In autoimmune skin diseases, your body's immune system mistakenly attacks your own healthy cells. The overzealous immune response may show up as rashes, plaques, blisters, scaly patches or skin tightening.
Some conditions go beyond skin-deep. They can affect the bones and joints and in some cases cause long-term damage to internal organs.
Although autoimmune skin conditions currently don't have cures, increasingly effective and targeted treatments can help reduce disease flares and promote remission.
Skin Disease Types
Autoimmune skin diseases are all inflammatory. However, "not all inflammation is autoimmune," says Dr. David Fiorentino, a psoriasis and autoimmune disease specialist and a professor of dermatology at Stanford University Medical Center in Palo Alto, California.
Some autoimmune skin diseases -- like certain blistering diseases -- affect only the skin. "Patients create antibodies against very specific components in the skin that result in blisters," Fiorentino explains.
Pemphigus affects the epidermis, the skin's outermost layer. Pemphigoid affects the skin layer under the epidermis.
Until recently, there were limited treatment options available for blistering autoimmune skin conditions. In June 2018, the Food and Drug Administration approved the biologic drug rituximab to treat adults with moderate to severe pemphigus.
With rheumatic skin disorders, skin effects may be part of a larger constellation of symptoms also affecting the bones, joints and internal organs. Rheumatoid arthritis, lupus, scleroderma and dermatomyositis are types of autoimmune diseases with skin effects.
Lupus occurs in a variety of forms including systemic lupus erythematosus and cutaneous lupus, which is limited to the skin. Women are more affected than men by far, accounting for about 90% of lupus diagnoses. Facial rashes like the signature 'butterfly' rash are common symptoms.
A type of drug originally developed for an entirely different condition is now central to lupus treatment. Hydroxychloroquine (Plaquenil) and chloroquine (Aralen) are oral antimalarial medications that are used to treat skin rashes, joint and muscle pain, inflammation of the lining of the heart or lungs, fever, fatigue and other lupus symptoms. Antimalarial drugs tend to have few, mostly short-term side effects.
Belimumab (Benlysta) is a biologic drug that was FDA-approved to treat lupus in 2011.
Sunscreen of 30 SPF or higher is a lupus treatment must. The sun's ultraviolet rays can trigger systemic attacks and skin flares, so sun avoidance is critical.
Dermatomyositis is an autoimmune disease with a characteristic purple or dusky red rash. This painful, itch rash typically appears on the face, eyelids, elbows, knuckles, back and chest. As dermatomyositis progresses, muscle weakness begins to appear and worsen throughout much of the patient's body.
In addition to prednisone and steroid-sparing drugs to treat the overall condition, antimalarial drugs like hydroxychloroquine can ease the persistent skin rash.
Sunscreen is part of treatment, as well as wearing sun-protective clothing and hats. As with lupus, sun exposure can trigger skin-related symptoms in dermatomyositis.
Scleroderma literally means "hard skin." Tough, tight skin is a hallmark of scleroderma. In systemic scleroderma, organs such as the lungs, kidneys and heart may be affected as well as the skin. Treatment depends on which organs are involved.
Unfortunately, the skin-tightening itself is difficult to treat, Fiorentino says. "It's such a unique thing for scleroderma, and the fact that we don't have good agents for that says it's still a pretty large puzzle for us."
Vasculitis in an autoimmune disease involving swelling and inflammation of the blood vessels. Skin rashes are among many possible disease effects. Purple-red, raised spots on the legs, known as 'palpable purpura,' is a classic sign. Repeated bouts of purpura can lead to patches of skin discoloration.
Vasculitis is treated with drugs including prednisone, rituximab, methotrexate and azathioprine.
Psoriasis and Psoriatic Arthritis
Psoriasis is an inflammatory skin disease that causes silvery red, itchy, scaly plaques over the skin and scalp. Psoriatic arthritis is a complication that can develop in up to a third of people with psoriasis. Psoriatic arthritis, which has similarities to rheumatoid arthritis, attacks and damages the joints. Pain, swelling and stiffness can affect bones and joints like the hands and knees, tendons, nails and even eyes.
Some treatments work for most autoimmune diseases across the board, while others are most effective for specific autoimmune or inflammatory skin conditions. However, treatment is individualized. Patients with the same diagnosis can respond differently to any single medication or combination.
Trial and error is often needed as doctors and patients with autoimmune skin conditions work in tandem to find what's most effective from the following medication categories:
-- Topical steroids.
-- Oral steroids.
-- Immunosuppressive drugs.
-- TNF inhibitors.
