Clinical Allergy. 1980, Volume 10, pages 77-90

An epidemic of extrinsic allergic alveolitiscaused by tap water

A MUITTARI. P. KUUSISTO, P. VlRTANEN.* A. SOVIJARVI. P.GRONROOS, A. HARMOINEN. P. ANTILA and L. KELLOMAKI

Tampere Central Hospital and *Nokia Health Center, Finland

(Receit^edS March 1979; accepted for publications 27 March 1979)

SummaryIn an industrial community. Linnavuori. (population 1000) over 100 people developedfever, cough, and dyspnoea 3 to 6 hours after sauna or bathing. Thisepidemic began inAugust of 1978 and ended gradually in December. The water source of the communitywas a small (0 4 km^) lake; in November it was found thai the water was contaminatedwith several bacteria, fungi, and algae. Precipitating antibodies to these bacterial andfungal antigens were not found in the sera of symptomatic patients. To show that tapwater, purified by the local waterworks, had provoked the symptoms, four clinicallytypical patients were each twice challenged. Two of the patients visited their usualpublic sauna, the two others took a bath at home. Two patients inhaled home tap wateraerosol, one inhaled lake water vapor and one home tap water vapor in hospital. Threeto six hours after seven of the eight challenges the patients showed two or more of thefollowing symptoms and signs: chills, fever, dry cough, dyspnoea, and inspiratorycrepitant rales. Six provocations increased the amount of segmented neutrophils and ineach case the lung diffusion capacity decreased significantly. Although the clinicalpicture resembles extrinsic allergic alveolitis, it is possible that bacterial endotoxinshave induced alternative pathway complement activation and release of leukocytepyrogens.

A respiratory syndrome much resembling exogenous allergic alveolitis, and causedby micro-organism-contaminated water from air humidifiers and ventilation systems,has become more commonly diagnosed in the 197O's. This disease is also calledhypersensitivity pneumonitis or humidifier fever. Banaszak. Thiede & Fink (1970)described four office clerks whose symptoms were shown to be caused by contamina-tion of the office ventilation system by a thermophilic actinomycete. Inhalation testswith the homologous antigen provoked similar symptoms. Fink et ai (1971) found

Correspondence: Dr A, Muittari, Department ofPultnonary Diseases. Tampere Cctitral Hospital.SF-36280 Pikonlinna. Finland,

0009-9090/80/0100-077$02.00 © 1980 Biackweii Scientific Publications 77

78 A. Muittari el al.

that a housewife suffering from an aggravating cough and dyspnoea developed hersymptoms because of the water in the heating and air humidifying plant, which wascontaminated by Mkropolyspora faeni. Precipitins to the antigen were found in thepatient's serum, and the inhalation provocation test was positive. Sweet et al. (1971)had a case of humidifier fever caused by a thermophilic actinomyces at the patient'shome. The histological picture of alveolitis was confirmed by open lung biopsy.Edwards. Griffiths & Mullins (1976) found that exogenous allergic alveolitis occurringin twenty of fifty employees at an office was caused by an amoeba, Naegleria gruheri.Rylander et al. (1978) claim that flavobacterial endotoxins caused humidifier fever inthree office clerks.

Printing plants usually require effective air humidifying systems, to assure asufficiently high and uniform air humidity. Pickering and coworkers (1976) described asyndrome occurring in nine printing workers. A number of different micro-organismswere isolated from the ventilation system, none of which, however, could with cer-tainty be held responsible for the disease. An isolated case of sauna-taker's disease wasfound to be caused in all probability by the fungus Pullularia (Metzger et al., 1976).This mould had contaminated a wooden ladle holding water for throwing on the hotstones to produce steam. In the literature, we have found only two reports of lake watercausing a syndrome of this kind. Patterson et al. (1978) found that tap water takenfrom a lake contained a pathogenic antigen which accumulated in air humidifiers.

Atterholm et al. (1977) described fifty-six persons who developed fever and respira-tory symptoms 4 hr after a hot bath. The cause of the symptoms was not found.

This is a report of an epidemic where, in a population of 750 adults, more than 100suffered from a syndrome resembling exogenous allergic alveolitis. The source ofdisease was found to be water from the waterworks.

