UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New Series No 168

From the Department of Dermatology Umeå University, Umeå, Sweden

INDIVIDUAL AND ENVIRONMENTAL RISK FACTORS FOR HAND ECZEMA

IN HOSPITAL WORKERS

by

Eskil Nilsson

Umeå University 1986

INDIVIDUAL AND ENVIRONMENTAL RISK FACTORS FOR HAND ECZEMA IN HOSPITAL WORKERS

Akademisk avhandling som med vederbörligt tillstånd av Rektorsämbetet vid Umeå Universitet för avläggande av medicine doktorsexamen kommer att offentligen försvaras i Rosa Salen, 9tr, Tandläkarhögskolan, Umeå, fredagen den 23 maj 1986, kl. 09.00

av

Eskil Nilsson

Umeå 1986

ABSTRACT

IN D IV IDU A L A N D E N V IR O N M E N TA L RISK FACTORS FOR H A ND ECZEMA IN HO SPITAL W ORKERS

Eskil Nilsson, Departments of Dermatology, Sundsvall Hospital,S-851 86 Sundsvall and Umeå University, S-901 85 Umeå Sweden.

Individual and environmental risk factors in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospital workers with a follow-up time of 20 months. Current hand eczema was analyzed in 142 wet hospital workers from this cohort with respect to the etiologic importance of irritants, allergens and contact urticants. The density of the microflora and the effect on the microflora of topical treatment with a potent corticosteroid were studied in 20 patients with hand eczema.’W et’ hospital work was found to increase the odds of developing hand eczema only twice compared to 'dry' office work. Nursing children under four years old and the lack of a dish-washing machine signifi­cantly increased the risk of contracting hand eczema. Unfavourable combinations of these domestic factors increased the risk as much as wet work. A history of atopic dermatitis approximately tripled the odds both in wet as well as in dry work.Histories of earlier hand eczema (HHE), metal dermatitis (HMD) and of atopy were analyzed as risk factors for hand eczema in 1857 women in wet work. HHE increased the odds by a factor of 12.9 and created a subdivision of the population into high risk individuals and normal risk individuals. HHE was found in half of the subjects with atopic dermati­tis, in one quarter of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics. A HMD increased the odds by a factor of 1.8. This increase was seen as a high risk level in subjects with HHE and as a normal risk level in subjects with no HHE. A history of atopic disease as a complement to information about HHE and HMD in­creased the odds by another 1.3 times. The predicted probability of de­veloping hand eczema ranged from 91 % in subjects with a combi­nation of HHE, HMD and atopy to 24% in subjects with none of these risk factors.Subjects with AD were found to suffer a more severe form of hand eczema with significantly higher figures for medical consultation, sick- leave, termination due to hand eczema, early debut, permanent sym­toms and vesicular lesions.Amongst the patients investigated for current hand eczema high risk individuals were overrepresented. It was claimed in 92.3% of the cases that trivial irritant factors had elicited the current episodes of hand eczema. In 35% of the cases the exposure to the irritant took place largely at home. Although contact sensitivity and contact urticaria were fairly common, they mostly seemed to be of minor impor­tance in the etiology of the current hand eczema.Staphylococcus aureus colonized eczematous lesions of the hands in 18/20 patients. The density exceeded 105 colony forming units/cm2 in 15/20 patients. Only three of these patients showed signs of clinical infection. Successful topical treatment with a potent corticosteroid significantly reduced the colonization of S. aureus.

Key words: Hand eczema, prospective study, hospital workers, irri­tants, contact allergy, contact urticaria, atopy, metal dermatitis, multi­variate regression analysis, evaluation of risk factors, microflora, S. aureus in hand eczema.

UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New Series No 168

From the Department of Dermatology Umeâ University, Umeå, Sweden

INDIVIDUAL AND ENVIRONMENTAL RISK FACTORS FOR HAND ECZEMA

IN HOSPITAL WORKERS

by

Eskil Nilsson

Umeå University 1986

2

A B S T R A C T

INDIVIDUAL AND ENVIRONMENTAL RISK FACTORS FOR HAND ECZEMA IN HOSPITAL WORKERSEskil N ilsson, Departments of Dermatology, Sundsvall H ospita l, S-851 86 Sundsvall and Umeå U n ive rs ity , S-901 85 Umeå, Sweden.

Ind iv idua l and environmental r is k facto rs in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospita l workers w ith a fo llow -up time of 20 months. Current hand eczema was analyzed in 142 wet hospita l workers from th is cohort w ith respect to the e tio lo g ic importance of i r r i t a n ts , allergens and contact u r t i - cants. The density of the m icro flo ra and the e ffe c t on the m icro flo ra of top ica l treatment w ith a potent co rticos te ro id were studied in 20 patients w ith hand eczema.'Wet' hospital work was found to increase the odds of developing hand eczema only twice compared to ‘ d ry ’ o ff ic e work. Nursing ch ildren under four years old and the lack of a dish-washing machine s ig n i f i ­can tly increased the r is k of contracting hand ezcema. Unfavourable combinations of these domestic facto rs increased the r is k as much as wet work. A h is to ry of atopic derm atitis approximately tr ip le d the oddsboth in wet as well as in dry work.H istories of e a r lie r hand eczema (HHE), metal derm atitis (HMD) and of atopy were analyzed as r is k facto rs fo r hand eczema in 1857 women in wet work. HHE increased the odds by a fac to r of 12.9 and created a subdivision of the population in to high r is k ind iv idua ls and normal r is k ind iv idua ls . HHE was found in h a lf of the subjects w ith atopic dermati­t i s , in one quarter of the subjects w ith atopic mucosal symptoms and in one f i f t h of the non-atopics. A HMD increased the odds by a fa c to r of 1.8. This increase was seen as a high r is k level in subjects w ith HHE and as a normal r is k level in subjects w ith no HHE. A h is to ry of atopic disease as a complement to inform ation about HHE and HMD increased the odds by another 1.3 times. The predicted p ro b a b ility of developing hand eczema ranged from 91% in subjects w ith a combination of HHE, HMD and atopy to 24% in subjects w ith none of these r is k fac to rs .Subjects w ith AD were found to su ffe r a more severe form of hand eczema w ith s ig n if ic a n t ly higher figures fo r medical consu lta tion , s ick-leave, term ination due to hand eczema, early debut, permanent symptoms and vesicu lar lesions.Amongst the patients investigated fo r current hand eczema high r is kind iv idua ls were overrepresented. I t was claimed in 92.3% of the casestha t t r iv ia l i r r i t a n t fac to rs had e lic ite d the current episodes of hand eczema. In 35% of the cases the exposure to the i r r i t a n t took place la rge ly at home. Although contact s e n s it iv ity and contact u r t ic a r ia were f a i r ly common, they mostly seemed to be of minor importance in the e tio logy of the current hand eczema.Staphylococcus aureus colonized eczematous lesions of the hands in 18/20 pa tien ts . The density exceeded 10^ colony forming units/cm 2 in 15/20 patien ts . Only three of these patients showed signs of c l in ic a l in fe c ­tio n . Successful top ica l treatment w ith a potent co rticos te ro id s ig n i­f ic a n t ly reduced the co lon iza tion of S. aureus.

Key words: Hand eczema, prospective study, hospita l workers, i r r i ta n ts , contact a lle rg y , contact u r t ic a r ia , atopy, metal de rm a titis , m ultiva ­r ia te regression analysis, evaluation of r is k fa c to rs , m ic ro flo ra , S aureus in hand eczema.

3

This thesis is based on the fo llow ing papers, which w il l be re ­

ferred to by th e ir Roman numerals:

I . Nilsson E, Mikaelsson B, Andersson S.Atopy, occupation and domestic work as r is k factors fo r hand eczema in hospita l workers.Contact Dermatitis 1985:13:216-223.

I I . Nilsson E, Back 0.The importance of anamnestic information of atopy, metal derm atitis and e a r lie r hand eczema fo r the development of hand derm atitis in women in wet hospital work.Acta Dermato-Venereologica 1986:66:45-50.

I I I . Nilsson E.Contact s e n s it iv ity and u r t ic a r ia in "wet" work. Contact Dermatitis 1985:13:321-328.

IV. Nilsson E, Henning C, H jö rle ifsson M-L.The density of the m icro flo ra in hand eczema before and a fte r top ica l treatment w ith a potent co rtico s te ro id .J Amer Acad Dermatol. In press.

4

C O N T E N T S

ABBREVIATIONS........................................................................................... 6

INTRODUCTION............................................................................................. 7

REVIEW OF THE LITERATURE...................................................................... 7

HAND ECZEMA.......................................................................................... 7Prevalence.................................................................................... 7C la s s if ic a tio n ............................................................................ 8

ATOPIC DERMATITIS.............................................................................. 9Epidemiology................................................................................ 9Diagnosis...................................................................................... 9Hand eczema in atopic d e rm a titis ......................................... 11

EXOGENOUS FACTORS IN HAND ECZEMA................................................. 12I r r i t a n ts ...................................................................................... 12A lle rg ic contact derm atitis of the hands......................... 14Atopy and contact s e n s it iv i ty ............................................... 15Contact u r t ic a r ia ...................................................................... 16Non-Immunological Contact U rtica r ia (NICU)...................... 17Immunological Contact U rtic a r ia (ICU)............................... 17Uncertain Mechanism Mediated Contact U rtica r ia (UMCU). 18Contact u r t ic a r ia in hand eczema......................................... 18Colonization of Staphylococcus aureus............................... 19

AIMS OF THE STUDY.................................................................................... 21

PATIENTS..................................................................................................... 22

Study design and study population ( I-11 ) ......................... 22Patients ( I I I ) ............................................................................ 23Patients ( IV ) .............................................................................. 23

METHODS....................................................................................................... 24

PAPERS I - I I ........................................................................................ 24Diagnosis of atopy and metal d e rm a titis ........................... 24C r ite r ia fo r hand eczema........................................................ 24Occupational exposure.............................................................. 25Domestic work.............................................................................. 25S ta tis t ic a l methods ........................................................ 26

PAPER I I I ........................................................................................... 27Characterization of hand eczema........................................... 27Patch te s ts .................................................................................. 28Prick te s ts .................................................................................. 28S ta t is t ic s .................................................................................... 28

5

PAPER IV............................................................................................. 29Characterization of hand eczema........................................... 29Sampling technique.................................................................... 29Id e n tif ic a tio n of the m ic ro flo ra ...................................... 30Treatment...................................................................................... 31A n tibac te ria l e ffe c t of clobetasol propionate................ 31S ta t is t ic s .................................................................................... 31

RESULTS....................................................................................................... 32

Prevalence of ind iv idua l r is k fa c to rs ............................... 32Hand eczema in the four occupations................................ 32Hand eczema in atop ies............................................................ 33Hand eczema in women in wet hospital work....................... 35M u ltiva ria te regression analysis of r is k fa c to rs 37Severity of hand eczema.......................................................... 43Investigated patients ( I I I ) ................................................... 45E a rlie r hand eczema in investigated pa tien ts .................. 45Current hand eczema in investigated pa tien ts .................. 45State of current hand eczema................................................. 46Contact a lle rg y .......................................................................... 47Contact u r t ic a r ia ...................................................................... 48Morphology of hand eczema in the bacte rio log ica l study( IV ) ............................................................................................... 51M icrobial f lo ra and e ffe c t of treatm ent........................... 53

DISCUSSION................................................................................................. 56

The cohort and patients stud ied........................................... 56Methodological aspects............................................................ 56Prevalence of hand eczema...................................................... 58Prevalence of atopy and metal d e rm a titis ......................... 58Indiv idua l r is k facto rs fo r hand eczema........................... 59Severity of hand eczema.......................................................... 61Occupational and domestic factors in hand eczema 61Contact a lle rgy and hand eczema........................................... 62Contact a lle rgy to metals in subjects w ith metal der­m a t it is .......................................................................................... 63Contact u r t ic a r ia and hand eczema....................................... 64Staphylococcus aureus in hand eczema................................. 66

SUMMARY AND CONCLUSIONS........................................................................ 70

ACKNOWLEDGEMENTS...................................................................................... 73

REFERENCES 74

6

A B B R E V I A T I O N S

AD Atopic derm atitis

AMS Atopic mucosal symptoms

NA Non-atopics

HMD H istory of metal derm atitis

HHE H istory of e a r lie r hand eczema

OR Odds ra t io

PP Predicted p ro b a b ility

7

I N T R O D U C T I O N

Hand eczema is a disorder of m u lt ifa c to r ia l e tio logy. There is

general agreement that ind iv idua l and environmental factors may

in te ra c t in a complex manner to e l i c i t th is common disorder. To

date knowledge of the in te rp la y between endogenous and exogenous

facto rs is very lim ite d . Extending th is knowledge must be consi­

dered a high p r io r i ty task in the struggle to discover the nature

of hand eczema. There are many advantages to be gained from an im­

proved understanding of the re la t iv e importance of ind iv idua l and

environmental fa c to rs . The accurate c la s s if ic a tio n of hand eczema,

occupational counselling, medico-legal considerations, prognostic

speculations and the outcome of therapeutic measures are a ll

dependent on the extent to which endogenous and exogenous facto rs

contribu te to the e tio logy of hand eczema. This study has been

designed to throw some lig h t on th is complex problem.

R E V I E W OF T H E L I T E R A T U R E

HAND ECZEMA

Prevalence. Epidemiological studies of hand eczema in various

populations have recorded a ra ther wide range of prevalence f ig u ­

res. Agrup (1) estimated tha t the prevalence of hand de rm atitis

in the general population in southern Sweden was 1.2-3.4%. As a

part of a study on nickel a lle rgy Peltonen (2) examined the hands

of 980 subjects in Finland and found hand eczema in 4%. In a study

in northern Norway (3) 14.667 adult subjects were asked about the

occurrence of a lle rg ic hand eczema during the preceding twelve

months. A pos itive rep ly was given by 4.9% of the men and 13.2%

8

of the women. The age of the women influenced the prevalence. Thus

15% of women between 25-34 years of age reported hand eczema while

fo r women between 45-49 years the fig u re was only 9.2%. In a pre­

valence study in the Netherlands an episode of eczema of the hands

and forearms la s tin g fo r three weeks and occurring during the past

three years was used as a c r ite r io n fo r a case of hand eczema.

In th is study the prevalence figures fo r 1982 were 4.5% fo r men

and 10.0% fo r women (4 ). A representative sample consisting of

1961 Danish women reported a h is to ry of hand eczema in 22% (5). In

a Finnish study of 617 wet hospita l workers, predominantly women,

44% had past or present hand eczema (6 ).

The various resu lts recorded in these investiga tions re f le c t some

of the problems innate in prevalence studies of hand eczema. As

hand eczema is a periodic disorder figures based on a s ing le exa­

mination w il l underrate the prevalence. Prevalence studies cover­

ing periods of time must re ly on anamnestic information w ith i ts

lim ita tio n s regarding accuracy of diagnosis. Another aspect of the

problem is how severe a derm atitis of the hands has to be before

i t can be diagnosed as ezcema. The d iffe rence in prevalence be­

tween the two sexes and the importance of wet work is obvious from

the figu res .

C la s s if ic a tio n . C la ss ifica tio n of hand eczema may be based on the

morphologic descrip tion of the eczema w ith terms such as vesicu-

lous-sqamous, nummular, wedding-ring, f in g e r t ip , hyperkeratotic

and pompholyx (7 ). These names re fe r to c lin ic a l features and say

very l i t t l e or nothing about the e tio logy . A common way to c la s s i-

9

fy hand ezcema is according to e tio lo g ic aspects. Thus the terms

i r r i t a n t or a lle rg ic contact derm atitis of the hands are used de­

pending on the cause.

As stated by Epstein hand eczema is almost always m u lt ifa c to r ia l

and therefore simple e tio lo g ic c la s s if ic a tio n s are doomed to f a i l ­

ure. In order to avoid the fru s tra t in g struggle w ith some of the

c la s s if ic a tio n s Epstein proposed tha t hand eczema should be ana­

lyzed fo r i t s endogenous and exogenous factors (8).

ATOPIC DERMATITIS

Epidemiology. The incidence of atopic disease varies w idely in the

great number of ex is ting investiga tions. A very complete survey of

th is top ic has been given elsewhere (6 ). Differences in diagnostic

c r i te r ia and selection of the population studied regarding age,

race and geographic d is tr ib u tio n are a ll probable explanations fo r

the d ifferences found. The cumulative incidence of atopic disease

varies from 15-25% in most reports (9 ). In a study on 7000 adult

twin pairs in Sweden 18% had or had had atopic disease (10). In

another Swedish study on 1325 unselected 7-year-old school c h i l ­

dren 15.1% had atopic disease and 8.3% had or had had atopic der­

m a titis (11).

