Skin problems related to Indonesian leather & shoe production and the use of footwear in Indonesia Febriana, Sri Awalia

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1 University of Groningen Skin problems related to Indonesian leather & shoe production and the use of footwear in Indonesia Febriana, Sri Awalia IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2015 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Febriana, S. A. (2015). Skin problems related to Indonesian leather & shoe production and the use of footwear in Indonesia [Groningen]: Rijksuniversiteit Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 CHAPTER 1 Introduction Sri Awalia Febriana Department of Dermatology & Venereology, Gadjah Mada University, Yogyakarta, Indonesia Department of Dermatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.

3 Introduction 1 10 The leather manufacturing industry as a whole has become the backbone of Indonesian export. 1, 2 Between January and September of 2013 its total annual export of leather and leather products was worth 163,605,136 US dollars 3, 4 and 6,500 workers were employed in medium and large factories. 5 Indonesian tanneries have been producing leather not only for domestic use but also for Europe, the United States, Australia, and Asia. Indonesia's footwear industry in particular has a long history. In the 1940s footwear manufacture for the foreign market began with the opening of a Czech factory, and the late 1960s marked the beginning of production for the domestic market. Since then Indonesia's footwear industry has continued to grow, and in various industrial locations throughout the country a broad variety of products are currently being manufactured for the market both at home and abroad. 6 According to SATRA (Shoes and Allied Trades Research Association, UK) Indonesia, along with the other leading countries in shoe production, produced 75.2% of 12.5 billion pairs of shoes manufactured worldwide in In 2008 the Indonesian footwear industry alone was producing 131 million pairs of shoes a year. 6 From January to September 2013 Indonesian footwear export was worth million US dollars 3, 4 and in the medium and large shoe industry alone 202,189 workers were employed, as well as millions of workers in other related industries. 5 If we consider the huge production in the leather and shoe manufacturing sector in Indonesia, the number of workers employed, and the associated skin hazards described below, it is clear that the burden of occupational skin diseases in this sector must be high. The manufacture of leather and shoes causes prolonged exposure of factory workers to many potent chemical irritants and sensitizers. During leather manufacture, employees working on various stages of leather preparation (including pre-treatment with water and lime as well as the processes of pre-tanning, tanning and finishing) come into contact with chemicals designed to alter the structure of animal hides. 2, 8-13 The workers are exposed to numerous materials such as leather, rubber, dyes, preservatives, and shoe adhesives (neoprene, epoxy resin and rubber glues) containing a broad spectrum of allergens Because of their exposure to these environmental hazards, together with very limited use of personal protective equipment (PPE), leather- and shoe-factory workers are prone to occupation-related skin problems.

4 Occupational skin diseases are those arising during occupational activity. These diseases, currently increasing in prevalence, are of great socioeconomic importance. Not only do they have major consequences for the affected patients and their families, but the annual cost to health insurance companies is equal to or even greater than that of other chronic inflammatory skin diseases like psoriasis and eczema. 15 In the USA the average annual cost per claim of Occupational Skin Disease was $3,552 and the average disability time 23.9 days. 16 In Germany, the annual cost to health insurance companies for each case of occupational hand eczema is about Epidemiological studies of occupational skin diseases (OSD) among leather factory workers in Europe were reported some decades ago in Sweden 18, and in 1996 an epidemiological study was made of occupational contact dermatitis (OCD) in Italian shoe factory workers. 14 The fact that no recent reports on this subject have been made may be the result of the more current outsourcing of leather and shoe manufacturing to Newly Industrialized Countries (NICs). Low labour costs, easy supply of raw materials, and a tradition of making shoes have been reasons for moving leather and shoe manufacturing industries to NICs. Another important issue is many industries in developed countries search for the countries t t o ta u at o o o a a o ut o a ot. 19 As a result, these countries are being burdened with the effects of hazardous industrial production processes. These conditions, in which workers are protected neither by their national regulatory frameworks nor provisions for a safe environment, places them under the tremendous hardship of work-related morbidity and mortality. 20 The problem of occupational diseases among tannery workers in Newly Industrialized Countries has been discussed in a few studies made in Argentina, India and Korea. 8-10, 21, 22 Studies related specifically to the shoe industry have been done in India, Thailand, and Poland. However, few of the published studies have focused on the kind of exposure, the potential sources of chemical and physical hazards, and the actual prevalence of occupational skin diseases in workers in these industries. Although in a quite different situation, patients who get shoe dermatitis because of conditions inside the shoe like occlusion and sweat have an exposure similar to that of shoe manufacturing workers For many hours every day, shoe consumers enclose their feet with materials like leather, plastic, rubber, cloth and shoe adhesive, all containing hundreds of chemicals. 28, 29 Different chemicals, combined with a hot and humid environment within the shoes, provide the perfect situation for the development of allergic contact dermatitis. 30 Additional factors like heat,

