Contents
40.1 Introduction . . . . 735
40.1.1 Range of Occupations . . . . 735
40.1.2 Type of Cutaneous Disease . . . . 735
40.1.3 Irritant Contact Dermatitis . . . . 736
40.1.4 Atopy as a Risk Factor . . . . 736
40.1.5 Wet Work . . . . 736
40.1.6 Hand Dermatitis . . . . 736
40.2 Nurses, Clinical Assistants, and Cleaners . . . 736
40.2.1 Medicaments . . . . 737
40.2.2 Glutaraldehyde . . . . 738
40.2.3 Ampholytes, Surfactants, Soaps . . . . 739
40.2.4 Diisocyanates . . . . 740
40.2.5 Thiomersal/Mercury . . . . 740
40.3 Surgeons . . . . 740
40.3.1 Antiseptics . . . . 741
40.4 Laboratory Personnel . . . . 741
40.5 Other Therapists . . . . 742
40.6 Veterinarians . . . . 743
40.6.1 Antibiotics . . . . 743
40.6.2 Feed Additives and Other Medicaments . . . 743
40.7 Laboratory Animal Handlers . . . . 744
40.8 Dental Workers . . . . 744
40.9 Conclusion . . . . 745
References . . . . 745
40.1 Introduction
Health personnel carry out a wide spectrum of jobs.
All of them are susceptible to various forms of con- tact dermatitis. A hospital is like a large factory;
many substances found in a hospital can be harmful to the skin. This group of workers belong to the fifth highest occupational risk category [1]. Mahler et al [2]. reported an average annual incidence of occupa- tional skin diseases of 7.3 per 10,000 health workers, with the highest incidence among younger people.
The biological and physical causes of these will not be considered in this chapter. Radiation and viral,
fungal, bacterial or animal factors may all cause oc- cupational dermatoses in health personnel, but rare- ly of the contact dermatitis type. Protective measures and general prevention must be organized for the health services, just as in big enterprises [3].
쐽 Health workers have high occupational risk, mainly in younger people.
40.1.1 Range of Occupations
Health personnel can be divided into three main groups. The first of these includes physicians, sur- geons, medical specialists, radiologists, laboratory specialists, and dental personnel. The second group includes nurses, clinical assistants, laboratory and ra- diology technicians, biologists, pharmacists, physio- therapists, and dialysis workers. The third group in- cludes office personnel, technical service workers, kitchen and laundry workers, cleaners and disinfec- tion area and sterilization area workers. Veterinar- ians deserve special attention because of their wide spectrum of work.
40.1.2 Type of Cutaneous Disease
Health care workers mainly suffer from irritant and/or allergic contact dermatitis and contact urti- caria. The prevalence of such diseases (assessed us- ing patch and prick tests) in health care workers (n=55) was found to be: 61% with irritant contact dermatitis, 31% with allergic contact dermatitis, and 27% with contact urticaria to latex [4]. Eleven per- cent of them showed both allergic contact dermatitis related to thiuram and contact urticaria to latex [4].
Ninety five percent of these cases were deemed to be work-related [4]. Nettis et al [5] found irritant and al-
Chapter 40
Health Personnel
Ana M. Giménez-Arnau 40
Core Message
lergic contact dermatitis to be work-related in 44.4%
and 16.5% of diagnoses respectively. Mahler et al [2]
observed rates of 54% for irritant and 51% for contact dermatitis.
쐽 Health workers mainly suffer from irritant and/or allergic contact dermatitis and contact urticaria.
40.1.3 Irritant Contact Dermatitis
Health care personnel are exposed to a variety of cu- taneous irritants. The most common type of contact dermatitis in health workers is irritant contact der- matitis. The frequent use of disinfectant solutions, detergents and soaps for hand washing can induce stratum corneum lipid disturbances and conse- quently a skin barrier defect [6]. Transepidermal wa- ter loss (TEWL) is increased with brush washing compared to simple hand washing [7]. Cumulative ir- ritant contact dermatitis favour sensitization to a wide range of common substances.
40.1.4 Atopy as a Risk Factor
Atopy is a risk factor. Personal or family background of atopy favors the development of hand dermatitis and contact urticaria [8]. Hand dermatitis occurred in 65% of those with atopic symptoms and in 75% of those who had unusually dry skin and atopic rela- tives. Among the remaining workers, only 33% had suffered from eczema elsewhere on the skin or on the hands [9, 10].
40.1.5 Wet Work
Hospital wet work also increases the risk of hand ec- zema. Previous irritant contact dermatitis produced by wet working predisposes to allergic reactions, mostly to nickel, fragrances or rubber chemicals. Of persons with allergic contact dermatitis, 55% had previously suffered irritant hand dermatitis, com- pared to 44% of those without positive patch test re- actions. Of those with sensitivity to fragrance, 70%
had suffered from hand dermatitis [11].
쐽 Atopy and wet work increases the risk of hand eczema in health workers.
40.1.6 Hand Dermatitis
As many as 75% of the occupational skin diseases in hospital cleaners were hand irritant contact derma- titis, 21% were allergic contact dermatitis and 4%
were candidosis of the finger webs. The causes of ir- ritant contact dermatitis were detergents, alkaline soaps, acids, sodium perborate and hypochlorite and hypobromite compounds [12–14]. Among these causes, the frequency of type IV thiuram allergy hand dermatitis has increased significantly (odds ra- tio 2.55, 95% confidence interval 1.25–5.20,P=0.01) since 1983 [15]. Euxyl K-400 is a preservative that is recognized as being a sensitizer, but it is only occa- sionally involved in occupational cases. Its presence in a liquid detergent named Prilan caused allergic contact dermatitis on the fingers of a female hospital cleaner [16]. Local and general prophylactic meas- ures must be extended in order to reduce occupa- tional hand dermatitis among hospital workers, in- cluding surgeons, nurses, cleaning personnel, kitchen workers, and clinical assistants, among many others.
