The increasing prevalence of immune-mediated diseases has led to widespread use of biologics such as TNF-α inhibitors.1 A known complication of these agents is Paradoxical Adverse Reactions (PARs), often manifesting as new-onset or worsened psoriasis. Clinically and histologically, these lesions typically mimic conventional psoriasis. Improvement upon drug discontinuation and worsening with continued therapy are characteristic.2 We present a rare case of paradoxical psoriatic alopecia associated with certolizumab pegol, successfully managed with bimekizumab.

A 29-year-old woman with ankylosing spondylitis, treated with certolizumab pegol for 1.5-years, presented with sudden-onset scalp hair loss and erythematous, scaly plaques. There was no mucosal, nail, or other cutaneous involvement, and she had no personal or family history of dermatologic disease. Laboratory findings were within normal limits. A punch biopsy from a scalp plaque revealed parakeratotic crusting with nuclear debris, superficial hemorrhage in the stratum corneum, focal acanthosis, and loss of the granular layer, along with mild spongiosis, interface vacuolar degeneration, and dyskeratosis (Fig. 1A–B), while PAS staining was negative. This clinicopathologic constellation was consistent with TNF-α inhibitor – related paradoxical psoriatic alopecia. Certolizumab was discontinued, and bimekizumab was initiated. During follow-up, partial hair regrowth with reduced scaling of the alopecic plaque was noted at week-4. By week-8, further regrowth and near-complete resolution were observed. At the 6-month follow-up, complete resolution of the scalp scaling and restoration of normal skin texture were achieved, with near-complete hair regrowth except for mild residual thinning along the midline (Fig. 2A‒C).

Fig. 1.

(A‒B) Histopathological findings from two punch biopsies showed similar changes: parakeratotic crust with nuclear debris and surface hemorrhage, partial acanthosis with loss of the granular layer, mild spongiosis, interface vacuolar degeneration, and isolated dyskeratosis, particularly around the follicles. In the dermis, perivascular lymphocytic inflammation was also noted.

Fig. 2.

(A) Hyperkeratotic alopecic plaques with scaling and erythema located in the frontoparietal area of the scalp at presentation. (B) Further hair regrowth and near-complete resolution of the alopecic plaque after 8-weeks of bimekizumab (320 mg) therapy. (C) Complete resolution of scalp scaling and restoration of normal skin texture at the 6-month follow-up, with near-complete hair regrowth except for mild residual thinning along the midline.

Paradoxical psoriatic alopecia is an uncommon manifestation of anti-TNF therapy. Although certolizumab pegol’s unique structure ‒ a pegylated Fab fragment lacking the Fc region ‒ was expected to reduce immunogenicity, several cases of alopecia have been reported (Table 1).3–6 The incidence of paradoxical psoriasis during TNF-α inhibitor therapy is around 5%, with a female predominance (60%–70%). Infliximab is most frequently implicated, followed by adalimumab, etanercept, certolizumab, and golimumab.2 Onset can range from weeks to years after therapy initiation;2 in our case, the reaction developed after 18-months of certolizumab exposure, consistent with this variability.

Histopathological findings in biologic-induced paradoxical psoriatic alopecia often demonstrate a psoriasiform pattern; however, increased dermal eosinophils, interface changes, and dyskeratosis have been reported as distinguishing features from classic psoriasis.7 In our case, parakeratosis and loss of the granular layer were accompanied by marked interface degeneration and dyskeratosis, supporting the diagnosis of a TNF-α inhibitor-related paradoxical reaction. Recognition of these histopathological differences may provide valuable clues in the differential diagnosis and guide more tailored therapeutic strategies.

The key mechanism involves excessive IFN-α production by plasmacytoid dendritic cells, promoting Th17 polarization and increased IL-17/IL-22, which activate keratinocytes and sustain inflammation. The presence of Th17 cells and IL-17 in affected lesions, along with good response to secukinumab, supports IL-17 inhibitors as viable treatment options.8

Treatment selection for TNF-induced PARs depends on severity and comorbid conditions. Given the dual inhibition of IL-17A and IL-17 F by bimekizumab, and its proven efficacy in both psoriasis and ankylosing spondylitis, it was chosen in this case.9 While data on its use in psoriatic alopecia are limited, our case aligns with emerging evidence favoring IL-17 – targeted therapy in managing TNF inhibitor – induced dermatologic reactions.

Although paradoxical reactions to IL-17 inhibitors, including bimekizumab, have also been reported,10 to our knowledge, this is the first published case of certolizumab pegol – induced psoriatic alopecia successfully treated with bimekizumab. Further studies are needed to clarify its long-term safety and efficacy in this rare condition.