Diagnosis. Attempts to define th is dermatologica! disorder were

made as early as in 1892 when Besnier (12) observed a fa m ilia l

d ispos ition and noted tha t the disorder which he named prurigo

diathésique occurred in association w ith a lle rg ic r h in i t is , asthma

10

and sometimes gas tro in tes tin a l symptoms. The term atopy was in t ro ­

duced by Coca & Cooke in 1923 and means a strange disease (13).

The word is Greek and can be transla ted as 'out of p lace '. In mod­

ern terminology the term atopy includes a lle rg ic rh inocon junctiv i ­

t i s , bronchial asthma, atopic de rm a titis , and certa in forms of

gas tro in tes tin a l a lle rgy and u r t ic a r ia .

A transferable fac to r was found in the serum of a lle rg ic persons

by Prausnitz & Klistner in 1921 (14). This transferab le fa c to r has

been id e n tif ie d as immunoglobulin E (IgE) and methods have been

developed to measure the to ta l and spec ific amount of IgE (15-

19). Atopic ind iv idua ls are commonly defined as having an in ­

creased l i a b i l i t y to form IgE antibodies when exposed to environ­

mental antigens. This commonly used generalization is true fo r

a lle rg ic r h in i t is and a lle rg ic asthma but not fo r atopic dermati­

t i s . The derm atitis which occurs in atopies is not a typ ica l atop­

ic disease since the importance of a lle rg ic factors is uncertain

(20-22). Approximately 20% of patients w ith severe fle xu ra l eczema

have normal serum IgE leve ls (22).

No absolute diagnostic c r i te r ia e x is t fo r atopic de rm atitis . Diag­

nostic guidelines have been proposed by Hanifin & Rajka (23).

These guidelines are based on a few basic and many minor c r i te r ia .

Lammintausta introduced a prognostica ily useful d e fin it io n of the

skin condition in subjects w ith atopic mucosal symptoms and non-

atopics. This condition was named atopic skin d iathesis and was

defined as fo llow s:

11

a) dry skin

b) a h is to ry of a low p ru ritu s threshold fo r two or three

of the fo llow ing non-specific ir r i ta n ts : sweat, dust,

rough material

c) white dermographism and

d) fa c ia l p a llo r / in fra o rb ita l darkenings

Atopic skin d ia thesis was found in 35% of the subjects w ith atopic

mucosal symptoms and in 18% of the non-atopics. This d ia thesis was

found to s ig n if ic a n t ly increase the r is k of hand eczema among em­

ployees engaged in wet work (6).

Hand eczema in atopic d e rm a titis . Several reports e x is t in which a

co rre la tion has been found between hand eczema and a personal or

fam ily h is to ry of atopy (1, 24-29). Atopic disease and especia lly

atopic derm atitis in childhood as r is k fac to rs fo r hand eczema in

adults have been the subject of two large studies during the la s t

few years. One study has been carried out by Lammintausta on wet

hospita l workers in Turku, Finland (6) and the other by Rystedt on

selected groups of atopies in Stockholm, Sweden (9). In both s tu ­

dies an increased r is k of developing hand eczema was found in sub­

je c ts who had had atopic derm atitis in childhood. Both authors

also found tha t a considerable number of subjects w ith e a r lie r

atopic derm atitis managed to work in high r is k occupations w ith ­

out developing hand eczema. Atopic skin d ia thes is , as defined by

Lammintausta, s ig n if ic a n t ly increased the r is k of hand eczema in

subjects with atopic mucosal symptoms and in non-atopics. In sub­

jec ts w ith atopic derm atitis Rystedt id e n tif ie d the fo llow ing e l i -

12

nica l markers as s ig n if ic a n t ly increasing the r is k of hand eczema:

eczematous involvement of the hands in childhood, widespread der­

m a titis in childhood, pers is ten t body eczema and d ry /itc h y skin.

In subjects w ith atopic mucosal symptoms and in non-atopic in d i­

viduals i t was found tha t d ry /itc h y skin s ig n if ic a n t ly increased

the r is k of hand eczema (9 ). Neither of these two studies was pro­

spective and i t was not possible to ca lcu late the re la t iv e impor­

tance of ind iv idua l versus environmental r is k factors in the de­

velopment of hand eczema.

EXOGENOUS FACTORS IN HAND ECZEMA

I r r i t a n ts . The f i r s t lin e in the capacity of the skin to protect

i t s e l f against external exposure is the surface f i lm , sometimes

ca lled the acid mantle because i t s pH is on the acid side (30).

The buffe r capacity of the surface f i lm varies amongst ind iv idua ls

and also from one body region to another (31, 32). The main pro­

te c tiv e function in the skin rests w ith the stratum corneum (32-

34). The f le x ib i l i t y and cohesion of the horny layer are depend­

ent on the water content (35-36). Reduction of the water-holding

substances w il l decrease the water content of the stratum corneum

and cracks and chapping w il l develop (37-39). C e ll-w a ll l ip id s

protect the water-holding substances (40). Detergents remove

lip id s and water-holding substances and cause a predisposition

to chapping (35, 41). A breakdown of the natural resistance of

the skin leads to increased water vapor loss and the in te g r ity

of the skin b a rrie r can be measured by transepidermal water

loss (42-44).

13

Acute i r r i t a n t derm atitis may be caused by strong ir r i ta n ts a fte r

a s ing le or a few app lica tions. Hand eczema may also occur a fte r

repeated assaults by weak i r r i ta n ts over a long period of time.

This derm atitis has been named 'wear and te a r' derm atitis and

'tra u m ite ra tive d e rm a titis ' (45). There is no te s t which can de­

termine whether an i r r i t a n t is re levant to a p a tie n t's de rm a titis .

Thus the evaluation of the re la t iv e importance of i r r i ta n ts in

patients with hand eczema has to be a c l in ic a l decision. Discus­

sions of i r r i ta n ts are usually focused on chemicals, solvents,

acids, a lk a li and surfactants. However, dry a ir , low humidity,

co ld , wind and f r ic t io n may be important con tribu to ry facto rs (8).

I t is very d i f f i c u l t to obtain s c ie n t if ic documentation of the

w idely-held opinion tha t contact w ith ir r i ta n ts is the most common

cause of hand eczema. C lin ica l evidence that surfactants aggra­

vate hand eczema is , however, overwhelming (8). Thus various kinds

of wet work involve occupational hazards to the hands (29, 46-50).

Some people seem p a r t ic u la r ly prone to develop i r r i t a n t derm atitis

(51, 52). I r r i ta b le skin seems to depend on co ns titu tion a l fac to rs

but so fa r i t has not been possible to id e n tify ind iv idua ls who

are p a r t ic u la r ly susceptible to i r r i ta n ts (53). Long c lin ic a l ex­

perience has shown tha t atopic skin has a reduced resistance to

i r r i ta n ts and consequently has an increased tendency to develop

i r r i t a n t derm atitis espec ia lly on the hands. According to the

recent find ings by Lammintausta and Rystedt th is reduced re s is t ­

ance does not seem to occur in a ll subjects with a h is to ry of

atopic derm atitis as a considerable number managed to work in r is k

occupations w ithout developing hand eczema (6, 9). In subjects

14

with atopic mucosal symptoms and in non-atopics Lammintausta iden­

t i f ie d atopic skin d ia thesis which was found to increase the r is k

of i r r i t a n t hand eczema (6 ). These observations ind ica te tha t a

reduced resistance to i r r i ta n ts does not occur in a ll subjects

w ith atopic derm atitis and may occur in subjects w ith atopic muco­

sal symptoms and in non-atopics.

A lle rg ic contact derm atitis of the hands. A lo t of in te re s t has

been focused on delayed contact s e n s it iv ity in the e tio logy of

hand eczema. Figures fo r a lle rg ic contact derm atitis among hand

eczema patients vary considerably (1, 29, 54). The most important

reason fo r th is va ria tion is probably the selection of the pa tien t

populations tested. A pos itive patch te s t in a pa tien t w ith hand

eczema does not mean tha t a contact a lle rgy is relevant fo r the

current hand derm atitis . Judging the relevance of a pos itive patch

te s t in hand eczema may be very d i f f i c u l t . An allergen is consi­

dered a primary cause of the derm atitis i f e lim ination leads to a

complete cure. I t is only too common fo r an allergen to be of

doubtful relevance. The proven contact a lle rgy may be only a con­

tr ib u to ry or aggravating fa c to r or of no s ign ificance at a ll to

the de rm atitis .

There has been no prospective study on the importance of a

delayed contact a lle rgy as a r is k fa c to r in hand eczema. A re tro ­

spective study on wet hospita l workers found tha t hand eczema was

s ig n if ic a n t ly more common amongst subjects w ith contact a lle rg y .

However, a considerable number of workers w ith contact s e n s it iv ity

to nickel and fragrance mix had managed to work w ithout deve-

15

loping hand eczema (6). Amongst hospital workers the fo llow ing

sens itize rs are reported to be common: rubber gloves, formalde­

hyde, ch lo roxy leno l, p e n ic i l l in , streptomycin, neomycin, p ipera­

zine, phenothiazines, hand creams, nickel and glutaraldehyde (55).

Atopy and contact s e n s it iv i ty . Delayed hype rsens itiv ity to can­

dida, tr ich o p h y tin , tubercu lin and other bacteria l and v ira l a n t i­

gens is diminished in patients w ith atopic derm atitis (56-61).

D in itrochlorobenzene (DNCB) which sensitizes over 90% of the nor­

mal population has been found to sens itize a lower proportion of

atopic patients (56, 62-64). S e n s it iv ity to RHUS-antigen was found

in 15% of atopies whereas 61% of non-atopics were sensitized (65).

The occurrence of delayed contact derm atitis and pos itive patch

tests in patients w ith atopic derm atitis is a subject which

produces contrad ictory find ings . One study found a pos itive patch

te s t reaction in 28% of AD patients as compared to 9% of

p so ria tics (66). In another study on 4000 patien ts, of whom 233

had atopic de rm a titis , a pos itive patch te s t reaction was no more

frequent in the atopies (26). Most studies on the prevalence of

contact s e n s it iv ity in patients w ith atopic derm atitis have

produced figures between 15% and 35% (1, 6, 26, 67, 68). Some

investiga to rs have found nickel a lle rgy to be more common in

atopic ind iv idua ls (69-71) whereas other investiga to rs have found

no such co rre la tion (72-75). Judging the relevance of a pos itive

patch te s t in a pa tien t w ith hand eczema may be even more

fru s tra t in g in atopies than in non-atopics. In atopies i t must be

assumed that endogenous facto rs and an increased s e n s it iv ity to

16

i r r i ta n ts play an important part in the e tio logy of the hand

eczema. Forsbeck et a l. (28) found tha t contact a lle rgy was as

common in AD patients w ithout hand eczema as in patients w ith hand

eczema. This fin d in g h igh ligh ts the problem of the relevance of

contact a lle rgy in subjects w ith atopic derm atitis and hand

eczema.

Contact u r t ic a r ia . Contact u r t ic a r ia (CU) may be defined as a

wheal-and-fla re response e lic ite d from w ith in a few minutes up to

h a lf an hour a fte r skin exposure to various agents. The term

(contact u r t ic a r ia syndrome) was proposed in 1975 to cover a broad

spectrum of c l in ic a l manifestations which may be provoked by the

causative agent (76). The fo llow ing staging fo r th is syndrome is

proposed by von Krogh & Mai bach (77).

Cutaneous reactions only:

Stage 1: loca lized u r t ic a r ia

derm atitis

non-specific symptoms ( itc h in g , t in g lin g ,

burning etc)

Stage 2 : generalized u r t ic a r ia

Extracutaneous reactions:

Stage 3: bronchial asthma

rh in o c o n ju n c tiv it is

o ro -laryngeal symptoms

gastro -in te s tin a i symptoms

Stage 4: anafylacto id reactions

17

Non-Immunological Contact U rtic a r ia (NICU). In NICU the reaction

is e l ic ite d w ithout previous sens itiza tion in most exposed in d iv i­

duals. A release of histamine and other vasoactive substances

w ithout invo lv ing immunological mechanisms is thought to be the

cause (78). This type of contact u r t ic a r ia is probably very

common. Many chemicals in common use have the a b i l i t y to provoke

NICU in a large number of normal ind iv idua ls (77). Agents such as

benzoic acid, sorbic acid, cinnamic acid and cinnamic aldehyde are

potent u rtica riogen ic substances. When exposure is optimal a majo­

r i t y of ind iv idua ls w i l l react w ith contact u r t ic a r ia a fte r a p p li­

cation of ra ther high concentrations to in ta c t skin. In lower

concentration they may provoke erythema but not a true u r t ic a r ia l

reaction . Thus the frequency and strength of NICU are influenced

by the concentration of the ind iv idua l chemicals and even by the

chemical composition of the vehicle (79).

Immunological Contact U rtic a r ia (ICU). Evidence of an a lle rg ic

mechanism in contact u r t ic a r ia has been rare. Immunological mecha­

nisms may be suspected when there has been a period of se n s itiza ­

tio n , the reaction is strong, tests on contro ls are negative and

passive trans fe r te s t is p o s itive . IgE spec ific fo r the antigen

has been found in some cases (80-83). U rtica r ia may also be caused

by a lle rg ic mechanisms in which sp e c ific immunoglobulin G and per­

haps immunoglobulin M may activa te the complement cascade through

the c lass ica l pathway (84-86).

18

While atopies and non-atopies do not d if fe r w ith respect to NICU

(79) i t is l ik e ly but poorly documented tha t ICU is more common

among atopies.

Uncertain Mechanism Mediated Contact U rtica r ia (UMCU). This type

o f contact u r t ic a r ia re fe rs to reactions fo r which the mechanisms

are unknown (77). Von Krogh & Mai bach have updated the contact

u r t ic a r ia syndrome and lis te d most of the substances known to

e l i c i t contact u r t ic a r ia in the three groups (77, 87).

The diagnosis of contact u r t ic a r ia had to be based on a carefu l

h is to ry of immediate reactions. Diagnostic tests guided by the

case h is to ry may be performed on in ta c t skin as open, occlusive or

intradermal and on s l ig h t ly affected or previously affected skin

as open or occlusive te s ts . A stepwise te s t procedure has been

recommended by von Krogh & Mai bach (77, 87).

Contact u r t ic a r ia in hand eczema. In a study of 33 food-handlers

w ith recurrent hand eczema i t was found that exposure of the hands

to various proteins aggravated the hand eczema. Itch in g , erythema,

u r t ic a r ia l swelling and dysh id ro tic vesicles were observed w ith in

10-30 minutes a fte r contact between the incrim inating prote in and

the affected skin. Contact u r t ic a r ia was found in 9 cases of

whom 3 reacted only when the suspected food was exposed to eczema­

tous skin. In to ta l 25 showed a pos itive scratch te s t w ith food

such as chicken, seafood, vegetables and spices. The term 'p ro te in

contact de rm a titis ' was introduced to describe th is phenomenon

(88). Immediate reactions which aggravate chronic hand derm atitis

19

have been reported by other authors. Thus le ttuce and endive (89),

wheat f lo u r , turkey and lamb (90) and apple and potato (91) have

been found to aggravate or e l i c i t hand derm atitis . Some of the

patients in these studies reacted with pos itive tests only on pre­

v ious ly derm atitic skin or a fte r intradermal tes ts .

Although case reports on contact u r t ic a r ia are numerous the epide­

miology in the general population and in populations w ith hand

eczema is unknown except fo r the study on food-handlers by H jorth

& Roed-Petersen (88).

Colonization of Staphylococcus aureus. The nose, a x illa e , perineum

and toe-webs are the only common resident c a rr ie r s ites of S.

aureus on human skin. Normal skin from other locations y ie lds S.

aureus in about 5% of the population (92). Higher c a rr ie r rates

w il l be found when ind iv idua ls are followed up over periods of

time (93). The carriage rate of S. aureus on normal hands has been

studied in various populations. In 13% of nasal ca rrie rs S. aureus

was cultured by the 'f in g e rp r in t1 technique compared to 4% of non­

ca rrie rs (94). In a study of 361 patients prepared fo r operation

i t was found that 24% carried S. aureus on th e ir hands (95). Among

hospita l s ta f f who had ju s t completed a ward round or treatment

68% carried S. aureus on th e ir hands compared with 25% of those

engaged in other duties in the same ward or who had ju s t washed

th e ir hands (96). A study on 50 nurses and 50 contro ls found tha t

28% of both groups carried S. aureus on th e ir hands. The mean

density was however lower among the nurses. A higher percentage of

the nurses carried 5. aureus on th e ir hands p e rs is ten tly during

a three-month period (97).

