Blisters form for a variety of reasons. We’re used to the small blisters that pop up when we break in new shoes or start using a new tool, but if a larger blister occurs, it can seem there’s cause for concern. 

Sometimes large blisters form from friction. We most commonly notice these blisters on people in wheelchairs or after a person has a long stay in the hospital or experiences a bed-confined illness. While these friction blisters are a significant wound, they don’t typically indicate another disorder.

Larger blisters may also surface when there’s significant inflammation or swelling in the body. If you’re hospitalized due to swelling or fluid-excess, a bulla (fluid-filled blister) may surface. If it doesn’t subside on its own, a bulla will either rupture or remain tense until it needs to be popped.

Blistering disorders of the skin are different from friction or inflammation-induced blisters. Commonly, these blisters come from one of two autoimmune disorders, pemphigoid or pemphigus, that causes a blister breakout on the skin. 

Pemphigus and pemphigoid are autoimmune conditions where your body produces antibodies that attach to the layers of the skin. The antibodies attach to the epidermis or sub-epidermis and create damage in that specific area. The damage results in a blister. 

If you’re experiencing an unexplained blistering rash on the skin, it may be time to consider one of these issues as the cause of your symptoms. 

Pemphigus: Top-Layer Blistering

Pemphigus appears as damage to the skin inside the top layer of the epidermis. The epidermis is the top layer of our skin, but it has multiple layers or regions within it. Pemphigus blistering disorders of the skin form blisters intraepidermally. There are different subtypes of this disorder, identified by where in the epidermis the blister forms and what causes the formation of the blister. 

Pemphigus Foliaceus

The most common blistering pemphigus subtype, pemphigus foliaceus (PF), indicates blisters in the most superficial layer of the epidermis. When we see this in patients, they have blisters on the surface of their skin that have already sloughed off. 

These areas have a “cornflake look” with little crusty spots flaking off the top layer of skin. Patients with pemphigus foliaceus most commonly have blistering rashes on their upper back, the central part of their nose, shoulders, and behind their ears.  

Interestingly, pemphigus foliaceus is more common in some areas of the world.

For example, we see more cases of it in Brazil and in the Mount Kilimanjaro region of Kenya and Tanzania. Some doctors attribute this to a kind of fly that’s common to these areas of the world. They suspect the bite of this fly triggers an immune reaction that causes the blistering disorder. That doesn’t mean that people in other areas, including the United States, can’t have the disorder. It can happen to anyone in any location — it’s simply more common in specific world areas.

Medications are a known trigger for pemphigus foliaceus. When your doctor makes a diagnosis of a blistering disorder of the skin, they may also look for an inciting medication. 

Pemphigus Vulgaris

Pemphigus vulgaris, another pemphigus subtype, results in blisters in a deeper layer of the skin. These blisters lie deeper in the epidermis and can produce blisters anywhere on the body, including on the mucous membrane. Blisters on the mucous membrane can affect the eyes, genitalia, or the mouth. 

The appearance and symptoms of pemphigus vulgaris can range from a few blisters in one location to blistering over the entire body that looks similar to a severe burn. Extreme cases are one of the few medical emergencies that exist in dermatology. When we suspect pemphigus vulgaris, it’s important to quickly identify this disorder and begin treatment immediately. 

Additionally, we will expediently refer patients to our colleagues in ophthalmology, obstetrics, or urology to work to prevent strictures from forming on the eyes or in the genital urinary canal if the condition worsens. 

Pemphigoid: Deep-Layer Blistering

Pemphigoid blistering disorders of the skin form below the epidermis (sub-epidermal blisters). Because of that, the blisters are more intense. Patients who experience pemphigoid are often older, typically in their 70s. 

Symptoms of pemphigoid begin with a rash that soon reddens and then turns to hives. The hives and redness worsen until the rash forms into a tense blister. This most commonly appears on the thighs, trunk, or waist, but it can involve mucous membranes as well, resulting in the need for multidisciplinary care, much like pemphigus vulgaris. 

Diagnosing and Treating Pemphigus and Pemphigoid 

Treatment for pemphigus or pemphigoid disorders is similar. Treatment begins with topical therapy and may eventually include systemic (oral or injectable) immune modulators. 

Most dermatologists first approach these blistering disorders of the skin with an immediate recommendation for topical therapy. If the patient presents flaking, red, superficial blisters in the chest and shoulders, central face, or behind the ears, and we suspect pemphigus foliaceus, we’ll start treatment with topical steroids right away. 

We also begin the diagnosis process immediately. Diagnosing pemphigus or pemphigoid is a combination of clinical assessment and biopsy. Reaching an accurate diagnosis is a fine science that begins with your doctor noticing and recognizing signs that lead to specific testing. 

If your doctor suspects one of these conditions, they’ll conduct an appropriate biopsy and order a Direct Immunofluorescence (DIF) test of the biopsied tissue. This test allows a specialized pathologist to examine the tissue in a special solution that shows exactly where the blister forms within the skin. Once they pinpoint the exact location of the blister, they can determine the type and subtype of the blistering disorder.

To further confirm the diagnosis, your doctor may also order a blood test to look for circulating antibodies in your blood that reveals the type of pemphigoid or pemphigus. 

Once we’re able to fully diagnose the issue, we typically prescribe oral or injectable medications to fight the autoimmune condition causing the blisters. The treatment may include systemic therapies such as immunomodulators and immunosuppressants. 

If you notice blistering, flaky skin, contact your dermatologist for an appointment right away. By quickly diagnosing and treating blistering disorders of the skin, we have a better chance of preventing the potentially damaging long-term effects these disorders can cause.