40.2 Nurses, Clinical Assistants, and Cleaners
Nurses, clinical assistants and cleaners commonly have their hands exposed to irritants, and so often suffer irritant contact dermatitis of the hands and forearms. This is significantly more frequent in wom- en under 30 years of age, mostly workers in training grades and surgical fields. In the majority of cases (90%) the lesions are irritant, and mainly related to disinfectants. Nevertheless, the importance of natu- ral rubber latex allergy, both delayed and immediate, is well established for nurses [17]. In some special cases, individual allergic contact reactions appear with drugs. Some pharmaceutical products have spe- cial relevance for them. (Table 1) As a result of this, the risk of sensitization is high.
40
Core Message
Core Message
쐽 Irritant contact dermatitis, delayed and im- mediate latex allergy, and contact reactions with drugs are common among nurses. The risk of sensitization is very high.
40.2.1 Medicaments
Occupation-related reactions to medications mainly occur in two exposed groups. The first group com- prises employees of pharmaceutical and chemical companies that are involved in their manufacture.
The second group includes professionals who use the drugs in a therapeutic setting. Of 14,689 patients (1978–2001) suspected of contact allergy, 33 were healthcare workers that exhibited occupational aller- gic contact dermatitis from drugs [18]. The most common sensitizers are antibiotics such as penicil- lins, cephalosporins, and aminoglycosides.
Streptomycin is a particularly important contact sensitizer, because of the severity of the reaction to it.
Minimal contact is needed to elicit the disease and the symptoms persist long after avoiding contact with the antibiotic (test 1% pet.) [19].Aminoglyco- sides are a closely related group of bactericidal anti- biotics derived from bacteria of genus Streptomyces.
Cross-reactions between aminoglycosides have been described in the literature. Aminoglycosides are commonly constructed from a disaccharide contain- ing glucosamine and deoxystreptamine linked by a glycoside bond. Two nurses with positive patch tests to amikacin and gentamicin has been reported [18].
Penicillin sensitizes through contact during injec- tions. Contact allergy to penicillin and its derivatives (ampicillin, amoxycillin, cloxacillin, oxacillin, flu-
cloxacillin) may be associated with immediate reac- tions of the anaphylactic type. Therefore, general measures for preventing anaphylactic shock must al- so be observed in people with penicillin contact der- matitis. Testing with penicillin must be done with ex- treme care. In vivo tests for allergy to penicillin have not been developed yet. Because of the risk of severe acute generalized reaction, testing with penicillin must only be done in hospitals. An open test with penicillin should be made prior to any other.A closed patch test should be carried out only when an open test is negative, and should be removed immediately if any generalized response is observed. Faced with an obvious and severe history of contact allergy to penicillin, the closed patch test should not be done, even if the open test is negative. There is no agree- ment on penicillin patch test concentration. Penicil- lin at 10,000 IU/g pet. is used at St John’s Institute of Dermatology, London. Patch testing can also detect generalized immediate allergies to penicillin, with- out contact dermatitis from this antibiotic [20, 21].
Cephalosporins are also contact allergens. A fairly significant number of cases have been reported in the last few years. The majority of those have oc- curred in nurses, although they also occur in labora- tory analysts and in patients. Usually patients reac- tive to cephalosporins do not react to penicillin, sug- gesting that the β-lactam ring does not cause the sen- sitization. The tetrazolic ring or amino-thiazol-al- koxy-iminicol group presumably constitutes the al- lergenic portion of the molecule. It is therefore common to obtain positive reactions in these pa- tients to ceftizoxime, cefotaxime, cefodizime, ceftazi- dime, cephazolin, cefuroxime, and ceftriaxome.
Cephalosporins can be tested at 10% to 20% in pet., or from 1% to 10% in aqueous solution [22–25].
The antipneumocystis drug pentamidine isethion- ate has been described as a cause of immunologic contact urticaria in nurses [26].
Meropenem is a β-lactam. Carbapenem is an anti- biotic used parenterally for pneumonias, especially in cystic fibrosis. Cutaneous adverse events include pruritus, urticaria, Stevens–Johnson syndrome and toxic epidermal necrolysis. Occupational allergic contact dermatitis has been observed in a nurse who reconstituted medications from powdered form into solution. The allergen could leak onto the nurse’s hands, either when the solution was drawn up the sy- ringe or during its injection. Face dermatitis was probably due to involuntary contact with the hands or airborne contact [27].
Propacetamol hydrochloride is a water soluble N,N-diethylglycidyl ester of paracetamol.After intra- venous administration, it is hydrolyzed into para- cetamol and N,N-diethylglycine by nonspecific plas-
Table 1.Special allergens for nurses [1]
Test
Cetrimide 0.25% pet.
Chlorhexidine digluconate 0.5% aq.
Chlorpromazine 0.1% pet.
Chloroxylenol 1% pet.
Glutaraldehyde 1% aq. or pet.