20

Various derm atitic conditions carry S. aureus more frequently

than normal skin. Candidiasis in in te rtr ig in o u s regions carries

S. aureus in 60% (98), p so ria tic plaques are colonized w ith S.

aureus in 20-50% (99-102). In a review a r t ic le by Leyden (103) the

fo llow ing frequency and density of S. aureus were reported in

various derm atitic conditions: seborrhoic derm atitis 21% w ith a

density of 13 000 cfu/cm^, neurodermatitis 90% with 600 000 c fu /2 2 cm , e x fo lia t iv e erythroderma 100% w ith 2 000 000 cfu/cm , chronic

2fa m ilia l benign pemphigus 90% w ith 4 000 000 cfu/cm scaling in -

2te rd ig ita l a th le te 's foo t 6% with 30 000 cfu/cm , macerated in te r -

2d ig ita l a th le te 's foo t 11% with 500 000 cfu/cm . Dermatitic skin

in atopies has shown both a high carriage rate and high counts of

5. aureus (104, 105). Although i t is well-known from c lin ic a l

experience tha t S. aureus is commonly iso la ted from eczematous

lesions of the hands no systematic q uan tita tive study has been

performed on the m icro flo ra of hand eczema.

21

A I M S OF T H E S T U D Y

1. Epidemiological : To investiga te the re la tiv e importance of some

ind iv idua l and environmental facto rs in the e tio logy of hand

eczema in newly employed hospita l workers.

2. C lin ica l : To study the importance of i r r i ta n ts , allergens and

contact u rtican ts in a selected group of newly employed wet hospi­

ta l workers w ith hand eczema.

3. Bacterio log ica l : To study the density of the m icrobial f lo ra

and i.e . S. aureus in hand eczema and the e ffe c t on the m icro flo ra

of a potent top ica l co rtico s te ro id .

22

P A T I E N T S

Study design and study population ( I - 11). The study has been

performed as a prospective cohort study. The cohort was co llected

from June 1979 to June 1981 and consisted of 2651 newly employed

workers in four hosp ita ls in the county of Västernorrland in

northern Sweden. At the preemployment examination, previous skin

diseases were recorded but played no part in the se lection fo r

employment. A fo llow -up questionnaire was sent to the employees

and answers were received from 2452 subjects (92.5%) a fte r a me­

dian observation time of 20 months (range 18.5-24.0). The frequen­

cy of atopic disease in the defau lte rs did not d if fe r from tha t

found in the to ta l cohort. Table I shows the number of employees,

percentage of females and median age of the occupational groups.

Nursing s ta f f included a ll kinds of s ta f f working w ith pa tien ts .

The fo llow ing subgroups were included: ward maids 964, nurses/

assistants 233, psych ia tric nurses 122, nursing assistants 117,

physicians 55, ch ild re n 's nurses 36, dental s ta f f 31, occupational

therap is ts 36 and chiropodists 1. Nursing s ta ff and kitchen

workers/cleaners performed wet work while o ff ic e workers and care­

takers/craftsmen performed mainly dry work.

Table I . Number of employees, sex and median age in the occupatio­nal groups

Number Female (%) Median age

Nursing s ta ff Ï613---------------5777---------------- 2525

Kitchen workers/cleaners 457 93.4 23

O ffice workers 269 91.8 22.5

Caretakers/craftsmen 113 16.8 29

23

Patients ( I I I ) . The patients in th is study consisted of 142

subjects from the to ta l cohort employed in hospital wet work who

consulted a dermatologist because of current hand eczema. 91% of

them were women and the mean age was 26.2 years. 72% were

employed in nursing occupations, 16% were cleaning personnel and

12% were kitchen workers.

Patients (IV ). Twenty pa tien ts , 16 females and 4 males, w ith hand

eczema were studied. The age of the patients ranged from 13-61

years. Patients who had received local or systemic a n tib io tic s or

local co rticos te ro ids w ith in the la s t two weeks were excluded as

were patients w ith severe suppuration, tenderness, adenopathy and

fever.

24

M E T H O D S

PAPERS I - I I

Diagnosis of atopy and metal d e rm a titis . At the preemployment

examination any h is to ry of atopic disease was noted by a spec ia lly

tra ined occupational nurse in a standardized manner. Atopic derma­

t i t i s was accepted as a diagnosis i f there was a h is to ry of

itc h in g , relapsing derm atitis s ta rtin g in infancy or childhood

w ith a typ ica l d is tr ib u tio n . Subjects w ith past or present atopic

derm atitis were recorded together. Atopic mucosal symptoms were

accepted as a diagnosis i f hayfever or asthma occurred when the

subject was exposed to pollen or fu rred animals. No other diagnos­

t ic tests or c r i te r ia fo r atopic disease were used.

A h is to ry of metal derm atitis was derived from a questionnaire

in which the employees were asked about an itch ing rash re la ted to

exposure to metal buttons, cheap jew elry or wristwatches.

C r ite r ia fo r hand eczema. At the preemployment examination the

employee was informed that the study concerned hand eczema and was

given some b r ie f information about the symptomatology of hand der­

m a tit is . The occurrence of hand eczema during the period studied

was id e n tif ie d in the fo llow -up questionnaire. The employee was

then asked to characterize h is /her eczema using one or more of the

fo llow ing f iv e a lte rna tives :

1. dry and chapped skin w ith rashes and small cracks

2. itch ing red macular and papular skin lesion

3. small vesicles

25

4. ruptured vesicles or excoriated skin

5. rough skin w ith cracks and scaling

The employee was asked about medical consu lta tion , s ick-leave and

i f he/she had le f t h is /he r current work because of hand eczema.

The time of onset and the nature, period ic or permanent, of the

eczematous symptoms were also recorded. Those who had stated in

the questionnaire tha t they had suffered from hand eczema w ithout

seeking medical advice were asked why they had not done so. In a

separate question the employee was asked about hand eczema p r io r

to the current work. The r e l ia b i l i t y of id e n tif ic a tio n of hand

eczema by questionnaire has been checked in th is study using 146

patients who attended the dermatological c l in ic w ith a hand derma­

t i t i s which they suspected was eczema. Of these pa tien ts , only

four had diagnoses other than eczema. One had palmar keratoderma,

two had pustular dermatosis of the palms and one had scabies.

Occupational exposure. Approximately 50% of the employees worked

part-tim e and 1/3 had changed th e ir work fo r other occupations at

the fo llow -up.

Domestic work. Six anamnestic parameters which re f le c t domestic

manual work from d iffe re n t points of view were recorded: the

nursing of ch ildren younger than four years of age; members of the

household; hours of housekeeping per week; hours per week spent

working w ith the hands on a hobby; use of washing machine and

dish-washer. The purpose was to investiga te the co rre la tion

between these parameters and the r is k of developing hand eczema.

26

S ta t is t ic a l methods. The m u lt ifa c to r ia l problem in th is study has

been analyzed using a m u ltiva ria te lo g is t ic regression technique

(106). The r is k of developing hand eczema was calculated as pre­

dicted re la t iv e odds ra t io s . The odds ra t io (OR) expresses the

re la tionsh ip between the odds (01) of ge tting hand eczema (E1) in

one group (01=E1/(1 -E1)) compared to odds (02) of hand eczema (E2)

in a second group (02=E2/(1-E2)). E1 and E2 denote the proportion

of hand eczema in the two groups. Then the odds ra t io (OR) w i l l be

0R=02/01=E2(1-E1)/E1(1-E2)

The r is k in per cent of developing hand eczema has been s t a t is t i ­

c a lly calculated and is expressed as predicted p ro b a b ility (PP).

The Student's ta te s t was used to compare re la t iv e frequencies.

Three m u ltiva ria te regression analyses of the in te rre la tio n sh ip

between ind iv idua l and environmental fac to rs w i l l be presented.

The fo llow ing facto rs were used in the three analyses.

The f i r s t analysis (A1): AD, AMS, NA and occupation.

The second analysis (A2): AD, AMS, NA, domestic facto rsand the three occupations dominated by women.

The th ird analysis (A3): AD, AMS, NA, HMD and HHE in women in wet hospita l work.

27

PAPER IIICharacterization of hand eczema. The fo llow ing factors regarding

hand eczema p rio r to the present work were recorded: time from on­

set, p e r io d ic ity and occupation at onset. The pa tien ts ' opinions

about factors which e lic ite d the current hand eczema and contact

u r t ic a r ia were sought. The state of the current hand eczema and

diagnosis of ongoing eczema at s ites other than the hands, were

noted.

Patch te s ts . Epicutaneous tes ting was carried out on 120/142

patients using the European standard series except fo r caine mix

and fragrance mix. Benzalconium ch loride 0.1% and coal ta r 5% were

added to the standard series.

An additional series of agents was tested on 55/120 consecutive

pa tien ts . This series consisted of d is in fec tan ts , preservatives,

em ollien ts, perfumes and colourings. Most of these were present in

products in common use in the hosp ita ls . The fo llow ing were in ­

cluded: lauromacrogol as i t is , macrogol as i t is , carbopol 1%,

EDTA 1%, propyl g a lla te 1%, sorbic acid 2.5%, triethanolam ine 5%,

chlorocresol 2%, m erth io late 0.1%, chloracetamide 0.1%, patent

blue V 2%, quinoline yellow 2%, ethanolamine 5%, Chlorhexidine

gluconate 1%, BHT 2%, bronopol 1%, propylene glycol 20%, isopropyl

m yristate 20%, cety l alcohol 5%, cetrim ide 0.1% and 0.01%, euca-

lyp to l 2% and hexachlorophene 1%. The European standard te s t

series was supplemented with the addition of caine mix and f r a ­

grance mix when tes ting these 55 consecutive patients.

28

The Finn Chamber technique was used w ith exposure to the allergen

fo r 48 hours. The tests were read a fte r 72 hours.

Prick te s ts . For contact u r t ic a r ia , p rick tests were carried out

as open tests on the upper back. They were read a fte r 15-30 min.

Histamine was included as a p os itive and saline as a negative

con tro l. I f the mean diameter of the wheal subtracted from the

negative reference was 3 mm or more, the reaction was regarded as

pos itive . Prick tests were performed on 41 out of 49 patients w ith

a pos itive h is to ry . Eight patients declined to have prick tests

fo r various reasons.

A screening series fo r contact u r t ic a r ia was conducted as a

supplement to substances suspected from case h is to r ie s . Included

in the 'hosp ita l screening se ries ' were three chemically id e n t i­

fie d substances (formaldehyde 2%, benzalconium ch loride 0.1% and

isopropyl m yristate 20%). The te s t series included some complex

chemicals and agents which were a l l in common use in the hospi­

ta ls : i .e . two liq u id soaps (B lido , Barnängen); three d is in ­

fectants (hand s p i r i t , M -s p ir it and H ib iscrub); four em ollients

(A tr ix , Sumabless, Helosan and C a lm uril), a green rubber glove and

a paper towel which was tested wet.

S ta t is t ic s . Student's t - te s t was used to compare re la tiv e frequen­

c ies. A s ign ificance level of 5% was chosen.

29

PAPER IV

Characterization of hand eczema. The eczema was characterized by:

erythema, papules, in f i l t r a t io n , vesic les, erosions, fissu re s ,

crusts and signs of c l in ic a l in fe c tio n w ith exsudation and yellow

crusts. The extension of the lesion was estimated and recorded as

small (<1/3), medium (1/3-2 /3) and large (>2/3) in re la tio n to the

to ta l area.

Sampling technique. The sampling technique of Williamson & Kligman

(107) was employed w ith some m odifica tion . A s te r ile s ilico n e rub-o

ber cy linder (inner area 5.3 cm ) was placed on the sampling

s ite of the skin and f i l le d w ith 2 ml 0.1% Triton X-100 in 0.075M

phosphate buffered saline pH 7.9. A fte r scrubbing fo r one minute

with a disposable 10 pi inocu la ting loop (Nunc A/S, Roskilde,

Denmark) the liq u id was transferred to a locally-produced anae­

robic transport device. To fa c i l i t a te sampling from the fingers a

special sampling device was constructed. In a piece of s ilico n e

rubber tubing (length 60 mm, inner diameter 20 mm) two holes w ith

a diameter of 14 mm fo r th ick fingers or 11 mm fo r th in fingers

were cut opposite each other. The sampling device was mounted on a

f in g e r, and f i l le d w ith the detergent bu ffe r. The oval enclosed

on a finge r of 14 mm diameter was 3.89 +/-0.26 cm (mean + /- SD

of 4 experiments) and that on a finge r of 11 mm diameter 3.372 2 + /- 0.21 cm . In finge r samples an estimated area of 3.6 cm was

used in a ll ca lcu la tions regardless of finge r diameter. Before

treatment, samples were taken from three s ite s ; 1) from the most

pronounced eczematous lesions; 2) from skin affected only w ith

30

erythema and 3) from c l in ic a l ly normal skin of the hands. A fte r

treatment the same skin areas were resampled.

Id e n tif ic a tio n of the m ic ro flo ra . The samples were d ilu ted ten fo ld

(10’ \ 10 '2, 10” 3) in peptone yeast broth (108) and plated in an

anaerobic glove box. Brain Heart Infusion Agar (BHIA), Lab M,

London, England; Trypticase Soy Agar (TSA), D ifco, D e tro it,

Michigan, USA; and TSA + 0.5% Tween 80, Kebo Lab, Stockholm,

Sweden, were incubated ae rob ica lly at 37°C fo r two days and BHIA

also anaerobically at 37°C fo r f iv e days. A ll bacte ria l colonies

w ith d iffe re n t morphology were quan tified from the appropriate

d ilu t io n and id e n tif ie d when the number of colony forming un its

(c fu ) reached 10/cm , which was the technical boundary of quanti­

ta t iv e estim ation. Coagulase-negative staphylococci were id e n t i­

fie d according to the s im p lifie d scheme of Kloos & S ch le ife r

(109). Staphylococci were separated from micrococci by th e ir ab i­

l i t y to produce acid aerob ica lly from glucose (110). Corynebacte-

r ia were divided in to 1ip o p h ilie s and n o n -lipop h ilics by the

growth of 1ip o h ilie s on TSA + 0.5% Tween 80 (111). Peptostrepto-

cocci, prop ion ibacteria and Sarcina sp. were id e n tif ie d according

to the VPI Anaerobe Laboratory Manual (108).

Before q uan tita tive bacte rio log ica l analyses d iffe re n t bacte ria l

species were combined in to three main groups: (1) S. aureus., (2)

other aerobes, and (3) anaerobes.

31

Treatment. Treatment given was 0.05% clobetasol propionate creamR R(Dermovat , Glaxo) and an em ollient (Essex cream , Essex) in the

fo llow ing in te rm itte n t schedule. Clobetasol propionate cream was

applied twice d a ily on days 1, 2, 3, 4, 8, 9, 12 and 14. The in e rt

cream base was used on days 5, 6, 7, 10, 11 and 13. The patients

were seen a fte r fourteen days and new samples were taken from the

same s ites as before treatment using the same technique.

A n tibac te ria l e ffe c t of clobetasol propionate. The in v it ro a n t i­

bacte ria l e ffe c t of clobetasol propionate (2000, 1000, 500, 250,

125, 62, 31 and 16 pg/m l) on S. aureus was investigated using the

agar d ilu t io n technique in ASM-PDM agar (Biodisc AB, Stockholm,5

Sweden) using 10 cfu as inoculum.

S ta t is t ic s . Geometric means of groups of bacteria were compared

w ith paired t- te s ts (112). A s ign ificance level of 5% was chosen.

32

R E S U L T S

Prevalence of ind iv idua l r is k fa c to rs . Of the to ta l cohort studied

we considered 22.6% to be atopies. A h is to ry of atopic derm atitis

was seen in 10.2% including 4.1% with both atopic derm atitis and

atopic mucosal symptoms. Pure atopic mucosal symptoms were found

in 12.4%. The prevalence figures fo r atopy were e sse n tia lly the

same in the four occupational groups. A h is to ry of metal dermati­

t is was reported by 26.3% of the women in wet hospita l work and

was more common in atopies than in non-atopics. The fo llow ing

re la t iv e frequency fo r HMD was found: AD 36.5% (p<0.001), AMS

31.4% (p<0.05) and NA 24.1%. A h is to ry of e a r lie r hand eczema was

reported by 22.4% of the women in wet hospital work. The fo llow ing

figures fo r e a r lie r hand eczema were found: AD 48%, AMS 24%, NA

18%, HMD 36% and subjects w ithout HMD 17%. A h is to ry of metal

derm atitis was more common in atopies (46.9%) and non-atopics

(40.0%) subjects w ith HHE than in atopies (26.7%) and non-atopics

(20.5%) without HHE (p<0.001).

