Friend or foe? Sebaceous cyst inflammation during ixekizumab therapy in psoriatic arthritis: case based review

Despite extensive review of the literature, no prior case reports directly associating ixekizumab with the de novo development or exacerbation of sebaceous cysts were identified. This suggests that such an occurrence is either rare or has not been previously reported. However, ixekizumab, like other IL-17 inhibitors, has been associated with increased susceptibility to infections and various immune-related adverse effects, which may provide indirect insights into the inflammatory response observed in this case.

The IL-17 signaling pathway plays a central role in mucocutaneous immunity, particularly in the skin, where it regulates neutrophil recruitment and stimulates the production of antimicrobial peptides by keratinocytes. This response forms a critical component of host defense against common pathogens such as Staphylococcus aureus and Candida species. Consequently, pharmacological inhibition of IL-17 A may impair barrier immunity and increase susceptibility to cutaneous and mucosal infections [4, 5].

Clinical evidence supports an increased risk of skin and soft tissue infections in patients treated with IL-17 inhibitors. One of the most frequently reported infections are fungal infections caused by Candida species, which can affect the skin, oral cavity, throat, and genital area [6,7,8].

In addition to these, other repeatedly described skin infections are caused by Staphylococcus aureus, herpes simplex, and herpes zoster [9].

In the context of bacterial infection, Sánchez Martín et al. described an interesting case of the development of staphylococcal toxic shock syndrome in a child receiving secukinumab, an IL-17 inhibitor for psoriasis. A 6-year-old girl, who had previously received two initial doses of the IL-17 inhibitor secukinumab for treatment-resistant plaque psoriasis, developed fever, rash, conjunctivitis, and anuria that rapidly progressed to toxic shock syndrome. After hospital discharge, she subsequently presented with a staphylococcal abscess on her lower extremity [10].

The above findings highlight the importance of considering infectious etiologies in cutaneous complications arising during IL-17 A blockade, especially when microbiological data are unavailable but clinical signs suggest localized inflammation and purulent involvement.

In this context, the sudden onset of purulent inflammation in a pre-existing, asymptomatic sebaceous cyst during ixekizumab therapy may be best understood as a localized infectious complication, rather than a paradoxical inflammatory reaction.

The following literature review summarizes known immune-related adverse events associated with IL-17 inhibitors.

Injection site reactions, particularly erythema and localized inflammation, are among the most commonly reported adverse effects of ixekizumab [11, 12]. While these reactions are typically self-limiting, they highlight the potential for localized immune activation following administration of the drug.

According to Messina et al., the most frequent skin-related adverse effects also include paradoxical psoriasis and eczema resembling atopic dermatitis. Other dermatological reactions such neutrophilic dermatoses, hypersensitivity reactions, lichenoid eruptions, vasculitides, bullous diseases, lupus-like reactions, pigmentation disorders, adnexal diseases and granulomatous dermatoses have been reported less commonly [13].

Eczematous eruptions have been documented in some patients undergoing ixekizumab therapy, typically emerging after three to four months of treatment [14]. These dermatologic manifestations suggest a broader spectrum of immune dysregulation affecting the skin, though their relevance to cyst inflammation remains speculative.

In addition to the above effects, paradoxical reactions have been increasingly documented in patients receiving IL-17 inhibitors. A systematic review identified 35 cases of paradoxical psoriasis induced by secukinumab, primarily of the palmoplantar and plaque types, with a median latency of 11 weeks [15]. Some patients required adjunctive therapy while continuing IL-17 inhibition, while others discontinued therapy altogether, switching to biologics with alternative mechanisms. Another small case series reported three patients with psoriasis who developed facial erythema, dryness, and pruritus during treatment with IL-17 inhibitors, including ixekizumab. These manifestations arose without prior atopic history and involved non-psoriatic distributions. While these were not cystic lesions, their occurrence underscores the possibility of atypical cutaneous immune responses in patients receiving IL-17 inhibition [16].