Penicillin 10,000 IU/g pet.a
Povidone-iodine 10% pet.
aSee section “Medicaments” in text
Core Message
ma esterases. Occupational allergic contact derma- titis was first described by Barbaud et al [28]. Since then, mainly palm and finger hand contact derma- titis and rare back or face dermatitis have been re- ported [29, 30]. Gielen et al consider this prodrug as an important cause of contact allergy (16.4%) [18].
The N,N-diethylglycidyl ester function of the propa- cetamol molecule is the most reactive part. Allergic contact dermatitis from propacetamol is not related to sensitization to paracetamol but to N,N-diethyl- glycine [31].
Chlorpromazine causes allergic contact dermatitis in nurses who inject or give out the drug in tablet form to patients, thus handling it with their fingers.
This is a particularly common occurrence when pul- verizing the tablets. This drug can sensitize by itself or in combination with photoallergic mechanisms (test 0.1% pet. or photopatch test if unexpectedly negative result appears) [32, 33].
Diacetylmorphine (heroin), morphine, and codeine are known for their histamine-releasing effects, caus- ing (nonimmunological) contact urticaria. Anaphy- lactoid reactions, especially severe asthma, have been documented from inhaling heroin. Occupational contact dermatitis consists of redness and swelling, accompanied by severe itching on the eyelids, with subsequent spread to the face and neck. The nurses affected opened capsules containing a mixture of caf- feine and diacetylmorphine (heroin) powder and handed it over to the patients [34].
Meclofenoxate is an analeptic of the central ner- vous system that may also sensitize nurses who inject it into patients [35].
Cyanamide (carbodiimide) is still used in some countries such as Spain for the treatment of alcohol- ism. Nurses can be sensitized from contact with tab- lets containing this drug when handling them in psy- chiatric wards. In many other countries tetraethyl- thiuram disulfide (Antabuse) represents a similar risk to nurses [36–38].
Potassium chloride has been reported as causing contact dermatitis in a nurse handling it in solution [39].
Ranitidine hydrochloride is an H2-receptor antag- onist commonly used for the treatment of peptic ul- cers. It is structurally related to cimetidine and fa- motidine. Chemical structure differences among these H2-receptor antagonists are too great for cross- reaction to occur. Two chemical groups could act as haptens: the terminal unsubstituted amino group and the furan group [40, 41]. Gielen et al reported seven cases of occupational allergic contact derma- titis by ranitidine in healthcare workers [18].
Occupational allergic contact dermatitis from handling other medicaments also has been reported
for nurses. Ethylenediamine sensitized a nurse who prepared and administered systemic aminophylline in a department of pneumology. Aminophylline is a 2 : 1 mixture of theophylline and ethylenediamine, which is used to make theophylline soluble [42].
Mesna (sodium 2-mercaptoethane sulfonate) is a mucolytic, administered by oral or intravenous routes, for example, as a uroprotective in combina- tion with cyclophosphamide. Besides other skin re- actions, it can produce allergic contact dermatitis in nurses from handling [43].
Many neoplastic drugs have been reported as be- ing responsible for irritant and allergic contact der- matitis, or contact urticaria (mitomycin, nitroureas, methotrexate, and nitrogen mustard). Occupational contact urticaria in a nurse from cisplatin prepared in infusion solution has been described. Cisplatin is used to treat solid tumors including ovarian cancer and testicular teratoma. Ammonium tetrachloroplat- inate 0.25% aq. and ammonium hexachloroplatinate 0.1% aq. were positive [44].
Vitamin B6was responsible for contact dermatitis on the hands, face and neck of a paramedical worker who injected vitamins B1, B6, and B12into his patient [45]. Allergic contact dermatitis induced by pyrithi- oxine (pyritinol hydrochloride), the active ingredient in Encephabol, has been described [18]. It is the dihy- drochloride monohydrate of pyritinol, a compound of pyridoxine (vitamin B6).The free sulfydryl (SH) group in thiol drugs may be an inducer of skin le- sions.
Nurses widely use formaldehyde as a disinfectant.
It is a strong irritant in high concentrations, and a sensitizer, even in weak solutions. The nails are also affected, losing their color and hardness, and parony- chia may be produced on the fingers. Its high sensiti- zation power can result in disseminated skin reac- tions from only local skin contact or inhalation in very sensitive persons (test 1% aq.) [46].
Among others, individual cases of occupational contact dermatitis induced by drugs such as meglu- mine diatrizoate (used in Angiografin, Urografin and contrast media), papain (immediate and delayed allergic reactions), dipyridamole, tylosin, boldo (diuretic herbal medicine), cascara (anthraquinone stimulant laxative) or methylprednisolone have been reported in nurses, pharmacists or veterinarians.
40.2.2 Glutaraldehyde
1,5-Pentanedial (glutaraldehyde) is a pharmacologi- cal agent used for the treatment of hyperhidrosis, as an antifungal agent, and for the treatment of warts and some bullous diseases such as Weber–Cockayne
40
syndrome, porphyria cutanea tarda, and epidermoly- sis bullosa acquisita. It has also been recommended for herpes zoster, herpes simplex and Pseudomonas infections.
Glutaraldehyde is an aliphatic dialdehyde, soluble in water, alcohol and many other solvents. It is em- ployed at 2% as a cold sterilizer for many instru- ments in hospitals (in bronchoscopy, cytoscopy, an- esthetics, renal dialysis, and so on). Unbuffered solu- tions of glutaraldehyde are stable and have little anti- microbial potential. When sodium bicarbonate is added, an alkaline pH of 8 results and a strong anti- microbial effect is obtained. Its antiviral, fungicidal and bactericidal activity is enhanced, but it remains stable for only 10–15 days. Activated glutaraldehyde retains the allergenic contact capacity of 1,5-pentane- dial [47, 48].