5 1 12 pressure and friction, together with standing and movement, can increase the development of skin sensitivity. 28 Evidence showed that there is an impressive change in the allergens producing contact dermatitis of the feet Unfortunately there are to date very few studies on shoe dermatitis and patterns of sensitivity to chemicals in footwear. Occupational Contact Dermatitis What is Occupational Contact Dermatitis and the burden of this kind of disease? Occupational skin disease is a pathological condition of the skin for which occupational exposure can be shown to be a major causal or contributory factor. 34 Occupational contact dermatitis ranks among the top three workrelated diseases; in all instances the diagnosis is allergic or irritant contact dermatitis or a combination of both. It is a reaction characterised by inflammation as a result of contact of the skin with substances found in the workplace In the pathogenesis of contact dermatitis, irritants and allergens are interwoven and endogenous and environmental factors are often involved as well. 36, 38 Occupational contact dermatitis constitutes over 90 95% of the wider spectrum of occupational skin diseases 36, not including chemical leukoderma, oil acne or chloracne, neoplasma, infections and infestation. 39 Occupational contact dermatitis is a common reaction of the skin due to contact with a number of chemical agents; it is a significant public health issue and considered to be the main cause of occupational dermatitis. Significant numbers of individuals are exposed every day to a variety of products which may provoke the development of OCD. This affliction, characterised by extreme itching, leads to many restrictions in daily life as well as loss of sleep and potential loss of income due to absenteeism and costs of treatment. Moreover, new products with new chemical components are constantly being launched into the market, exposing both workers and consumers to their possible ill effects. These facts point to the need for expertise in risk assessment as well as continual and adequate surveillance and diagnosis of individual patients Epidemiology of occupational contact dermatitis The average incidence of registered OCD in some countries lies between 0.5 and 1.9 cases per 1000 full-time workers per year 42 and is regarded as one of the leading causes of occupational morbidity and absenteeism. 44 The ascertained prevalence of occupational contact dermatitis may vary depending on differences in case definition. This definition can further vary

6 according to whether it is based on employer reporting, employee selfreporting, skin patch test results, workers compensation claims, or clinical diagnosis. 36, Some countries require mandatory notification of potential cases of OCD; this yields a high reporting rate but increases the possibility that non workrelated dermatitis may be included. Such reporting methods, however, do typically employ a consistent system of assessment. In all of three countries (Denmark, Finland and Germany) having compulsory national registration the incidence of reported cases was similar, with rates of five to eight cases per 10,000 workers per year There was a tendency for incidence to decrease with time: 10.7 per 10,000 workers in as compared with 4.9 per 10,000 workers in The Danish Register of Occupational Diseases reported an incidence of eight cases per 10,000 workers per year. 52 By contrast, the incidence rates registered by self reporting are variable The Netherlands reported considerably higher rates (15 per 10,000) 53 than did the UK (1.3 per 10,000) 54 or Australia (2.2 per 10,000) 55. The highest rates of occupational skin diseases were reported in population studies that relied on self-reporting Pathomechanism of contact dermatitis Contact dermatitis is a common inflammatory disorder of the skin induced by repeated exposure to irritants (irritant contact dermatitis) or allergens (allergic contact dermatitis). Even though it is clinically possible to differentiate between these diseases, they have significant similarities of clinical manifestation, histological and imunohistopathology features and molecular patterns. In both ACD and ICD the cascade of inflammation produced by epidermal and dermal cell activity appears to be similar and related. 56 Considering the strong similarity between both types of contact dermatitis, the important question arises: how to differentiate between skin irritation and skin allergy? The important difference is in the pathophysiological mechanism, involving allergen specific T-cells in the development of allergic contact dermatitis. Both types of contact dermatitis involve cell immunity, but ICD follows the activation of innate immunity whereas ACD is the result of the activation of acquired immunity and the induction of specific pro-inflamatory T-cell effectors. 56 The pathophysiology of contact sensitization consists of a sensitization phase and an elicitation phase. The sensitization phase begins with the person's first contact with the allergen and continues until he is sensitized and competent to generate a positive ACD reaction; this phase takes 4 days

7 to several weeks. The elicitation phase begins upon elicitation and continues until the clinical manifestation of ACD, which is fully developed in 1-4 days Clinical features and symptoms of occupational contact dermatitis Contact dermatitis can be acute, chronic or intermediate and there are no completely specific clinical features and symptoms for ACD or ICD. Acute dermatitis usually presents as papules, and occasionally as vesicles or bullae. 57 A histological characteristic of acute eczematous reactions is spongiosis of the epidermis, which leads to the formation of vesicles and bullae which can appear in both allergic and irritant contact dermatitis. 58 By continual contact with suspected substances chronic contact dermatitis may develop, with clinical characteristics like pruritus, lichenification, erythema, scaling, fissures and excoriation. 57 A nice example of the distinction between ACD and ICD can be made on the is placed onto the skin and occluded, erythema and slight infiltration occur, strictly limited to the patch test area. However, with substances capable of provoking an allergic reaction there is a markedly pruritic, infiltrated, popular or vesicular reaction that extends beyond the borders of the occlusion chamber. This happens when the amount of substance needed to elicit an allergic reaction is less than the amount necessary to elicit an irritant reaction. Recruitment of particularly sensitized cells and the release of non-specific cytokines facilitate an allergenic response outside the area of direct contact. 57 In occupational contact dermatitis, slow improvement seems to occur after a patient spends several consecutive days away from the workplace; symptoms fade during long vacation periods and recur promptly upon resumption of work. 35, 42, 59 Pruritus is the hallmark symptom of occupational contact dermatitis, but is marked by great variety in onset and intensity. An atopic dermatitis background can make pruritus worse, affecting the daily life of patients with irritant contact dermatitis. Milder symptoms like stinging sensations can appear, but these are not general symptoms of the irritancy. 60 Detailed description of symptoms can be helpful in differentiating between contact dermatitis and other dermatoses. 57