Notably, more severe inflammatory complications have also been documented. For example, a case report described a 35-year-old male receiving ixekizumab for psoriasis who developed a severe otitis media, which progressed to facial nerve paresis and a nasopharyngeal abscess [17]. This represents an uncommon and severe infectious complication associated with IL-17 A blockade. Unlike the generally mild upper respiratory tract infections more frequently reported during treatment with biologics, this case illustrates that ixekizumab may, in rare instances, predispose to aggressive infections in the upper aerodigestive tract.

Furthermore, there is growing evidence suggesting a potential association between ixekizumab therapy and the development or exacerbation of inflammatory bowel disease (IBD) [18]. Reports have described both de novo onset and flares of pre-existing IBD in patients receiving IL-17 inhibitors, including ixekizumab, pointing to the possibility that these agents may provoke dysregulated inflammatory responses in susceptible individuals. This immunological imbalance may, in theory, extend beyond the gastrointestinal tract and contribute to extraintestinal manifestations, including cutaneous inflammation such as that observed in our case. Supporting this, a published case series detailed four patients who developed new-onset IBD while being treated with IL-17 A inhibitors for dermatologic or rheumatologic conditions [19]. Moreover, an additional report described paradoxical indeterminate colitis emerging years after the initiation of IL-17 inhibitor therapy, masked for a period by concurrent use of other biologics [20]. These cases illustrate the potential for delayed or unrecognized inflammatory complications and underscore the need for heightened clinical vigilance.

Further, an illustrative case of ixekizumab-induced interstitial lung disease (ILD) provided histopathologic evidence of Th17-mediated pulmonary inflammation, including IL-17 A-positive lymphocytes and granulomatous changes [21]. This suggests that IL-17 inhibition may provoke paradoxical immune activation in non-target tissues, possibly via disruption of Th17-regulated pathways.

Furthermore, severe acute systemic reactions following the initial doses of ixekizumab have been reported, indicating that, in some cases, the drug can provoke intense immune responses that might manifest in various organ systems [22].

Literature also reveals a case that further expands the spectrum of potential immune-mediated complications associated with IL-17 inhibition. A case report described the development of multifocal motor neuropathy in a patient with psoriatic arthritis shortly after initiating ixekizumab therapy. Notably, the neuropathy progressed even after discontinuation of the drug. Although a definitive causal relationship could not be established, the close temporal association raises the possibility of a neuroimmunologic adverse effect linked to IL-17 A blockade [23].

Beyond these reactions, two recently reported cases illustrate further potential for autoimmune complications following ixekizumab use. One involved a psoriasis patient who developed a hypopigmented eruption clinically and histopathologically resembling mycosis fungoides [24]. Another publication described a paradoxical onset of Behçet’s disease after initiating ixekizumab for psoriasis, suggesting that IL-17 A inhibition may, in rare instances, precipitate systemic immune dysregulation in predisposed individuals [25].

Taken together, these findings expand our understanding of non-traditional paradoxical reactions to IL-17 inhibitors, suggesting the need for heightened vigilance in recognizing atypical inflammatory manifestations, even in anatomical sites not commonly associated with IL-17-driven pathology. While cysts themselves are not classic autoimmune phenomena, their sudden inflammation under therapy may reflect a localized loss of immune tolerance, possibly mediated by shifts in Th17/Treg balance, altered neutrophil responses, or microenvironmental cytokine changes within the pilosebaceous unit.

Despite IL-17 A inhibitors such as ixekizumab have been associated with immune-related and infectious adverse effects, emerging evidence suggests they may be safe and effective in patients with comorbid central nervous system conditions, including multiple sclerosis. Preliminary evidence from systematic reviews suggests that both secukinumab and ixekizumab may be used safely in individuals with MS, either as monotherapy or in combination with disease-modifying therapies (DMTs). These findings may indicate a broader immunological compatibility of IL-17 A blockade, although further studies are needed to confirm long-term safety across different immune-mediated conditions [26].

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