Hand eczema in the four occupations. Hand eczema p rio r to the

current work had occurred in 21.7% of the nursing s ta f f , in 20.4%

of the kitchen workers/cleaners, in 23.5% of the o ff ic e workers

and in 8.2% of the caretakers/craftsmen.

Table I I shows the to ta l occurrence of hand eczema in the four

occupations during fo llow -up. The d iffe rence in hand eczema

between wet and dry work is small and seems to diminish in the

more severe forms of hand eczema. I t is open to question whether

33

Table I I Hand eczema in occupational groups; median obser­

vation time: 20 months

Nursings ta f f

Kitchenworkers/cleaners

O fficeworkers

Caretakers/craftsmen

Total number in the group (*)

Hand eczema (%)

1599 450 264 110

- by questionnaire 41 37 25 17

- as cause of medical consultation

9.8 14 7.6 7.3

- as cause of s ick- leave

1.9 3.6 1.5 0

- as cause of termina­tio n of current work

2.0 2.4 0.4 0

(*) A small d e f ic i t due to incomplete questionnaires.

the figures re a lly re f le c t the importance of the current work as a

causal fac to r fo r hand eczema, as 50% had been working part-tim e

and 1/3 of the workers had le f t th e ir jobs at the time of the

fo llow -up. However, no s ig n if ic a n t d iffe rence in the occurrence of

hand eczema was seen between fu ll- t im e and part-tim e workers and

only 5.8% of the employees w ith hand eczema reported tha t the

eczema started a fte r the cessation of work.

Hand eczema in a top ies. Hand eczema p rio r to the current work had

occurred in 52.5% of the subjects w ith atopic de rm atitis , in 21.7%

of the subjects w ith atopic mucosal symptoms and in 16.3% of the

non-atopics. During the fo llow -up subjects w ith atopic derm atitis

Tabl

e II

I.

Hand

ec

zema

in

atop

ies

and

non-

atop

ics

in ho

spita

l w

ork

34

</>S- cGD CD E03 cO -t-> -M CD 4 - S- 03 03 S-

CJ CJ

Oto>)

S- CD Q ^ S-o£CDO

4 -4 -O

i -CD

S-o

to c s_ CD CD x: cU 03

-*-> CD

O

4 -03

cnC

< to cr> r ^ o Oz 00 t—

CO

oo r>v <_ LO o oz ^— r—<

Q LT> o o o o«a: CM CM

CX> LO

< CO CM «3- oz O CM

CM*— <“

C/3 C\) lo CO o COz : CO CM<

*d-

o cr> LO co o< C\J CO

CM CM

< r^ . CO r- COz CO T—

COCD r >

oo <d- LO CO r_‘ COz LO CO X—<

CM

o CO LO CO< to CO r—

CM CO LO

< : CD to x-1 s—’z CO CO

CM

LO o

OO to to *d- <_* CMz: CTl «d-< <—

CO LO

«a- T— *— LOQ to to CO<c r~

CL e3 <D oO > •i—s> 03 +->CD 1— CD 03

03 i— CCD O 1 •r—

JC CD •r— j* : E4-> s- T3 CJ s- j *

■r— cd •i— CD i -C ^— . 03 E to -M O

•r- C c««• C <+- o 4 - 4 -

S- o o •<- O O -MCD 03 • r— +-> C

JO E 4-> CD 03 CD CD CDE a> to 00 +J to to S_13 Nl CD CJ r - 3 3 i -C CJ 3 03 3 03 03 3

CD CT CJ 00 O CJ CJr— C03 ■O >> to O to tO 4~

-M c JO 03 CJ 03 03 OO 03

1— m 1 1 1 1 AD=a

topi

c de

rmat

itis

with

or

with

out

atop

ic

muc

osal

sy

mpt

oms

AMS=

atop

ic m

ucos

al

sym

ptom

sN

A=n

on-a

topi

cs

35

had higher frequencies of hand eczema than subjects w ith atopic

mucosal symptoms and non-atopics (Table I I I ) . The d iffe rence

between the groups increased in the more severe forms of hand

eczema. Sick-leave because of hand eczema was fa i r ly uncommon (0-

3.4%) in most occupations but fo r subjects w ith atopic derm atitis

employed in wet work occupations, the figures were higher (7 .3-

8.2%). Of the subjects on s ick-leave, 75% had been absent from

work fo r less than one month. Most employees with hand eczema do

not consult a doctor. The fo llow ing reasons were given by 677

employees: the hand eczema was mild (69.0%), the employee treated

himself w ith various top ica l remedies (43.9%), the eczema healed

fa s t spontaneously (36.5%) and other reasons (17.4%).

Hand eczema in women in wet hospita l work. Table IV gives the

figures fo r the occurrence of hand eczema in women in wet hospita l

work. From the to ta l fig u re i t can be seen that hand eczema was

reported by 41% and only 2.4% had been on sick-leave. 2.2% had

le f t th e ir current work because of hand eczema. Atopic de rm a titis ,

metal derm atitis and e a r lie r hand eczema increased the occurrence

of hand de rm atitis . Many subjects w ith hand eczema had suffered

th e ir f i r s t bout of eczema p r io r to the current wet work. The

fo llow ing figures fo r HHE in subjects w ith current hand eczema

were found: AD 68%, AMS 45%, NA 42%, HMD 55% and without HMD 42%.

Thus 46% of a ll subjects w ith current eczema had had hand eczema

before the observation period.

Tabl

e IV

. C

urre

nt

hand

ec

zema

in

1857

wo

men

in 'w

et'

hosp

ital

wor

k36

LjJ CO s3-z: •:n CO CO tO X— 7—CM CMo Sfz: r” coLU O 'vi­ CO *3* LO□= T— co CMm

Q CO tos:31 CM LO 00 r— T—COO COz x— co CDQ r**. to IO COs : CO LO *—•31 «çj-

to CD LOto 1 ^ r^v T-lCO CO

Z *3-T- 00 X—oo LO LO T— COs: CM *vf-«a: CM

co Cv.

Q *3- to< CD LO cor_

*3- CM03 r — t— CM CM+-> in *3" X—O CO

1—

,__ ___ IOto cs z •— o-*-> •r—c 03 4->o E CD 03E a> S- +■>

No o 03 3C\J CD C IO tov--- ■ c c C

T3 o o CD o03 C • r— o >E 03 03 +->a> -C to f— CD 03N <D 03 Cu 4-> 3 O 1CD S- C cr E

CD CD T3 O s-"O JD S- >> CD •p- CDc E S- JD E to 4->03 3 3z: Z O 1 I 1 1

EO4->Q.

03toOO

Q.O-M03

+->13O4->5i-O

to-C E+-> o• r - +->^ o.to >>

•r- tO

s-CL)T3

CDE

+-> 03 03 tOE o

(_> to q_ CD =3 O O-O E T-Q. >io o o s_

• r - - r - 4-> O Q. CL 03 +-> O O I to -*-> 4-i C *r- 03 03 O -C II II C II

OO II Q O S <C 21 <c «a: z z: HH

E=hi

stor

y of

earli

er

hand

ec

zem

a

37

P re d ic te d r e la t iv e o d d s ra t io

9 .0Nursing staff

8 .0K itchen w o r k e r s / c le a n e rs7 .0

6 .0

5.0

Office workers4 . 0

3 .0 Caretakers/craftsmen

2.0

A DAM SNA

Figure 1. Predicted re la t iv e odds ra t io fo r hand eczema in

atopies and non-atopics in the occupational groups. NA, AMS and AD

as defined in Table I I I .

M u ltiva ria te regression analysis of r is k fac to rs . In the regres­

sion analysis named A1 the fo llow ing facto rs were found to s ig n i­

f ic a n t ly influence the occurrence of hand eczema: atopic dermati­

t is (F=54, p<0.0001), occupation (F=14.4, p<0.0001). Figure 1

38

shows a summarized schematic descrip tion of the predicted re la t iv e

odds ra tio s of developing hand eczema fo r atopies and non-atopics

in the four occupations. Subjects w ith atopic derm atitis showed

odds approximately three times higher than non-atopics in both wet

and dry work. Nursing s ta f f showed odds approximately three times

higher than caretakers/craftsmen and twice as high as o ff ic e

workers. The group termed caretakers/craftsmen was small and the

pred ic tion is therefore uncertain in th is group. The predicted

p ro b a b ility of hand eczema fo r th is analysis ranges from 16% in

non-atopic caretakers/craftsmen to 62% in nursing s ta f f w ith

atopic derm atitis (Table V).

Table V. Predicted re la t iv e odds ra tio s (OR) and predicted proba-

b i l i ty (PP) fo r hand eczema in the occupationalI groups

NA AMS AD

OR PP

%

OR PP

%

OR PP

%

Nursing s ta ff 3.2 37 4.1 44 8.8 62

Kitchen workers/ cleaners

2.7 33 3.5 39 7.5 58

O ffice workers 1.5 22 2.0 27 4.2 44

Caretakers/craftsmen

1.0 16 1.3 20 2.8 34

AD, AMS, NA as defined in Table I I I .

39

In the regression analysis named A2 the fo llow ing factors s ig n i f i ­

can tly increased the occurrence of hand eczema: atopic derm atitis

(F=54, p<0.001), occupation (F=14.4, p<0.0001), children younger

than four years old (F=13.9, p<0.001) and lack of dish-washing

machine (F=8.6, p<0.05). From the population in th is analysis

16.4% had children younger than 4 years old and 70.4% had no d ish­

washing machine. Figure 2 shows the odds ra tio s fo r hand eczema in

atopies and non-atopics in the d if fe re n t occupations when consi­

deration was taken of the importance of the s ig n if ic a n t domestic

parameters. The predicted odds fo r the most favourable and the

most unfavourable combinations of the two s ig n if ic a n t domestic

parameters in the occupations have been outlined . The odds fo r

hand eczema in an occupation is twice as high fo r subjects w ith

the most unfavourable combination of domestic facto rs as fo r

subjects with the most favourable combination. O ffice workers w ith

an unfavourable combination of domestic parameters show as great a

r is k of developing hand eczema as wet workers w ith a favourable

combination of home fa c to rs . Wet work in combination w ith unfa­

vourable domestic facto rs increased the odds by four times com­

pared to dry work and a favourable combination of domestic fac­

to rs . The predicted p ro b a b ility of hand eczema fo r th is analysis

ranges from 18% in non-atopic o ff ic e workers w ith the most

favourable combination of domestic facto rs to 72% in nursing s ta f f

w ith atopic derm atitis and the most unfavourable combination of

domestic factors (Table V I).

40

Predicted re la t iv e o dd s ra tio

Nursing s ta ff+ C -D

10Kitchen w o rk e rs / cleaners +C - D

Nursing sta ff - C +D O ffice w orkers +C -D

Kitchen w o rk e rs / c leaners - C +D

O ffice w orkers -C +D

NA AMS AD

♦ C = children <4 yrs old- C = no « » «♦ D = d ish -w ash in g m achine- D = no

Figure 2. Predicted re la t iv e odds ra tio s fo r hand eczema in

atopies with the most favourable and unfavourable combinations of

domestic work. NA, AMS and AD as defined in Table I I I .

41

Table VI. Predicted odds ra tio s (OR) and predicted p ro b a b ility

(PP) fo r hand eczema in atopies and non-atopics w ith the most

favourable and unfavourable combinations of s ig n if ic a n t domestic

fac to rs .

NA AMS AD

OR PP%

OR PP%

OR PP%

Nursing s ta ff +C -D 4.1 48 5.5 55 11.4 72

Kitchen/cleaning +C -D 3.5 44 4.6 50 9.5 68

Nursing s ta ff -C +D 2.1 32 2.7 38 5.6 56

O ffice workers +C -D 2.0 31 2.6 37 5.5 55

Kitchen/cleaning -C +D 1.7 28 2.3 34 4.7 51

O ffice workers -C +D 1.0 18 1.3 23 2.7 38

+C = ch ildren < <% years old AD, AMS, NA as defined in-C = no children < 4 years old Table I I I .+D = dish-washing machine -D = no dish-washing machine

In the regression analysis ca lled A3 the fo llow ing facto rs were

found to influence the occurrence of hand eczema: h is to ry of

e a r lie r hand eczema (F=540, p<0.0001), h is to ry of metal derm atitis

(F=68, p<0.001) and atopic derm atitis (F=38, p<0.001). Figure 3

shows the in te rre la tio n of HHE, HMD and atopy in a summarized

schematic descrip tion of the predicted re la tiv e odds ra tio s of

hand eczema. HHE increased the odds by 12.9 times and created a

subdivision of the population in to two groups which d if fe r con­

siderably as regards r is k of developing hand de rm a titis . HMD

fu rth e r increased the odds by 1.8 times and AD and AMS by another

1.3 times. The predicted p ro b a b ility of hand eczema in th is analy-

42

s is ranges from 24% in non-atopic subjects w ithout HMD and without

HHE to 91% in subjects w ith AD, HMD and HHE (Table V II) .

Predicted re lative odds ratio

AD. AMS,• (31.0)

30

25NA (23.1)H M D •

20

AD, AMS (17.3)

15

*}* (12.9)HHE No HM D

10

HMDNo HHE ( 1.0 )No HMD

HHE HHE HHEHM D HMD

Atopy

Figure 3. Relative odds ra tio s fo r hand eczema in the various

groups during 20 months of 'wet' hospita l work. HHE=history of

hand de rm a titis ; AD, AMS, NA as in Table I I I ; HHE, HMD as in Table

IV.

43

Table V II. Predicted re la t iv e odds ra tio s (OR) and predicted

p ro b a b ility (PP) fo r hand eczema and i t s consequences in women in

wet work.

Hand eczema Medical Sick-leave Changed consulta tion work

OR PP% PP% PP% PP%

31 91 57 14 14

31 91 42 5.6 9.1

23.1 88 28 5.6 5.5

17.3 84 53 6.6 10

17.3 84 37 2.6 6.5

12.9 80 25 2.6 3.9

AD

HMD- NA

AD

j\MS

No HHE-No HMD-NA 1.0

2.4 43 48 22 14

2.4 43 34 9.5 9.1

1.8 36 22 ; 9.5 5.5

1.3 30 44 11 10

1.3 30 30 4.3 6.5

1.0 24 19 4.3 3.9

Medical consu lta tion : AD pCO.OOl, HHE p<0.01 Sick-leave: AD p<0.01, HMD p<0.05 Changed work: AD p<0.01

Severity of hand eczema. The consequences of the current hand

eczema in women in wet work as regards medical consu lta tion , s ick-

leave and term ination of work due to hand eczema were analyzed

s ta t is t ic a l ly . I t was found tha t AD (F=35.4, p<0.001) and HHE

(F=9.4, p<0.01) increased the need fo r medical consu lta tion .

Atopic derm atitis (F=6.7, p<0.01) and HMD (F=6.1, p<0.05) in ­

44

creased sick-leave and AD (F=7.3, p<0.01) increased the termina­

tions due to hand eczema. The predicted p ro b a b ility of medical

consu lta tion , sick-leave and term ination were found w ith in the

fo llow ing ranges: medical consulta tion 19-57%, sick-leave 2.6-22%,

term ination 3.9-14% (figu res as a percentage of the to ta l number

fo r current hand eczema). Figures fo r medical consu lta tion , s ick-

leave and term ination in the various groups are given in Table

V II. Table V III shows tha t vesicu lar lesions, permanent symptoms

and onset w ith in four months were s ig n if ic a n t ly more common in

subjects w ith atopic de rm a titis . 'Dry and chapped skin w ith rashes

and small cracks' was recorded as the only symptom of the current

hand eczema in 24% of subjects w ith atopic de rm a titis , in 43% of

subjects w ith atopic mucosal symptoms (p<0.01 vs AD) and in 46% of

the non-atopics (p<0.01 vs AD).

Table V I I I . Severity of hand eczema

AD ' AMS NA

Number of employees w ith hand eczema

145 119 634

% % %

Vesicular lesions 44**

22* * *

22

Permanent symptoms 20*

10***

6.1

Onset of hand eczema w ith in the f i r s t 4 months of occupation

76**

59* * *

54

*) p<0.05, versus AD; * * ) p<0.01 AD

, versus AD; * * * ) p<0.001, versus

45

Investigated patients ( I I I ) . Past or present atopic derm atitis

w ith or w ithout mucosal symptoms was found in 46% of the subjects.

Atopic mucosal symptoms w ithout a h is to ry of atopic derm atitis

were seen in 12% and 42% were considered non-atopics. A h is to ry of

metal derm atitis appeared in 41%.