8 Diagnosis of occupational contact dermatitis Establishment of the diagnosis of occupational contact dermatitis is quite complicated since there are no specific clinical and histopathological characteristics. 37 Diagnosis of OCD involves two fundamental steps: 1) recognizing the existence of an occupational exposure and 2) assessing whether that exposure represents a cause or substantial aggravating factor in the patient s dermatitis. Usually, OCD improves when the patient is off work for more than a week and intensifies when work is resumed. To reach an accurate diagnosis, the dermatologist relies on comprehensive history taking, thorough skin examination and skin testing. A workplace visit is also included to gain important information in the investigation of suspected occupational dermatitis To arrive at an accurate diagnosis of OCD it is vital that the physicians involved have an adequate level of knowledge and skill as well as experience in this field. Moreover, it is important and often difficult to be able to confirm the relationship between OCD and a patient's exposure. Screening of the complete study population by one or more trained dermatologists using standardized criteria is the most reliable and therefore preferred method. 36 Mathias proposed 7 criteria for establishing occupational causation and aggravation of contact dermatitis 62 : 1) Is the clinical appearance consistent with contact dermatitis? 2) Are there workplace exposures to potential cutaneous irritants or allergens? 3) Is the anatomic distribution of dermatitis consistent with the form of cutaneous exposure in relation to the job task? 4) Is the temporal relationship between exposure and onset consistent with contact dermatitis? 5) Are non-occupational exposures likely as causes? 6) Does avoiding exposure lead to improvement of the dermatitis? and 7) do patch test or provocation tests implicate a specific workplace exposure? 63 The validity of these criteria was assessed by Ingber and Merims. 64 From a different angle, Rycroft et al (1996) stated that the clinical assessment of dermatitis in the workplace is based on four considerations: dermatitis and not atopic, seborrhoeic, discoid, stasis, or unclassified eczema; 3) Is it irritant contact dermatitis or allergic dermatitis and As mentioned by Mathias under point 3, the anatomical distribution and the type of skin lesion must be consistent with the nature of exposure. Nicholson calls attention to several more points, namely whether personal

9 1 16 protective equipment was used by workers (and used in a recommended manner), workers' behaviour, and the physical form of the hazardous substances. 43, 61 In relation to the latter, for example, contact dermatitis due to solid particles shows skin lesions with well-defined borders on the areas of exposure. Contact dermatitis caused by gases, fumes and vapours affects mainly exposed areas such as the face and eyelids, whereas dust or airborne substances can cause contact dermatitis in areas both exposed and underneath the clothing. Contact dermatitis due to liquid substances predominantly affects the dorsal aspect of the hands and fingers, finger webs and forearms. These facts illustrate that the clinical appearance of OCD can be intricate, and to diagnose it requires a systematic and thorough approach. 61 A comprehensive clinical history, skin examination and appropriate patch testing are essential for differentiating between Irritant Contact Dermatitis (ICD) and Allergic Contact Dermatitis (ACD). 35, 65 In spite of negative patch test results, for example, OICD may nonetheless be indicated if there is a temporal relationship with exposure to the irritant at work. 43 Moreover, OICD is generally confined to the area in contact with the irritant, whereas OACD may present a more widespread rash. In general, both OICD and OACD improve when the patient is off work for more than a week and intensify when the patient returns to work. However, when exposure is discontinued OACD improves more slowly than OICD and recurs more quickly, within a few days after returning to work. Cumulative irritant contact dermatitis, on the other hand, usually recurs gradually within days or weeks when exposure is resumed and is clinically indistinguishable from ACD. We must be extremely careful in our interpretation of all of the above facts because of the presence of so many confounding factors. 18, 61 There are 9 points to be considered in the assessment of occupational allergic contact dermatitis (OACD), as follows: 1) history of occupational exposure; 2) amount of time between occupational exposure and the actual onset of dermatitis; 3) patterns of the dermatitis consistent with occupational exposure; 4) positive patch test with appropriate vehicle and concentration; 5) repetition of patch test when excited skin syndrome is suspected; 6) positive Repeat Open Application Test (ROAT) to determine clinical relevance; 7) application, where needed, of serial dilutions of the tested chemical; 8) review of control for non-irritating concentrations and performance of a special (not commonly used) test for allergens; 9) clearing of dermatitis when allergen is removed or exposure is significantly decreased. 61, 66 The criteria for occupational allergic contact dermatitis based on the Danish study are: 1) positive patch test reaction to a

