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Identifying Prurigo Nodularis: 11 Differential Diagnoses To Rule Out

Medically reviewed by Raj Chovatiya, MD, PhD, MSCI
Written by Aminah Wali, Ph.D.
Posted on January 5, 2024

Itchy skin, although bothersome, doesn’t always have a clear cause. Prurigo nodularis (PN) shares symptoms with other conditions, making it difficult for doctors to determine the specific condition or conditions you actually have. To make things even more complicated, PN usually occurs alongside another skin condition, so it’s common to have more than one at the same time. To receive a quicker diagnosis and proper treatment for PN, it’s important to rule out other conditions.

This article will cover skin conditions with symptoms similar to PN and techniques that clinicians may use to help tell them apart.

Getting a Prurigo Nodularis Diagnosis

Prurigo nodularis, also called nodular prurigo, is a skin condition that causes constant, intense itching (also called chronic pruritus). The itchiness will usually cause a person to keep scratching (this is known as the itch-scratch-itch cycle), causing raised bumps called nodules or papules to form on the skin. The skin may also become dry and scaly.

A PN diagnosis typically requires a visit to a dermatologist. They’ll start with a physical exam and ask about your history of symptoms. The results of these examinations help doctors make a clinical diagnosis of PN. If you have other symptoms and your doctor wants to understand what might be causing your PN, they may use additional testing to gather more information.

Testing for the Underlying Cause of Prurigo Nodularis

To understand the cause of your PN, and if another health condition is suspected, a doctor may perform blood tests to see if there is another illness, such as hepatitis or thyroid problems, that could explain your symptoms. They may also remove a tiny sample of skin from an affected area — called a skin biopsy — and look at the cells under a microscope. Additionally, they may perform immunofluorescence, a technique that can identify specific proteins in the skin sample by making them glow. By getting a close look at the skin cells, a doctor can find clues that set PN apart from other diseases.

Itchy skin may also be a sign of allergies connected with contact dermatitis. To rule this out, a doctor may use patch testing to see if your symptoms could be related to an allergic reaction.

Differential Diagnosis for Prurigo Nodularis

The process of ruling out other conditions that can mimic signs and symptoms of PN is called differential diagnosis. In a differential diagnosis, these similar conditions are considered when exploring a possible diagnosis. Although some of these conditions are diseases that may look similar to PN, others are pruritic (itchy skin) conditions that may appear together with PN.

Getting the right diagnosis is the first step to starting the right treatment plan. Without a clear diagnosis, you may not receive the right treatment, and your symptoms could get even worse. If you have symptoms of PN, these are some conditions your dermatologist will likely consider.

1. Eczema

Atopic dermatitis — the most common form of eczema — is another condition that causes itchy skin and can lead to repeated scratching. Many people with PN also have atopic dermatitis. There are many overlapping symptoms, which can make it difficult to diagnose PN. However, when compared with eczema, nodules are more likely to indicate PN.

2. Acquired Reactive Perforating Dermatoses

Acquired reactive perforating dermatoses are a group of skin diseases in which a person is missing the normal tissue that helps give shape to the skin. This missing tissue between the dermis and epidermis — the layers of tissue that make up the skin — can cause skin lesions (distinct marks or injuries) and pruritus. These skin lesions usually have a keratotic plug in the middle, which is a hard bump made up of dead skin cells. This makes them look different from the nodules generally seen in PN.

3. Actinic Prurigo

Actinic prurigo causes a person’s skin to have a severe reaction to sunlight, resulting in intense itching and raised bumps on the skin. Unlike PN, which is a long-lasting or chronic condition, actinic prurigo is an acute (sudden and short-term) disease that appears under certain conditions. Actinic prurigo is also more common in younger people, whereas PN is more common in older adults.

4. Epidermolysis Bullosa

Epidermolysis bullosa (EB) can cause itchy skin and skin lesions that look like those seen in PN. To tell the conditions apart, a doctor can perform immunofluorescence on a skin sample to see if the cells have antibodies — proteins made by the immune system — that are unique to EB.

