Delayed drug hypersensitivity reaction to secukinumab in a patient with hidradenitis suppurativa

Discussion

Secukinumab is a selective IL-17A inhibitor that is US Food and Drug Administration-approved for the treatment of plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. It is also increasingly being used in the off-label treatment of other inflammatory skin conditions, including HS. Secukinumab is typically well-tolerated and demonstrates a favourable safety profile with nasopharyngitis and upper respiratory infections listed as the most frequent side effects.

To our knowledge, we present the fifth documented case of a cutaneous delayed-type hypersensitivity reaction (type IV reaction) to secukinumab. Shibata et al described a 52-year-old woman with psoriatic arthritis who developed a papular eruption 3 days after the fourth dose of secukinumab. Skin biopsy confirmed a drug hypersensitivity eruption, and reintroduction of the medication prompted a relapse of the dermatitis.3 Another report described a similar case in which a psoriasis patient developed a widespread papular eruption after the fourth dose of secukinumab. Skin biopsy exhibited ‘focal parakeratosis, exocytosis of lymphocytes, rare apoptotic keratinocytes, and a perivascular infiltrate of lymphocytes and rare eosinophils in the upper dermis’.4 The patient’s condition gradually improved with systemic corticosteroids and discontinuation of the offending drug. In a third report, Wong and Chung described a 24-year-old woman with axial spondyloarthritis who developed a maculopapular eruption of the lower extremities in association with mild liver dysfunction after her 15th dose of secukinumab. No skin biopsy was performed. Her condition spontaneously normalised after discontinuation of secukinumab.5

Most recently, Darrigade et al described a case of a 51-year-old woman with psoriatic arthritis who, after the second administration of secukinumab, developed pruritic, erythematous skin lesions on the abdomen and breasts. A biopsy was not performed. However, patch testing revealed a positive reaction to secukinumab, and resolution was noted after 3 weeks of treatment with antihistamines and oral and topical corticosteroids.6 Although patch testing was not performed in our case, confirmatory histopathology was obtained, which specifically implicates a psoriasiform pattern of drug hypersensitivity. Furthermore, the Naranjo algorithm scoring for our patient, a questionnaire designed to assess the probability of whether a suspected adverse drug reaction is due to the drug rather than alternative aetiologies, was seven and compatible with a probable adverse drug reaction to secukinumab.

Of note, there have also been reports describing pustular exacerbations of plaque psoriasis treated with secukinumab as well as secukinumab-induced new-onset psoriasiform eruptions involving the fingertips and nails.7 8 Skin biopsies were not performed in these cases, which makes histological comparison to our case difficult. However, the decidedly different clinical features observed in these cases suggests that these represent entities distinct from the hypersensitivity reaction described by our group and others.

Furthermore, it is well known that HS and psoriasis are chronic inflammatory skin diseases that share common pathogenetic mechanisms involving tumour necrosis factor-alpha and IL-17. The two conditions have been known to co-occur, both on their own as well as part of syndromes, such as SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) and PsAPASH (psoriatic arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa). Despite the immunopathogenetic similarities and comorbid nature seen in HS and psoriasis, multiple factors, including characteristic clinical and histopathological features, timing of eruption and resolution with discontinuation of the offending drug, indicate that this patient experienced a type IV hypersensitivity reaction, not a co-occurrence of psoriasis.

Biologics, including monoclonal antibodies like secukinumab, have the potential to be immunogenic and can lead to the formation of antidrug antibodies that can precipitate undesirable effects, including decreased therapeutic efficacy or even drug hypersensitivity reactions. Secukinumab has been shown to be associated with a lower incidence of clinical immunogenicity in comparison to other biologics, such as adalimumab and infliximab.9 Nevertheless, clinicians should be aware that secukinumab still carries the potential to trigger significant cutaneous eruptions that mandate timely drug discontinuation and potentially administration of corticosteroids for resolution.