An Unexpected Event: Severe Cutaneous Adverse Reaction and Eosinophilia to First Injection of Adalimumab
Creators: name: Salvati, Lorenzo
name: Matucci, Andrea
name: Nencini, Francesca
name: Portelli, Francesca
name: Massi, Daniela
name: Parronchi, Paola
name: Vultaggio, Alessandra
Publisher: name: Zenodo
Year: 2019

description: Introduction: Adalimumab is a fully human recombinant IgG1 isotype antibody targeting TNFα, a major inflammatory cytokine implicated in the pathogenesis of numerous inflammatory diseases. Delayed hypersensitivity reactions to adalimumab leading to treatment discontinuation are rare.

Materials: We report the case of a 65-year-old man affected by Crohn’s disease who presented with a generalized pruritic maculopapular rash associated with fever and blood eosinophilia that developed 8 days after the first subcutaneous injection of adalimumab. In the last 5 months before starting maintenance therapy with adalimumab, the patient received multiple vaccinations: quadrivalent flu vaccine (split virion, inactivated), pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed), first and second dose of hepatitis B (rDNA) vaccine (adsorbed), and meningococcal conjugate vaccine (A-C-Y-W135). At the induction phase, 4 doses (160mg) of adalimumab (Imraldi®) were injected simultaneously on the lateral surfaces of both arms and both thighs. After 8 days an intense erythema appeared on the injection sites rapidly spreading to most part of the body. Fever developed, with temperatures up to 38.2°C. The patient presented to the Emergency Department where hydrocortisone 100mg, clorfenamine, and ranitidine were administered intravenously (IV). The next day the patient started oral prednisone 25mg and bilastine. One week later, as symptoms persisted, the patient referred to our outpatient clinic. He presented with pruritic 10 cm in diameter oval-shaped erythematous infilitrated patches at the 4 injection sites and a generalized maculopapular erythema characterized by disseminated dark red and purplish itchy burning papules confluent in infiltrated plaques on the arms, legs, and trunk without head-neck involvement. The remainder of the physical examination was unremarkable.

Results: Laboratory tests revealed blood eosinophilia (880 per mm3), increased eosinophilic cationic protein (192μg/L, reference range 0-15μg/L), and increased IgE levels (449KU/L). Other laboratory tests were normal. A diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) was made. Considering RegiSCAR scoring system, the case had a total score of 2 (possible DRESS). Therefore, pulse steroid therapy (250mg IV methylprednisone daily for 3 days) was initiated with consequent cutaneous improvement: at the 4 injection sites complete resolution of erythema with fine desquamation occurred. A skin biopsy was performed revealing mild superficial perivascular lymphocytic infiltration. In the following weeks, prednisone 25mg was tapered untill remission of signs. One month later, the patient was totally recovered and a new management of Crohn’s disease was planned. 

Conclusion: This case represents a type IVb hypersensitivity reaction to first injection of adalimumab (possible DRESS according to RegiSCAR scoring system), warning the clinician on the possibility of this rare event. Type IVb hypersensitivity reactions are Th2-cell mediated delayed reactions characterized by recruitment and activation of eosinophils via IL-5, IL-4, IL-13 and eotaxin. Interestingly, in this patient the immunization with conjugate vaccines (pneumococcal and meningococcal vaccines) that was performed in the preceding weeks to adalimumab’s injection (14 and 12 weeks respectively) might have resulted in policlonal T cell activation facilitating or worsening the adverse drug reaction observed.

Funding: none

Informed consent was obtained from the patient for publication of this poster and accompanying images.

This poster was presented at XXXII Congresso Nazionale della Società Italiana di Allergologia, Asma ed Immunologia Clinica SIAAIC in Milan, Italy on June, 2019