Cortisone creams, ointments, foams, gels, lotions and sprays can ease skin lesions. Some are available over the counter. Prescription-strength topical steroid treatments primarily contain these ingredients:
-- Desonide. Brands include Desonate, DesOwen, LoKara, Tridesilon and Verdeso.
-- Triamcinolone 0.1%. Brands include Aristocort A, Cinolar, Triacet, Triamcot and Zytopic.
-- Clobetasol. Clobex is the brand name for this potent topical drug for severe scalp psoriasis.
NSAIDS (nonsteroidal anti-inflammatory drugs)
Over-the-counter or prescription-strength NSAIDs reduce inflammation and ease skin rash symptoms such as itching, burning and pain:
-- Ibuprofen (Advil, Motrin).
-- Naproxen (Aleve, Naprosyn.)
Prednisone is a steroid medication used to treat a wide number of autoimmune diseases, especially in the acute phase where there is high risk of organ damage. However, steroids have many long-term side effects, so other medications are preferable if possible. Prednisone is sometimes used in conjunction with other lupus drugs to reduce the dosage.
"Prednisone is not an ideal treatment," says Dr. Ana-Maria Orbai, a rheumatologist and director of the psoriatic arthritis program at Johns Hopkins Medicine in Baltimore. "In most rheumatic diseases, there are lots of side effects and a lot of damage accumulated from using prednisone. So, we are trying to get away from prednisone," says Orbai, who is also an assistant professor of medicine in the division of rheumatology at Johns Hopkins.
Prednisone can make certain conditions worse. "We know that oral prednisone for psoriatic disease, for example, is not going to help because it has the risk of turning psoriasis into unstable psoriasis," Orbai says. "When people get off prednisone the disease often flares. Prednisone has cardiovascular side effects, increases risk of infections -- all infections -- and osteoporosis, and has a bunch of other risks." That includes making blood sugar go high, which is especially relevant for people with diabetes.
Adapting the treatment to react to the disease and its specific drivers and mechanisms is preferable, Orbai says.
Steroid-sparing medications (immunosuppressive drugs).
These drugs treat autoimmune conditions, including those with skin effects, and provide an alternative to prednisone.
-- Methotrexate (Trexall) is a broad (not targeted) injectable medication to suppress the immune system. Common side effects include mouth sores, nausea, fatigue, chills, fever and low white blood cell counts.
-- Mycophenolate (CellCept), an oral medication created to prevent organ rejection after a transplant, is sometimes used to treat conditions like lupus and blistering skin diseases. Common side effects include diarrhea, low red and white blood cell counts, high blood sugar and infections.
-- Azathioprine (Imuran) is also used to prevent transplant rejection and can treat skin conditions such as pemphigus, lupus and dermatomyositis. Common side effects include stomach pain, loss of appetite, nausea and vomiting.
Disease-modifying antirheumatic drugs, or DMARDs help control psoriatic arthritis symptoms such as inflammation and also prevent or reduce long-term joint damage.
-- Leflunomide (Arava). Common side effects of this oral medication include loss of appetite, back pain, diarrhea, headaches and dizziness.
-- Sulfasalazine (Azulfidine). Common side effects of this oral medication include upset stomach, nausea, vomiting, loss of appetite and diarrhea.
Biologic agents target and block specific proteins in the body that play a role in its inflammatory and immune responses. These medications target one of these types of cells:
-- B-cells, which make antibodies.
-- Chemical messengers, such as tumor necrosis factor, or TNF, which causes inflammation.
Drugs called TNF blockers suppress the inflammatory response by targeting TNF. These include:
-- Etanercept (Enbrel). Enbrel is a self-injectable drug whose common side effects include dizziness, injection site reactions and upper respiratory infections.
-- Adalimumab (Humira). Also self-injectable, common side effects include headache, infections, nausea and back pain.
-- Certolizumab (Cimzia). For this self-injectable drug, upper respiratory infection, urinary tract infections and headaches are common side effects.
-- Golimumab (Simponi). This self-injectable medicine also comes in an intravenous version (Simponi Aria), which is given in a clinical setting. Common side effects include fever, sweats or chills, muscle aches and cough.
-- Infliximab (Remicade). Given as an intravenous infusion in a clinical setting, common side effects include headache, nausea, white patches in the mouth and yeast infections in women.
These biologics are also known as monoclonal antibodies:
-- Secukinumab (Cosentyx), which neutralizes interleukin 17-A (1L-17), is used to treat active psoriatic arthritis. Common side effects of this self-injectable drug include cold symptoms, diarrhea and upper respiratory infections.
-- Ixekizumab (Taltz) also targets IL-17A to treat psoriatic arthritis. For this self-injectable drug, upper respiratory infections, nausea and fungal infections are common side effects.