E a rlie r hand eczema in investigated p a tie n ts . Hand eczema p r io r to

current employment occurred in 66.7% of the subjects. No d i f fe ­

rence was found between atopies and non-atopics in the occurrence

of previous hand eczema. The time lapse since the onset of e a r lie r

hand eczema ranged from 4 months to 30 years (mean 5 years). The

p e r io d ic ity of e a r lie r hand eczema was characterized as once or

tw ice in 7.5%, sometimes in 52.5%, often in 39.8% and permanently

in none. Occupation at the time of onset of the e a r lie r eczema was

given as wet work by 40.1%, in d u s tr ia l work by 4.2% and dry work

by 16.2%, while 39.4% did not connect the onset o f hand eczema

w ith any occupation.

Current hand eczema in investigated p a tie n ts . The current hand

eczema was considered by 92.3% of the employees to be e lic ite d by

external contacts. Water, cleaning agents, physical fa c to rs , d is ­

in fec tan ts , food s tu ffs and the wearing of gloves were the most

commonly reported causes. Contact w ith e l ic i t in g facto rs was con­

sidered to take place mostly at work by 57.2%, egually at work and

at home by 21% and mostly at home or in le isu re time by 13.8% of

the pa tien ts . A h is to ry of contact u r t ic a r ia was reported by

49/142 (34.5%) and was more common a fte r exposure to substances in

the home. Various kinds of food, cleaning agents and animals were

46

most commonly considered to provoke contact u r t ic a r ia at home and

in le isu re time. The agents most commonly reported at work were

cleaning agents, vegetables and rubber gloves.

State of current hand eczema. At the time of the in ves tiga tio n ,

100/142 patients had eczema of the hands. Recent hand de rm a titis ,

w ithout c l in ic a l signs of ongoing eczema except fo r minor erythema

and dry or chapped sk in , was seen in 42/142 pa tien ts . The f o l ­

lowing s ites of the current hand eczema were noted: in te rd ig ita l

and dorsal aspects of the fingers 82%, palms of fingers 32%, dorsa

of hands 41%, palms of hands 28% and f in g e r- t ip s 15%. Vesicles

were present in 43%, erosions and/or crusts in 33% and lic h é n i­

fic a tio n s in 11%. The lesions itched in 61% of the patients w ith

ongoing hand eczema.

The c lin ic a l p ic tu re was described as a red vesicu lar scaly eczema

in 93%, f in g e r - t ip eczema in 6% and neurodermitis in 1%. Ongoing

eczema at s ites other than the hands was seen in 35/142 (24.6%).

Atopic eczema was present in 23, metal derm atitis in 4, seborrhoic

eczema in 3, neurodermitis in 2, ichthyosis w ith eczema in 1, ex­

terna l o t i t is in 1 and nummular eczema in 1 pa tien t. From these

fig u re s , i t is obvious tha t approximately 1/3 of the patients w ith

atopic derm atitis and hand eczema had manifestations at other

s ite s .

The exogenous causes of current hand eczema were judged to be

mostly (>50%) of occupational o r ig in in 72%. Of the subjects

investiga ted, 14.8% were on sick-leave fo r some period because of

current hand eczema.

47

Contact a lle rg y . Delayed contact s e n s it iv ity was found in 45 of

the 120 patients tested. There were 71 pos itive te s ts , of which

54 were re levant. The allergens are lis te d in order of decreasing

frequency in Table IX. Of the patients tested, 68 were atopies and

52 non-atopics. No s ig n if ic a n t d iffe rence between them was seen in

the to ta l number of pos itive tests or in reactions to n icke l.

Nickel and/or cobalt a lle rgy was found in 25 of the 45 patients

w ith contact a lle rg y . Of a l l the women tested 83% had had th e ir

ears pierced. Contact a lle rg y to nickel was found in 18/88 (20.5%)

of those w ith pierced ears and in 1/18 (5.6%) of those w ithout

pierced ears. The d iffe rence is s ig n if ic a n t (p<0.05).

Table IX. Positive patch te s t reactions in 120 patients

%

nickel 18.2cobalt 7.4balsam of Peru 5.8carba mix 4.1formaldehyde 4.1benzalkonium chloride 4.1PPD mix 3.3wood tars 3.3thiuram mix 2.5*caine mix 1.8*fragrance mix 1.8colophony 1.7chromium 1.7P-phenylenedi ami ne 0.8

*) As a % of 55 patients tested.

A h is to ry of metal derm atitis was found in 33/68 (48.5%) of the

atopies and 18/52 (34.6%) of non-atopics, the d iffe rence not being

s ig n if ic a n t. Of 51 patients w ith a h is to ry of metal d e rm a titis , a

48

p o s itive patch te s t to n ickel and/or cobalt was obtained in only

19/51 (37.3%). J h e corresponding fig u re fo r atopies was 12/33

(36.4%) and fo r non-atopics 7/18 (38.9%). Among subjects w ith no

h is to ry of metal de rm a titis , a p o s itive te s t to n ickel and/or

cobalt was found in 4/35 (11.4%) of the atopies and 2/34 (5.9%) of

the non-atopics.

In only 2 out of 10 patien ts a lle rg ic to rubber chemicals was

there a c lear co rre la tion between occupational exposure to rubber

gloves and the current hand eczema.

Many patients suspected tha t they had contact a lle rgy p r io r to

patch tes ting and had tr ie d to avoid the a llergens. Although minor

exposure o f the hands to the d if fe re n t allergens was common, few

patients thought tha t contact a lle rg y played any s ig n if ic a n t ro le

as a cause of the current episode of hand eczema.

Contact u r t ic a r ia . Tables X and XI (113-135) show the figu res and

relevance fo r p os itive prick te s ts . Substances which occur in the

agents tested and known from the l i te ra tu re to e l i c i t contact

u r t ic a r ia have been lis te d in the tab les. One or more pos itive

p rick te s t reactions were seen in 32 out of 41 patients tested. In

22, the pos itive te s t(s ) was re levant. The to ta l number of posi­

tive s was 68 and the relevance to contact u r t ic a r ia on normal or

de rm atitic skin was 32/68.

49

s-03

COO) O co C +-> 05 <D +J -X co ojQ 05 Z CO jQU CCU CO CO <D O O

• r - C<D 03 S- U 0303S- O o c c

ooo

CD+->05E05 * JZ ^ i- 03 05 r- O <— Oco .c

s- >>CD -C JZ 4-> -fc -Q QJ "— '=3 t- O £_ "O O-* C

^ v — vr— Xco O-'—CO CO r-C c O03 03 .cJO JZ o05 05 *3" oS~ % - OO r—05 05 t— 03CL CL--* «\ r— ^ >>—N«3- o IX CLc o o o f o r IX O

oo r— OO O ---t— <J CL1T— (— k— 03 O *oo O OO JZ — JZ r- r— O X■--- O '— >> U XU 4-> r— *—CO f— 00 03 0303 03 03 <J r—E E r- O3 r— 3 * >> c<f- >>^- — Q. 03s- 4-> S- r- O JZ• 03 0) 03 CO 4->: cl U Q.— " C l 03 S-<13

4->5"O03

C03+■>03CL

c:o

CO

<13OC05> OO <1)03oc

oQ. OO OO 00

03E03sz4->Oi-T303>03 3 O <4— 03 4-> S- -Û =3 C O 03 "O 03 II jQ CO

0303

03+J

Q.03

coOCl.

X03JZ03

O O 03 O0 “O 03 -— Ks- 4-> 03 oo 05 CO > X3C0 r— +-> 1— o •r—

r— -C CO 03 r— r —03 OO O ■i— O 03 CÛ<J S- •r— '■—•r- 03 E >> E S-E T3 13 E 03 0) 1— o.03 X • r— -C JZ 03 03-C XI C t— O JZ 5 O COO 03 o >> 3 O <o t— CO

-o _X C L X S- +-> •r— c 0303 «— r— O 03 T3 CO s- 03 r—r— 03 05 z «— C S- -r- +-> 3 X C0 JZCL E N CL CL Q3 03 3 Z E •r— O 03E S- C O E <13 CL O* 03 r— s- r— E•r- O 03 CO O Z 05 T- •i— 05 +-> 03 3OO *+- -Q O 03 O-1— i— <j <C I c/)r—„—* OC CÛ E■-- - ■»—" LU

co -Q i-+ j 3 -p- + jC S- Ü.T 05 <J C0 S_ CO -r-O t- “O 03 -Q C Cf- *i- 05

O 03 C i— JZ > 03 03 JZ O S- C Q. O II ■ 00 *03S- <13 OS >

O - 03 • “O0303

OQ.II

CLC0Q. ..E <13 O O O C 05 < > 03

*03 'Cd

Tabl

e XI

. P

ositi

ve

pric

k te

st

reac

tions

in

41 pa

tient

s te

sted

w

ith

subs

tanc

es

repo

rted

by hi

stor

y as

e

liciti

ng

co

ntac

t u

rtic

ari

a

50

COfö CD +-> -X CO CJ -Q IÖ =3 L- CO JDU CcCD CO 03 CD O Oc

<D n3 S- U CD•i- i*_

CD S-

— 03 03 03 C\J CM CM t— t— *—LO * 0 0 O <— CM CO CM PO PO

CO CO CM CM CM *—

1 1"—" LO t— r ~ r —CO CO CM CM Oco *— t— X— _CX— ----------- O

r> OCO CO 1—O CO CD CD fö03 * - E E

O 3 r —CM * * co co *4-CO co co co co S- S- 4->r - C O O O X— T” CD CD CD

'— Q . Q . (J

CO

<DOcfö> OsJCD

aja:

COoCL

« t C O r r - r -

XLU

CCDQtL

WO O D CD<D 4-> +-> O 03

r - (O (O L L C-Q •+-> E S- fö föfö O O fÖ CD S-

4-> Q-4-> O Q . OCD03CD

>

CO '—' -»-> □= C I—cd nz03«— fO

s- s- 03 C• r—•1— C CDfÖ fö •1— •r—-C -C co c r—

co _X _c r— fÖ i—C <— fÖ co CO 4-> 03 fö CD O

CD •r— t— fÖ O o r— E*CD E E Cf— fÖ O "O •r— O CD4-> E EO •r— CDS- C sz

CL. <=c o Rel

evan

ce:

as in

Tabl

e

51

In 24 atopies a to ta l of 46 pos itive prick tests was seen, and in

17 non-atopics 22. Although the fig u re in the atopies was higher,

the d iffe rence is not s ig n if ic a n t.

Most patients w ith relevant contact u r t ic a r ia were aware of i t

p r io r to te s tin g , and i f possible they avoided the substances

responsible. Some with a pos itive te s t fo r the complex chemicals

in the hospita l screening series remembered a h is to ry of immediate

reaction on the hands espec ia lly on derm atitic skin. In a small

number of pa tien ts , predominantly those who reacted to rubber and

d is in fe c ta n ts , immediate u r t ic a r ia l reaction caused real problems

because of the d i f f ic u l t y of avoidance. In two pa tien ts , p rick

tests were po s itive to both benzalconium chloride and the emol­

l ie n t Helosan which contains i t .

Morphology of hand eczema in the bacte rio log ica l study (IV ). The

eczematous lesions sampled showed the fo llow ing morphology before

treatment: erythema w ith papules and/or in f i l t r a t io n was noted in

20/20, vesicles in 16/20, erosions, fissures and crusts were seen

alone or in combination in 14/20, signs of c l in ic a l in fec tions

w ith exsudation and yellow crusts were seen in 3/20. Because of

the lo ca liza tio n of the eczematous lesions a m a jo rity (43/56) of

a ll samples taken at the f i r s t v is i t were from fingers and only

13/56 from other parts of the hands. The extent of the eczematous

lesions was estimated as small in 4/20, medium in 14/20 and large

in 2/20 patien ts . Nine of the patients were on sick-leave during

treatment. At fo llow -up the eczematous lesions were suppressed and

the skin was e sse n tia lly normal-looking in 18/20 patients and in

the other 2/20 patients the eczema was much improved.

52

Table X II. Frequency of iso la ted bacteria before and a fte r top ica l

treatment with clobetasol propionate

Bacteria Eczema Erythema Normal skinn = 20 n = 16 n = 20

Before A f te r ^ Before A fte r Before A fte r

Aerobes

Staphylococcus aureus 18 6 13 4 8 2

S. epidermidis 6 8 7 3 6 3

S. warnerii 1 0 2 0 1 0

S. cohnii 0 0 1 0 0 0

S. ca p itis 0 0 1 1 2 0

S. hominis 1 2 2 1 3 0

S. hemolyticus 1 0 0 1 0 0

S. saprophyticus 1 0 . 0 0 0 0

Micrococcus species 3 2 1 0 1 311 31Corynebacteria 7 7 0 3 1 2 4 12)Corynebacteria 7 1 2 1 0 1 1

C o liform bacteria

ìerobes

1 0 1 0 0 0

Propionibacteria 1 0 0 0 0 0

Peptostreptococci 8 11 10 13 12 11

1) l ip o p h ilic2) n o n -lip o p h ilic3) a ll iso la tes from the non-atopic group of patients4) a fte r treatment skin was normal-looking in 18/20 patients

53

M icrobial f lo ra and e ffe c t of treatm ent. The incidence of the

iso la ted organisms is shown in Table X II. Before treatment the

incidence of S. aureus in eczema was 18/20, in erythema 13/16 and

in normal skin 8/20. Treatment w ith clobetasol propionate reduced

the incidence of S. aureus in the three sampling s ites to 6/20,

4/16 and 2/20 respective ly .

Table X I I I . Bacteria l counts' expressed as colony forming un its

(CFU) before and a fte r top ica l treatment w ith clobetasol propio­

nate

Staphylococcus Other aerobes Anaerobesaureus

CFU/cm2 CFU/cm2 CFU/cm2

Normal skin Before 1. 7*- 0.9 2.1 ± 0.9 1.9 i 1.1

n = 20 A fte r 1.1 - 0.3 1.9 t 0.7 1.9 ± 0.8

Erythema Before 3.4 - 1.4 2.5 - 0.9 2.2 - 1.1

n = 16 A fte r 1.3 - 0.6 2.1 - 0.7 2.2 ± 1.0

Eczema Before 4.8 ± 1.5 2.4 ± 1.2 1.9 ± 1.4**

n = 20

-----------------

A fte r 1.3 ±

_L_

0.6 2.4 ± 0.8 1.9 t 1.0

* +** 10.log, geometric mean - SDa fte r treatment skin was normal-looking in 18/20 pa tien t

54

?The bacteria l geometric mean counts/cm before and a fte r treatment

are shown in Table X I I I . The mean density before treatment of2 2 aureus in eczema was 56 000 cfu/cm , in erythema 2 600 cfu/cm

2and in normal skin 45 cfu/cm . The mean count of S. aureus in

the three s ites d if fe rs s ig n if ic a n t ly (p<0.01). Treatment reduced

the counts of S. aureus in the three sampling s ites s ig n if ic a n t ly :

in e a r lie r eczema to 22 cfu/cm (p<0.001), in previous erythema to

21 cfu/cm^ (p<0.001) and in normal skin to 13 cfu/cm^ (p<0.05).

The occurrence of other aerobes or anaerobes did not d i f fe r s ig n i­

f ic a n t ly in the three sampling s ites before treatment. Nor was

there a s ig n if ic a n t reduction in the geometric mean count of these

bacte ria l groups in the three s ites a fte r treatment.

Before treatment 5. aureus constitu ted 89% of the to ta l aerobic

f lo ra in eczema, 73% in erythema and 41% in normal skin. A fte r

treatment S. aureus constitu ted 21%. of the to ta l aerobic f lo ra in

eczema, 22% in erythema and 24% in normal skin. Before treatment5 25. aureus was found in densities exceeding 10 cfu/cm in the

eczematous lesions of 15 pa tien ts . Only 1 patien t had more than6 o

10 cfu/cm . The three patients w ith c l in ic a l signs of in fec tion

had the fo llow ing counts fo r S. aureus: 3.0 x 10^, 3.2 x 10^ andfi o

2.3 x 10 cfu/cm . The two patients who did not carry 5. aureus in

th e ir eczematous lesions were non-atopics. The mean count fo r S.

aureus in the atopies did not d i f fe r s ig n if ic a n t ly from the

counts tha t were found in the non-atopics.

55

F if ty fre sh ly iso la ted c l in ic a l s tra ins of S. aureus were tested

fo r the an tibac te ria l e ffe c t of clobetasol propionate in v i t r o . No

in h ib ito ry e ffe c t of the substance was demonstrated in the dose

range tested.

56

D I S C U S S I O N

The cohort and* patients stud ied. The cohort in th is study was

dominated by young women newly employed in four Swedish hosp ita ls .