Glutaraldehyde causes brown discoloration, irri- tant and allergic contact dermatitis, mainly in nurses, clinical assistants and cleaning workers in hospitals due to various sources of exposure [49, 50] (Table 2).
Cases of hand eczema produced by this biocide are increasing. Clinical symptoms often show some chronicity, perhaps because glutaraldehyde is also employed as a leather tanning agent, in wallpaper, in photographic film and in other industries. Although glutaraldehyde and formaldehyde do not seem to cross-react [51, 52], some patients show positive aller- gic reactions to both substances [53, 54] (test 1% aq.
or pet., but beware false-positive reactions [55]).
Waters et al [56] investigated work practices and glutaraldehyde exposure in relation to cutaneous symptoms and lung function. Disinfection activities were timed and counted, personal exposures estab- lished, and control measures documented. Skin problems were defined as “an itchy rash that was coming and going for six months.” Bodily location was categorized as local (hand and forearm) or re- mote (distant from hand and forearm) symptoms.
Exposure values were above the exposure limit (0.10 ppm). Skin symptoms were 3.6 times more like- ly to be reported by exposed workers. Hand and fore- arm cutaneous symptoms were significantly asso- ciated with glutaraldehyde exposure. Significant cross-shift reductions in lung function parameters were observed.
Although the National Institute of Occupational Safety and Health in the USA has published guide- lines for the safe handling of glutaraldehyde, the number of incidences of allergic reaction to it ap- pears to be rising. In Australia, the occupational ex- posure standard, expressed as a permissible expo- sure limit ceiling value, was reduced from 0.20 to 0.10 ppm. In the USA it is 0.05 ppm [56]. Natural rub- ber latex glove material is more permeable to gluta- raldehyde than styrene-ethylene-butadiene-styrene thermoplastic elastomer material [57]. Exposure controls for glutaraldehyde are required to improve skin care. Exposure monitoring methods also need to be reviewed.
쐽 Cases of hand eczema produced by gluta- raldehyde are increasing. Clinical symp- toms often show some chronicity, perhaps because glutaraldehyde is also employed in other industries. Although glutaraldehyde and formaldehyde do not seem to cross- react, some patients show positive allergic reactions to both substances.
40.2.3 Ampholytes, Surfactants, Soaps Ampholytes are used as disinfectants in many differ- ent places, but have been widely used by hospital per- sonnel. Desimex, Ampholyt G and Tego 103 G are dodecyldiaminoethylglycine hydrochloride. Ampho- lyt G does not contain benzyl alcohol or formalde- hyde. Tego 103 G contains the active ingredients 9- lauryl-3,6,9-triazanonanoic acid and 7-dilauryl-1,4,7- triazaheptane, benzyl alcohol, and a small quantity of formaldehyde. Cases of allergic contact dermatitis have been described. Because of the chemical nature of these substances, some patients may also be reac- tive to ethylenediamine, but this special cross-reac- tion is rare [58, 59].
Dodecyl-dimethyl-ammonium chloride and bis- (aminopropyl)-laurylamine are detergents, disinfec- tants, and amphoteric tensioactives used to clean op-
Table 2. Sources of glutaraldehyde exposure in healthcare workers [50]
Instrument sterilization Embalming
Tissue fixation
Radiographic development
Preparation of allergen and collagen extracts for injection Medical treatment of
Epidermolysis bullosa Herpes simplex Hyperhidrosis Onychomicosis Warts
Core Message
erating rooms and other areas. They are bactericidal, virucidal and active against HIV1. They are used at concentrations of 0.25%. Both may cause allergic contact dermatitis in hospital workers. Patch tests must be from 0.01% aq. to 0.1% and 1% aq. [60]. The use of protective gloves and systematic prevention of contact is recommended. Dinitrochlorobenzene, ni- trogen mustards and squaric acid diethylester are ex- amples of such substances.
Gigasept AF, a detergent-disinfectant for surgical instruments, is capable of inducing burning eyes and coughing fits after direct exposure to its vapor. De- spite protective measures (gloves and masks), skin lesions and other symptoms can persist. The aller- gens were dimethyldidecylammonium chloride 0.1%, N,N-bis(3-aminopropyl)dodecylamine 1.0%
and N,N-bis(3-aminopropyl)dodecylamine [61].
Antiseptics that commonly cause contact derma- titis in nurses, clinical assistants and cleaners are widely used in different hospital wards. The majority of exposures occur in dental and surgical personnel.
Chloramine-T (sodium p-toluenesulfonchloramine) has been found to be a sensitizer for nurses [62].
Chloramine-T is used as sterilizer, disinfectant, anti- septic and chemical reagent (test 0.05% aq.). Allergic contact dermatitis from undecylenamide diethanol- amide in a liquid soap has been described in a hospi- tal worker [63].
Methyldibromo glutaronitrile (1,2-dibromo-2,4- dicyanobutane) is used as preservative in soaps and many other products. It is found mainly in the pre- servative Euxyl K400 combined with phenoxyetha- nol. Occupational allergic contact dermatitis from this agent is increasing in frequency. Patch test of 0.1%, 0.3% and 0.5% in pet. was positive in two nurs- es sensitized to methyldibromo glutaronitrile at work [64]. The British Contact Dermatitis Society have recommended adding methyldibromo gluta- ronitrile to standard series in all UK patch testing centers.
