AT PDA 2017

SAN FRANCISCO – Blistering diseases are easily misdiagnosed and may resemble psoriasis or other conditions, but a routine histology and clinical examination aren’t sufficient diagnostic starting points.

“You have to have some kind of immunological test,” according to Peter Marinkovich, MD. “Pathologists will try to give you as much information as they can on the routine histology, but don’t use that as a diagnostic.”

If not properly identified, autoimmune blistering diseases can lead to chronic overexposure to steroids and resultant side effects without addressing the underlying problem, said Dr. Marinkovich of the department of dermatology at Stanford (Calif.) University.

Dr. Marinkovich gave one example of a patient who had been diagnosed with bullous pemphigoid several years before, and who was becoming Cushingoid as a result of steroids. But the diagnosis was made on the basis of histopathology and clinical appearance alone.

“Nobody had done the immunofluorescence test,” he explained at the annual meeting of the Pacific Dermatologic Association. “I did it, and it turned out she had linear IgA disease. The patient went through 2 years of toxicity just because nobody had done the immunofluorescence test.” Instead, the patient improved when placed on dapsone, which is much less toxic than prednisone.

Direct/indirect immunofluorescence is the highest-yield test for patients with blistering disease. “It’s the best way, I believe, to make the diagnosis,” Dr. Marinkovich said. If that test isn’t available, serum taken during an active phase can also be used. But serum samples can turn up false negatives, so dermatologists should consider collecting and testing serum samples several times.

Another useful tool is salt-split skin analysis, which will demarcate antigens to the roof or floor of the blister. Specifically, it helps distinguish bullous pemphigoid and epidermolysis bullosa acquisita.

In the future, Dr. Marinkovich said, ELISA (enzyme-linked immunosorbent assay) testing will have greater importance for diagnosis and disease monitoring, not just for pemphigus but for subepidermal bullous disorders as well.

Autoimmune blistering diseases do respond to prednisone treatment, although not as well as some other conditions. However, symptom improvement can mask the true cause of the disease.

“It’s easy for physicians to give steroids, and the patients will be happy for the time being; but that doesn’t solve the problem in the long term,” Dr. Marinkovich cautioned. “These are chronic conditions, and the patient will continue to require prednisone, and they’ll get more and more side effects, which could have been avoided if someone had done a more thorough investigation.”

Topical agents such as tetracycline, niacinamide, and topical steroids are more useful in pemphigoid than for pemphigus, because pemphigoid involves local immune factors that the agents can target, while pemphigus can be driven by antibodies alone, which are not as responsive to these treatments.

When systemic therapies are necessary, prednisone is a useful tool, but aim for the lowest possible dose, he said. Reducing prednisone dose is challenging in and of itself. Dropping the dose too quickly can lead to more long-term exposure, because a steep drop can lead to a rebound in the disease, which leads to a higher dose.

“The patient is on this roller coaster ride, up and down, up and down, and that alone can ramp up disease activity,” said Dr. Marinkovich. “Lowering steroid more steadily is a better way to go. This calms the disease down by itself.”

When steroids can’t be completely tapered, which is almost always the case in pemphigus and common in pemphigoid, add steroid-sparing agents such as mycophenolate and azathioprine.

If the steroid-sparing agents don’t get patients down to 10 mg/day prednisone or below, then consider using rituximab and intravenous IgG.

In Europe, physicians are using rituximab earlier in the course of disease, a strategy that appeared effective in a study published in the Lancet ( 2017 May 20;389[10083]:2031-40 ). “The evidence suggests to me that earlier use of rituximab tends to reduce the total amount of steroids that the patients are using and has the potential to reduce the duration of the disease,” Dr. Marinkovich said. “That’s a trend that will be going on in the next couple of years here in the United States.”

Dr. Marinkovich is an investigator on a clinical trial funded by Syntimmune.


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