Scientists say they’ve engineered cells capable of automatically detecting and treating psoriasis flare-ups in lab mice — in an early step toward a “precision” therapy for the chronic skin disease.
Experts said they were “excited” by the findings, reported Dec. 16 in the journal Science Translational Medicine. But they also cautioned that a lot of work lies ahead.
In the United States, more than 5 million people have psoriasis, according to the U.S. National Institutes of Health. The disease arises from an abnormal immune system response that triggers a rapid turnover of skin cells. As a result, people with psoriasis periodically develop thick, scaly patches on the skin that can be itchy or painful.
Joel Gelfand, MD, MSCE, and colleagues conducted a population-based cohort study of patients aged 18 to 89 years in the United Kingdom with no medical history of HIV, cancer, organ transplants or hereditary disease, including albinism and xeroderms pigmentosum, prior to the beginning of the study. The data source was the Health Improvement Network, a primary care medical records database in the United Kingdom, with data collected from 2002 through January 2014 and analysis completed in August 2015.
Patients prescribed psoralen, methotrexate, cyclosporine, acitretin, Humira (adalimumab, AbbVie), Enbrel (etanercept, Amgen), Remicade (infliximab, Janssen), Stelara (ustekinumab, Janssen) or phototherapy for psoriasis were classified as having moderate-to-severe psoriasis. Patients not receiving the treatments were classified as having mild psoriasis.
Researchers analyzed 937,716 control group patients without psoriasis and 198,366 patients with psoriasis, including 186,076 with mild psoriasis and 12,290 with moderate-to-severe psoriasis.
Any incident cancer excluding melanoma skin cancer had an adjusted hazard ratio (HR) of 1.06 (95% CI, 1.02-1.09) in the overall psoriasis group, 1.06 (95% CI, 1.02-1.09) in the mild psoriasis group and 1.08 (95% CI, 0.96-1.22) in the severe psoriasis group.
Incident lymphoma had an adjusted HR of 1.34 (95% CI, 1.18-1.51) for the overall psoriasis cohort, 1.31 (95% CI, 1.15-1.49) for the mild psoriasis cohort and 1.89 (95% CI, 1.25-2.86) for the severe psoriasis cohort. Nonmelanoma skin cancer had an adjusted HR of 1.12 (95% CI, 1.07-1.16) overall, and 1.09 (95% CI, 1.05-1.13) and 1.61(95% CI, 1.42-1.84) for the mild and severe psoriasis cohorts, respectively. Lung cancer had an adjusted HR of 1.15 (95% CI, 1.03-1.27) in the overall psoriasis cohort, and 1.12 (95% CI, 1.01-1.25) and 1.62 (95% CI, 1.16-2.28) in the mild and severe psoriasis cohorts, respectively.
Breast, colon and prostate cancer and leukemia did not have significant associations with the psoriasis cohorts.
“Patients with psoriasis who received treatment with systemic medications or phototherapy were shown to be at a higher risk for malignant neoplasms compared with controls,” the researchers concluded. “Dermatologists who care for patients with psoriasis should consider incorporating current cancer screening guidelines and counseling, such as smoking cessation, into their daily practice.” – by Bruce Thiel
Psoriasis Treatment May Trigger Significant Adverse Effects:
A Dutch study in Clinical Kidney Journal suggests that a treatment for psoriasis and multiple sclerosis may induce a dangerous adverse effect, particularly in women. The finding is potentially important, because while treatment with fumaric acid esters (FAE) has been around for more than 40 years, it is now being used more widely in the United States, Germany, and other areas.
Study results indicate that FAEs may be associated with a higher incidence of Fanconi syndrome, which is characterized by a generalized dysfunction of the proximal renal tubules. FS can lead to a host of complications, including an impaired resorption of glucose, amino acids and phosphate. Another complication is osteomalacia, which can lead to bone fractures and bone pain. Pharmacologic agents such as tenofovir, ifosfamide, and aminoglycoside antibiotics have previously been associated with FS, but data around FAEs has been sparse.
The current study looked at cases of FS associated with FAE treatment diagnosed at two Dutch university nephrology departments, the Dutch and German national pharmacovigilance databases and six previously reported cases–11 cases in total. All 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years. Patients received long-term FAEs treatment with a median treatment duration of 60 months. Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria.
Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation.
In an earlier study, doses of FAEs prescribed exceeded those recommended in current psoriasis guidelines, but the current study found development of FS even at or slightly below recommended doses. “The reported cases of FAE-associated FS share several phenotypical similarities,” the study authors observed.
“All cases involved females. Sex differences in renal proximal tubular function and in the expression of organic anion receptors have been described and such differences could underlie differential risks for male and female patients to develop FAE-associated FS. However, we cannot exclude selective reporting due to the relatively small sample size described in our case series. Whether there is a predominance for females to develop FS remains to be determined. Furthermore, all patients reported with FS were treated long term with FAEs,” they wrote.
“Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome,” the authors concluded. “Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome.”