쐽 Occupational allergic contact dermatitis from methyldibromo glutaronitrile is increasing in frequency.
40.2.4 Diisocyanates
Diisocyanates are a group of substances widely used as hardeners in paints, surface coatings and foams.
In hospitals, diisocyanates also are found as a con- stituent of soft casts. They are a cause of occupation- al asthma and have been described as causing cuta- neous problems, both as irritants and as sensitizers.
When using soft casts, the extremity is covered by a layer gauze. The cast is dipped into water and ap- plied while wearing rubber gloves and sometimes a barrier cream. Because of the potential for asthma, the ventilation is often switched on during the cast- ing. When dipping the cast, the forearms above the level of the gloves often get into contact with the wa- ter. Having applied the cast, the extremity of the pa- tient is rubbed in light circular motions, so that the cast fits perfectly. The dipping water is reused several times, accumulating diisocyanates from each use.
The sensitizing potential of diisocyanates has pre- viously only been described sporadically. Few studies in animals or in exposed populations support diisoc- yanates as sensitizers. Larsen et al [65] conducted a study among the nursing staff of an orthopedic out- patient, clinic patch testing five types of diisocya- nates. Just one nurse presented a doubtful reaction towards diaminophenylmethane and isophorene dii- socyanate. Nine had no reactions to the five diisocya- nates used in the patch test. Their observations sug- gest that diisocyanates are primarily irritants rather than sensitizers in the professional setting studied.
No relationship between exposure time and severity of symptoms was observed.
40.2.5 Thiomersal/Mercury
Thiomersal was originally found to induce an allergy when a nurse was vaccinated against viral hepatitis.
As a result of further contact with this preservative during the vaccination of schoolchildren, she showed allergic contact dermatitis on the hands. The vac- cines from Biomed that she had been exposed to con- tained 0.01% thiomersal [66]. Two cases (an ophthal- mologist and a nurse) of occupational dermatitis due to mercury vapor from a broken sphygmomanome- ter has been described. Patients suffered from itchy erythema with high fever followed by generalized ex- anthem. The air concentration of mercury vapor was higher than permissible levels (0.05 mg/m3at a con- centration of 9.9 mg/m3) [67].
40.3 Surgeons
Chemical components of rubber gloves commonly cause allergic contact dermatitis of the hands and forearms in surgeons. Although many different sub- stances can sensitize, the most frequent are those
40 Core Message
tested in the thiuram mix of the standard series. Less frequent are mercaptobenzothiazole and others test- ed in the mercapto mix. Release of thiurams and car- bamates from rubber gloves varies between brands.
Glove powder could enhance contact dermatitis and urticaria. Knowledge about cutaneous reactions from gloves has increased enormously in recent years. The main reason is the broad knowledge of type I allergy to natural rubber latex and recognition of the relatively large number of patients and health care personnel who suffer from this hypersensitivity.
Orthopedic surgeons use acrylic bone cement for fixation of prostheses to the bone of the hip joint.
Bone cement contains methyl methacrylate monomer and polymethyl methacrylate. The monomer is a strong lipid solvent. The hand dermatitis caused by allergy to methacrylate is usually a dry, pruriginous, fissured, chronic eczema of the fingertips, sometimes with paresthesia and tingling or burning sensations.
Gloves usually do not protect the hands from acrylic bone cement. Indeed, even if two pairs of rubber gloves are worn, the sensitized surgeon may still suf- fer from contact with the acrylic cement because enough acrylic penetrates both pairs if the surgeon makes contact for a sufficient duration [68–70]. Co- lophony has also been identified as a causative agent of allergic contact dermatitis in an orthopedic sur- geon who suspected paper-based surgical clothing to be the cause [71].
40.3.1 Antiseptics
Antiseptics are present in surgical scrubbing agents in the preoperating room. Some surgeons contract chronic, dry, pruritic, irritant contact dermatitis of the dorsum of the hand from such agents. It is not in- frequent for superimposed allergic contact derma- titis to appear, because these substances also have al- lergic capacity. The most commonly employed are:
hexachlorophene G 11 (test 1% pet.), dichlorophene G 4 (test 1% aq.), tribromosalicylanilide (TCSA) (test 1% pet.), dibromosalicylanilide (test 1% pet.), triclos- an (Irgasan DP 300) (test 2% pet.), Fentichlor (test 1%
pet.), chlorhexidine (test both acetate and gluconate 0.5% aq.) [72],p-cresol (test 1% aq.), Dowicides (phe- nolic substances) (test 1% pet.), imidazolidinyl urea (test 2% pet.), sodium hypochlorite (test 0.5% aq.), sodium hyposulfite (test 1% aq.), and benzydamine hydrochloride (test 5% aq. or pet.) [73].
Some quaternary ammonium compounds are of special interest. The most common and widely used is benzalkonium chloride (alkylbenzyldimethylam- monium chloride), a cationic detergent used as a pre- operative skin disinfectant, and also for surgical in-
struments. Its presence in cosmetics, soaps, medica- ments and its capacity to sensitize are well known.
Some people allergic to benzalkonium chloride may need to avoid other quaternary ammonium com- pounds because of cross-reaction [74–77]. Patch test- ing with 0.1% aq. can also provoke irritant reactions.
True allergic responses may be obtained by testing with 0.01% aq., but a dilution series plus ROAT is rec- ommended.