Materials and methodsIn an industrial community with about 1000 inhabitants, a respiratory disease ofepidemic character broke out in August 1978. Of the adult population, roughly one offive developed fits of shivering, fever to 38 0-39 0 C. headache, pain in muscles andjoints, dry cough and dyspnoea. Most patients showed their symptoms 3-6 hr afterthey had taken a sauna, hot bath, or shower, but many also showed them afterlaundering and dish-washing. The symptoms usually lasted 8-16 hours.

This community takes its household water from a small (0-4 km-), shallow lake. InAugust 1978 the water had turned distinctly bluish-green and developed a musty smell.The filtering sand in the water purification plant had last been renewed in 1961, and thewater was chlorinated only after filtration. Before being filtered the lake water wasneutralized with hexamethaphosphate.

On 13 November 1978,an analysisof the crude lake water revealed aconsiderabledecline of quality: (a) an abnormal nitrogen-phosphorus balance; (b) a high concent-ration ofcoliform bacteria; (c) a growth of/l5/?^rg/7/w5/wm/g'am5 and algae; (d) a faintlymusty smell.

Distribution of questionnaires to identify (hose affectedA questionnaire on the occurrence of symptoms (Table 1) was carried out on the 783inhabitants of the community on 28 and 29 November. Two hundred and thirty-fivechildren of 15 years or less were separated, and so were those aduUs who were known tosuffer from a chronic obstructive lung disease (five persons with asthma, two with

Extrinsic allergic alveolitis caused hy lap water 79

Table I. Questionnaire 1 was sent to 548 inhabitants over 15 years old

Questionnaire No. I

Are you suffering from cuugh. difficulty of breathing, or fever?Dn the .symptoms occur ctmiiimously''Do (he symploms occur occasionally'.'Do ihe .<iympl(>ms gei H-or.se some hours after you have taken a .fauna, hoi bath or shower?For how long have you been having these symptoms?Have you been found lo suffer from a lung disease?

chronic bronchitis, two with emphysema). Of the remaining 539, 285 had had feverand/or cough and/or dyspnoea for at least 2 weeks: a second questionnaire (Table 2)was sent to them. Twelve persons did not return this questionnaire and thirty wereconsidered healthy. Of those 243 adults who had suspected symptoms. 105 had clearlyfound that their symptoms set in 3-6 hr after they had taken a sauna, hot bath, orotherwise had been in contact with hot tap water: fever reactions occurred in seventy-six some of whom also developed a cough and/or dyspnoea, whereas cough and/ordyspnoea but no fever was experienced by twenty-nine of the 105. Fifty-four persons

Table 2. Questionnaire 2 was sent to 285 sympiomatic people. Twelve persons did not return it

Questionnaire No. 2

Which of the following symptoms have you experieneed—coniinuously?—occasionally?slight difficulty of breathingsevere difficulty of breathingcoughfeverfits of shiveringpain in muscles or jointsheadachepain in the chestloss of weightother symptoms—which?

/.5 the occurrence of occasional symptoms—evidently—possibly—notconnected with the inhalation of steam, for instance in the sauna, bath, or shower?

If the following symptoms are occasional and connected with the inhalation of steam, how soon do they set in andhow long do they last?cough sets in after hours, and last for hoursdifficulty of breathing ,, ,,fever

W'/icn did the symploms first occur?

Have you consulted a doctor for your symptoms?

80 A. Muittari et at.

thought that their symptoms possibly occurred after contact with the water, whileeight-four had respiratory symptoms occasionally, but saw no connection with the useof water. It seemed evident that, of those 527 persons over 15 years ofage who returnedboth questionnaires, at least 105 suffered from a syndrome of epidemic character,resembling exogenous allergic alveolitis, and the pathogenic factor seemed to be thetap water.

Bacteriological and mycological analyses of the waterThe following culture media were used for fungi and yeasts: Sabouraud dextrose agarwith antibiotics, mycobiotic agar, brain-heart infusion agar, N + G agar for micro-polyspora faenii, and thioglycoleate broth for actinomycetes. The incubation tempera-tures were 20, 37 and 56 C. For bacteriological analyses the usual culture media wereused.

Results of bacterial and fungal culturesA sample of tap water, taken on 13 November at the municipal health service centre.grew Aspergillus fumigatus, Mucor and a species of Absidia fungi. On 24 November,three more samples of water were taken: sample 1 at a patient's home (patient 1),sample 2 at a local public sauna, and sample 3 from the lake which supplied thecommunity with water. All these samples grew Candida guillermondii. Sample I alsogrew Acinetobacleria. sample 2 Pseudomonas tnaltophila. and sample 3 Aeromonashydrophila, Acinetohacter and E. coli.