Therefore the conclusions may be considered relevant only fo r

s im ila r ind iv idua ls in s im ila r working conditions. However, as the

ind iv idua l factors were found to be most important in the e tio logy

of hand eczema, the main find ings are probably s ig n if ic a n t fo r

young women in the general population.

The patients w ith hand eczema who were c l in ic a l ly investigated

are not representati ve of the general population. These patients

represent the top of the epidemiologic iceberg of hand eczema and

r is k ind iv idua ls are overrepresented. This indicates that i t is

not possible to draw u n c r it ic a l conclusions of the nature o f hand

eczema in the population from a selected group of patien ts.

This study shows tha t most eczemas are m ild , pe riod ic , often s e lf-

lim it in g and in many cases they can be dealt w ith by s e lf - t r e a t ­

ment measures.

The patients with hand eczema in the bacte rio log ica l study were

consecutive out-pa tien ts in a dermatologie department and were not

selected except according to the exclusion c r i te r ia and the accep­

tance requirements fo r p a rtic ip a tio n in th is p a rticu la r study.

Methodological aspects. The prospective cohort study design used

in th is investiga tion has many advantages over retrospect!*ve

57

epidemiologic studies. The design makes i t possible to quantita te

and compare the re la t iv e importance of ind iv idua l and environ­

mental fac to rs . Furthermore i t is possible to fo llow the f i r s t

period of employment in a r is k occupation. I t must be assumed that

th is period provides the most su itab le opportunity fo r revealing

ind iv idua l d ifferences as regards the r is k of developing hand

eczema. Various measures w ith the passage of time w i l l probably

equalize the d ifferences between the groups. Thus patients w ith

hand eczema w i l l reduce i r r i t a n t exposure, use em ollients or

top ica l co rtico -s te ro ids and high r is k ind iv idua ls especia lly w i l l

change th e ir work and get lo s t in re trospective studies.

Follow-up in the cohort study was done by questionnaire. The f in a l

questionnaire was designed a fte r a p ilo t-s tu d y on 400 employees

using a tes t questionnaire. The to ta l response rate to the fo llo w -

up questionnaire was acceptable and the p a rtia l drop-out ra te fo r

the various questions was lim ite d to a few percent.

I t was not possible to study the prevalence of hand eczema by

means of c l in ic a l examination of each episode of eczema fo r the

whole cohort over a period of 20 months. Therefore, we had to

re ly on anamnestic inform ation about hand eczema given in the

fo llow -up questionnaire. The combination of information about the

symptomatology of hand eczema given before employment followed by

a questionnaire was found to be a re lia b le way of diagnosing hand

eczema.

58

Atopy has been diagnosed exc lus ive ly by case h is to ry . This im­

poses lim ita t io n s , but i t is simple and p ra c tic a lly useful in a

large epidemiological study. As no absolute diagnostic c r i te r ia

fo r atopic disease e x is t we have accepted th is compromise.

Prevalence o f hand eczema. The prevalence of hand eczema in women

p r io r to th e ir current employment in wet work was 22.4% which

corresponds to the fig u re found in a study of a randomized sample

of Danish women (5 ). Thus any selection of the studied cohort

regarding previous hand eczema is u n like ly .

The prevalence of hand eczema amongst those engaged in wet hospi­

ta l work in th is study is s im ila r to the one found by

Lammintausta (6). Lower prevalence figures have been found in

other studies (47, 137, 138). The possible reasons fo r these d is ­

crepances have been given e a r lie r . The low fig u re fo r the occur­

rence of hand eczema in occupations dominated by men v e r if ie s

previous find ings of the sex d iffe rence (1-4).

Prevalence o f atopy and metal d e rm a titis . The prevalence figures

fo r atopy obtained in our study are somewhat higher than the 15.1%

found by Kjellman (11) in a study where he questioned 7-year-old

ch ild ren in Sweden. Several investiga tions e x is t and varying

figu res fo r atopy have been found (6 ).

The high fig u re fo r metal de rm atitis may be explained by the fa c t

tha t the cohort consists predominantly of young women w ith common

exposure to metals.

59

Ind iv idua l r is k facto rs fo r hand eczema. When atopic derm atitis

was used as a r is k fa c to r fo r developing hand eczema without

considering e ithe r previous hand eczema or metal derm atitis i t

was found to increase the odds approximately three times. This

increase was seen in wet as well as in dry work. The figures fo r

hand eczema among wet work employees with atopic derm atitis are

s im ila r to those found in a previous study (6).

The regression analysis on women in wet work c le a rly demonstrated

the great importance of information about e a r lie r hand eczema and

metal de rm atitis . I t is obvious tha t many ind iv idua ls w ith e a r lie r

hand eczema w il l su ffe r from recurrency i f they are engaged in wet

work. These high r is k ind iv idua ls cons titu te approximately h a lf of

the subjects w ith AD, one quarter of the subjects w ith AMS and one

f i f t h of the non-atopics.

One possible explanation fo r the great importance of e a r lie r hand

eczema is tha t there is an endogenous ch a ra c te ris tic of the sk in ,

a skin v u ln e ra b ility fa c to r, which predisposes the person to

develop i r r i t a n t hand de rm a titis . As the population consists of

women, i t may be assumed tha t they have been exposed to some

degree of i r r i t a n t occupational and domestic work in the past

which sometimes, but not always, may have caused hand eczema. Thus

e a r lie r hand eczema may be considered a major ind ica to r of th is

endogenous fa c to r, which may correspond to the 'a top ic skin d ia ­

th e s is ' as defined by Lammintausta. This assumption is supported

by Lammintausta who id e n tif ie d 'a top ic skin d ia thes is ' in 1/3 of

the subjects w ith AMS and in 19% of the non-atopics. Atopic skin

60

d ia thesis involved a s ig n if ic a n t ly increased r is k of developing

hand eczema. No id e n tif ic a tio n of th is atopic skin d ia thesis was

made in subjects w ith atopic de rm a titis . I t was, however, found in

both Lammintausta's and Rystedt's studies tha t a considerable

number of employees w ith atopic derm atitis had managed to work in

wet occupations w ithout developing hand eczema. In the present

study 39% of the subjects w ith AD reported no occurrence of hand

eczema and these were predominantly subjects w ithout e a r lie r hand

de rm a titis .

The importance of endogenous fac to rs in the e tio logy of hand

eczema in subjects w ith atopic derm atitis is underlined in a study

by Rystedt (9 ). In a report by Forsbeck et a l. (28) i t was found

tha t 50% of the subjects w ith AD and current eczema had th e ir

f i r s t bout of eczema p r io r to th e ir f i r s t employment. In another

re trospective study on occupational* dermatosis i t was found tha t

the re la t iv e odds of developing occupational skin diseases were

calculated to be 13.5 times higher in atopies than in non-atopics

(139).

There are other possible explanations fo r the great importance of

a h is to ry of hand eczema. For example hand eczema in the past may

leave a non-restored skin b a rrie r fo r a long time and thus in ­

crease the r is k of recurrency (140, 141).

A co rre la tion between hand eczema and a h is to ry of metal dermati­

t is could be found on two levels in th is study. At both leve ls

61

HMD increased the odds by 1.8 times. According to the hypothesis

presented h igh -risk subjects are those with HMD and an inherited

d ispos ition to i r r i t a n t hand eczema occurring predominantly in

atopies. This hypothesis is supported by a find ing by Peltonen

(142) that almost a ll n ickel sens itive females a f f l ic te d w ith hand

eczema were atopies. Further support is provided by the find ing

tha t hand derm atitis in n ickel sens itive females seems to fo llow

one of two causes: mild and trans ien t or chronic and d isab ling

(143). In addition i t was reported tha t atopy made the prognosis

fo r hand eczema worse in n ickel sens itive women.

Severity of hand eczema. Most hand eczemas were mild w ith period ic

symptoms and the employee could handle the disorder using s e lf ­

treatment methods. Most subjects w ith hand eczema also managed to

work during the observation period and the figures fo r s ick-leave

were very low in most groups thus confirm ing previous find ings

that most hand eczemas are mild (6).

Subjects w ith atopic de rm atitis developed a more severe hand

eczema than subjects w ith atopic mucosal symptoms and non-atopics.

This d iffe rence in seve rity was not observed by Lammintausta (6)

perhaps because her study was re trospective and subjects w ith

atopic derm atitis who get severe hand eczema early on in th e ir

careers might have le f t th e ir jobs and thus have been lo s t to the

study.

Occupational and domestic fac to rs in hand eczema. Wet work only

doubled the odds of developing hand eczema over dry o ff ic e work.

62

This d iffe rence between a high r is k and a low r is k occupation is

unexpectedly small. One explanation may be tha t the population

consists of women and i t must be assumed that they are exposed to

a considerable amount of i r r i t a n t domestic work. Two anamnestical-

ly ava ilab le parameters of domestic work namely 'nursing of

ch ild ren younger than 4 years o ld ' and 'no dish-washing machine'

were found to co rre la te s ig n if ic a n t ly w ith the occurrence of hand

eczema, probably because they increased the i r r i t a n t load to above

the average le ve l. These find ings v e r if ie d the c l in ic a l experience

tha t the nursing of small ch ildren often gives r ise to hand eczema

amongst women. Furthermore i t seems ju s t i f ie d to recommend the use

of dish-washing machines to people su ffe ring from hand eczema.

The re la t iv e importance of wet work may be greater in patients

w ith a vulnerable skin fa c to r. This assumption could not be docu­

mented in the present study as no comparison was possible between

wet and dry work regarding previous hand eczema and metal dermati­

t i s . However, the c lin ic a l investiga tion of the women in wet work

w ith hand eczema supports th is assumption as most of these high

r is k ind iv idua ls claimed tha t th e ir hand eczema had been e lic ite d

by t r i v ia l i r r i ta n ts .

Contact a lle rgy and hand eczema. The patients w ith hand eczema who

were patch tested had been exposed to the current wet work fo r 20

months at the most. Thus i t must be assumed that sens itiza tion in

most patients w ith contact a lle rg y must have occurred p r io r to

the current work. This assumption is supported by the find ing tha t

63

no sens itiza tion occurred in connection w ith the spec ia lly de­

signed hospita l patch te s t series. Although sens itiza tion has

occurred e a r lie r , hand eczema may recur a fte r occupational or

domestic exposure to re levant a llergens. Nevertheless, most em­

ployees with contact a lle rgy could not corre la te the current

episode of hand eczema to any obvious exposure to the a llergen. I t

must however be emphasized tha t allergens such as n ickel and

balsam of Peru are very common in the environment and some expo­

sure of the hands is in e v ita b le . Delayed contact s e n s it iv ity was

seen in 38% of the patients tested. In another study of hospita l

workers, a pos itive patch te s t was found in 38% of the patients

who had consulted an occupational doctor, and in 26% of a ll

patients tested who had e a r lie r or current hand derm atitis (6 ).

The frequency of contact a lle rg y to ind iv idua l allergens was

esse n tia lly s im ila r to that of a previous study of hospita l wet

workers w ith hand derm atitis (6 ). One probable reason fo r the

high fig u re fo r nickel a lle rgy is tha t the patients were predomi­

nantly young women, a large number of whom had pierced th e ir ears,

which g rea tly increases the r is k of n ickel a lle rgy (144, 145).

These find ings were v e r if ie d in the present study.

Contact a lle rgy to metals in subjects w ith metal derm atitis

Contact a lle rgy to n ickel and/or cobalt was found in only 37.3% of

the subjects w ith a h is to ry of metal de rm a titis . In two previous

stud ies, contact a lle rg y to metals was found in 58% and 70% re ­

spective ly , of women w ith a h is to ry of metal derm atitis (4, 5). A

study by Boss & Menné (144) indicates tha t a h is to ry of metal

derm atitis is re levant in most cases. They found tha t although

64

only 5/13 women with a h is to ry of metal derm atitis were a lle rg ic

to n icke l, 12/13 developed derm atitis when exposed to the su­

spected ear ring fo r 48 hours. The i r r i t a n t e ffe c t of n ickel is

one possible explanation fo r the non-a lle rg ic cause of metal

derm atitis (146). Patients in the present study were mainly women

w ith optimal exposure to metals through pierced ears. Furthermore,

atopies were overrepresented. In two recent studies i t has been

shown tha t a pos itive h is to ry o f metal derm atitis w ith negative

te s t is common in atopies (147, 148). These facts may explain the

high figu re fo r non-a lle rg ic metal de rm atitis .

Contact u r t ic a r ia and hand eczema. Contact u r t ic a r ia w ith a wheal-

and-fla re reaction on normal skin is eas ily recognized by an

exposed ind iv idua l and i f possible he/she should avoid e l ic i t in g

agents. However, contact u r t ic a r ia does not always appear in the

form of a d is t in c t whealing reaction . In non-immunological contact

u r t ic a r ia , the concentration and nature of the u rtica riogen ic

substances p a r t ic u la r ly in fluence the strength of the reaction . A

low, suboptimal concentration may provoke erythema, while a high

concentration may provoke u r t ic a r ia (79). Sometimes repeated

exposure may be necessary (113). Exposure of derm atitic skin may

e l i c i t contact u r t ic a r ia and thus the u rtica riogen ic substances

may be of c l in ic a l relevance fo r de rm atitic but not fo r normal

skin (88-90). The case h is to rie s of some patients indicated tha t

contact u r t ic a r ia was re levant only fo r derm atitic skin on the

hands.

65

Prick tests have been performed to trace u rtica riogen ic substances

in the present study. A prick te s t should be in terpreted as posi­

t iv e only with caution. However, substances which produce a posi­

t iv e prick tes t do have u rtica riogen ic properties which may be of

c l in ic a l relevance, espec ia lly in derm atitic skin i f exposure is

op tim a l.

In patients with a h is to ry of contact u r t ic a r ia , p rick tes ting was

carried out fo r two d if fe re n t reasons. F ir s t ly , anamnestically

suspected agents were tested, and secondly a screening series was

carried out w ith substances in common use at the hosp ita l. The

relevance of the pos itive reactions varies according to the two

reasons fo r te s tin g . When the te s t was motivated by the h is to ry , a

pos itive re su lt was re levant fo r contact u r t ic a r ia . Judging the

relevance of a pos itive prick te s t in the series is d i f f i c u l t .

Some patients w ith a pos itive te s t did have a pos itive h is to ry ,

and fo r them the relevance seems obvious. In subjects w ith a

negative h is to ry , a po s itive te s t is probably of less c lin ic a l

s ign ificance . Some patients may, however, have had signs of weak

immediate reactions on eczematous skin which have not been recog­

nized as contact u r t ic a r ia .

Most reports of contact u r t ic a r ia are lim ited to one or a few

cases. L i t t le is known about the prevalence and the relevance in

d if fe re n t populations w ith hand eczema (8). Figures in the present

study ind icate tha t contact u r t ic a r ia may be common. Most of the

d iffe re n t kinds of food which produced pos itive prick tests in

th is study are known from the l i te ra tu re to provoke contact u r t i ­

ca ria .

66

Formaldehyde has been reported as a cause (113-115). A p rick te s t

w ith formaldehyde 0.1-0.6% produced a weak reaction in the study

by Anderson & Maibach (113). The high concentration used in th is

study may explain the high frequency of pos itive te s ts . A labora­

to ry assistant w ith occupational exposure to formaldehyde was the

only pa tien t w ith a re levant prick te s t.

Rubber is another well-known u rtica riogen ic substance (116-

119). Apart from natural la tex , the glove tested contained zinc-

d iethyl-d ith iocarbam ate (ZDC) which may induce contact u r t ic a r ia

(120). The high frequency of pos itive prick tests may ind ica te a

non-immunological u rtica riogen ic e ffe c t of the glove. This is

based on the fa c t tha t substances w ith non-immunological u r t i ­

cariogenic properties give r ise to contact u r t ic a r ia in a large

number of exposed ind iv idua ls (79). This view is supported by the

common occurrence of skin complaints in connection w ith th is

p a rtic u la r glove. Apart from the rubber glove, few pos itive prick

tests to the complex chemicals were found. Most of them contained

one or more substances known to e l i c i t contact u r t ic a r ia . Further

investiga tions are needed to id e n tify the substance responsible

and to c la r i fy the nature and c lin ic a l s ign ificance of the posi­

t iv e tests found.

Staphylococcus aureus in hand eczema. This study shows tha t hand

eczema in atopies as well as in non-atopics is regu la rly colonized

by S. aureus in quan titie s s im ila r to those found in atopic derma­

t i t i s (105). Severe atopic derm atitis has shown higher densities

° f S. aureus in some investiga tions (104, 149). Colonization by S.

