Some types of amyloidosis affect only the skin. Primary localized cutaneous amyloidosis (PLCA) is the general term for amyloidosis that occurs in the skin but doesn’t affect internal organs or other tissues.

In this article, we’ll focus on nodular amyloidosis, the rarest type of PLCA. We’ll explain the causes of nodular amyloidosis, its signs and symptoms, and ways it may be treated.

What Causes Nodular Amyloidosis?

In primary cutaneous amyloidosis, abnormal proteins called amyloids build up in clumps between the top two layers of skin — the epidermis and the dermis. These protein deposits often accumulate in and around normal skin structures called dermal papillae. The buildup in these areas contributes to the visible skin changes and symptoms seen in PLCA.

There are three types of PLCA, named based on the skin symptoms they create. These subtypes are:

• Lichen amyloidosis — This type causes very itchy, rough, scaly bumps (called keratotic papules) that are about 2 to 3 millimeters wide. These may appear red, reddish-brown, dark brown, or purplish, depending on your skin tone. The bumps often develop on the front of the legs and sometimes on the forearms, back, or scalp.
• Macular amyloidosis — This type leads to flat, mildly itchy patches that may appear dusky-brown, blue-grey, or hyperpigmented, commonly found on the upper back, torso, or limbs.
• Nodular amyloidosis — This type involves firm, nonitchy nodules (small bumps) that may be amber, brown, pink, or purplish, depending on your skin tone. They may develop alone or in groups from about 5 to 20 millimeters in size, and they often appear on the hands, feet, face, or neck but can also develop on other areas of the body.

Lichen amyloidosis causes very itchy, scaly discolored patches on the shins, forearms, and other body parts. (CC BY-NC-ND 3.0 NZ/DermNet)

Scientists believe that plasma cells — a type of white blood cell — play a role in causing nodular amyloidosis. Under normal conditions, plasma cells help protect us from infections by making proteins called antibodies, which recognize and fight off germs.

In nodular amyloidosis, some plasma cells in the skin start producing abnormal pieces of antibodies called light chains. These light chains misfold and clump together, forming the amyloid deposits that build up in the skin and cause symptoms.

Who Gets Nodular Amyloidosis?

PLCA is more commonly reported in people from Asia, South America, and the Middle East, according to DermNet, and it’s considered rare in people of European origins. It affects males and females at equal rates, according to Medscape. The average age at which people develop nodular amyloidosis is 55. There is some evidence that skin amyloidosis can run in families. About 10 percent to 15 percent of people with PLCA have a family history of the condition.

People with nodular amyloidosis are often also diagnosed with autoimmune conditions. The most common is Sjögren’s disease. In this condition, immune cells attack the glands in your eyes and mouth that make tears and saliva. The most common symptoms are dry eyes and mouth. About 1 in 4 people with nodular amyloidosis also have Sjögren’s disease.

What Are the Symptoms of Nodular Amyloidosis?

People with nodular amyloidosis often notice unusual skin changes called nodules or skin lesions. These are firm, raised bumps that may appear on their own or in small groups. Each bump is usually less than an inch wide, but sometimes they grow together to form larger patches.

Nodules may be pink, red, yellow, brown, or purplish, depending on your skin tone. Some can feel tender or itchy, though many people don’t feel any discomfort at all. In some cases, the nodules can ulcerate, meaning the top layers of skin break down and leave an open sore.

You might have just one nodule or several in different areas of the body.

These nodules can appear anywhere on your skin, including your face, limbs, torso, and genitals. The most common sites are near the ends of your arms and legs, such as the hands, feet, elbows, and ankles.

One study found that around 20 percent of people with nodular amyloidosis had nodules in multiple areas of the body.

Research suggests that the location of nodules may be linked to the chance of being diagnosed with an autoimmune condition, especially Sjögren’s disease. One study found that females over the age of 70 who had nodules on the torso or lower limbs were most likely to also be diagnosed with Sjögren’s. In contrast, people with nodules on the face or upper body were much less likely to have the condition.

How Is Nodular Amyloidosis Diagnosed?

Diagnosing nodular amyloidosis involves several steps. Because its symptoms can look similar to other conditions — such as skin cancer or systemic amyloidosis (a type of amyloidosis that affects the whole body) — your dermatologist (a doctor who specializes in skin conditions) will work to rule out other possible causes.

The most reliable way to confirm nodular amyloidosis is with a skin biopsy, where a small sample of tissue is removed from an affected area for testing. There are two main techniques your doctor might use, both done under local anesthesia so the area is numb and you shouldn’t feel pain during the procedure:

• In a shave biopsy, a thin layer of skin is gently scooped from the surface using a small blade.
• In a punch biopsy, a tiny, circular tool is used to remove a small plug or core of skin.

The biopsy site usually heals within a few weeks and may leave a small scar. Mild soreness or tenderness afterward is common.

A pathologist will examine the tissue under a microscope to look for amyloid fibrils. Your doctor may also order additional tests to check for systemic amyloidosis or other conditions:

• Blood tests and urine tests — ​​Help detect abnormal light chains, which may indicate systemic amyloidosis or a plasma cell disorder
• Electrocardiogram — Measures the heart’s electrical activity and can detect signs of cardiac amyloidosis (amyloidosis that affects the heart)
• A complete blood count — Measures the number and sizes of your red and white blood cells and platelets
• A comprehensive metabolic panel — Gives information about your liver, kidneys, blood sugar, and overall metabolic function

How Is Nodular Amyloidosis Treated?

Nodular amyloidosis is usually a long-term condition with good outcomes. Only 1 percent to 7 percent of people with nodular amyloidosis develop systemic amyloidosis, a more serious condition that affects the entire body. Because of this small risk, it’s important to keep up with regular checkups so your healthcare provider can monitor for any signs of systemic disease.

Many people seek treatment for nodular amyloidosis because they’re concerned about how the skin nodules look or feel. Treatment often focuses on improving appearance and reducing discomfort.

Common Treatment Options

The following treatments aim to shrink or remove the nodules:

• Topical corticosteroids — These creams and ointments can help reduce inflammation and itching. They may be used under occlusion (with a dressing) to help the medicine absorb better.
• Intralesional corticosteroids — A small amount of corticosteroid is injected directly into a nodule to help flatten it.
• Cryotherapy — Liquid nitrogen is used to freeze the affected skin, which may help shrink or remove the nodules.
• Surgical excision — Nodules can be cut out by a dermatologist in a minor surgical procedure.
• Laser therapy — High-intensity light is used to target and break down the nodules.
• Dermabrasion — This procedure involves removing the top layers of skin to scrape away the nodule.
• Electrodesiccation and curettage — The nodule is scraped off, and an electric current is applied to destroy remaining tissue and reduce bleeding.

These treatments may cause temporary pain, scarring, or infection, and in many cases, nodules return after treatment.

Supportive Care at Home

Some additional steps can help manage symptoms:

• Applying moisturizers and emollients to soothe the skin
• Using cool compresses to relieve itching
• Avoiding scratching, which can make nodules worse or lead to infection

Systemic Treatment

If your nodules don’t respond to skin-focused treatments, your doctor may consider systemic therapy — medications that affect your whole body. These may include immunosuppressants (drugs that calm the immune system) or medications that slow down abnormal cell growth. Systemic treatment is typically used only in more persistent or widespread cases and is guided by a specialist.

Talk With Others Who Understand

MyAmyloidosisTeam is the social network for people with amyloidosis and their loved ones. On MyAmyloidosisTeam, more than 2,700 members come together to ask questions, give advice, and share their stories with others who understand life with amyloidosis.

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