Immunohgical testsImmunodiffusion tests, performed with serum samples of symptomatic patients,showed that none of the antigens produced from the above-mentioned bacterial,fungal and yeast strains gave positive precipitin tests.

A sample of tap water (650 ml), taken on 24 November, was lyophilized, and theevaporation residue was dissolved in 10 ml of water. The concentrated antigen wasbroken down by ultrasonic radiation (30 min) and further concentrated 50-100 fold ina Minicon concentration chamber. The final concentration of the original watersample was about 7000 fold. This concentrate was used for studying the serum samplesof six symptomatic patients by immunodiffusion. No precipitins were found.

The same water concentrate was diluted with Coca solution (1:20, 1:100, and1: 1000), and the dilutions were used for intracutaneous tests with four symptomaticpatients. The results were read after 15 min, 3,6. and 48 hr. No skin reactions of type I,III. or IV were observed in any of the patients.

Performance of water provocation tests(1) Sauna provocation tests. Patients 1 and 2 visited a local public sauna. Three daysbefore, their lung diffusion capacity (DL, single breath; Cotes, 1965) had been mea-sured, and total and differential leucocyte counts had been performed. After the saunathe patients came to the hospital, where their symptoms were followed, their axillarytemperature was measured, and their lungs were auscultated every 2 hr. DL wasmeasured on theday of the provocation test between 14.00 and 15.00 hours and againat 8.00 hours the following morning. Total and differential leucocyte counts wereperformed on the test day at 15.00 hours and 19.00 hours and on the following morningat 8.00 hours.

Extrinsic allergic alveolitis caused by tap water 81

(2) Bath provocation tests. Patients 3 and 4 took a hot bath at home in the morning.At the hospital they were subjected to the same tests as the sauna-takers. Their D|. wasmeasured for the first time on the test day between 14.00 and 15.00 hours, and againafter 1 day and 7 days (patients 3) and after 10 days (patient 4). The DL reference valuefor patient 3 was taken on 19 December 1978, and for patient 4 on 2 January 1979 (figs4 and 5).

(3) Water aerosol provocation tests. Patients I and 3 were given a water aerosolinhalation test with tap water that they had brought from home. Their basal D| wasmeasured on the morning of the previous day at 8.00 hours (patient 3) and 6 daysbefore the test (patient 1). On the morning of the test day, total and differentialleucocyte counts were performed, the temperatures were taken, the patients were askedhow they felt, and their lungs were auscultated. They then inhaled 2 ml of waterthrough a De Vilbiss No. 40 medical atomizer. If no symptoms had occurred after 15min. another 2 ml of water was inhaled. The symptoms were followed, the tempera-tures measured and the lungs auscultated every 2 hr. Total and differential leucocytecounts were performed at 11.00, 14.00 and 17.00 hours. DL was measured on the testday between 14.00 and 15.00 hours and again 1 day and 10 days later (patient I) and 9days later (patient 3).

(4) Steam provocation tests. A water sample was allowed to boil in a saucepan, andthe patient inhaled the steam at 15 min intervals, first for a period of 5. then 10, andfinally for 15 min. The same parameters were measured as in the water aerosolprovocation tests.

Case descriptionsTo confirm that the epidemic was caused by tap water, four patients with a typicalhistory were selected from the group of 105 symptomatic persons and subjected tovarious water inhalation tests in order to reproduce the symptoms.

Patient 1The patient was a 57-year-old welder, who had given up smoking 21 years ago. Hisfather was asthmatic. A mild hypertension had been diagnosed 2 years before thisstudy.

The present disease. At the beginning of August 1978 the following symptomsbegan to appear following with sauna-taking: after 3-4 hours, a dry, hacking coughand headache; after 5-6 hours, fits of shivering, fever to 38 0-39 OC and. at the sametime, dyspnoea. Symptoms of this kind had occurred three times after a sauna andtwice after a hot shower. After cold showers the symptoms did not occur. Four yearsearlier the patient had experienced similar symptoms three or four times after sauna-taking.

A physical lung examination and a chest X-ray gave normal findings, and no raleswere heard on auscultation.

Laboratory tests. On 14 November dynamic and volumetric spirometries werenormal. On 15 November the lung diffusion capacity was 76% of the calculated normalvalue. A methacholine test with a 2 5% solution was positive.