10 substance present at the workplace; 2) skin contact with the substance on the relevant skin area; 3) sufficient exposure intensity and duration to explain the dermatitis. 67, 68 Workplace survey and inspection Survey and inspection of the workplace are crucial 69 ; identification of hazards in the worker s environment is an essential step in diagnostic procedure 61 and should be carried out with several aims in mind: 1) to assess the risks in the workplace that could cause health damage; 2) to review previous risk assessments and controls that have been introduced and ensure that this is still being done properly; 3) to investigate further aspects of the environment where a person has suffered from occupational skin disease Two things are essential in workplace surveys and inspection: 1) the working process must be observed while actually in process, and 2) the observer must have enough time to observe the plant thoroughly. 37, 62, 69 Detailed information that must be acquired during the working process includes: 1) organization of the factory; 2) demographic data (number of workers and shift patterns); 3) technical notes on the working process (how the work is carried out; potential irritants and sensitizers to which workers are exposed and their degree and extent of skin contact); 4) preventive measures (broad impression of working conditions, protective installations and protective personal measures); 5) workers' skin complaints and clinical assessment; 6) epidemiological evaluation to estimate the frequency of occupational dermatoses; 7) etiological evaluation; and 8) summary of findings and recommendations for future investigation. 37, 62, 70 Sources of information on exposure to contact allergens All chemicals, whether or not they are responsible for ICD or ACD, could be regarded as irritants when present in concentrations high enough to induce irritation. Allergens are chemicals which behave as haptens. Some studies have shown that thorough investigation of exposure to contact allergens is beneficial for the prevention, treatment, and prognosis of patients with allergic contact dermatitis Exposure information can be acquired from different sources such as: 1) publications; 2) product labelling and declarations; 3) material safety data sheets (MSDS); 4) inquiries to manufacturers or suppliers; 5) chemical analysis and product databases; and 6) Online data bases and sources of information. 68, 74-76

11 1 18 Considering point 2 above, one of the best sources of information about the contents of chemical products (including the presence of contact allergens) should be product labelling and declarations, but unfortunately not all manufacturers confirm to the requirements for inclusion of all contents when labelling their products. Information about compounds added to materials is sometimes not stated in the declaration. 73 According to European regulations on the classification, labelling and packaging of substances and mixtures (Regulation EC No 1272/2008), for example, sensitizers are substances which after an initial exposure may provoke an allergic skin reaction (skin sensitizer); those have code R43- may cause redness and inflammation of the skin, but generally heal within a short period of time, have code R38. This code should be mentioned on labels, but is often omitted. A further complication is that consumers and physicians need to have sufficient knowledge to read and understand chemical names. Material safety data sheets (MSDS) explain the hazards of all chemicals produced, distributed, or used in a workplace. They also provide safe procedures for handling or working with the substances and include information such as physical data, toxicity, health effects, first aid, reactivity, storage, disposal, protective equipment, and spill-handling procedures. MSDS formats can vary from source to source between countries, depending on national requirements. 73, 75 When a dermatologist is trying to determine whether a particular product or substance may be the cause of a particular case of occupational skin disease he will look first at the MSDS. 77 However, according to an Australian study, sensitizers are frequently omitted from the MSDS and clinicians are often unsuccessful in obtaining crucial information from manufacturers; as a result the MSDS is inadequate for the protection and diagnosis of workers with suspected OCD. 78 significant intrinsic skin irritation and sensitisation hazards. The MSDS users have three options while using MSDS: take the information at first value, ignore the information, or treat the information as a stimulus to undertake more detailed investigation followed by an analysis of the 77 Another way to acquire useful information about ingredients in chemical products is to make inquiries to manufacturers or suppliers. However, although some manufacturers are willing to provide prompt and detailed information on specific products, this is a time consuming and not always successful approach, as a supplier may not even have access to detailed information.

12 To stay abreast of the rapid changes in chemical exposure in the workplace and the development of personal protective equipment, web-based sources of information are becoming increasingly important. There are many recommended websites, including those of national institutes (e.g for occupational health and safety and health insurance); ministries of employment; societies of contact dermatitis, task forces, national research centres; and corporations in many European countries such as Germany, Great Britain, the Netherlands, Denmark and other Scandinavian countries, as well as Austria and the United States. These sites provide reliable data in terms of authenticity and accuracy, they are easy to access and they offer comprehensive information. This information includes facts about hazardous substances, a database of protective gloves for various kinds of exposure, a platform on skin protection, health and welfare service information on occupational skin diseases and their prevention, information about safe handling of hazardous substances, information on MSDS, a platform to raise awareness, patient information on skin testing, and the database of occupational allergens Patch test examination It is important to identify any offending allergen in order to remove it from the worker's environment; this can play a significant role in the worker's recovery and help to prevent new cases of disease. 43 The most essential tool for the study of allergic contact dermatitis is patch test examination. When one is diagnosing occupational allergic contact dermatitis it is necessary to identify a broad series of allergens including baseline series, series of specific occupational allergens, and materials to which patients are exposed in the workplace. 61 This is made possible by patch testing. In the diagnosis of allergic contact dermatitis, two steps are essential: 1) to demonstrate the connection of a contact allergy to one or several allergens, and 2) to demonstrate the clinical relevance of the reaction. In the first step, we have to assess the morphology of the reaction and decide whether the response represents a true- or a false-positive allergic reaction. If there is an indication of contact sensitivity to a defined allergen, we still have to demonstrate its relevance in the clinical situation. 79 To assess the clinical relevance of a positive patch test reaction, we need to know whether the responsible allergen is the primary cause or only an aggravating factor of the patient s dermatitis. An allergen is clinically relevant if we can establish that exposure has taken place and that the patient s dermatitis can be partially or totally linked to the exposure. 61, 80

