Paradoxical psoriatic alopecia is emerging as a rare complication of biologic therapy, especially TNF-α inhibitors, predominantly affecting younger female patients.
Biologic therapies – celebrated for transforming the treatment of chronic inflammatory diseases – may unexpectedly trigger hair loss in the form of paradoxical psoriatic alopecia, researchers say.
A new systematic review of 97 patients, including a recently reported case, reveals that this rare complication disproportionately affects younger women, most often after TNF-α inhibitor therapy.
The researchers’ findings have been published this month in the Australasian Journal of Dermatology.
“While paradoxical psoriatic alopecia has largely been reported alongside TNF-α inhibitors, there are increasing reports of this developing following exposure to more recently introduced biologics such as ustekinumab, secukinumab and, as in our case [report], ixekizumab,” they wrote.
“To date, no definitive treatment guidelines have been proposed and studies have been limited to the examination of biologics in a singular primary disease.
“Moreover, the demographic, clinical outcomes and histological features in patients with paradoxical psoriasis induced by non-TNF-α inhibitor biologics are limited, particularly in cases associated with alopecia.”
The analysis synthesises 45 studies and highlights the demographic, clinical, and histological hallmarks of this emerging phenomenon.
TNF-α inhibitors accounted for 91% of cases, though interleukin inhibitors such as secukinumab, ixekizumab, and ustekinumab were also implicated.
Patients typically present with erythematous, scaly plaques and noticeable hair thinning, confirmed by positive pull tests and trichoscopic findings, including arborising vessels and exclamation mark hairs.
Biopsies reveal decreased follicular density, sebaceous gland atrophy, psoriasiform epidermal changes, and a mixed inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils – features that clearly distinguish paradoxical psoriatic alopecia from primary psoriatic alopecia or alopecia areata.
The researchers highlighted the case of a 24-year-old woman with ankylosing spondylitis, who developed paradoxical psoriatic alopecia after treatment with adalimumab and later ixekizumab.
Scalp biopsy confirmed eosinophil-rich infiltrates and sebaceous gland atrophy. Her hair regrew following discontinuation of ixekizumab and topical clobetasol, highlighting the potential reversibility of the condition when promptly recognised.
“With cessation of ixekizumab and topical clobetasol dipropionate shampoo three times per week, the alopecia remitted,” the researchers wrote.
The review showed that nearly 90% of patients achieved partial or complete remission, with one-third recovering hair without stopping biologic therapy.
Switching to alternative biologics was common, though responses were variable, emphasizing the need for individualized treatment strategies.
“Paradoxical psoriatic alopecia may also be dose-related,” the researchers wrote.
“There is a report of one patient receiving adalimumab for Crohn’s disease for 18 months before a dose increase to 40mg weekly from 40mg every second week was thought to have triggered the psoriatic alopecia.”
Although the precise mechanism remains unclear, proposed pathways include cytokine imbalance, T-cell repolarisation, TNF/type I interferon disequilibrium, and IL-33-mediated follicular changes.
Genetic factors, such as TNF receptor polymorphisms, may explain why only a subset of patients develop alopecia, the researchers said.