Red and white blood pictures were normal, and so were quantitative serumimmunoglobulins (IgG 15 0 g/I) and complement (S-Ci. S-C4)- The serum did notcontain precipitins to the following antigens: Micropolyspora faeni. Thermoactino-

82 A. Muittari et al.

% « §

11^

^ CQ * - '

CO o T?

•a

i =

a Q

Extrinsic allergic alveolitis caused by tap water 83

myces vulgaris, Aspergillus fumigatus. Aspergillus glaucus umbrosus. Antinuclear anti-bodies were negative.

Water provocation tests. (Table 3; Figs I and 2) (see 'Performance of waterprovocation tests'), (a) On 21 November a water aerosol inhalation test with tap watertaken at the patient's home induced symptoms, but no clear temperature reaction norany leucocytosis. A considerable (18%) decrease of DL was observed, however, (b) On 4December the patient visited a public sauna as usual, and then came to the hospital forexamination. He now developed typical symptoms, fever and a rise in segmentedneutrophilic leucocytes. End-inspiratory crepitant rales could be heard on auscul-tation, and DL decreased significantly.

On 7 December a transbronchial biopsy was taken from the lower right lobe in

70 -

60 -

15.11. 21.11.22.11. 1.12 4.IZ 5.12.

Oate

Fig. 1. The effecl of home lap water aerosol inhalation and sauna on the single breath diffusing capacity (DL)and efrectivc lung volume (VA) of case No. 1.

39,0

38,0

37,0

36,0

Segmented^leucocytes

Leucocytes -

Segmented,leucocytes

Crepitont rfllesMuscle pains

Chills, dyspnoea

Cough,headache . _ . - • "•— .—""

1 •'•-T 1 \ ,,Lymphocytes

I I

10a.m.

12

4

2

.12

4

.1978

10p.m.

8 10a.m.

5.12.1978

100 ;

80

60 .

4Q -

20

Time

Dole

Fig. 2. The effect of sauna taking on the symptoms and signs, on the amount leucocytes, percentual amountof segmented neutrophils and lymphocytes and on the body temperature of case No. I.

84 A. Muittari et al.

connection with bronchoscopy. On the bronchiolar walls there was a clear fibrosis. Noimmunoglobulins could be observed in the lung tissue by immunofiuorescence.

Course of the disease. As the disease seemed to be chronic, and the Di after thewater provocation tests was only 60";,, prednisolone therapy with a daily dose of 30 mgwas started on 8 December. The mild exertional dyspnoea and the dry cough clearlyimproved, and after 3 weeks of treatment DL was 70%.

Patient 2This was a 35-year-oId plumber with no atopic diseases in the family. He hadpreviously been very healthy and had given up smoking 10 years ago.

The present disease. Beginning in the middle of August 1978, the following symp-toms occurred four or five times after sauna-taking: after 1-2 hr. dry cough andheadache; after 3 5 hr. strong fits of shivering, fever to 39 C and mild dyspnoea. Whenthe patient began to suspect that his symptoms were caused by the sauna, he only tookshowers, but the symptoms continued as before. Even dish-washing induced coughand headache. The patient's general condition impaired, and he gave up his habitualconstitutionals. A physical lung examination on 17 October gave normal findings, andchest X-ray was normal.

Laboratory tests. On 28 November dynamic and volumetric spirometries as well asDL were within the normal range. The methacholine test was negative.

The blood picture was normal, and so were quantitative immunoglobulins (IgG170 g/1) and complement. Precipitin tests were negative: antinuclear antibodies, on theother hand, -l-l :50.

Water provocation tests. (Table 3 and Fig. 3). (a) On 29 November a steamprovocation test performed at the hospital with lake water (see 'Steam provocationtests') induced symptoms. There was no clear temperature reaction, but a mild

110

y 100

9 0

80

70 \~ LOM woter

28.11. 29.11. 30.11. 1.12.

Date

4.12. 5.12.

Fig. 3. The effect of the lake water vapor inhalation and sauna on theDt and VA of case No. 2.

Extrinsic allergic alveolitis caused by tap water 85

leucocytosis developed and DL decreased, (b) On 4 December the patient took a saunaat the same time as patient 1. More symptoms occurred than after the previous test,and inspiratory crepitant rales were heard. A temperature reaction, leucocytosis. and aclear decrease in DL were furthermore observed.

