Galcanezumab-induced psoriasis-like lesions of the eyebrows: A case report and review of CGRP's role in cutaneous inflammation

Abstract

Introduction

Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have shown excellent efficacy and tolerability in patients with migraine. However, their systemic side effects, particularly on the skin, where CGRP plays a key role in regulating inflammation and immune responses, are not fully understood. We present a case of psoriasiform skin lesions associated with galcanezumab.

Case report

A 65-year-old female with chronic migraine and medication overuse headache, with current 27 monthly migraine days (MMD) of high intensity, initiated treatment with galcanezumab after failure with onabotulinumtoxinA. Three weeks after the first dose, she developed erythema, itching, and scaling on both eyebrows, diagnosed with psoriasis-like lesions. The patient had no prior history of dermatological conditions. Despite improvement in migraine frequency (three MMD of mild intensity), the lesions persisted, leading to treatment discontinuation following three doses. Five weeks after discontinuation, the lesions resolved, but migraine worsened (22 MMD). Fremanezumab was subsequently initiated, achieving migraine control (13 MMD of mild intensity) without dermatological lesions recurrence over 12 months.

Conclusion

This case highlights a potential dermatological adverse effect of galcanezumab, emphasizing the need for skin monitoring in patients receiving anti-CGRP therapies. Calcitonin gene-related peptide blockade may disrupt cutaneous immune balance, triggering inflammatory conditions such as psoriasiform lesions.

Graphical abstract

This is a visual representation of the abstract.

Introduction

The introduction of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies has revolutionized migraine treatment by targeting the CGRP pathway, a key mediator of migraine pathophysiology. ¹ While these therapies demonstrate favorable safety profiles, their systemic effects—particularly on the skin, where CGRP regulates neurogenic inflammation and immune responses—remain incompletely characterized.^2,3 Moreover, anti-CGRP monoclonal antibodies may exert off-target effects in diverse tissues, as suggested by recent reviews. ⁴

Calcitonin gene-related peptide is abundantly expressed in cutaneous sensory nerve endings surrounding hair follicles, sweat glands, and vasculature. ⁵ It maintains skin homeostasis by modulating interactions between keratinocytes, Langerhans cells, and mast cells, suppressing pro-inflammatory T helper 1 (Th1)/Th17 pathways while promoting anti-inflammatory Th2 responses.^6,7 Postauthorization safety data suggest that 5–10% of patients on anti-CGRP therapies develop cutaneous reactions, including psoriasis exacerbations, eczematous eruptions, and urticaria.^8,9

We present a case of galcanezumab-induced psoriasis-like lesions where the temporal association, dose–response relationship, and resolution upon discontinuation strongly suggest a drug-mediated effect. This observation aligns with CGRP's known role in cutaneous immunity: by neutralizing CGRP, galcanezumab may disrupt its anti-inflammatory effects, potentially unmasking latent Th1/Th17-driven inflammation, ¹⁰ underscoring the need for dermatological monitoring with these therapies.

Case presentation

A 65-year-old female with chronic migraine and multiple comorbidities (hypertension, type 2 diabetes mellitus, dyslipidemia, anxiety-depressive syndrome, recurrent renal lithiasis) was being followed in a specialized headache unit, where she initiated treatment with galcanezumab after previous failure with botulinum toxin. The patient had a history of episodic migraine with aura since adolescence, which transitioned to chronic migraine 6 years prior to presentation. Her headaches were nearly daily, of moderate to severe intensity, pulsating in quality, and accompanied by nausea, vomiting, photophobia, and phonophobia. During this follow-up, she also met the diagnostic criteria for medication-overuse headache according to the International Classification of Headache Disorders, 3rd edition. ¹¹ At the baseline assessment (September 2022), the patient was receiving alprazolam and paroxetine for anxiety-depressive syndrome. Clinical evaluation revealed a high disease burden, characterized by persistent symptoms (monthly migraine days [MMD] 27, monthly headache days 27, acute medication days per month 17). Patient-reported outcomes (PROs) further indicated substantial disability (Headache Impact Test 6 64, Migraine Disability Assessment 31). Due to the patient's comorbidities (nephrolithiasis, depression, and overweight), oral preventive treatment was not initiated, and onabotulinumtoxinA (BTX-A) therapy was opted for instead. In accordance with the PREEMPT paradigm, preventive therapy with BTX-A was initiated, starting with 155U followed by 195U every 3 months. Despite four treatment cycles over 15 months, no clinically meaningful improvement was achieved.

Due to the lack of efficacy, treatment with galcanezumab was initiated. In November 2023, the first dose of 240 mg was administered, followed by a second dose of 120 mg in December and a third in January 2024. Three weeks after the first dose, the patient developed erythema, itching, and scaling on both eyebrows. She was evaluated by dermatology in mid-January, after having received three monthly doses, who described the lesions as “diffuse yellowish hyperkeratosis on an erythematous base, consistent with psoriasiform lesions” (Figure 1). Targeted history-taking revealed no evidence of cutaneous (desquamation, irritation, pruritus) or articular (pain, stiffness) symptoms elsewhere. She also reported no personal or family history of psoriasis or psoriatic arthritis. Basic laboratory tests, including complete blood count, coagulation studies, and serum biochemistry, were normal; no autoimmune serologies were performed given, the absence of systemic features. No diagnostic skin biopsy was performed, as the lesions were considered clinically characteristic. Topical corticosteroids were initiated, with partial improvement. As the skin reaction was not initially attributed to galcanezumab and given the significant improvement in migraine frequency and intensity, the decision was made to continue anti-CGRP therapy.