67

aureus seems to p a ra lle l the severity of the eczema and c lin ic a l

signs of pyoderma are lacking in most cases in sp ite of S. aureus 5 2counts >10 cfu/cm . Absence of c lin ic a l pyoderma in sp ite of high

counts of S. aureus has also been found in studies on atopic

derm atitis (104, 105).

The densities of S. aureus a fte r top ica l treatment w ith a potent

co rticos te ro id were equal in normal skin and healing eczematous

lesions and were s im ila r to those found by McBride et a l. (97) on

the skin of normal hands. The density of other aerobes and anae­

robes did not d i f fe r between eczematous lesion and normal skin

before treatment and no s ig n if ic a n t changes were caused by the

top ica l co rtico s te ro id . These find ings are in agreement w ith a

study by Chan et a l. (150) in which no s ig n if ic a n t d iffe rence in

the m icro flo ra of normal skin was caused by the app lica tion of

triamcinolone acetonide compared to white petrolatum base. The

density of aerobes other than 5. aureus found in th is study are

s im ila r to previous find ings on the palms of healthy ind iv idua ls

(151).

A ll iso la tions of a l ip o p h il ic corynebacteria in our study were

obtained from non-atopics. This is in accordance w ith a study by

Aly et a l. (105) on atopic derm atitis where no l ip o p h ilic coryne-

bacteria were found in the lesions and very few on normal skin.

From these observations i t seems possible that atopic skin might

d i f fe r from non-atopic skin in i ts colonization^ by l ip o p h ilic

corynebacteria.

68

In te rm itte n t treatment w ith clobetasol propionate during 14 days

produced a h igh ly s ig n if ic a n t reduction and sometimes e lim ina tion

of S. aureus. A study by Leyden & Kligman (149) on atopic derma­

t i t i s showed a s lig h t but non -s ign ifican t reduction of S. aureus

a fte r one week's treatment w ith 0.25% fluocinolone acetonide.

The higher mean count of 5. aureus, the less potent s tero id and

the shorter treatment period in th e ir study are a ll possible

explanations fo r the d iffe rence found. Our find ings also contrast

w ith those of Marples, Rebora & Kligman (152) who studied the

e ffe c t of triamcinolone acetonide 0.1% on the growth of a sing le

S. aureus s tra in which had been inocculated in experimental skin

lesions. This study found tha t the stero id suppressed the experi­

mental lesions but did not influence the m u ltip lic a tio n of the

bacteria .

Normal skin has an e f f ic ie n t defence against fore ign microorga­

nisms. Many d iffe re n t mechanisms are of importance in th is

defence. In the eczematous lesion one or more of the defense

mechanisms may be disturbed and favour the co lon ization of bacte­

r ia (153). The reason fo r the se lec tive , heavy co lon ization of S.

aureus in hand eczema is unknown. I t is well-known, however, tha t

prote in A in the ce ll wall o f S. aureus has a high a f f in i t y to IgG

(154) and to fib ro n e c tin (155). Both IgG and fib ro n e c tin might be

present in eczematous les ions, which in turn could favour staphy­

lococcal co lon ization and m u lt ip lic a tio n . Therefore a suppression

o f the eczematous inflammation by the potent top ica l c o rtic o ­

s te ro id may elim inate the prerequ is ites fo r the co lon ization of S.

aureus and o ffe r a possible in te rp re ta tio n of our re su lts .

69

Corticostero ids in therapeutic concentrations have been re ­

ported to in h ib it the metabolism of certa in microorganisms in ­

cluding S^_aureus (156). However, th is explanation is less l ik e ly

since we were unable to demonstrate an in h ib it io n of the growth in

v it r o of 50 d if fe re n t s tra ins of S. aureus by clobetasol pro­

pionate in the dose range 16-2000 mg/ml.

70

S U M M A R Y A N D C O N C L U S I O N S

1. The odds fo r developing hand eczema in wet occupations domi­

nated by women (nursing/kitchen/clean ing work) was only approxi­

mately twice tha t of dry o ff ic e work. Most eczemas even in wet

work were mild and period ic and only a few gave r ise to s ick-

leave. Many sufferers could handle the disorder using s e lf ­

treatment measures.

2. An increase in the i r r i t a n t domestic load on women's hands

through nursing babies and the simultaneous lack of a dish-washing

machine w il l increase the r is k of hand eczema as much as a wet

work.

3. A h is to ry of atopic derm atitis increased the odds of deve­

loping hand eczema approximately three times both in wet and in

dry work. As a s ing le fa c to r information about previous atopic

derm atitis was of lim ite d value as a pred ictor of the r is k of

developing hand eczema.

4. For women with a previously manifested d ispos ition towards

hand eczema, the odds of developing hand eczema was 12.9 times

higher than fo r those w ith no previous hand eczema i f they go in to

wet hospital work. This increase in the r is k of hand eczema was

great and created a subdivision of atopies and non-atopics in a

high r is k group and a norm al-risk group. Half the subjects w ith

atopic de rm a titis , one quarter of the subjects w ith atopic mucosal

symptoms and one f i f t h of the non-atopics belonged to th is high

71

r is k group. This find ing indicated tha t among atopies as well as

non-atopics there are two subgroups which d if fe r considerably re ­

garding the r is k of developing hand eczema.

5. A h is to ry of metal derm atitis increased the odds of developing

hand eczema by a fac to r of 1.8. This increase was seen in in d i­

viduals in one high r is k and one normal r is k leve l. Metal dermati­

t is may develop as a cause of contact a lle rgy and probably through

the i r r i t a n t or other e ffec ts of metals. Metal derm atitis was more

common in subjects w ith vulnerable skin.

6. Information about atopic disease as a supplement to in fo r ­

mation about previous hand eczema and metal derm atitis was of very

lim ite d value when p red ic ting the r is k of developing hand eczema

in women who s ta r t wet work. One important observation was however

tha t subjects w ith previous atopic derm atitis w i l l su ffe r from a

more severe hand eczema.

7. By means of simple anamnestic information about e a r lie r hand

eczema, metal derm atitis and atopic disease i t was possible to

obtain a very d iffe re n tia te d prognostic information about hand

eczema and its consequences in women in wet hospita l work.

8. In wet work employees w ith a d ispos ition to hand eczema who

seek medical advice fo r current hand eczema, t r i v ia l i r r i ta n ts in

wet and domestic work played an important part in the e tio logy of

the current hand de rm a titis . Contact a lle rg y and contact u r t ic a r ia

were f a i r ly common. However, in most patients contact a lle rg y and

contact u r t ic a r ia seemed to be of minor importance in the e tio logy

of the hand eczema.

72

9. Hand eczema was commonly colonized by S. aureus in high counts

in atopies as well as in non-atopics. The density of S. aureus was

high even i f the eczema showed no signs of c l in ic a l in fe c tio n .

Successful top ica l treatment of the eczema w ith a potent c o rtic o ­

ste ro id s ig n if ic a n t ly reduced or elim inated the co lon ization of

S. aureus.

73

A C K N O W L E D G E M E N T S

I wish to express my sincere g ra titude and appreciation to :

Associate professor Ove Bäck fo r his continuous, s tim u la ting s c ie n t if ic guidance throughout these investiga tions . Without his p o s itive c r it ic is m and encouraging support th is work would never have been completed. I t has been a p r iv ile g e fo r me to have Ove as my supervisor and mentor.

Associate professor Lennart Gip, head of the department of derma­to logy, Sundsvall ho sp ita l, fo r his great in te re s t and fr ie n d ly support during th is study.

Associate professor Bo Mikaelsson fo r unvaluable p a rtic ip a tio n in the planning of the epidemiological part of the study.

My co-authors, Claes Henning, MD, Sture Andersson, PhD (in memorial), Marie-Louise H jö rle ifsson , BS, fo r very pleasant and valuable co llabora tion .

Professor Sture Liden and professor S ig fr id Fregert fo r importantadvice in the planning of th is study.

Mrs Vivianne Enqvist fo r p a tie n t, exce llen t secre ta ria l assistance and fo r her always fr ie n d ly and he lp fu l a ttitu d e to the work. Her s k i l fu l typing and never ending support have been a p re requ is ite fo r completing th is study.

Ms B irg it ta Lagerlind and Mrs Siv Carlsson fo r unvaluable secre­ta r ia l work w ith the numerous questionnaires.

Mrs U lla Berg fo r s k i l fu l te s ting of the patien ts.

Associate professor Hans Nyqvist fo r s ta t is t ic a l assistance.

Colleagues and nurses at the Occupational Health Care of Väster­norrland fo r th e ir extremely valuable con tribu tion to th is study.

Colleagues and s ta f f at the Department of Dermatology, Sundsvall Hospital and the Department of Dermatology, U n ivers ity H ospita l, Umeå fo r constant encouragement.

My w ife Ingrid and my daughters Karin and Helena fo r a ll th e ir patience, love and support through a ll the years.

This investiga tion was made possible by generous grants from the Swedish Work Environment Fund (ASF) 79/58.

74

R E F E R E N C E S

1. Agrup G. Hand eczema and other hand dermatoses in southSweden. Acta Derm Venereo! (Stockh) 1969;49 suppl 61.

2. Peltonen L. Nickel s e n s it iv ity in the general population.Contact Dermatitis 1979;5:27-32.

3. Kavli G, Ftfrde OH. Hand dermatoses in Tromstf. Contact Derma­t i t i s 1984;10:174-177.

4. Lantinga H, Nater JP, Coenraads PJ. Prevalence, incidenceand course of eczema of the hands and forearms in a sampleof the general population. Contact Dermatitis 1984;10:135-139.

5. Menné T, Borgan 0, Green A. Nickel a lle rgy and hand dermati­t is in a s t ra t i f ie d sample of the Danish female population: an epidemiological study including a s ta t is t ic appendix. Acta Derm Venereol (Stockh) 1982; 62:35-41.

6. Lammintausta K. Risk facto rs fo r hand derm atitis in wetwork. Academic d isse rta tio n , Turku, 1982.

7. Rook A, Wilkinson DS, Ebling FJG (eds). Textbook of dermato­logy, 3rd e d itio n . Oxford: Blackwell Sci Pubi, 1979:329-331.

8. Epstein E. Hand d e rm a titis : p rac tica l management and current concepts. J Am Acad Dermatol 1984;10:395-424.

9. Rystedt I . Hand eczema and long-term prognosis in atopic de rm atitis . Acta Derm Venereol (Stockh) 1985;65 suppl 117.

10. Edfors-Lubs ML. A lle rgy in 7000 twin pa irs . Acta A lle rgo l 1971;26:249-285.

11. Kjellman M. Atopic disease in 7-year-old ch ild ren . Acta Pediatr Scand 1977;66:465-471.

12. Besnier E. Premiere note et observations p ré lim ina ire pour se rv ir d 'in tro d u c tio n à l'e tu de des prurigos diathésiques. Ann Dermatol S yph ilig r 1892;3:634-648.

13. Coca AF, Cooke RA. On the c la s s if ic a tio n of the phenomena of hypersensitiveness. J Immunol 1923;8:163-182.

14. Prausnitz C, Ktistner H. Studien Liber die Überempfin d i ich- ke it.Z b l Bact 1921;86:160-169.

15. Ischizaka K, Ischizaka T, Hornbrook MM. Physicochemical properties of reagin ic antibody. V. Correlation of reagin ic a c t iv ity w ith E-globulin antibody. J Immunology 1966;97:840- 853.

75

16. Johansson SGO. Raised leve ls of a new immunoglobulin class (IgND) in asthma. Lancet 1967 ; i i : 951-953.

17. Rowe DS, Tackett L, Bennich H, Ischizaka K, Johansson SGO, Andersson SG. A research standard fo r human serum immunoglo­bu lin E. B u lle tin of the World Health Organization 1970;43: 609-611.

18. Johansson SGO, Bennich H, Berg T. The c lin ic a l s ign ificance of IgE. Progr C lin Immunol 1972;1:157-168.

19. Johansson SGO. In v it ro diagnosis of reagin mediated a l le r ­gic diseases. A lle rgy 1978;33:282-298.

20. Hanifin J. Atopic de rm a titis . J Am Acad Dermatol 1982;6:1-13.

21. Atherton DJ. A lle rgy and atopic eczema I. C lin Exp Dermatol 1981;6:191-203.

22. öhman S, Juhlin L, Johansson SGO. Immunoglobulins in atopic de rm atitis . Excerpta Med*1972;119-126.

23. Hanifin JM, Rajka G. Diagnostic features of atopic dermati­t i s . Acta Derm Venereo! (Stockh) 1980;60 suppl 92:44-47.

24. Bandmann HJ, Agathos M. Die atopische Handdermatitis. Derma­tosen in Beruf und Umwelt 1980;28:110-113.

25. Glickman FS, S ilvers SH. Hand eczema and atopy in house­wives. Arch Dermatol 1967;95:487-489.

26. Cronin E, Bandmann HJ, Calnan CD, Fregert S, H jorth N,Magnusson B, Maibach HI, Malten K, Meneghini CL, P ir i lä V,Wilkinson DS. Contact derm atitis in the atop ic. Acta DermVenereol (Stockh) 1970;50:183-187.

27. B re it R, Leutgeb Ch, Bandmann HJ. Zum neurodermi tischenHandekzem. Arch Dermatol Forsch 1972;244:353-354.

28. Forsbeck M, Skog E, Asbrink E. Atopie hand de rm a titis : Acomparison w ith atopic derm atitis w ithout hand involvement, especia lly w ith respect to influence of work and development of contact se n s itiza tio n . Acta Derm Venereol (Stockh) 1983;63:9-13.

29. Wilkinson DS, Bandmann HJ, Calnan CD, Cronin E, Fregert S,H jo rt N, Magnusson B, Maibach HI, Malten KE, Meneghini CL,P ir i lä V. The ro le of contact a lle rgy in hand eczema. Trans St John's Hosp Dermatol Soc 1970;56:19-25.

30. Rook A, Wilkinson DS, Ebling FJG (eds). Textbook of dermato­logy, 3rd ed, Oxford: Blackwell Sci Pubi, 1979:363.

76

31. Dowling GB, Naylor PFD. Defence mechanisms of the skin against a lka line substances. Trans St John's Hosp Dermatol Soc 1960;44:12-34.

32. Kligman AM. The biology of the Stratum Corneum. In: The Epi­dermis. Ed: Montagna W & Lobitz WC Jr. New York, AcademicPress. 1964:387-433.

33. Epstein W, Maibach HI. Cell renewal in human epidermis. Arch Dermatol 1965;92:462-468.

34. Weinstein GD, Van Scott EJ. Autoradiographic analysis of turnover times of normal and p so ria tic epidermis. J Invest Dermatol 1965;45:257-262.

35. Smeenk G. The influence of detergents on the skin : ac lin ic a l and biochemical study. Arch K lin Exp Dermatol 1969;235:180-191.

36. Smeenk G, Polano MK. Methods fo r comparative estimation of the ir r ita n c y of various detergents on human skin. Trans St John's Hosp Dermatol Soc 1965;51:220-232.

37. Blank IH. Cutaneous b a rrie rs . J Invest Dermatol 1965;45:249- 256.

38. Blank IH. The mechanism of the action of soaps and deter­gents on the skin. In: The Evolution of Therapeutic Agentsand Cosmetics. Ed. Sternberg TH & Newcomer VD.New York, Me G raw-H ill, 1964:80-85.

39. Middleton JD. The mechanism o f.a c tio n of surfactants on the water binding properties of iso la ted stratum corneum. J Soc Cosmet Chem 1969;20:399-412.

40. Middleton JD. The mechanism of water binding in stratum corneum. Br J Dermatol 1968;80:437-450.

41. Rook A, Wilkinson DS, Ebling FJG (eds). Textbook of dermato­logy, 3rd ed, Oxford: Blackwell Sci Pubi, 1979:364.

42. Malten KE, Spru it D, Boemaars HD et a l: Horny layer in ju ry by solvents. Berufsdermatosen 1968;16:135-147.

43. Shahidullah M, R affle EJ, Rimmer AR, Fra in-Bell W. Transepi- dermal water loss in patients w ith de rm atitis .Br J Dermatol 1969:81:722-730.

44. Spruit D, Malten KE. Estimation of the in ju ry of human skin by a lka line liq u id s . Berufsdermatosen 1968;16:135-147.

45. Hagerman G. 'T raum ite ra tive ' ( to x ic ) eczema. Dermatologica 1957;115:525-529.

46. Fregert S. Occupational derm atitis in a 10-year m ateria l. Contact Derm atitis 1975;1:96-107.

77

47. Stagis H. Occupational derm atitis among hospita l cleaners. Academic d isse rta tio n , U n ivers ity of Aarhus, Aarhus 1976.