13 1 20 In searching for offending allergens in the preparation of patch testing for patients we can use information from a variety of sources. Besides that obtained from patient interviews, we can obtain information from textbooks, journals, material safety data sheets (MSDS), workplace visits, and the MEDLINE Resources Guide. 73, 75 Misclassification can easily occur when it is (erroneously) assumed that the mere absence of a positive patch test reaction implies a diagnosis of ICD. A positive patch test reaction has to be assessed for its relevance. Occupational skin problems in the leather industry As stated above, leather factory workers are exposed every day for long periods of time to potentially sensitizing chemicals. 11, 12 They come into contact with irritant and allergenic products and extreme environmental conditions which make them more susceptible to developing occupational skin problems. Diseases of the skin were found to be caused by toxic, irritant or sensitizing chemical substances including acid burns due to sulphuric acid, chrome ulcers caused by trivalent chromium, and contact dermatitis caused by exposure to lime solution, chromate, solvents or dyes. 10 Some compounds (benzene-based dyes and formaldehyde) which are used in the tanning process are considered to be carcinogenic to humans. 8 Although there is a high risk in the leather industries, occupational skin diseases are rarely reported. Those reports which are available include five cross sectional studies published in India, Argentina and Korea. 8-10, 21, 22 Shukla, Ory and Rastogi conducted a study in Indian tanneries. Rastogi et al (2008) reported that 9% of male workers drawn randomly from 10 tanneries in India had skin rash and papules along with complaints of itching. 8 Shukla et al (1991) carried out a comprehensive occupational study in 20 tanneries in an Indian urban slum area. They did a walkthrough survey in the workplace to quantify occupational and safety hazards and Personal Protective Equipment (PPE) practices. 10 Ory reported that 23% of 418 labourers in Indian tanneries had dermatitis. 9 In addition, in Brazil, a study of 110 male tannery workers revealed that 40% of them had occupational skin lesions. 21 Although skin diseases were indeed noted in all of the studies above, the research was focused primarily on occupational health problems in general and not specifically on the prevalence of occupational skin diseases. However, Lee et al did conduct a study in a leather tannery which focused on occupational dermatoses (1991). Besides contact dermatitis, workers were found to have other occupational related skin diseases like calluses, paronychia, burns, physical traumas, vitiligo and oil acne. 22

14 The reported point prevalence of occupational skin disease among tannery workers in Newly Industrialized Countries is between 2.6 and 26.4%. 8-10, 21 The wide range of point prevalence figures between countries is probably caused by differences in the definition of cases, as well as differences in working conditions, periods of screening and data collecting. Occupational skin diseases in shoe manufacturing industry 1 21 Footwear is defined as any garment or piece of clothing worn over the feet for protection. Historically, footwear throughout the world has varied according to climate, environment, terrain and available raw materials. They also varied due to the influence of technology, fashion, and the development of local cultures; these are in turn also influenced by other cultures 6 Shoe manufacturing has been delocalized from developed countries to Newly Industrialized Countries, including Indonesia, for several reasons like cheap labour, availability of materials, and ecological issues. 7 A great variety of materials are used in the production of shoes. Shoe uppers can be made from leather, rubber, or synthetic materials such as polyurethane and neoprene foam. 12, 13, 29 Outer and inner soles are made of rubber, polyurethane, polyvinylchloride or a combination of ethyl vinyl acetate and rubber polymers. Many kinds of adhesives like urethane, neoprene, hot melt, and natural rubber are used for different parts of the shoes, and to retain the shoe's shape, heel- and toe-stiffeners or counters are added. 13, 81 In shoe factories the various parts of the shoes are prepared and assembled. During the preparation process workers are cutting and edging shoe uppers, soles, insoles, quarters and linings. Workers are also priming, washing, gluing and sewing to assemble the various parts of the shoes. During the last steps in the finishing and packing department, workers are cleaning the shoes, trimming, adding waterproofing agents and packing the shoes for shipping As is true of the leather industry, the shoe manufacturing industry also exposes workers to many potential physical and chemical hazards. A number of epidemiological studies show a significant relationship between physical and chemical exposure during footwear manufacturing and adverse health effects, especially occupational skin diseases. 82, 83 The irritant activity of adhesives and solvents used in the production cycle and the sensitizing activity of allergens contained in adhesive, leather, rubber and dyes are well known. 12, 14, 29, 82 According to an epidemiological study in 5 Italian shoe factories between 1992 and 1994, 14.6% workers suffered