Figure 1.

Psoriasiform lesions: diffuse yellowish hyperkeratosis on an erythematous base, exclusively localized to the eyebrows.

In early February 2024, the patient was evaluated by her neurologist, showing persistent skin lesions despite topical corticosteroid treatment for 3 months, thus mutually decided to discontinue galcanezumab treatment.

After discontinuation, omitting doses of February and March resulted in a resolution of the lesions within five weeks, but worsening of migraine. Consequently, a switch to fremanezumab treatment was made in April 2024, achieving adequate migraine control without recurrence of skin lesions after 12 months of treatment. The relationship between migraine frequency, PROs, and skin lesions progression is illustrated in Figure 2.

Figure 2.

Temporal evolution of migraine burden and skin lesions occurrence during treatment with galcanezumab and fremanezumab. (a) Monthly migraine days (MMD) over time, showing frequency improvement during treatment with galcanezumab and fremanezumab, and the occurrence and resolution of the skin lesions. (b) Temporal evolution of Headache Impact Test (HIT)-6 and Migraine Disability Assessment (MIDAS) scores during treatment with galcanezumab and fremanezumab, highlighting the onset and resolution of the skin lesions.

Discussion

In Spain, access to anti-CGRP monoclonal antibodies is regulated by national and regional prescribing criteria, which include a diagnosis of migraine with ≥8 MMD at baseline and prior failure of at least three preventive treatments. In cases of chronic migraine, BTX-A must be among the failed therapies. The treatment decision in this patient complied with these criteria, following inadequate efficacy of multiple preventive strategies including BTX-A.

This case likely represents a probable galcanezumab-induced psoriasiform skin lesions, supported by the temporal relationship (onset at 3 weeks post-initiation), dose–response effect (worsening with subsequent doses), resolution after discontinuation, and nonrecurrence with fremanezumab, suggesting a drug-specific effect rather than a class-effect.

The biological plausibility stems from CGRP's established role in cutaneous neuroimmune regulation.^5–7 Beyond its vasodilatory properties, CGRP maintains skin homeostasis by suppressing pro-inflammatory Th1/Th17 responses while promoting anti-inflammatory Th2 cytokines and regulatory T-cell activity.^6,7 In our patient, cutaneous lesions resolved approximately five weeks after discontinuation of galcanezumab, a time frame that aligns with the expected plasma elimination based on its mean half-life of around 27 days.^12,13 This temporal pattern reinforces the biological plausibility of a drug-induced reaction, as it is consistent with pharmacokinetic clearance. Similar variability in the onset and resolution of dermatologic adverse events has been described with anti-CGRP monoclonal antibodies, including chilblains, fixed drug eruptions, alopecia, and delayed hypersensitivity reactions, suggesting that individual pharmacodynamics, local tissue kinetics, or immune recovery may influence the timing of cutaneous improvement.^8,14–23 Moreover, the absence of recurrence under fremanezumab, despite targeting the same CGRP pathway, further supports the notion of a drug-specific rather than class-specific phenomenon. Our patient's reaction likely reflects disruption of this delicate immune balance, where galcanezumab's CGRP neutralization may have attenuated Th2-favoring effects, permitting unopposed Th1/Th17-mediated inflammation.

Consistent with this hypothesis, emerging literature reports similar cutaneous reactions with anti-CGRP therapies.^8,14–23 Two cases of psoriasis or psoriatic arthritis exacerbation ⁸ and an intertriginous and flexural exanthema with erenumab have been described, ¹⁴ along with eczematous eruptions ¹⁵ or chilblains^16,17 and nonimmediate hypersensitivity reactions receiving fremanezumab.^18,19 Alopecia has also been highlighted as an emerging adverse event, documented in a case series and pharmacovigilance review suggesting possible immune or neurovascular contributions, ²⁰ and further illustrated by a case of localized injection site alopecia under fremanezumab likely reflecting an immune-mediated mechanism. ²¹

Regarding galcanezumab, reported adverse effects include induced fixed drug eruption,22 chilblains,^16,17 and delayed hypersensitivity reaction. ²³ This last case with tolerance to fremanezumab and erenumab.

While these cases share our patient's Th1-skewing pathophysiology, our presentation differs through its distinctive eyebrow localization and complete nonrecurrence with fremanezumab despite shared CGRP-targeting mechanisms.

Several limitations warrant consideration. First, as a single case report, our findings cannot establish causality or prevalence. Second, the absence of histopathological confirmation leaves some diagnostic uncertainty. Third, the paradoxical nonrecurrence with fremanezumab remains biologically unexplained, though differences in antibody epitopes or affinity may play a role.

Conclusion

This case demonstrates that galcanezumab may induce psoriasiform cutaneous lesions, likely through CGRP blockade, disrupting skin immune homeostasis—a mechanism supported by existing literature on CGRP's role in cutaneous inflammation. Clinicians should be aware of this potential adverse effect and monitor patients receiving anti-CGRP antibodies for such reactions. Further research is needed to better understand the underlying mechanisms and identify patients at increased risk for these cutaneous side effects.

Clinical implications

• Anti-CGRP monoclonal antibodies may be associated with rare cutaneous reactions, such as psoriasiform lesions.

• Calcitonin gene-related peptide blockade could disrupt cutaneous immune balance, predisposing to inflammatory reactions, particularly in patients with underlying psoriasis.

• It is crucial to monitor patients treated with anti-CGRP antibodies for cutaneous adverse effects.

• Further studies are needed to understand the pathophysiological mechanisms and associated risk factors.