken and become pale in comparison to the surrounding skin. 
• Repetitive scratching, picking, and rubbing can cause permanent skin changes such as nodular thickening, dark pigmentation, and skin thickening.
• The skin between the nodules is typically dry and itchy. New nodules may continue to form, but old nodules may spontaneously fade and leave scars. 
• Secondary infections, stress, and depression may occur.

PN can cause severe itching, particularly at night, or when the nodules come into contact with clothes. For many patients, itching resolves only after PN is scratched to the point of blood or discomfort which can lead to infections.

Although the specific etiology of prurigo nodularis (PN) is unknown, symptoms are likely to be caused by nerve and immune system abnormalities in the skin. For example, PN can be found in patients with stasis eczematous dermatitis, a type of dermatitis of the lower legs caused by blood pooling or "stasis" in the veins. 

PN can develop at any age, although it is most common in individuals between 20 and 60. Both sexes are affected equally.

Possible risk factors for PN include:

• Race: African Americans are at higher risk of PN.
• Genetics: Autoimmunity and genetic factors appear to be involved in the progression of this condition. In 50% of PN cases, an inherited condition such as asthma, eczema, hay fever, or hives is present.
• Personal or family history: Many patients have a personal or family history of eczema or atopic dermatitis, asthma, hay fever, or other allergies.
• Insect bites: PN may be triggered by insect bites and underlying infections.
• Underlying conditions: People with certain underlying diseases such as kidney failure, HIV, or hepatitis C infection; certain bacterial and parasitic infections; thyroid disease; lymphoma; liver disease; anemia due to iron deficiency; nutritional abnormalities or metabolic disease such as gluten enteropathy; diabetes; and many other conditions are at risk of PN.
• Strict diets: Because it is associated with patients who follow strict diets, particularly a ketogenic diet, PN is frequently referred to as a "keto rash." A keto diet involves high fat intake and low carb intake, which triggers a metabolic state of ketosis in which the body uses stored fat for energy. 
• Gut imbalance: According to researchers, the gut microbiota may be implicated in this connection (the microorganisms in the digestive tract). As a result, PN may emerge from a gut microbiota imbalance that affects the immune system.
• Medications: PN can be caused by some drugs such as pembrolizumab, paclitaxel, and carboplatin (chemotherapeutic drugs). In many cases, PN is likely to be caused by extended immune system activation following therapy.
• Others: Sweating, clothing, heat, and emotional stress can all exacerbate symptoms.

Despite the fact that PN appears to be fairly common, especially in patients with related or precipitating conditions, its prevalence in the general population has not been studied. Patients with PN typically have all three underlying causes (atopic, psychological, and nutritional).

Diagnosis is typically made based on clinical signs and treatment response. Dermatologists may suspect prurigo nodularis (PN) when a patient has severely itchy skin and nodules.

To confirm a diagnosis of PN, a skin biopsy may be performed. Under a microscope, the skin will appear swollen and abnormal, sometimes mimicking squamous cell carcinoma. The size of nerve fibers and nerve terminals may be greatly enlarged.

Your dermatologist will recommend blood tests, allergy tests, kidney and liver function tests, etc. to understand the possible underlying causes of PN.

The goal of prurigo nodularis (PN) treatment is to resolve or minimize itching and prevent skin pigmentation. By breaking the itch-scratch cycle, the nodules and damaged skin are given time to recover. 

The most popular method of treating PN is to use topical or intralesional steroids. Phototherapy or systemic immunosuppressives are usually required in more severe cases or in patients who are resistant to treatment.

Localized treatment

• Emollients (sometimes with methanol)
• Intravenous oral and topical steroids 
• Intraocular steroids injections 
• Phenol and local anesthetic lotions
• Coal tar creams
• Calcipotriol ointment
• Capsaicin cream 
• Cryotherapy with liquid nitrogen 
• Pulsed dye laser (can decrease the vascularity of specific lesions)

Systemic treatment

• Antihistamines 
• Systemic corticosteroids
• Cyclosporin, methotrexate and azathioprine
• Thalidomide (in severe cases)
• Naltrexone (an opiate-receptor antagonist)
• Systemic retinoids such as acitretin
• UV exposure
• Psoralen combined with ultraviolet A treatment
• Immunomodulatory macrolide roxithromycin with or without anti-fibroblast medication tranilast
• Gabapentin

Breaking the itch-scratch cycle

• Psychological counseling
• Habit reversal therapy
• Anxiolytic drugs
• Antidepressants such as amitriptyline and doxepin

Self-care and trigger prevention

• Stop using soaps or shower gels to wash as they can dry out the skin.     
• Apply emollients regularly throughout the day to maintain good skin health.
• Monitor side effects and undergo regular blood tests.
• Control the urge to scratch.
• Keep fingernails trimmed.
• Keep rooms cool and avoid sleeping with heavy bedding.
• Wear breathable clothing.
• Wear gloves or mittens while sleeping to avoid unintentional scratching.

Dietary modifications

Maintain a balanced diet while limiting the intake of refined foods and increasing the intake of anti-inflammatory foods.

• Foods to avoid
  • Trans fat
  • Red meat
  • Fried food
  • Processed food with high levels of additives and preservatives 
  • Refined sugar and flour
• Foods to eat
  • Starchy vegetables (potatoes, sweet potatoes, corn, beets, and squash)
  • Fruits (bananas and dates)
  • Legumes (lentils and beans)
  • Whole grains (rolled oats, and quinoa)
  • Spices (basil, cinnamon, cumin, curry, ginger, and turmeric)
  • Wholesome fats (salmon, herring, flaxseeds, and chia seeds)
  • Dark chocolate
  • Green tea

Investigational therapies

• Thalidomide
• Lenalidomide
• Opioid receptor antagonists
• Neurokinin-1 receptor antagonists
• Monoclonal antibody therapies

Even though there are several PN treatment options available, it may take some time to properly manage PN. Patients most likely benefit from a combination of topical, pharmacological, and lifestyle adjustments. 

PN is a pruritic, inflammatory skin condition with several underlying comorbidities. Case studies have reported a link between PN and cancer, including lymphoma and solid organ tumors. Because of its rarity and severity, PN is classified as an actual disability.

PN is difficult to treat because it can take months or even years to clear and may not resolve fully. It is important to follow your dermatologist's advice and report any problems with your therapy so that various options can be explored.