Course of the disease. On 2 January 1979, the patient had been laundering anddish-washing. Perhaps for this reason, his DL on 3 January was only 76% of thenormal. Corticosteroid therapy was started, and the follow-up is still going on.

Patient 3A 35-year-old driller, who had no atopic diseases in the family. The patient hadabstained from smoking for five years. He had previously suffered from mild heartarrhythmias.

The present disease. At the end of September 1978 the patient noticed that hedeveloped a dry cough 1-2 hr after sauna-taking and fits of shivering accompanied bypain in muscles and joints 4-6 hours after the sauna. He had no difficulty of breathing,but his temperature rose to 38 C and, as it fell again, he sweated strongly. Dish-wash-ing caused the same kind of symptoms, though milder.

On 29 November a physical lung examination gave normal findings, and chestX-ray was also normal.

Laboratory tests. Dynamic and volumetric spirometries were within the normalrange: D| was normal, too. The methacoline test was negative. Red and white bloodpictures were normal. Prick skin tests were negative, quantitative immunoglobulins(IgG 12 0 g/1) were within the normal range, and so were S-C3 and S-C4. Precipitin testswere negative.

Water provocation tests (Table 3 and Fig. 4). (a) On 12 December 1978, the patienttook a hot bath at home. At the hospital he was found to have typical symptoms, andtemperature and leucocyte reactions were observed. The lung diffusion capacity haddecreased considerably, (b) On 20 December the patient was subjected to a water

30

20

10

00

90

80

70

-

Boit> ot horn*

y \

X \

0 012.12. 13.12. 19.12. 20.12. 29.12.

Date

Fig. 4. The effect of bath, home tap water and hospital tap water aerosol inhalation on the DL and VA of caseNo. 3.

86 A. Muittari etal.

aerosol provocation test with tap water from his own home. The test result was clearlypositive. For the sake of control, another water aerosol provocation test was per-formed on 29 December this time with tap water taken at the hospital. The latter testdid not provoke any symptoms whatever.

Patient 4This 31-year-old housewife had a brother who suffered from allergic rhinitis. Thepatient had never smoked, and was previously very healthy. In her home there weretwo air humidifiers which operated on the aerosolizing principle.

The present disease. At the end of August 1978 the patient began to wake up at nightbecause of difficulty of breathing. At the same time she had a dry cough and feltfeverish, and her muscles ached. She took a hot shower in the evenings, and thesymptoms set in 3-4 hr later. When she noticed a connection between her symptomsand the hot shower, she began to take cold showers, and the symptoms disappeared.Dish-washing with hot water provoked the same symptoms.

It may be worth mentioning that 6 years earlier both the patient and her husband,during a period of one year, suffered fits of shivering, fever and dyspnoea after takinghot baths.

On 28 November 1978, a physical lung examination was performed. End-inspira-tory crepitant rales were hear on auscultation. The chest X-ray was normal.

Laboratory tests. The red and white blood pictures were normal. The quantitativeimmunoglobulin test showed an increase in IgG (210 g/1), antinuclear antibodies were1:50 + . Serum complements were within the normal range and precipitin tests werenegative.

Water provocation tests (Table 3 and Fig. 5). (a) On Dec. 8, the patient took a bathat her home and came to the hospital for examination. Symptoms occurred, andcrepitant rales clearly increased. The temperature reaction was slight, but the totalleucocyte count after 6 hr was 23-9 (x lOVl). After 24 hr the leucocyte count wasnormal (76) again. The proportion of neutrophilic segmented leucocytes rose to 92%,while the lymphocytes decreased to 2%. On 18 December DL was 65%, and predniso-

90 r

2t 80 -

70 ~

60 - [1uIn bath

ot home ,

30 mg A1 ^ 20mg

Prednfsolan UHome tap wotervapor

e-i2. 16.12. 2.1. 3.1,

Dote

Fig. 5. The effecl of bath, prednisolon treatment and home tap water vapor inhalation on the DL and VA ofihe case No. 4.

Extrinsic allergic alveotitis caused by tap water 87

lone therapy (30 mg/day) was set in. A fortnight later the dry cough, mild exertionaldyspnoea and crepitant rales disappeared completely and DL had increased to l(f%. (b)On 3 January 1979. the patient was subjected to a water steam provocation test withtap water from her home. This test was negative.

