Controlling complicated psoriasis

Dermatologists and their patients have benefited immensely from the expanded armamentarium of treatment options for plaque psoriasis. Nevertheless, they may still be challenged by patients with coexisting systemic diseases or other psoriasis phenotypes.

Speaking at the 40^th annual Hawaii Dermatology Seminar (Waikoloa, Hawaii, February 2016), Kristina Callis Duffin, M.D., M.S., offered ideas for managing a variety of individuals who she described as presenting with “situations not covered in textbooks or cases you call your friends about”.

Complexity from comorbidities

Patients with endstage renal disease and severe psoriasis comprise one challenging group because treatment with methotrexate and cyclosporine is contraindicated for them. Dr. Duffin notes that none of the biologics are eliminated through the kidneys and so any-etanercept (Enbrel, Amgen/Immunex), adalimumab (Humira, Abbvie), infliximab (Remicade, Janssen), or ustekinumab (Stelara, Janssen)-could be used without dose adjustment. As a caveat, however, patients with kidney failure will require particularly close monitoring for infection as it is a risk associated with both their renal disease and treatment with a biologic.

Options for biologic therapy in a patient with multiple sclerosis (MS) are more limited, however, because MS is a contraindication to use of an anti-TNF agent. Dr. Duffin said phototherapy is her first choice for managing a patient with MS whose psoriasis requires more than topical medications. In addition, she has used methotrexate safely, although she cautioned there have been rare reports of optic neuritis in patients on methotrexate.

Should a systemic agent be required, one might consider the interleukin-12/23 antagonist, ustekinumab, or dimethyl fumarate (Tecfidera, Biogen IDEC).

“Ustekinumab was evaluated as treatment for relapsing-remitting MS in a phase 2 trial, and its findings should provide some reassurance about prescribing ustekinumab for patients with MS,” says Dr. Duffin. She is associate professor of dermatology, University of Utah, Salt Lake City.

“Although it was not helpful, it was safe as it did not worsen MS clinically or radiographically.”

The rationale behind using dimethyl fumarate off-label relates to the fact that it is approved for the treatment of MS in the United States while fumarates are available in Germany as a treatment for psoriasis. Patients treated with dimethyl fumarate should be monitored for lymphopenia and told that side effects include nausea, diarrhea and flushing, Dr. Duffin says.

Patients who develop psoriasis while being treated with an anti-TNF agent for inflammatory bowel disease (IBD; Crohn’s disease, ulcerative colitis) present a conundrum considering that these biologic agents are used to treat psoriasis. Dr. Duffin said she has had good success using ustekinumab to “kill two birds with one stone” in these individuals.

“Ustekinumab is approved for psoriasis, and results of Phase 3 clinical trials demonstrate it was effective compared with placebo for improving Crohn’s disease in patients who had been refractory to anti-TNF therapy,” she said.

“I now have a series of ten patients switched to ustekinumab after developing psoriasis while on an anti-TNF for IBD, and they have all done well from the standpoint of controlling both their cutaneous and bowel disease.”

Challenging phenotypes

For Dr. Duffin, getting guttate psoriasis under control can involve a two-pronged approach that addresses the infectious component and the skin disease. She said that if a patient with guttate psoriasis has recurrent streptococcal pharyngitis, she collaborates with an infectious disease specialist about whether to place the patient on an antibiotic regimen or consider tonsillectomy.

Topical modalities are her first-line treatment for the psoriasis, although narrowband UVB phototherapy or traditional systemic therapy with cyclosporine or methotrexate are considered for individuals with a more extensive area of involvement.

If these approaches fail, Dr. Duffin suggests considering ustekinumab. She reported her personal experience using it in three patients with good results. Two patients achieved prolonged remission after one and three doses, respectively.

The biologics are also something dermatologists might consider for patients with palmar-plantar psoriasis who failed conventional therapies, whether their disease is pustular or non-pustular. Based on her experience again, Dr. Duffin cautioned that there is no one biologic that stands out as being the agent of choice in this situation, and she added that she has occasionally seen palmar-plantar disease worsen in rare patients started on a biologic.

The presence of another skin disease, particularly contact dermatitis or eczema, as a mimicker or comorbidity is also something to consider in patients with palmar-plantar psoriasis, she said.

If it is determined that the patient has psoriasiform dermatitis with coexisting psoriasis and contact dermatitis or eczema, apremilast (Otezla, Celgene) may be a rational choice as this agent has been reported effective for treating both contact allergy and eczema.

“Apremilast is in development as a possible treatment for eczema and may eventually be approved for that use. In the meantime, management of patients with psoriasis and features of eczema or contact dermatitis may be a good niche for this new agent,” Dr. Duffin says.

On the topic of pustular psoriasis, Dr. Duffin also cautions against using oral or intramuscular corticosteroids for treating plaque psoriasis considering the many patients she has seen who develop a severe pustular flare when given a systemic corticosteroid.

Dr. Duffin says there are situations where she considers an oral corticosteroid for psoriasis management, but they are used with certain caveats:

• Plaque psoriasis flares due to oral corticosteroid dose reduction and only if the patient has been started on another systemic agent, such as cyclosporine, methotrexate, or a biologic

• Psoriatic arthritis flares using a low dose for a short course

• Palmar-plantar psoriasis flares as a last resort

• Pustular psoriasis of pregnancy if cyclosporine and other therapies are not working or contraindicated.

Disclosure: Dr. Duffin receives grant/research support and is a consultant to and/or scientific advisory board member for a number of companies that market products for treatment of psoriasis.