MAUI, HAWAII – The strong association between psoriasis and cutaneous T-cell lymphoma warrants a low threshold for skin biopsy in psoriasis patients, particularly since the two diseases can be tough to differentiate, experts emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
Indeed, skin biopsy is appropriate in any psoriasis patient with atypical features or psoriasis that isn’t responding to treatment, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia.
Dr. Joel M. Gelfand
"I’ve found that my psoriasis patients actually like to be biopsied. They’ve been living with their disease for an average of 20 years, and they’re curious," he said. "And they’re also suspicious. They wonder, ‘How could I have this for 20 years and it’s still here?’ They’re worried that it’s really cancer or something else. So my patients never decline a biopsy of psoriasis," he said.
The literature on psoriasis and solid malignancies is "a mess," with some observational studies showing a positive association and others not, Dr. Gelfand noted.
In contrast, the studies looking at psoriasis and cutaneous T-cell lymphoma (CTCL) have been consistently positive. Case in point: when Dr. Gelfand and colleagues turned to the U.K. General Practice Research Database to study more than 153,000 psoriasis patients and nearly 800,000 controls, they found participants with mild psoriasis had a 4.1-fold increased relative risk of developing CTCL, while those with severe psoriasis had a 10.75-fold increased risk (J. Invest. Dermatol. 2006;126:2194-201).
One limitation of large, observational studies is that it’s hard to know whether some psoriasis patients who developed CTCL were initially misdiagnosed and actually had CTCL all along, Dr. Gelfand said.
"We have a large lymphoma study group at Penn, and we see all kinds: we see some patients who clearly had psoriasis for many years and then developed erythrodermic CTCL, and we have people who clearly were misdiagnosed as having psoriasis," he said.
Dr. Craig L. Leonardi
Whether the increased lymphoma risk is caused by psoriasis itself, as opposed to the chronic use of immunosuppressive drugs employed in treating the skin disease, remains uncertain. To date, the studies are mostly reassuring that the psoriasis medications don’t significantly increase the risk. One thing that is clear, however, is that CTCL can progress very rapidly in a patient who is on potent immunosuppressive therapy for what is mistakenly thought to be psoriasis.
"The patient with tumor-stage mycosis fungoides is not a person you want to hit with a TNF inhibitor," Dr. Gelfand observed.
The distinction between severe psoriasis and CTCL can be tricky, according to veteran psoriasis researcher Dr. Craig L. Leonardi of Saint Louis University.
"In the last 13 years, while we’ve been developing the biologic agents, every now and then we’ll get a patient in a research trial who actually has CTCL. This is in an environment where patients are being examined closely, and yet the clinician is totally fooled by it," Dr. Leonardi said. "These drugs have evolved to the point that we get PASI-75 responses in the 70%-85% range. Most patients will have a rocking experience on these medications. So it’s a good general rule that if you find somebody who doesn’t respond, it’s time to start thinking about other diagnoses."
When Dr. Gelfand’s suspicions are raised, he typically biopsies one or two representative lesions after the patient has been off of topical steroids for at least a week, since the medication can reduce the epidermal infiltrate.
Dr. Alan Menter
Be cautious if the histologic specimen is going to be read by a general pathologist. The situation is fairly straightforward if the report comes back as unequivocally psoriasis or CTCL. But if the report says, ‘psoriasiform dermatitis NOS’ it’s appropriate to insist that a dermatopathologist takes a look at the slides, Dr. Gelfand said.
"A lot of malpractice cases come across my desk, and ‘failure to diagnose’ is always a big one," said Dr. Guy F. Webster of Thomas Jefferson University, Philadelphia.
"It’s not always melanoma, either," he continued. "The story is always that somebody had a rash for a long time. It looked like eczema, psoriasis, whatever. And the physician treated it without ever questioning the diagnosis when the patient didn’t get better."
Dr. Alan Menter noted convincing evidence that, at pretreatment baseline, psoriasis patients, like those with rheumatoid arthritis, have a slightly increased risk of lymphoma.
"It’s kind of sensitive to talk to patients about the cancer issue. They all ask, ‘Is there a chance you’ll cause cancer by giving me this biologic drug?’ You have to gently tell them they are already at slightly increased risk," Dr. Menter said.