쐽 Chemical components of rubber gloves commonly cause allergic contact dermatitis of the hands and forearms in surgeons.
Antiseptics present in surgical scrubbing agents in the preoperating room induce irritant contact dermatitis of the dorsum of the hand.
40.4 Laboratory Personnel
In pharmaceutical laboratories, mainly in product synthesis areas, contact dermatitis may arise in the pharmacologists who synthesize such products. Very often the sensitizers are not the final compounds.
Sensitizations have been published as individual case reports, and substances mentioned include vitamin K3 sodium bisulfite [78, 79], codeine [80], cephalos- porins, cytosine arabinoside [81], 3,4-dicarbethoxy- hexane-2,5-dione [82], 2-aminophenyldisulfide [83], ethyl-2-bromo-p-methoxyphenylacetate [84], ethyl- chlorooximidoacetate [85], pyridine in Karl Fischer reagent [86, 87], simvastatin [88] and n-acetyl-cys- teine [88].
Hypersensitivity to azathioprine is well known, but not that to an intermediate product (5-chloro-1- methyl-4-nitroimidazole) which has been shown to be present in the end product of azathioprine tablets in a sufficient amount to induce allergic contact der- matitis in a man working on its synthesis (test at 0.1% pet.) [89]. Vitamin A acetate has also been re- ported to be a sensitizer in the industrial production of vitamins (test at 1% pet.) [90]. DDC (dicyclohexyl carbodiimide), diisopropyl carbodiimide and di- methylaminopropylethyl carbodiimide are com- pounds widely used in peptide chemistry as coupling reagents. Sensitization occurred in two laboratory workers. Because they are highly toxic substances, patch tests must be done from 0.1% acet. or lower concentration [91].
Core Message
Contact dermatitis caused by alcohols is of special interest. Amyl, butyl, ethyl, methyl, and isopropyl al- cohols can all cause allergic contact dermatitis, though rarely. Contact allergy to alcohols may cause a generalized allergic reaction when alcohol is in- gested. Nevertheless, contact reactions to alcohol do not necessarily signify that a systemic reaction will develop after drinking alcoholic liquor [92–94].Alco- hol can be an allergen for nurses, physicians and la- boratory technicians. It can produce irritant contact dermatitis and nonimmunological contact urticaria.
Its effects can be produced by external or internal ex- posure. Contaminants are common in alcohol. Pure ethanol should be used for patch testing. Because of its volatility, interpreting the results can be difficult.
In occlusive patch testing, immediate fading of the reaction suggests irritancy. If the reaction remains clearly visible after 4 days, it may be allergic. Repeat- ed testing with lower dilutions may confirm this. Al- cohols can be tested undiluted, although many differ- ent concentrations have been used, the lowest being 1% [95].
Laboratories use many other different substances capable of producing dermatitis in their personnel.
As the working environments are so diverse, aimed patch testing needs to be performed, guided by a careful history. The substances that have been de- scribed as causing allergic contact dermatitis in la- boratory technicians are, for example, propylene ox- ide in preparing tissue specimens in a histopatholog- ical laboratory (test in ethanol at 0.1–11%) [96].
dl-Limonene (dipentene) has been used as a non- toxic substitute for xylene as a wax solvent and a cleaning agent for use by laboratory technicians. Hy- droperoxides in autoxidized d-limonene have also been identified as potent contact sensitizers in labor- atory workers, and they may be present in new sol- vents such as Parasolve [97].
Pyridine-related molecules [98], and a new isothi- azolinone [99] also produce allergic contact derma- titis in such workers.
New immersion oils were recently introduced in order to address ecological concerns. Allergic contact dermatitis to oils is a well recognized phenomenon (Fig. 1). It was initially described in 1997 by Sommer et al [100] and in 1998 by LeCoz and Goossens [101].
Many cases have been reported since then [102–112].
Technicians and physicians working in cytogenetic, bacteriology, and hematology laboratories were the workers affected. Contact dermatitis or airborne al- lergy mainly involves the forearms and hands, as well as the face and neck. Irritant reactions must also be considered. The product responsible was usually Lei- ca immersion oil (Leica Microsystems, Wetzler, Ger- many). According to the material safety data sheet,
the oil content is: modified cyclohexyl epoxy resin (45%), modified bisphenolic epoxy resins (35%), 1,4- butanediol diglycidylether (10%) and phthalates (4%). A breakdown performed with the oil’s ingre- dients confirmed sensitization to liquid modified ep- oxy resin components contained at >80% concentra- tion. Diglycidyl ether of bisphenol A (DGBEA) (Mol.
Wt. 340 Da), a low molecular weight monomer, was probably the main sensitizer [100]. Positive reactions have also been described to cycloaliphatic epoxy res- in and to the diluents phenyl glycidyl ether and cresyl glycidyl ether. Epoxy resin is a strong contact aller- gen that can induce sensitization after a single expo- sure in about 50% of those exposed. Their incorpora- tion into microscopic immersion oil was, unfortu- nately, not needed and could have been avoided [113].
쐽 New ecological immersion oils induce allergic contact dermatitis. Diglycidyl ether of bisphenol A was probably the main sensitizer. Epoxy resin is a strong contact allergen. Their incorporation into microscopic immersion oil was an unnecessary and avoidable oversight.
40.5 Other Therapists
Some substances have been reported to be respon- sible for occupational contact dermatitis in other personnel involved in special therapeutic proce- dures.