-- Guselkumab (Tremfya) is an IL-23 blocker approved to treat moderate to severe psoriasis and psoriatic arthritis. Common side effects of this self-injectable drug include upper respiratory infections, headaches, bronchitis and diarrhea.
-- Ustekinumab (Stelara) blocks both IL-12 and IL-23 proteins to ease inflammation from psoriatic arthritis. It can be self-injected under the skin or given intravenously. Common side effects include flu-like symptoms, stomach pain, nausea and vomiting, and vaginal itching or discharge.
-- Rituximab (Rituxan). Rituximab, which targets CD20 proteins, is given by an intravenous infusion lasting several hours. Common side effects include nausea and vomiting, headaches, dizziness and weakness.
For patients on any of these drugs, regular monitoring including blood tests is important. Patients should let doctors know immediately about any new symptoms that occur.
Psoriasis Drug on Horizon
A possible breakthrough drug to treat moderate to severe plaque psoriasis may be headed for approval from the Food and Drug Administration. A clinical trial comparing a newly developed biologic called bimekizumab found it more effective in clearing plaque psoriasis than the FDA-approved biologic called ustekinumab (Stelara). The study was funded by the UCB Pharma, the maker of bimekizumab.
"The big news is: We've never had a drug this strong," says Dr. Mark Lebwohl, the dean for clinical therapeutics and a professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York City. "It's incredibly fast and it's got a durable effect."
Bimekizumab is an injectable drug that's given every four weeks. It's unique in that it blocks two closely related proteins involved in the body's immune response, says Lebwohl, senior author of the year-long, multicenter study published Feb. 6 in The Lancet.
By blocking IL-17 and IL-17F, bimekizumab reached at least 90% improvement of psoriasis in 85% of patients, compared with about 50% of patients on ustekinumab in the study.
Yeast infections at a higher rate than for similar drugs was the most notable side effect of bimekizumab, particularly of the mouth (oral thrush).
Biologic drugs are expensive. For instance, the list price for a 30-day supply of ustekinumab (Stelara) can reach nearly $12,400 per month, according to the manufacturer's website. However, most insurance covers these drugs, with some restrictions. If approved, bimekizumab costs would likely be comparable to other biologics, Lebwohl says.
People with autoimmune skin diseases want to be proactive. That can include making lifestyle choices to optimize their health, learning as much as possible about their condition and participating in research.
"The healthier a person is, the better they can manage the disease and their risk factors," Orbai says. "Being health-conscious, having a healthy diet, exercising and having good physical function is always a good goal and is associated with people doing better with their rheumatic disease."
Some nonmedication treatments like light therapy aren't particularly effective for autoimmune skin diseases, Fiorentino says. "But we know a few things we can do behaviorally to prevent disease from getting worse," he says. "(Avoiding) sun exposure and smoking would be the two big things that really have been shown to make an impact for many of these disorders," he says, including lupus and dermatomyositis.
Diets touted as autoimmune diets haven't been shown to really help, Fiorentino says: "We don't have good data where people have been randomized to a certain diet versus another." Consulting a dietitian with experience in autoimmune diseases can help patients sort out diet claims, manage their weight, promote heart health and make good food choices.
"What I've noticed is there's a real thirst for patients wanting to take more control for themselves and their disease," Fiorentino says. "They're always asking: What can I do? What can I be changing? I want to feel like I have some control."
At centers like Stanford and others, where specialists are doing laboratory studies and conducting clinical trials on these complex conditions, patients' participation can really make a difference, Fiorentino says.
By involving themselves in research, Fiorentino says, "Patients can get a little bit of locus of control over their disease, because they feel like they're doing something. They're actively trying to move forward."
Progress is being made. In psoriatic arthritis, for example, treatment innovations have blossomed. Initially, "We had one class of medications that was FDA-approved for the treatment of psoriatic arthritis," Orbai notes. Those were the TNF-inhibitor drugs.
"But then they discovered the role of interleukin-17 and interleukin-23 and came up with, in less than 15 years, medications actually targeting those pathways," Orbai continues. "And there are people who achieve clearance from the disease."
That means that about 30% of patients who walk into her clinic with rashes and swollen joints will experience remission, Orbai says: "Our numbers are modest, but if someone can achieve true remission, that means we really nailed this and that pathway was addressed."
Over the past decade, leaps have been made in understanding how these diseases work and in interest in new drug development by pharmaceutical companies, Fiorentino says. "We finally now have tools to really study these complicated diseases," he says. "I think we're going to crack them and make really major advances in the next five to 10 years."