15 from occupational contact dermatitis; 6% had hyperkeratosis of the fingertips and 3.2% had pruritus sine materia Epidemiological studies on occupational health problems have been published on shoe manufacturing workers in Newly Industrialized Countries like India, Thailand and Portugal. 82, 83 However, the presence of occupational skin disease was mentioned only in the case of one shoe manufacturing worker in Thailand (13.6%). 83 As described in the first paragraph of this chapter, shoe manufacturing in Indonesia is an industrial sector that is increasing in response to a growing demand. The industry is labour intensive and concentrated in the small village industry for in-country production and in large scale units for export products. Indonesia is the largest footwear exporter after China and Vietnam. 84 Despite the significant number of workers in shoe manufacturing in Indonesia, there is still no published study on the actual risk and prevalence of occupational skin diseases in this industry. Shoe dermatitis Prior to 1940 shoe dermatitis was considered a dermatologic curiosity. We refer here to allergic contact dermatitis of the feet with a prevalence range from % of all cases presenting in a patch test clinic , 85, 86 In daily practice, patients are sometimes sceptical about their physicians' diagnosis that shoes may be responsible for their eczema. 87 Conversely, many patients attribute their foot eczema to a contact allergy to their shoes. Feet have specific anatomical features with the highest concentration of eccrine sweat glands in the plantar area, and in combination with the wearing of shoes this can increase maceration and enhance the absorption of chemicals; this creates an environment which favours the development of allergic contact dermatitis. 31, 88 Daily for many hours or intermittently for months or years and often under extreme conditions of temperature, humidity, barometric pressure and physical disturbances. 28, 89 We enclose our feet with leather, plastic, rubber, cloth and adhesives containing hundreds of chemicals. Skin contact with these chemicals, in combination with accumulation of sweat, produces hydration of the stratum corneum, and the heat, pressure, and friction accompanying movement and standing promote the development of sensitivity. 27, 28 Epidemiology of shoe dermatitis According to statistics available from patch test clinics, the prevalence of allergies due to shoe materials ranges from % , 85, 86 Epstein (1969) 90 documented 43 cases of shoe dermatitis over a period of 5 years;

16 Angelini (1980) 23 reported 108 positive cases over 4,5 years and Bajaj (1991) observed 1 case of shoe dermatitis every 2 weeks in the Dermatology Outpatient Clinic in Allahabad, India. 24 A review of admissions to the dermatology section of the Veterans Administration Hospital in the Bronx, New York for the five year period , revealed that approximately 1.9% of 2,243 admissions were due to dermatitis venenata caused by shoes The highest prevalences of shoe dermatitis have been recorded in warm climates. 30, 85, 86 According to a study of India 92 and Pakistan 30, 86, in tropical countries high temperatures and humidity combined with the large number of chemicals involved in shoe manufacturing, as well as the uncommon use of socks during summer and the rainy season, make shoe dermatitis a frequent phenomenon. There was, however, no correlation between the length of time that shoes were worn and the appearance of the dermatitis. 91 A predominance of shoe dermatitis among females was reported in studies in Belgium by Nardelli et al (female: male ratio (7:3)) 93, in India (6:4) 85, and in Pakistan (8:2) 30 but these differ from other studies which show equal incidences of shoe dermatitis in both genders. 25 In fact, a male predominance was reported in Spanish children with shoe dermatitis (male: female, ratio 8:2) 32 and in a Kansas study (7:3). 94 The differences in prevalence of shoe dermatitis in many publications appear to be due to differences in the study population or the design of the study: whether it was a case-control, cross sectional or follow-up study, or one using case ascertainment. 48 Many publications measure the prevalence of shoe dermatitis based on the number of cases with a positive patch test taken from all patients tested in a large clinic. 94, 95 Clinical features The clinical characteristic of shoe contact dermatitis is a rash limited to the dorsa of the foot. 90 The eruption tends to be bilateral and symmetrical, and its pattern can correspond with the shoe design. Redness may occur in the affected skin, which may vesiculate or remain dry and scaly. Secondary infection results in swelling, tenderness and pus formation. 28, 87, 90 There are two clinical patterns of shoe dermatitis: 1) hyperkeratotic lesions, usually caused by hypersensitivity to rubber soles, and 2) erythematous and/or scaly lesions on the dorsum of the feet, usually caused by sensitivity to chrome used in leather tanning and resins used in adhesive and synthetic leather. Most patients have dermatitis of the ante dorsal portion of the foot. The dermatitis usually starts on the dorsal

17 1 24 surface of the big toe as mild erythema with scaling, gradually became vesiculated, and at the same time showed a tendency to involve the back of the adjoining toe. In some cases the dermatitis remains localized to these areas; in others there is gradual involvement of the distal half of the dorsum of the foot; in still other cases the interdigital webs were also involved, spreading in a few cases to the plantar surface. The dermatitis either remains unilateral or involved the dorsal surface of the other foot in a similar fashion. In some cases the involvement of the second foot is almost simultaneous but in others it occurred after weeks and even months. When the involvement becomes extensive, the clinical picture is that of an intensely erythematous, exudative process covering the entire anterior half of one or both feet, usually only the dorsal surfaces but sometimes extending to the soles. The involved areas are macerated, denuded, oedematous, and secondarily infected. 91 Secondary infection results in swelling, tenderness and pus formation. In developing countries, the feet are the dirtiest parts of the body and understandably the dermatitis of the feet is often infected. 96 Occasionally the hands are also affected as a result of handling the shoes. 28 The design of the footwear determines to a large extent the appearance of the shoe dermatitis. Sandals may cause an eruption at one or more of the spaces between the toes and especially under straps over the instep and around the ankles. In patients with stocking dermatitis the skin lesions follow the figure of the stocking, involving the fossae poplitea and inner thigh in patients allergic to long stockings. 28 Employing only clinical criteria in diagnosis can be misleading since only two thirds of the patients had clinical characteristics of shoe contact dermatitis. A major diagnostic problem encountered in clinical practice is impetiginisation of the lesions, which often made dermatitis spread beyond the area of contact. Two other important factors that make the clinical features of shoe dermatitis atypical are previous medication and infection. Before consultation, the dermatitis is often treated with herbal concoctions, assorted medications and irritant soaps. Secondary sensitization to medicaments is not uncommon and often spreads the rash and produces atypical patterns. 96 Shoe dermatitis caused by rubber materials can have many kinds of skin lesions: amine antioxidants, especially IPPD, can cause acute and severe eczema; dermatitis caused by accelerators tends to be more subacute than chronic eczema and can also present as hyperkeratosis, purpura achromias and urticaria. 97 Leucoderma or achromia can be caused by the dispigmentary action of phenolic compounds sometimes used in footwear manufacture, such as the rubber antioxidant monobenzyl ether of

