Influenza vaccine‐associated cutaneous lupus erythematosus

A 53‐year‐old woman presented with a skin lesion on her right arm. The patient had systemic lupus erythematosus (SLE), which was controlled by a stable regimen of hydroxychloroquine 200 mg twice daily, mycophenolic acid 360 mg twice daily and prednisolone 5 mg daily. The only cutaneous manifestation of her disease had been a malar rash at diagnosis 19 years previously. On physical examination, an erythematous, annular skin lesion, 50 × 40 mm in size, with central clearance, was seen on the posterior aspect of the patient’s right arm (Fig. 1). She reported that the lesion started as a pruritic, erythematous papule, coinciding with the exact location at which an influenza vaccine had been administered 3 days previously. Upon noticing the papule, the patient had self‐medicated with 0.1% hydrocortisone butyrate cream daily for a few days. Despite this, the skin lesion evolved over the span of 2 weeks to the annular lesion with which she presented. She reported no other systemic symptoms or signs, and physical examination also failed to reveal any. The patient had previously received the influenza vaccine annually for several years without ever experiencing any local or systemic reactions. Annular lesion with indurated edge on the posterior aspect of the patient’s right arm coinciding with the site of influenza vaccine injection. Histological examination of a biopsy taken from the lesion revealed a superficial and deep perivascular and periadnexal dermal lymphoplasmacytic infiltrate (Fig. 2) with aggregates of CD123‐positive plasmacytoid dendritic cells and an interface dermatitis with basal cell vacuolar damage and occasional Civatte body formation. Hale colloidal iron stain revealed increased levels of deep dermal mucin. (a) Superficial and deep lymphoplasmacytic infiltrate and prominent oedema of the papillary dermis. (b) Inset: perivascular and periadnexial infiltrate with focal interface dermatitis. Haematoxylin and eosin, original magnification (a) × 100; (b) × 200. Based on the temporal and spatial association of the skin findings with the administration of the influenza vaccine, as well as the histology findings, a diagnosis of lupus erythematosus (LE)‐specific skin disease, specifically localized acute cutaneous LE (CLE)1 [Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)2 – mild disease1] to the influenza vaccine was made. The lesion spontaneously decreased in size over days, resolving completely within 4 weeks. Because of the immunocompromised state of patients with LE, the risk of acquiring influenza is increased, as are the associated morbidity and mortality. Influenza infection has also been associated with disease flares in patients with SLE.3 For this reason, the annual influenza vaccination is recommended for all patients with LE.4 Our patient was administered the trivalent influenza vaccine (Vaxigrip®; Sanofi Pasteur, Lyon, France) based on recommendations issued by the World Health Organization (WHO) for the Northern Hemisphere for 2018/2019.5 The safety and efficacy of the influenza vaccine is well documented, including in patients with SLE. Only one previous case of dermatological complication to influenza vaccine in a patient with SLE has been reported in the literature, which was a nonspecific rash.6 Compared with healthy recipients, patients with SLE more commonly experience itching, pain and redness at the site of influenza vaccination.3 Patients with SLE have a weaker humoral response to the influenza vaccine,3 8 especially patients on treatment, including glucocorticoids and mycophenolate.3 The paucity of reported cases of CLE reactions to viral vaccinations make it difficult to elucidate the pathophysiological mechanism underpinning such a phenomenon. Molecular mimicry has been proposed as a potential mechanism for the development of SLE secondary to bacterial vaccines. Antibacterial antibodies to pneumococcal polysaccharides found in the pneumococcal vaccine may crossreact with double‐stranded DNA, precipitating systemic disease.9 Isomorphic phenomena have been described,10 but our patient had a single, annular lesion and had never experienced lesions caused by koebnerization. However, it is difficult to ascertain whether this patient would have developed CLE to the influenza vaccine had she not had SLE. Interestingly, a high disease activity was previously found to be an independent factor for attenuated immunogenicity to the influenza A vaccine.11 In conclusion, this is the first documented case of a CLE reaction to the influenza vaccination, to our knowledge. Nevertheless, we recommend that at‐risk patients, including those with SLE, continue to receive the vaccine annually as advised by WHO.5 Conflict of interest: the authors declare that they have no conflicts of interest