In addition to the four patients participating in the water provocation tests, eleventypical cases were examined at the out-patient department of the hospital. The patientsbelonged to the original group of 105 symptomatic persons, and had seeked medicaladvice at the health service centre, from where they were referred by the doctor to thehospital for further examination.

Five of the eleven patients were women. The age range of the patients was 17-57years, mean age 38 years. Beside the usual case history, physical examination and chestX-ray., the following data were collected:

Complete blood picture, precipitin tests (see Patient I). quantitative immunoglobu-lins, antinuclear antibodies, serum complements (S-C? and S-C4). prick skin tests, andtuberculin test.

The clinicophysiological tests were: dynamic and volumetric spirometries anddiffusion capacity (DJ .

Seven patients had at least three symptomsof four possible (fever, cough, dyspnoea,general symptoms) (Table 4). The others had two symptoms. All these acute symptomsset in 2-6 hr after a sauna, bath or shower. In addition to the acute symptoms, as manyas ten patients had chronic symptoms which were independent of contact with water.

Cough and dyspnoea occurred in patients 8, 9, 10, 11, 12, 13 and 15. The otherpatients had: dry cough (patient 6); cough, temperature rise and tiredness (patient 7);cough and impaired general condition (patient 14).

Table 4. Acute and chronic symptoms of eleven typical cases. Acute symptoms set in2-6 hr after sauna, warm balh or shower

Palient No.sex andage (years)

5. male, 306, male, 577, female, 54

8, female, 28

9. female, 36

10, male, 5311, mate. 34

12, male. 34

13. mate, 43

14, female, 17

15, female. 27

Acute symptoms

ayslemic acuteFever Cough Dyspnoea symptoms

+ + + -+ -1- + —- + + —

+ -1- + —

+ - + —

+ + + Headache+ — + Muscle and

joint pains+ — — Malaise

-1- -f- + —

— + + Chest pains

+ — + Joint pains

Chronicsymptoms

.

Chronic dry coughCough, fevertirednessCough,mild dyspnoeacough.mild dyspnoeaCough, dyspnoeaCough and sputum.dyspnoeaCough, tiredness.mild dyspnoeaCough, sputumtiredness, dyspnoeaCough,TirednessCough, sputumdyspnoea, weight loss

88 A. Muittari et al.

In spite of the relative abundance of symptoms, auscultation revealed inspiratorycrepitant rales only in two cases (patients 7 and i 1). DL as well as dynamic andvolumetric spirometries were within the normal range for all the patients. On the basisof prick tests, patient 14 was found to be atopic. IgG was rather on the higher side inpatients 9. 11, 12 and 14. Other immunoglobulins were normal, and none of thepatients were found to have negative precipitin tests. Antinuclear antibodies, too, werenegative, and serum complements were within the normal range.

Measures for improving ihe water qualityOn 5 December 1978, the filtering sand of the water purification plant was renewed andthe purification process was changed so that the water was chlorinated (Na-hypochlor-ite) both before and after filtration. At the same time the use of hexamethaphosphate asneutralizing agent was abandoned.

On 18 January 1979. chlorine (50 mg/1) was let into the water mains over 12 hr.In spite of ihese measures, on January 25 patient 12 experienced cough and

tiredness after a shower, and after six hr this temperature rose from 36-9 to 37 8 C andthe leucocytes from 8 5 to 19 7. The patients diffusion capacity did not decrease,however. On 30 January patient 3 was subjected to a water aerosol provocation testwith tap water taken at his home. Fits of shivering occurred after 2 hr, and a headacheafter 8 hr. The temperature rose slightly (36-6-*37 03 C), but DL did not change at all.Neutrophilic leucocytes increased a little (7 9-^117) in 10 hr.

The results of these two water provocation tests show that the measures forimproving the quality of the water have been only partly successful.

DiscussionThe case descriptions of those fifteen patients who were more thoroughly examined,greatly resemble exogenous allergic alveolitis. The patients experienced at least two ofthe following symptoms 3-6 hr after taking a sauna, hot bath or shower: fever, cough,dyspnoea, general symptoms (malaise, pain in muscles and joints). Water inhalationprovocation tests performed with patients 1 ^ produced the same kind of symptoms,although usually of a milder nature.

In the provocation tests the diffusion capacity (D|) proved to be a very sensitiveindicator. For instance, in the tap water aerosol provocation test, patient 1 had only aslight rise of temperature (36 2-*36-4''C) and the leucocytes, too, increased onlyslightly (6 0-^6 7). but Di decreased by 18"/. In the four exposure tests the amount ofsegmented neutrophils increased considerably both absolutely and relatively.