18 hydroquinone; it can also be caused by 4-tert-buthylphenol formaldehyde resin (PTBFR) used in neoprene rubber and synthetic leather. 27 There is also a purpuric eczematous type due to toxic capillaritis caused by sensitization to IPPD, an amine used as an antioxidant in black rubber manufacture. 27 Shoe dermatitis due to the mercaptobenzothiazole allergen can mimic palmo plantar psoriasis or pustular psoriasis. 98 Diagnosis and differential diagnosis 1 25 An accurate diagnosis of shoe dermatitis depends on history, clinical features, positive patch test reactions to shoe allergens and shoe materials, and the patient s ability to wear proper substitute shoes without dermatitis. 27, 99 A positive reaction to one or more of the known allergens in shoes is sufficient evidence for making a diagnosis of shoe dermatitis, unless the history and physical findings suggest otherwise. 28 The irritant/allergen can be dispersed by sweat, with the result that the original eruptions are submerged in a diffuse rash that can mimic any form of dermatitis. 87 Shoe dermatitis is often incorrectly diagnosed as a fungus infection, atopic eczema and sometimes plantar psoriasis, lichen planus and pustulosis plantaris, juvenile plantar dermatitis, and keratoderma plantaris should be considered. 27, 90 In contrast to a fungal infection, shoe dermatitis tends to be symmetrical, spares the webs of the toes and does not cause crumbling of the nails. Negative results after testing scraps of skin with potassium hydroxide and failure to respond to appropriate fungal infection treatment may well be the point at which shoes are first suspected. 87 In children with atopic dermatitis, the skin lesion could resemble subacute or chronic shoe dermatitis, and friction with the shoes could trigger an atopic condition. 28 Correct diagnosis of contact dermatitis can be achieved with thorough knowledge of the clinical features of skin reactions and various contactants. 57 A patient's medical history is also important when making a diagnosis of contact dermatitis. The family history of contact dermatitis seems to be less important than environmental factors, although heredity was found to be significant among twins with nickel contact allergy. 100 An established history of previous allergic contact dermatitis could indicate unintentional contact with the same haptens if there were an eruption of contact dermatitis episodes. 57 In the case of acute onset of shoe dermatitis it is useful to take a cautious history of a patient's exposure to contactants during the days previous to the skin eruptions. The sudden aggravation of chronic dermatitis or its recurrence over short intervals can help to establish its cause or aggravating factors.

19 Anatomical features of shoes/construction of the shoes 1 26 It is to be expected that the precise chemicals causing shoe dermatitis will vary depending on differences in countries, times and manufacturing techniques employed. 29, 32 Having detailed information on shoe construction and the substances involved in the manufacturing process is important for diagnosing and treating shoe allergy. 29 Ordinary shoes when cut lengthwise are seen to consist basically of two parts, upper and lower. The upper shoe consists of all parts above the sole which cover the upper and front parts of the foot. Shoe uppers include the vamp (front part of the shoe), the quarters (the side and back parts of the shoe) and shoe linings. Shoe uppers can be made from leather, synthetic leather, cotton and cotton fabrics. For many years shoes were made from chrome tanned leather, and later vegetable and synthetic leather were used for certain purposes. 28 Shoe counters were usually made of leather, but in women's shoes they were often made of polyethylene and fibreboards. Most shoes have linings to improve comfort and extend the lifespan of the shoes. Shoe lining is placed on the side part of the shoe around the vamp and quarter and may consist of leather, synthetic leather and/or fabrics. 28 Linings are usually impregnated with a fungicide to prevent mildew. The toe box is an important part of the shoe that protects the toes. 91 It was formerly made of leather or nitrocellulose resin but is currently composed more and more of plastic materials extruded between cotton fabrics. 28, 101 The lower part of the shoe or shoe sole consists of an inner sole, midsole and outer sole. The inner sole is usually made of leather and attached to the midsole with rubber adhesives. The midsole is made of a layer of fabric glued onto a mixture of ground cork and rubber or a rubber sheet. The inner sole covers the joint between the upper and the sole and attaches the upper to the lower components. The majorities of insole boards are made from cellulose and are treated with additives to prevent bacterial growth. The outer sole is the part of the sole that is exposed directly to the ground; it can be made of various types of materials like plastic, rubber, leather and wood. Some shoes are manufactured using two or more materials with different densities to provide softer and more flexible midsoles for comfort on the inside and durability on the outside. Heels and toe counters and durable shoes made from fibreboard and leather coating can contain rubber additives like mercaptobenzothiazole and thiurams. 101 Chemical substances causing shoe dermatitis Financial setbacks in the shoe industry in 1919 triggered the efforts of shoe manufacturers to find cheaper materials. Many kinds of bonded, laminated,

