Diagnosing prurigo nodularis (PN) can be difficult, as it shares symptoms with many other skin conditions, including intense itching and raised bumps. As part of the diagnosis process, a doctor may examine your skin cells under a microscope, a technique related to a branch of biology called histology.

In this article, we’ll look at histology and how it can help a doctor figure out exactly what’s causing your skin symptoms. Coming up with an accurate diagnosis is an essential first step toward getting the treatment — and relief — you need.

What Is Histology?

Doctors use histology to diagnose skin conditions by examining the structure and changes of skin cells and tissues under a microscope. They can also use it to confirm a suspected diagnosis or monitor treatment.

The examination is performed by a pathologist — a doctor trained in studying body tissues. Pathology is the study of disease. Combining histology and pathology to study tissues related to disease is known as histopathology.

A pathologist can perform a number of tests on a tissue sample to see how it looks and reacts. The first step is to see what the bit of tissue looks like to the naked eye. This is called the gross description, which includes the sample’s size, color, shape, and consistency.

The microscopic description involves a closer look at the cells in the sample. The pathologist can use different staining techniques to see which cell parts are present. They’ll identify and count the types of cells in the sample and note anything that looks unusual. Their findings will be summarized in a medical report called a pathology report, which the doctor who ordered the tests will receive.

When Is Histology Performed in Prurigo Nodularis?

Histology can help give an accurate diagnosis in people with symptoms of prurigo nodularis. Your doctor may order histology tests of your skin lesions if you don’t respond to treatment or if you have complications such as bleeding.

However, histology isn’t always used to diagnose PN because it requires an invasive test called a biopsy, which involves removing a sample of the affected skin. Most PN histology studies are done with a punch biopsy — a sharp, hollow instrument removes the inner and outer layers of skin with a sharp. The biopsy is usually taken from the middle of a lesion or nodule after the area is numbed. You may have to avoid applying topical creams or ointments before the skin biopsy is performed.

Histology can help differentiate PN from skin conditions with similar symptoms, such as pruritus (itching) and nodules (hard bumps). Even though other conditions may look and feel the same as PN, the affected skin looks different under the microscope.

Skin diseases that are part of the differential diagnosis — the list of other possible conditions — for PN include:

• Atopic dermatitis — The most common type of eczema
• Pemphigoid nodularis — A rare skin disease that causes blistering
• Psoriasis — A condition characterized by thick, flaky patches of skin
• Lichen simplex chronicus — A condition that causes raised patches and chronic itching
• Scabies — An itchy rash caused by mites
• Dermatofibroma — A benign growth (not skin cancer)

Histologic Changes in Prurigo Nodularis

Prurigo nodularis can cause changes to the skin that a pathologist will see under the microscope. The presence or absence of these changes can help your doctor make a diagnosis. The most common histologic changes in PN involve thickened skin, inflammation, and nerve fiber density.

Thickening of Skin

PN lesions are characterized by skin that’s thicker than healthy skin. Some of this thickening is the result of damage caused by scratching. Many findings related to thickened skin are not specific to PN and can also be seen in conditions like lichen simplex chronicus.

The pathologist will describe this change based on what part of the skin looks abnormal or thicker. If you have prurigo nodularis, you may see the following terms on your pathology report:

• Hyperkeratosis — The stratum corneum (outer layer of skin) is thicker because of an overproduction of keratin, a tough, fibrous protein found in skin, hair, and nails.
• Hyperplasia — The epidermis (top two layers) is thicker and may be irregular.
• Hypergranulosis — The stratum granulosum (thin layer of cells in the epidermis) is thickened.

PN lesions might have an increased number of fibroblasts — cells that make connective tissue — making the area thicker and harder, which is known as fibrosis. Fibrosis is often seen in the papillary dermis, the layer of connective tissue between the epidermis and the dermis (inner layer of skin).

The hairy palm sign is also common in PN lesions. This term refers to a tissue sample that is thick and ridged, like it would look if taken from your palm — but, unlike the palm, has hair follicles.

Inflammation

Inflammation can be identified by higher numbers of immune cells, especially mast cells. Mast cells release compounds involved with the inflammatory process, such as histamine and substance P, which cause itching and pain. Histamine may also play a role in increasing the number of fibroblasts.

PN lesions may have raised levels of immune cells like neutrophils and lymphocytes, which are types of white blood cells. These immune cells release inflammatory chemicals called cytokines that can damage the tissue.

Levels of eosinophils (another type of white blood cell) present in prurigo nodularis are normal, however. Eosinophil levels are usually higher than normal only in parasitic infections, cancer, and allergic reactions.

A staining test called direct immunofluorescence can help distinguish PN from autoimmune diseases that can cause itching, such as bullous pemphigoid, pemphigoid nodularis, and epidermolysis bullosa. Prurigo nodularis is not an autoimmune disease, so a negative result could point to PN. However, a person can have PN and autoimmune diseases at the same time.

Changes in Nerve Fibers

Prurigo nodularis is a complex condition that involves both the nervous system and the skin. PN lesions may have larger and more numerous nerve fibers and nerve endings, known as nerve hyperplasia. Hyperplasia results from the increase of mast cells, which release a nerve growth factor, so a pathology report may mention “nerve fiber density.”

Pathologists may also note that the sample contains more Merkel cells than there are in healthy tissue. Merkel cells are located close to epidermal nerve endings and play an important role in how you perceive the sense of touch.

Changes to the nerve fibers and increased Merkel cells may account for the intense itchiness that occurs with prurigo nodularis.

Reading Your Pathology Report

Depending on how many tests are necessary, it can take a few days to a few weeks to get the report after your biopsy. You can have a copy of your report, but you should expect it to use many technical terms that you may not be familiar with. Your doctor or dermatologist (a specialist in treating the skin) can interpret the report’s results for you and explain what they mean.

Some results may be noted as abnormal, but that doesn’t always mean there’s a problem. If you have any questions or concerns about your pathology report, be sure to discuss them with your doctor. They can help you understand what the results mean and how they might help with the diagnosis or management of your condition.

Talk With Others Who Understand

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

Have you had a biopsy to diagnose PN? Did you discuss the results with your doctor? Share your experience in the comments below, or start a conversation by posting on your Activities page.