40
Fig. 1.Chronic allergic contact dermatitis with dyshidrotic fea- tures in a laboratory technician, due to epoxy resin in immer- sion oil (Leica) (courtesy of A. Goossens)
Core Message
A physiotherapist suffered allergic contact derma- titis from benzydamine hydrochloride and lavender fragrance, contained in Difflam gel, a topical nonster- oidal anti-inflammatory agent [114].
Isothiazolinone derivatives contained in Parmetol caused allergic contact dermatitis in a radiology technician. Parmetol is used in radiographic devel- oping solutions [115].
Metaproterenol produced airborne contact der- matitis in a respiratory therapist who routinely ad- ministered Alupent (metaproterenol sulfate), Muco- myst (acetylcysteine) and Bronkosol (isoetharine) in aerosolized forms [116].
Benzoyl peroxide included in a hardener sub- stance, Lucidol hardening gel, has been demonstrat- ed to induce recurrent eczema of the face, neck and arms for 2 years in an orthopedic technician [117].
40.6 Veterinarians
Veterinarians are exposed to many organic, biologi- cal and chemical substances that may produce aller- gic contact dermatitis. Occupational dermatoses have been reported in 48–77% of veterinarians. Sen- sitized veterinarians can suffer asthma, rhinitis and contact dermatitis from dander, hair, bristles, or sali- va from cows, horses, cats or dogs [118, 119]. Specific IgE and prick/scratch tests are diagnostic. Clinically, allergic contact urticaria, allergic contact dermatitis, or both reactions can be observed [120]. Bovine am- niotic fluid (BAF) caused a severe and extensive eruption in a 30-year-old nonatopic veterinarian.
Patch test and prick test proved negative, though a
weak reaction to the patch was visible by the fourth day. Only an intradermal test was positive to BAF pure and at 1/10. In other similar patients, RAST has been useful for confirming the allergic nature of the relatively common protein contact dermatitis [121].
40.6.1 Antibiotics
Certain antibiotics are used more often in veterinary than in human medicine. Spiramycin, tylosin and benzyl penicillin diethylaminoethylester (penetha- mate) are the most important. Spiramycin and tylo- sin [18] are used to treat enteritis in pigs, mastitis in cows, and respiratory infections in household pets [122]. Penethamate hydriodide is used for local or intralesional treatment of mastitis in cows. It cross- reacts with penicillin [123].
40.6.2 Feed Additives
and Other Medicaments
Hormones, vitamins, minerals, antibiotics, growth stimulants, preservatives, metals, antioxidants and certain other substances are present in animal feeds (Table 3). Health personnel who handle these addi- tives may experience allergic contact dermatitis. For example, vitamin A and vitamin D3 contain 5%
ethoxyquin as an antioxidant preservative. Ethoxy- quin (6-ethyl-1,2-dihydro-2,2,4-trimethylquinoline) is a contact sensitizer. Quindoxin, a growth-promot- ing factor, is a common sensitizer and it also induces photodermatitis [124, 125, 128]. Quindoxin is an anti-
Table 3.Animal feed additives [135, 136]
Function Test
Amprolium Growth promoter 10% aq.
Arsanilic acid Growth promoter 10% pet.
Bacitracin zinc Growth promoter 20% pet.
Chlortetracycline hydrochloride Growth promoter 5% pet.
Sulfacetamide Growth promoter (prevents enteral infections) 5% pet.
Tylosin tartrate Growth promoter (prevents Gram-negative infections) 5% pet.
Diethylstilboestrol Fattening cattle 1% pet.
Ethoxyquin Antioxidant preservative 1% pet.
Ethylenediamine Antiseptic 1% pet.
Medroxyprogesterone acetate Abortions 1% pet.
Neomycin sulfate Prevention of dysentery 20% pet.
Nitrofurazone Prevention ofSalmonella infection 1% pet.
Penicillin Prevention of mastitis 10,000 IU/ga
Thiabendazole Worm control 1% pet.
Piperazine Worm control 1% pet.
Phenothiazines Worm control 1% pet.
aSee Sect. 40.2.1,“Medicaments”
biotic of the quinoxaline family, a growth promoter.
It has been reported to induce contact and photocon- tact dermatitis. Its derivatives olaquindox and carba- dox have been used as feed additives for growth pro- motion in pigs, rabbits and other animals. It is ex- tremely difficult for breeders to avoid exposure to dust containing relatively highly concentrations of olaquindox. A very low dose of olaquindox produces contact dermatitis, mainly by phototoxic or photoal- lergic mechanisms. In some cases persistent light re- actors are developed. Olaquindox has an absorption spectrum between 256 nm and 373 nm.
The patients suffer eczema of the hands, wrists, forearms, face and neck with severe itching and light intolerance. In some cases farmers have a history of other photoallergies, for example to chlorpromazine, sunscreens, cosmetics and others. Halquinol, a chlor- inated derivative of 8-hydroxyquinoline, is added to animal feeds to prevent Escherichia coli and Salmo- nella infections. Halquinol causes irritant, allergic and photoallergic dermatitis, and sometimes allergic contact urticaria and airborne dermatitis [126].
Dinitolmide, which is used to control coccidiosis in chicken factories [127], and nitrofurazone, used for the treatment of salmonellosis in pigs and as a growth promoting factor for cattle and swine, can al- so cause allergic contact dermatitis in veterinarians [128]. Chlorpromazine and other phenothiazine de- rivatives are used by veterinarians and farmers for the sedation of animals. The occurrence of contact dermatitis and photodermatitis in a farmer due to chlorpromazine used for the sedation of pigs sug- gests that this type of medicament should be includ-
ed in a patch test series for veterinarians (Table 4) [129]. Occupational contact allergy to lincomycin and spectinomycin in chicken vaccinators has been docu- mented [137].
