STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.
Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.
Interferon-Induced Cytokine Psoriasis
Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.
Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”
The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.
An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”
Antimalarial Psoriasis
“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”
Efalizumab-Interruption Psoriasis
Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”