Contact urticaria and protein contact dermatitis in the Finnish Register of Occupational Diseases in a period of 12 years

Although occupational contact urticaria (CU) and protein contact dermatitis (PCD) are considered frequent among workers with exposure to proteinaceous materials, data on occupations at risk and the main causes of these occupational skin diseases are relatively limited.


| INTRODUCTION
Contact urticaria (CU) is defined as a wheal and flare reaction of the skin after contact with an eliciting substance, which appears immediately and usually clears within a few hours. 1,2 Protein contact dermatitis (PCD) is a slightly controversial entity. Its mechanism is not known, but in occupational settings, it is customary to diagnose PCD when immediate allergy to a proteinaceous material is associated with eczema on the contact site. It may be accompanied by an initial wheal reaction consistent with CU. Work-related exposure to proteinaceous materials such as food is known to carry a risk of occupational CU and occupational PCD. 3,4 In fact, CU and PCD are rarely diagnosed outside occupational dermatology. 5,6 Previous literature on the epidemiology of CU and PCD is relatively limited. To provide more detailed data on occupations at risk and causative agents of CU and PCD, we analyzed data of the Finnish Register of Occupational Diseases (FROD) in a period of 12 years.

| RESULTS
Skin diseases are among the most common occupational diseases in Finland. During the 12-year period 2005-2016, the FROD included a total of 5265 newly recognized cases of occupational skin disease. 9 During this period, a total of 570 cases were filed in the FROD with a diagnosis of CU and/or PCD, which represents 11% of all recognized cases of occupational skin diseases. Among these, CU or PCD was reported as the first diagnosis in 556 cases, in 13 as the second, and in one as the third diagnosis. Occurrence of CU and PCD per year shows a decreasing trend in 2005-2016 as is illustrated by

| Causes
The reported causes of CU and/or PCD are presented in Table 1. Proteins of animal origin defined as animal dander and excretions, and animal-derived foods, were reported as causes of CU and PCD in 326 cases (57% of cases with CU and/or PCD). In 265 (81%) of these, the cause was cow dander. Proteins of plant origin including flours, other plant-derived foods, grain, animal feed, and ornamental and other plants were the causes of CU and PCD in 171 cases (30% of all cases with CU and/or PCD). The most common individual causative allergen among plant proteins was wheat flour, which was the reported cause in 41 cases. However, in 20% of the cases caused by flours, the culprit grain was not defined in register data (Table 1).
Natural rubber latex (NRL) proteins were the cause in 48 cases (8.4% of cases with CU and/or PCD) and thus constituted the third most common allergen group among cases with CU and/or PCD.
There is a clear decrease in the amount of annually registered cases of CU and/or PCD caused by NRL ( Figure 2). Chemicals were the cause of CU in 25 cases (4.4%). Among chemicals, the persulfates present in hair bleach products were the most commonly recorded cause of CU, followed by carboxylic acid anhydrides, which are used as epoxy hardeners by the electronics industry. Enzymes such as those used as flour additives were an uncommon cause of CU and/or PCD.

| Occupations at risk
Incidences of CU and/or PCD in occupations at risk and their main causes of CU and/or PCD are presented in Table 2 occupations of health and dental care. In hairdressers, the most commonly recorded cause was persulfates.
In addition to the occupations shown in Table 2, there were several occupations with a single case of CU and/or PCD. Among them, there were eight cases with higher education in various natural sciences who worked for universities, universities of applied sciences, and other research units, and were therefore likely to be researchers.
In most of them (six of eight), the causative agent was rat.
Occupations of 15 cases with CU and/or PCD was recorded as "unknown." In all of them, the industry was "education," mostly vocational education. These cases are likely to represent students. Their causes of CU and/or PCD included cow dander (three cases), animal-derived foods (three cases), ammonium persulfate (two cases), NRL (two cases), flour and plant-derived foods (three cases), and rat and ornamental plants (one case of each).

| DISCUSSION
In the present study based on nationwide registry data, CU and PCD were analyzed as one group, since they are not reliably distinguishable Causes of occupational contact urticaria and protein contact dermatitis in a total of 570 cases allergic contact dermatitis. 9 Occupations with the highest incidence of CU and/or PCD included bakers, pastry cooks and confectionery makers, farmers (mixed crop and animal producers) and farm relief workers, occupations in veterinary medicine, chefs and cooks, gardeners, and hairdressers. The most common causes of CU and/or PCD were cow dander, flour and grain, NRL, and food.
According to the underlying mechanism, CU may be classified into immunological or allergic CU (ICU) and nonimmunological CU (NICU). ICU occurs in previously sensitized individuals and is a type I hypersensitivity reaction mediated by allergen-specific immunoglobulin E (IgE) 10 and may be complicated with mucosal and systemic symptoms. The mechanism of NICU is not completely understood, but it is a nonimmunologic immediate reaction that occurs without prior sensitization and limits itself to the skin. 1 In CU, concomitant airway diseases caused by the same allergen is common. 11 PCD is an allergic skin reaction induced by proteins of plant or animal origin, which clinically is a recurrent, itchy, sometimes vesicular eczema on the contact site of the causative agent. 12 The immunological mechanisms of PCD remain to be fully elucidated. It is considered mainly to be caused by type I allergy, although also a combination of types I and IV hypersensitivities has been suggested. 13  Previously reported causes of CU and PCD include a variety of proteinaceous substances such as plant-and animal-derived foodstuffs, NRL, enzymes, and in cases of CU, some chemicals 4,18,[20][21][22][23] In our data, the most common causative agent was cow dander, which was recorded as a cause in 46% of cases with CU and/or PCD. Cow dander has for long been the most frequent cause of occupational CU in Finland. 24,25 PCD caused by cow dander has been reported previously. 26,27 It is also a well-known cause of occupational asthma and allergic rhinoconjunctivitis in farmers. [28][29][30] Grain, in the form of flour, cultivated grain, or animal feed, was the second most important cause of CU and PCD in our data. Flour was the most frequent cause in bakers and other food-handling occupations, and a frequent cause in occupations involved in cattle breeding. Immediate allergy to flour is among the most frequent causes of occupational respiratory diseases, and bakers are a known risk group of occupational asthma and rhinitis. [31][32][33][34] In contrast to our results, in a study from Denmark on professional food handlers with hand dermatitis, flour was not so prominent among the skin prick test-positive allergens. 3 Instead, vegetables and fruits were the most commonly positive allergen groups. The reason for this difference might be that in the Danish study, the flours were tested as commercial extracts, whereas in Finland, the flours have since the early 1990s been skinprick tested "as is," moistened with a small amount of water, with prick-to-prick technique. This was based on findings that fresh foods are more effective in the skin-prick test than commercial food extracts. 35 More recently, a concern has been raised on the variable and sometimes low antigen content of commercial skin-prick test extracts for several important occupational allergens including wheat flour and cow dander. 36,37 Occupational type 1 allergy to NRL was a major concern in health care workers in the 1990s. In the 2000s, a decline in new cases of occupational CU caused by NRL has been observed. 38