Fragrances fuelling fibromyalgia? Patch tester's insights into a complex rheumatic disorder

Fibromyalgia (FM) affects millions of people worldwide, about 2% of adults, females twice as frequent as men.1 This rheumatic disorder is primarily characterized by chronic widespread pain of muscles, joints and connective tissues, along with debilitating symptoms such as fatigue and sleep problems. It is a heterogeneous condition, and identified risk factors comprise, among others, age, sex, the presence of other connective tissue diseases, viral infections and, importantly, stressful or traumatic events.1 Unfortunately, its exact aetiology and pathogenesis remain largely elusive, and research boldly continues to decipher this enigmatic and still somewhat controversial entity. In particular, the question remains whether other environmental triggers may still be of importance. In this regard, dermatologists might have something valuable to contribute to the FM research arena. In the patch test clinic, for example, patients with (many) strong (2+) or extreme (3+) patch test reactions sometimes develop systemic (“f lulike”) symptoms. Moreover, patients suffering from socalled systemic contact dermatitis (SCD or systemic allergic dermatitis [SAD]), that is, who following the previous skinsensitization to an allergen develop various symptoms after systemic exposure to the same or a crossreactive substance, may also present with extracutaneous symptoms, including musculoskeletal pain and arthralgia. Extracutaneous symptoms in cases of contact allergy do not only ref lect the wonderful underlying immunological phenomena of the contactallergic mechanism but also remind us that skin sensitizers do not only cause skin disease (i.e., “dermatitis”), but potentially also, due to systemic exposure, more diverse and generalized symptoms. Most cases of SCD/SAD have been attributed to metals (e.g., nickel or gold)2 and drugs,3 although other contact allergens, such as spices and fragrances, may also be involved.4,5 Interestingly, some authors have observed that systemic exposure to, and subsequent delayedtype hypersensitivity from, metals released from dental alloys might be important in patients suffering from rheumatic diseases, including FM, and they have postulated that continuous systemic exposure might contribute to ongoing systemic inf lammation,6 as such contributing to the chronic pain and associated symptoms these patients experience. Others have shown that a reduction of metal exposure in metalsensitized patients might result in improvement, of FM, suggesting that metalinduced inf lammation might indeed be an important factor in some patients.7 Although data from studies on metal hypersensitivity offer interesting insights, there are only few, and they have dealt with only a limited number of participants, with little to no controls involved, and (metal) allergy testing, if performed, was usually based on invitro assays. In this issue of The Journal Bruze et al. hint towards contact allergy, and systemic exposure to contact allergens, as possible contributing factors to the development of FM.8 As a part of a larger project, investigating the connection between contact allergy and FM, the authors have shown, for the first time, in a large and welldesigned in vivo (patch test) study, including two different control groups, that FM patients have a contact allergy profile that matches “dermatitis patients" rather than "the general population.” This important observation might suggest that FM patients are prone to develop contact sensitization and/or that contact allergy somehow contributes to the onset and maintenance of FM. Compared to the general population, FM patients are not just more frequently sensitized to metals (nickel, which confirms previous observations) but, surprisingly, also to Myroxylon pereirae resin (Balsam of Peru) and Fragrance mix I. These substances share mutual Received: 4 November 2022 | Accepted: 4 November 2022