40.7 Laboratory Animal Handlers
Allergic disease is a serious occupational health con- cern for individuals who have contact with laborato- ry animals. Urticaria is the most common skin man- ifestation, although contact dermatitis may also oc- cur [130]. The overall prevalence of allergic disease among laboratory animal handlers is about 23% and respiratory allergy is much more common than skin allergy. There are few data on the incidence or preva- lence of skin conditions. A study performed in Swe- den by Agrup and Sjöstedt [131] revealed a prevalence of 14% of contact urticaria to rats, but this appears to be an unusually high rate. Another study of pharma- ceutical industry and university laboratory workers found no increase in urticaria [132]. Evidence from the study of Aoyama et al indicates that skin allergy tends to be accompanied by respiratory allergy symptoms [137].
40.8 Dental Workers
Dentistry is a high-risk occupation for irritant and allergic hand eczema and also contact urticaria in- duced by latex allergy. Irritant contact dermatitis is most common. In 1947, Stevenson [138] and Moody [139] reported, for the first time, on an occupational- ly acquired allergic contact dermatitis in a dental technician. Many reports on allergies of dental per- sonnel to (meth)acrylates have been published [140–142].
A recent Swedish study showed a prevalence of contact allergy to acrylates of below 1% among den- tists, and in most cases this did not have serious med- ical, social or occupational consequences [143]. On patch testing, 50% of dentists studied presented at least one positive reaction. The most frequent aller- gens were nickel sulfate, fragrance mix, gold sodium thiosulfate and thiuram mix. Similar results were ob- tained from a Korean study of dental technicians [144]. Metals including potassium dichromate, nickel sulfate, mercury ammonium chloride, cobalt chlo- ride and palladium chloride showed high positive rates. A lower patch-positive reaction to acrylics was observed.
A different picture of the influence of sensitization to dental composite resins upon working ability is given in Finnish study, in which 6/7 dental personnel
40
Table 4.Contact allergens reported in veterinarians [133, 134]
Penicillin 10,000 IU (g pet.a)
Formaldehyde 1% aq.
Streptomycin 1% pet.
Mercaptobenzothiazole 2% pet.
Dihydrostreptomycin 0.1% pet.
Merthiolate 0.1% pet.
Erythromycin base 1% pet.
Piperazine 1% aq.
Oxytetracycline 3% pet.
Tuberculin 10% aq.
Penethamate 1% pet.
Bovine tuberculin 10% aq.
Spiramycin (Rovamycin) 10% pet.
Ethoxyquin 1% pet.
Tylosin (tartrate) 5% pet.
Quindoxin 0.1% pet.
Procaine HCl 1% pet.
Chlorpromazine 0.1% pet.
Benzocaine 5% pet.
aSee Sect. 40.2.1,“Medicaments”
could not continue in clinical dentistry. Contact aller- gy to (meth)acrylate was seen in around 20% of the tested patients in another Swedish study, with allergy to three predominance test substances: 2-hydroxye- thyl metacrylate, ethyleneglycol dimethacrylate and methyl methacrylate. A third of the patients allergic to (meth)acrylates had been on sick leave due to der- matitis [145].
Among acrylates, the unpolymerized products are the most allergenic, whereas the end-products ob- tained after polymerization have little or no allergen- ic capacity. The usual clinical appearance is a scaly, fissured dermatitis of finger pulps, sometimes ac- companied by sensations like burning, tingling or numbness, which can last for several weeks after the dermatitis subsides [146]. The dominant hand is mainly affected. An uncommon clinical picture in- volves the left palm and fingers [147, 148].Very late re- actions are rare and can be considered as true sensi- tization or active sensitization [149].
Occupational contact dermatitis in a dental tech- nician from the colophonium at dental baseplates [150] and in a dental nurse from the glutaraldehyde and glyoxal from cold sterilization of instruments [151] has been described.
Work-related face dermatitis has been reported in Swedish dentist; 4.5% from composite and bonding materials, compared to 3.1% from other materials (nickel sulfate) [152]. Finnish dental nurses consid- ered their masks to be the main cause (5.4%) [153].
The face mask was also the most common cause of face dermatitis in Norwegian dental hygienists [154].
The importance of skin protection by gloves, no- touch product packaging and careful work tech- niques not questioned. But its usefulness is question- able [155]. The type of protective glove that should be recommended for dentistry is not clear. Medical gloves for single use are not impermeable to various acrylate monomers. A combination of a thin copol- ymer glove under a medical glove for single use of- fers good protection [156].
쐽 Dentistry is a high-risk occupation for irritant contact hand eczema dermatitis.
Among acrylates, it is the unpolymerized products that are the most allergenic. The importance of skin protection by gloves, no-touch product packaging and careful work techniques is not questioned. But its usefulness is questionable.
40.9 Conclusion
Healthcare workers are exposed to many agents ca- pable of inducing irritant or allergic contact derma- titis and also contact urticaria. Skin complaints should be assessed with both prick and patch testing.
It is necessary to identify the agents responsible in order to learn how to avoid them. Nevertheless, we need to develop effective prophylactic and preventive measures.
Acknowledgements. I dedicate this review chapter to Professor Jose G. Camarasa. He taught us to understand and to love immunodermatology.
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