20 coated and impregnated fabrics and papers were introduced. Modern footwear has become a labyrinth of thousands of chemicals. 89 In a textbook published by Duhring in 1877, socks and shoe linings were considered to be the cause of foot dermatitis, and it was not until 1930, when patch testing began to be widely used by dermatologists, that shoes were found to be a cause of dermatitis. 28 In the early 1930s shoe dermatitis was caused mainly by shoe dye. By the late 1930s reports of dermatitis caused by shoe leather began to be common, and the blame fell on various substances involved in the tanning, finishing and dyeing of leather. In the 1940s many cases of shoe dermatitis were reported and attributed to various resins, fillers, plastics and rubber adhesives which were replacing dyes and leathers as sources of contact dermatitis. Gaul and Underwood investigated 160 cases of dermatitis arising from footwear. They patch tested all of these patients with various materials from their footwear, showing clearly the shift from leather and dye to other adhesive materials in shoes as sources of contact dermatitis. 89 Blank and Miller (1952), in their report of cases of contact foot dermatitis, emphasized the relevance of rubber adhesives in women s shoes Allergens causing sensitization in shoe dermatitis patients can be found in leather, rubber components, dyes, nickel, leather preservatives and shoe adhesives. 27 Chromium compounds have been found to be the predominant allergens in India 24, 85, 92, 103, 104 and European countries like Italy 23, Belgium 93, and the UK 105, and also, according to a multi-centre study, in Germany, Austria and Switzerland. 31 Rubber chemicals were found to be more important in Australia 25 and Pakistan 86, and also in North America, according to a study made by the North American Contact Dermatitis Group. 106 In a prospective study conducted in Lahore, Pakistan shoe adhesives were found to contain the most common allergens. 30 Rubber and rubber chemicals. Rubber and rubber allergens have in various publications been reported to be common sensitizers, varying greatly depending on the manufacturer and country of origin. Some rubber products contain multiple sensitizing agents to which patients may be allergic. 97 The most common rubber allergens are mercaptobenzothiazole 94, 107, 108, followed by thiurams, carbamate and PPDA derivatives. 29 Rubber allergens are also found in athletic shoes and canvas sneakers. Ethyl butyl thiourea was detected within inner soles of athletic sport shoes and identified as a causative allergen in 10 patients with severe shoe dermatitis. Ethyl butyl thiourea is a chemical accelerator in some neoprene (polychlorprene) rubber products. 109 This inner sole material is similar to that used in skin divers' wetsuits, which have also occasionally been

21 associated with contact allergic reactions. 109 In addition to thiourea, styrenated phenol has also been identified in athletic shoes. 110, In a series of case studies of 4 Canadian patients with shoe contact dermatitis attributed to canvas sneakers, all of them reacted to a thiuram mix as well as to pieces of their suspected shoes. Thiurams in the rubber parts of the shoes were first suspected to be causative. The website of the shoe manufacturer mentioned that the shoe was made from unvulcanized rubber soles attached to canvas fabrics. Chemical analyses did not confirm this and the soles did not contain thiurams and thiocarbamates. This discrepancy could have been explained by the presence of 2- benzothiazolyl-n, and n-diethylthiocarbamysulfide (BT-DEC), which have structures similar to those of thiurams and MBT, but these substances could also not be found during chemical analysis of the shoes. 112 Phenylenediamine derivates such as N-iso propyl-n-phenylphenyleneddiamine (IPPD), N-phenyl-n-cyclohexyl-p-phenylenediamine (CPPD), and N-dipheniyl p-phenylenediamine (DPPD) are the most important rubber antioxidants with respect to their sensitization capacity. These phenylenediamine derivatives are found in almost all black coloured rubber. 97 Rubber boots made of black or dark coloured rubber worn by Japanese farmers were proved to contain IPPD, causing shoe dermatitis in this population of workers. Para-phenylenediamine (PPD) is a widely used precursor in many processes. 113, 114 Sensitization to PPD in a 10-year period was diagnosed in 4% of patients tested. Most cases of contact allergy to PPD occur from contact with hair dye. 115 In the case of positive reactions to PPD in shoe dermatitis patients, it is possible that the PPD cross reacts with certain rubber additives; therefore PPD allergy could simply suggest rubber rather than dye sensitivity. In Iran, some soles of Maleki shoes were made from rubber tyres. A man with rubber dermatitis on his foot soles had a positive patch test reaction to PPD and it was thought that this could be due to his maleki shoes. Another highly sensitizing rubber antioxidant is monobenzyletherhydroquinone, which usually causes contact leukoderma. 116 In a case of rubber boot dermatitis, which affects the dorsum and the soles and spreads up the legs to the top edge of the boot, the skin lesions were erythematous with vesicles and sometimes with blisters and intense itchiness. The responsible allergens were rubber vulcanizing accelerators from mercapto and thiuram groups. 27