48. Calnan CD, Bandmann HJ, Cronin E, Fregert S, H jorth N,Magnusson B, Malten K, Meneghini CL, P ir i lä V, Wilkinson DS. Hand derm atitis in housewives. Br J Dermatol 1970;82:543- 548.

49. Marks R, Cronin E. Hand eczema in hairdressers. Australas J Dermatol 1977;18:123-126.

50. Cronin E, Kul 1i vanijaya P. Hand derm atitis in hairdressers. Acta Derm Venereol (Stockh) 1979:59 suppl 85:47-50.

51. Björnberg A. Skin reactions to primary i r r i ta n ts in pa­tie n ts w ith hand eczema. Isacsons T ryckeri, Gothenburg 1968.

52. Kligman AM, Wooding WM. A method fo r the measurement andevaluation of i r r i ta n ts on human skin. J Invest Dermatol 1967;49:78-94.

53. Kligman AM, Epstein W. Updating the maximization te s t fo rid e n tify in g contact a llergens. Contact Derm atitis 1975;1 : 231-239.

54. Jordan WP. A lle rg ic contact derm atitis in hand eczema. Arch Dermatol 1974;110:567-569.

55. Rook A, Wilkinson DS, Ebling FJG (eds). Textbook of dermato­logy, 3rd ed, Oxford: Blackwell Sci Pubi, 1979:481.

56. Palacios J, F u lle r EW, Blaylock WK. Immunological c a p a b ili­tie s of patients w ith atopic de rm a titis . J Invest Dermatol 1966;47:484-490.

57. Rajka G. Delayed dermal and epidermal re a c t iv ity in atopic derm atitis (Prurigo Besnier). Acta Derm Venereol (Stockh) 1967;47:158-163.

58. Rajka G. Atopic Derm atitis. Voi 3 in the series of Major Problems in Dermatology. VB Saunders Company L td ., London, Philadelphia, Toronto 1975.

59. Grove DI, Reid JG, Forbes I . Humoral and c e llu la r immunity in atopic eczema. Br J Dermatol 1975;92:611-618.

60. Blaylock WK. Atopic de rm a titis : Diagnosis and pathobiology.J A lle rgy C lin Immunol 1976;57:62-79.

61. Angelini G, Meneghini CL. Contact and bacte ria l a lle rg y in children w ith atopic de rm a titis . Contact Dermatitis 1977;3: 163-174.

78

62. Epstein WL, Kligman AM. Some facto rs a ffec ting the reactionof a lle rg ic contact de rm a titis . J Invest Dermatol 1959;33: 231-243. .

63. Lowney ED. Attenuation of contact sens itiza tion in man. J Invest Dermatol 1968;50:244-249.

64. Rogge JL, Hanifin JM. Immunodeficiences in severe atopic de rm atitis . Arch Dermatol 1976;112:1391-1396.

65. Jones HE, Lewis CW, Mcmarlin SL. A lle rg ic contact s e n s it i­v i ty in atopic de rm a titis . Arch Dermatol 1973;107: 217-222.

66. Epstein S, Mohajerin AH. Incidence of contact s e n s it iv ity in atopic de rm a titis . Arch Dermatol 1964;90:284-287.

67. Rudzki E, Grzywa Z. Contact s e n s it iv ity in atopic dermati­t is . Contact Derm atitis 1975;1:285-287.

68. Bandmann HJ, B re it R, Leutgeb C. Kontakta lle rg ie und Derma­t i t i s atopica. Arch Invest Dermatol 1972;244:332- 339.

69. Epstein S. Contact derm atitis due to nickel and chromate. Arch Dermatol 1956;23:236-255.

70. Dobson RL. Discussion. J Invest Dermatol 1963;41:416-418.

71. Watt TL, Baumann RR. Nickel earlobe de rm atitis . Arch Derma­to l 1968;98:155-158.

72. Calnan CD. Nickel de rm a titis . Br J Dermatol 1956;68:229-236.

73. Caron GA. Nickel s e n s it iv ity and atopy. Br J Dermatol 1964;76:384-387.

74. Wilson HTH. Nickel de rm a titis . The P rac titione r 1956;177: 303-308.

75. Peltonen L. Atopia ja n ik k e lia lle rg ia . Academic D isserta­tio n , U n ivers ity of Turku, Turku, 1979.

76. Mai bach HI, Johnson HL. Contact u r t ic a r ia syndrome. Contact u r t ic a r ia to d iethylto luam ide. Arch Dermatol 1975;111:726- 730.

77. von Krogh G, Mai bach H. The contact u r t ic a r ia syndrome -1982. In: Kligman AM, Leyden JJ, eds.: Safety and e ffica cyof top ica l drugs and cosmetics. Grune & S tra tton , New York 1982:249-267.

78. Monroe EW, Jones HE. U rtic a r ia . An updated review. Arch Dermatol 1977;113:80-90.

79. Lahti A. Non-immunologic contact u r t ic a r ia . Acta Derm Vene- reol (Stockh) 1980;60 suppl 91.

79

80. Roupe G, Strannegaard 0. Anaphylactic shock e lic ite d by top ica l adm inistration of B ac itrac in . Arch Dermatol 1969; 100:450-452.

81. Henry JC, Tschen EH, Becker LE. Contact u r t ic a r ia to para- bens. Arch Dermatol 1979;115:1231-1232.

82. Schmidt H. Contact u r t ic a r ia . Contact Dermatitis 1978:4:230- 232.

83. Zschunke E. Contact u r t ic a r ia , derm atitis and asthma from cockroaches. Contact Derm atitis 1978;4:313-314.

84. Bernstein IL , Englander BE, Gallagher JS et a l. Localized and systemic h yp e rse n s itiv ity reactions to human seminal f lu id . Ann Intern Med 1981;94:459-465.

85. Pepys J. C lin ica l and therapeutic s ign ificance of patterns of a lle rg ic reactions of the lungs to e x tr in s ic agents. Am Rev Resp Dis 1977;116:573-588.

86. Monroe EW. U rtic a r ia . In t J Derm. 1981;20:32-41.

87. von Krogh G, Mai bach HI. The contact u r t ic a r ia syndrome - an updated review. J Am Acad Dermatol 1981; 5:328-342.

88. H jorth N, Roed-Petersen J. Occupational prote in contact derm atitis in food handlers. Contact Dermatitis 1976;2:24-42.

89. Krook G. Occupational de rm atitis from Lactuca sa liva ( le t ­tuce) and Chicorium (endive). Simultaneous occurrence ofimmediate and delayed a lle rgy as a cause of contact dermati­t i s . Contact Dermatitis 1977;3:27-36.

90. Maibach H. Immediate h yp e rse n s itiv ity in hand de rm a titis .Role of food-contact de rm a titis . Arch Dermatol 1976;112:1289-1291.

91. Andersen KE, Lowenstein H. An investiga tion of the possible immunological re la tio n sh ip between allergen extracts from birch po llen , hazelnut, potato and apple. Contact Dermatitis 1978;4:73-79.

92. Noble WC. M icrobiology of human skin , 2nd ed. Lloyd Luke Ltd, London 1981:67-73, 114-119, 166, 208, 229, 353-354.

93. Henning C, H illborgh U, L indva ll K, Marqvardsen 0, SellersJ, Wahl in S, Ransjö U. Comparison of Staphylococcus aureus carriage and skin in fe c tio n rates in hospita l and o ff ic e employees. J Hyg (Camb) 1979;83: 437-444.

94. Noble WC, Valkenburg HA, Wolters CHL. Carriage of Staphylo­coccus aureus in random samples of a normal population. J Hyg (Camb) 1967;65:567-573.

80

95. Polakoff S, Richards IDG, Parker MT, Lidwell OM. Nasal and skin carriage of Staphyloocuccus aureus by patients under­going surgical operation. J Hyg (Camb) 1967;65:559-566.

96. Noble WC. Ward in fe c tio n s . Trans St John's Hosp Dermatol Soc 1968;54:83-88.

97. McBride ME, Montes LF, Fahlberg WJ, Knox JM. M icrobial f lo ra of nurses' hands. I I I . The re la tionsh ip between staphylococ­cal skin populations and the persistence of carriage. In t J Dermatol 1975;14:129-135.

98. Nilsson E, Henning C. The bacte rio log ica l f lo ra in candidio- sis of the skin. Curr Ther Res 1977;22:27-32.

99. Aly R, Maibach HI, Mandel A. Bacteria l f lo ra in psorias is . Br J Dermatol 1976;95:603-606.

100. Marples RR, Heaton CL, Kligman AM. Staphylococcus aureus in psorias is . Arch Dermatol 1973;107:568-570.

101. Noble WC, Savin JA. Carriage of Staphylococcus aureus in psorias is . B r it Med J 1968;1:417-418.

102. Selwyn S. Bacteria l in fec tions in a skin department. Br J Dermatol 1963;75:26-28.

103. Leyden JJ. A n tib io t ic usage in dermatological p ractice . In t J Dermatol 1974;13:342-352.

104. Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic de rm a titis . Br J Dermatol 1974;90:525- 530.

105. Aly R, Maibach HI, Shinefeld HR. M icrobial f lo ra of atopic de rm atitis . Arch Dermatol 1977;113:780-782.

106. Maddala GS. Lim ited - dependent and q u a lita tiv e variables in econometrics. Cambridge U n ivers ity Press, 1983.

107. Williamson P, Kligman AM. A new method fo r the quan tita tive investiga tion of cutaneous bacteria . J Invest Dermatol 1965;6:498-503.

108. Hoi deman LV, Cato EP, Moore WEC. Anaerobe laboratory manual, ed 4. V irg in ia Polytechnic In s t itu te , Blacksburg, V irg in ia , 1977.

109. Kloos WE, S ch le ife r KH. S im p lified scheme fo r rou tine iden­t i f ic a t io n of human Staphylococcus species. J C lin M icrobiol 1975;1:82-88.

110. Sch le ife r KH, Kloos WE. A simple te s t system fo r the separa­tion of staphylococci from m icrococci. J C lin M icrobiol 1975;3:337-338.

81

111. Smith RF. Characterization of human cutaneous lip o p h il ic d iphtero ids. J Gen M icrobiol 1969;55:433-443.

112. Nie NH, Hull CH, Jenkins JG et a l. S ta tis t ic a l package fo r the social sciences, ed. 2. McGraw-Hill, New York, 1975.

113. Andersen KE, Maibach HI. M u ltip le app lication delayed onset contact u r t ic a r ia : possible re la tio n to ce rta in unusual form alin and te x t i le reactions? Contact Dermatitis 1984;10: 227-234.

114. Helander I . Contact u r t ic a r ia from leather containing fo r ­maldehyde. Arch Dermatol 1975;111:726-730.

115. Lindskov R. Contact u r t ic a r ia to formaldehyde. Contact Der­m a titis 1982;8:333-334.

116. Nutter AF. Contact u r t ic a r ia to rubber. Br J Dermatol 1979: 101:597-598.

117. Förström L. Contact u r t ic a r ia from latex surgical gloves.Contact Derm atitis 1980;6:33-34.

118. Kleinhans D. Contact u r t ic a r ia to rubber gloves. Contact Dermatitis 1984;10:124-125.

119. Meding B, Fregert S. Contact u r t ic a r ia from natural la texgloves. Contact Derm atitis 1984;10:52-53.

120. Helander I , Mäkele A. Contact u r t ic a r ia to zinc di ethyld i -thiocarbamate (ZDC). Contact Derm atitis 1983; 4:327-328.

121. Rudzki E, Gryzwa Z. Immediate reaction to balsam of Peru,cassia o il and ethyl v a n i l l in . Contact Dermatitis 1976;2:360-361.

122. Forsbeck M, Skog E. Immediate reactions to patch tests w ith balsam of Peru. Contact Derm atitis 1977;3:201-205.

123. Fisher AA. Contact d e rm a titis , 2nd ed. Lea & Febiger, P h ila ­delphia, 1973:283-286.

124. Gaul LE. Derm atitis from cethyl and stearyl a lcohol. Arch Dermatol 1969;99:593.

125. Pearson RSB. Potato s e n s it iv ity : an occupational allergen in housewives. Acta AUergol 1966;21:507.

126. Rostenberg A Jr. Contact u r t ic a r ia from food. Arch Dermatol 1970;101:491.

127. Cronin E. Immediate-type h yp e rse n s itiv ity to potato. Contact Dermatitis Newsletter 1973;13:358.

82

128. Fisher AA. A lle rg ie 'p ro te in ' contact derm atitis due to food. Cutis 1975;16:793.

129. HannukseTa M, Lahti A. Immediate reactions to f r u i t s and vegetables. Contact Derm atitis 1977;3:79-84.

130. Van Ketel WG. Skin eruptions caused by vegetables and f r u i t including pears. Contact Derm atitis 1982;8 :352.

131. Herrmann F, Sulzberger MB, Baer RL. Prevention of allergens in to the human skin. N.Y. State J Med 1944; 44:2452.

132. Edwards EK. Contact u r t ic a r ia to cow's m ilk . Cutis 1981 ;28: 450-451.

133. Fisher AA. A lle rg ic contact u r t ic a r ia to raw beef: h is to -pathology of the sp e c ific wheal reaction at the scratch te s t s ite . Contact Derm atitis 1982;8:425.

134. Beck HI, Knudsen Nissen B. Type-1 reactions to commercial f is h in non-exposed ind iv idua ls . Contact Dermatitis 1983;9: 219-223.

135. Beck HJ, Knudsen Nissen B. Contact u r t ic a r ia to commercial f is h in atopic persons. Acta Derm Venereol (Stockh) 1983:63: 257-260.

136. H jorth N, Roed-Petersen J. A lle rg ic contact derm atitis in ve terinary surgeons. Contact Dermatitis 1980;6:27-29.

137. Dahlqvist I , Fregert S. Occupational dermatoses in hospita l personnel. Berufsdermatosen ‘1970;18:261-268.

138. Barregård L, Stenberg B. Arbetsrelaterade handeksem hos sjukhuspersonal. Läkartidningen 1982;79:1355-1356.

139. Shmunes E, Keil JE. Occupational dermatoses in South Caro­lin a : A descrip tive analysis o f cost variab les. J Am AcadDermatol 1983;9:861-866.

140. Malten KE. Thoughts on i r r i t a n t contact de rm a titis . Contact Dermatitis 1981;7:238-247.

141. Fregert S. Manual of contact de rm atitis . 1st ed, Munksgaard, Copenhagen 1974:38-40.

142. Peltonen L. Nickel s e n s it iv ity . An actual problem. In t J Dermatol 1981;30:342-353.

143. Christensen OB. Prognosis in n ickel a lle rgy and hand eczema. Contact derm atitis 1982;8:7-15.

144. Boss A, Menné T. Nickel sen s itiza tio n from ear p ie rc ing . Contact Dermatitis 1982;8:211-213.

83

145. Larsson-Stymne B, Widström L. N icke la lle rg i hos s k o lf lic k o r - en fö l jd av håltagning i öronen? Läkartidningen 1983;80: 2973-2974.

146. Wahlberg JE, Wahlberg E. Skin ir r ita n c y from nickelsu lfa te and te s t patches. Contact Dermatitis 1985;13: 224-225.

147. Fischer T, Rystedt I . Fa lse -pos itive , fo l l ic u la r and i r r i ­tan t patch te s t re a c t iv ity to metal sa lts . Contact Dermati­t is 1985;12:93-98.

148. Möller H, Svensson A. Metal s e n s it iv ity : pos itive h is to rybut negative te s t indicates atopy. Contact Derm atitis 1986;14:57-60.

149. Leyden JJ, Kligman AM. The case fo r s te ro id -a n tib io t ic com­binations. Br J Dermatol 1977:96:179-187.

150. Chan HL, Aly R, Maibach HI. E ffect of top ica l c o r tic o ­stero id on the m icrobial f lo ra of human skin. J Am Acad Dermatol 1982;7:346-348.

151. Noble WC. M icrobiology of human skin , 2nd ed, Lloyd Luke Ltd, London 1981:71.

152. Marples RR, Rebora A, Kligman AM. Topical s te ro id -a n tib io ­t i c combinations. Arch Dermatol 1973;108:237-240.

153. Noble WC. M icrobiology of human skin , 2nd ed, Lloyd Luke Ltd, London 1981 ;3-106.

154. Forsgren A, S jöquist J. "Protein A" from S. aureus I . Pseudo-immune reaction w ith human ï-g lo b u lin . J Immunol 1966;97:822-827.

155. Rydén C, Rubin K, Speziale P et a l. F ibronectin in receptors from Staphylococcus aureus. J B iol Chem 1983;258:3396-3401.

156. Raab W. E ffects of local co rticos te ro ids in skin in fe c tio n s . Dermatologica 1976; 152 Suppl 1:67-79.