5. Multiple Keratoacanthomas

Multiple keratoacanthomas are benign (noncancerous) skin tumors that are linked to other underlying diseases, such as Ferguson-Smith syndrome and Grzybowski syndrome. Although the tumors can appear similar to PN lesions, a doctor can tell the difference between the diseases by looking at the cells under a microscope. The cells look different under a microscope than in PN. People with keratoacanthomas will also usually lack the itching associated with PN.

6. Psoriasis

Psoriasis is a chronic skin condition that may occur alongside PN. Although it also causes constant itching and scratching, psoriasis forms raised patches on the skin rather than the papules and nodules associated with PN.

7. Nodular Scabies

Nodular scabies is an infectious disease spread by mites that burrow into the skin. A person’s body reacts to the mite infestation and develops an itchy rash and nodules on the skin, resembling PN. Because nodular scabies is infectious (unlike PN), evidence that a person was recently exposed to scabies or in contact with someone with itchy skin could help point to scabies rather than PN. A person with scabies is also more likely to show signs of picking at the skin than someone with PN.

8. Pemphigoid Nodularis

Bullous pemphigoid is a condition that can cause blisters on the skin. Pemphigoid nodularis, a type of bullous pemphigoid, can also result in the formation of nodules similar to those found in PN. Although they may look similar and may even occur together, PN doesn’t cause blisters as seen in pemphigoid nodularis. A doctor can tell the diseases apart by studying a skin sample under a microscope or using immunofluorescence because pemphigoid nodularis has specific antibodies not seen in PN.

9. Lichen Simplex Chronicus

Lichen simplex chronicus is another condition brought on by the itch-scratch-itch cycle. Similar to those with PN, people with lichen simplex chronicus have leathery skin and red, itchy patches. A skin biopsy and patch testing may be used to tell lichen simplex apart from PN.

10. Hypertrophic Lichen Planus

Hypertrophic lichen planus is a disease in which inflammatory cells of the immune system attack the body’s own skin cells. This can lead to skin lesions that could be mistaken for PN. Clinicians can look at the skin cells under a microscope to tell the difference between PN and lichen planus.

11. Dermatillomania

PN is a dermatological condition and not “all in your head.” However, in some people, behavior and/or mental health issues can make prurigo worse. Dermatillomania is a psychiatric condition also known as compulsive skin picking or neurotic excoriations. In dermatillomania, a person picks at their skin repeatedly, ultimately causing bleeding sores and scarring. This can lead to skin lesions that mimic those seen in PN. If a doctor thinks dermatillomania may be contributing to your prurigo, they may refer you to a psychologist for further testing.

The Burden of a Delayed Diagnosis

Even with modern approaches, overlapping symptoms with other conditions can make it difficult to get a PN diagnosis. It may take a long time and visits to several different doctors. As one MyPrurigoTeam member reported, “One doctor before diagnosis said I had scabies.” Another team member shared their frustration: “PN is so challenging! First, trying to get a diagnosis, being told by every [dermatologist] that it’s acne or dermatitis.”

If you’re living with an itchy skin condition that’s negatively affecting your quality of life, seek out a dermatologist with experience in recognizing prurigo nodularis to get an accurate diagnosis. They can use whatever tests are needed to help diagnose your condition or conditions and prescribe treatments that may provide some relief.

Talk With Others Who Understand

MyPrurigoTeam is the social network for people with prurigo nodularis and their loved ones. On MyPrurigoTeam, more than 2,500 members come together to ask questions, give advice, and share their stories with others who understand life with PN.

Have you been diagnosed with multiple skin conditions? Were you incorrectly diagnosed before finding out you had prurigo nodularis? Share your experiences in a comment below or on your Activities page.

      Posted on January 5, 2024
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      Raj Chovatiya, MD, PhD, MSCI is an assistant professor of dermatology at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Learn more about him here.
      Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here.

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