Use of off-label therapy prevented new blisters in woman, 69, with EBA
Case suggests approved oral med may be treatment option for rare skin disease
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Off-label treatment with apremilast, an oral medication approved for certain inflammatory conditions, helped prevent new inflammatory blisters in an older woman with epidermolysis bullosa acquisita (EBA), a rare autoimmune disease in which blisters form in layers of the skin in response to injury.
The 69-year-old woman, who had both inflammatory and noninflammatory skin lesions, saw her condition improve within a month after starting apremilast, according to a research team in Japan who detailed her case. The treatment, sold under the brand name Otezla for two other autoimmune conditions, works by blocking phosphodiesterase 4 (PDE4), an enzyme involved in inflammation.
The researchers say the woman’s case appears to be the first in which this drug was successfully used — in combination with a prescription corticosteroid, or man-made steroid — to prevent blisters in an EBA patient.
“Our findings suggest that PDE4 [blockage] may be a potential therapeutic option for inflammatory EBA,” the researchers wrote.
Still, the team noted that “further accumulation of cases is needed to confirm the efficacy of PDE4 [suppressors] in EBA.”
The case was described in the form of a letter to the editor, titled “Refractory Epidermolysis Bullosa Acquisita Treated With Apremilast,” published in The Journal of Dermatology.
EBA is a form of epidermolysis bullosa (EB), a group of conditions characterized by fragile skin that blisters and tears easily. This form is caused by self-reactive antibodies that target type VII collagen, a protein needed for the attachment of the epidermis — the skin’s top layer— with the dermis, or the underneath skin layer.
This disease type can be classified as inflammatory, characterized by reddened and inflamed blisters, or mechanobullous, marked by blisters without surrounding redness or inflammation. Some people, like this woman, experience features of both forms, which makes treatment even more challenging.
Apremilast approved in US for 2 inflammatory diseases
Apremilast is an oral PDE4-suppressing therapy approved in the U.S. for treating psoriatic arthritis and plaque psoriasis, both inflammatory diseases that typically affect the skin, joints, and mouth. It’s been used off-label, or for conditions for which it’s not approved, to treat a number of dermatologic conditions for which standard therapies haven’t worked.
Previous studies have shown increased PDE4 levels in the skin of people with inflammatory EBA, as well as beneficial effects with PDE4-suppressing therapies in mouse models of the disease.
Now, researchers from two universities in Osaka detailed the med’s use in this woman’s case.
The patient, who has both EBA types, had been experiencing itchy, reddened skin, as well as erosions and blisters on her trunk and limbs, for two years. Her symptoms also affected her mouth and nails, and she had milia, which are small white spots that appear as the skin heals.
Analysis of samples of inflamed skin blister tissue using a microscope showed immune cell infiltration in skin layers below the epidermis. There was also deposits of IgG and IgA, two types of antibodies, in a layer between the epidermis and the dermis. The researchers also reported the presence of antibodies against type VII collagen, which further supported an EBA diagnosis.
The woman initially received treatment with two oral anti-inflammatory medications: prednisolone, a corticosteroid, and colchicine. The colchicine was discontinued due to abnormal liver enzyme levels. The prednisolone lessened the red, inflamed lesions, but blisters without surrounding inflammation continued to appear on the woman’s hands and feet.
Doctors then introduced intravenous immunoglobulin (IVIG), which delivers healthy antibodies to help regulate immune activity. Two monthly treatment cycles “completely resolved” those symptoms, the researchers noted.
However, when the woman’s prednisolone dose was reduced, she developed inflamed lesions and difficulty swallowing due to erosions in her esophagus, which is the tube that connects the throat to the stomach.
Reintroducing monthly IVIG reduced her skin symptoms, but the inflamed lesions would come back any time treatment intervals were extended or the prednisolone dose was reduced. Shortening the IVIG interval, increasing prednisolone dosage, and adding an immunosuppressive medication, mycophenolate mofetil, also failed to fully control the disease.
Treatment allowed woman to cut steroid use
Given her persistent symptoms, the researchers turned to apremilast, introduced at a dose of 60 mg daily.
According to the team, this treatment prevented the development of new inflamed blisters within one month, allowing IVIG discontinuation and gradual reduction of the woman’s prednisolone dose. The team noted that “withdrawal of IVIG and subsequent tapering of [prednisolone] was achieved.”
No apparent adverse effects were reported during treatment.
“To our knowledge, this is the first reported case of EBA that was successfully treated with apremilast in combination with [oral prednisolone],” the researchers wrote.
The team noted, however, that further studies are needed to determine whether PDE4-suppressing therapies could become a useful treatment option for people with EBA.
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