Although, in practice, only hot water induced symptoms, they were provoked in thetests by room-tempered tap water aerosols in patients 1 and 3. Obviously, a coldshower does not produce enough water for the pathogenic factor in the water to beinhaled in sufficient amounts.

Cases reported from Sweden (Atterbom et al.. 1977) are very similar to thosedescribed here. In the Swedish report, however, most patients developed symptomsonly after a hot bath, and a few after a hot shower. Unfortunately. DL was notmeasured in the Swedish study.

None of the patients in the present study had roentgenological changes in the lungs.This is in agreement with those previous reports where the etiology of the syndromeremained unclear (Pickering et at., 1976; Atterholm et al.. 1977) or where a bacterialendotoxin was found responsible (Rylander et ai, 1978). When the pathogen has been

Extrinsic allergic alveolitis caused by tap water 89

a thermophilic actinomyces, there have usually been typical roentgenological changesin the lungs (Banaszak f/a/, 1970; Sweet e/a/., 1971).

The material presented here comprised, in addition to the acute symptoms, twelvepatients with chronic symptoms. This seems to point either to a continuousexposure tothe antigen or to a possible development of fibrosis.

However, only patient I already had a low Di. before the water provocation tests,and in patient 4 the Di,. lowered after the bath provocation test, began to normalizeonly when prednisolone was set in. The other thirteen patients had a normal D | , andthe dynamic and volumetric spirometries were also normal. A transbronchial biopsywas taken only of patient 1, and it showed slight peribronchiolar fibrosis.

Furthermore, only three patients (4, 7 and 11) had end-inspiratory crepitant ralesindependent of previous water contact, which may indicate chronic damages.

It is quite evident that the epidemic described here was caused by microorganism-contaminated water. When the polluted water, after a rather dissatisfactory purifica-tion process at the waterworks, was neutralized with hexamethaphosphate beforebeing filtered through sand, the microbial growth may even have increased.

To prove with certainty the etiology of a disease of this kind, the followingdiagnostic criteria should be fulfilled (MRC Symposium, 1977); (a) the typical patho-graphy should be clinically established; (b) the pathogenic micro-organism in the watershould be found; (c) precipitating antibodies to an antigen of the micro-organismshould be found; (d) the symptoms should be reproducible by inhalation tests with thehomologous antigen.

In this study no precipitins to the tap water or to antigens prepared from bacteriaand fungi in the water were found in patients sera.

It is quite possible that the epidemic was caused by bacterial endotoxins which,inducing alternative pathway complement activation, released leucocyte pyrogens.

According to our Public Health Law, the only criterion for the microbiologicalquality of household water is the content of fecal indicator bacteria. Obviously, othermicro-organisms should also be checked, at least when the water quality is dubious.

From earlier reports and the present study it appears that the etiology of humidifierfever cannot always be clarified. Nevertheless, by inhalation tests with the suspectedwater it is possible to establish whether the pathogenic factor is actually to be sought inthe water. By renewed water provocation tests with sensitized patients the success ofattempts to improve the water quality may be assessed.

ReferencesATTERHOLM. 1.. HALLBERG,T..GANROT-NORDIN. K . &RINGERTZ. O, (1977) Unexplained acute fever after a

hot bath. Lancet, ii, 684.BANASZAK, E . F . . THIEDE. W . H . & FINK. J . N . (1970) Hypersensitivity pneumonitis due to contamination of

an air conditioner. A'CM' England Journal of Medicine. 283, 271.COTES, J.E, (1965) Lung function. Assessment and application in medicine. Blackwell Scientific Publications.

Oxford.EDWARDS. J.H.. GRIFFITHS. A. J. & MULLINS, J. (1976) Protozoa as sources of antigen in "humidifier fever'.

A'a/urf, 264.438.FINK, J.N.. BANASZAK, E.F., TraEDE. W.H. & BARBORIAK. J.J. (1971) Interstitial pneumonitis due to

hypersensitivity to an organism contaminating a heating system. Annals of Internal Medicine. 74. 80,MtTztiER. W J,. PATTERSON. R. . FINK, J . SEMERDJIAN. R. & ROBERTS, M . (1976) Sauna-takersdisease. Jama.

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