Reprinted fran Annals c£Allergy, Asthma, & Immunology TO. 79, Number 3, September 1997

Review articleSupported by a grant from Zeneca Pharmaceuticals

Sick building syndrome-a wolf in sheep'sclothing*EmU J Bardana, Jr, MD

Objective: Reading this article will acquaint the reader with possible outcomesassociated with the diagnosis of "sick building syndrome." The definition, epide-miology, and precipitating events of this symptom complex are distinguished fernother defined building-related illnesses.

Data source: The author's experience with many patients presenting with, thisdiagnostic label and selected studies ou indoor pollution and "sick building syn-drome" arc carefully reviewed.

Study selection: Pertinent scientific investigations on "sick building syndrome"and previously published reviews on this arid related subjects that met the educa-tional objectives were critically reviewed.

Results: "Sick building syndrome" is a pseudodiagnosis composed of nonspe.cific. transient symptoms without proven biologic markers. Its application in theclinical setting invites frequent subsequent linkage to other similar vague diagnosesassociated witti chronic debility and lack of therapeutic intervention.

Conclusion: The reader is encouraged to avoid the use of this term in favor of aSimpler, descriptive diagnosis (eg, transient office-related annoyance andAjr irrita-tion) or if this seems inadequate, adoption of the diagnostic label of "idiopathicbuilding intolerance."

Ann Allergy Asthma Frorounol l997;79:283-94.

INTRODUCTIONThere is an increasing awareness thatpoor indoor air quality may generate avariety of deleterious effects on humanhealth.' In recent years this has becomea major publjc health concern. This isnut surprising when one considers thatWE spend a majority of our time trav-eling or working in a succession ofindoor mkroenvirontnems.2 Althoughbuildings arc intended to provide rela-tively safe and comfortable environ-ments for individuals to Jive and work,

* From the Oregon Health Science* Univer-sity. Division of Allergy and Clinical Immunol-ogy. Ponlind, Oregon.

Presented at iht November, '996 AmericanCollege oF Allergy. Asthma and ImmunologyMeeting in Boston.

Received for publication May 16. 1997.

SUMAccepted for publication in revised form Au-n 1.1997-

it has become apparent that they do notalways achieve, this goal. Althoughthere are no governmental health stan-dards specifically applicable to com-mercial, buildings, the federal govern-ment either directly or indirectlyregulates many products associatedwhh indoor pollution.-1 There are vol-untary guidelines within the Environ-mental Protection Agency's BuildingAir Quality guide.' in Europe, theWorld Health Organization has alsodeveloped indoor air quality guide-lines?

Although the first modem building-associated illnesses were recognizedprior to I960, it was not until after theArab oil embargo of 1973 that com-plaints of physical discomfort with as-sociated irritant symptoms were re-ported with increasing frequency in themedical literature. Much of the interest

and research began in Scandinaviancountries and the United Kingdom inthe late 1970s.6 In 1983 at a WorldHealth Organization meeting in Ge-neva, a new symptom complex "sickbuilding syndrome" was initiallycoined? The complaints of afflicted of-fice workers included drynexs of theskin and mucous membranes, mentalfatigue, headaches, general pruritus,and airway infections.8 Most involvedbuildings were of a commercial natureand had in common the fact that theywere heavily populated, carpeted, andeither infrequently or poorly cleaned."

In the previous decade there has-been increasing debate about thesymptom complex of "side buildingsyndrome." The growing dissatisfac-tion with the term originates firm thetotal absence of consistent case defini-tion of the "syndrome," the lack ofbiologic markers for most symptoms,or even groups of symptoms, and fail-ure to tind consistent associations be-tween "sick building syndrome "symp-toms and any building contaminant^)across a large number of buildingsstudied.'0-" It has been argued that uti-lization of this term has not improvedour understanding of the occurrence ofthese symptoms, and funher, that tolabel an entire building as "sick" or"healthy" has no scientific founda-tion." Unfortunately, the media haveoften contributed to the problem bylinking any building-associated com-plaint under this misleading and some-times disquieting term.12 In the UnitedStates expanding litigation has soughtto link "sick building syndrome" withan equally controversial and unscien-tific symptom complex of "multiple

VOLUME 79. OCTOBER. IW7 2U3

Table 1. Definition of Terms Frequently Employed li Office Building-Related HeeHHProblems

. Problem buildingAn ofoe building where worker complaints of ill health are more common thanmight be reasonably expected.

• Building-related IllnessAn office building In which one or more workers develop an accepted, well-defined

Illness for which a specific cause is found. The cause £ dsady related to thebuilding, eg< hypersensitivity pneumonitis. humidifierfever, Legionnaire'spneumonitis, etc,

• Sick building syndromeAn office building in which an Ill-defined Illness develops In one cr more workers.

The illness demonstrates great variability among the workers and no causativeagent is apparent or found despite significant evaluation

• Tight building syndromeGenerally used to designate an engineering or architectural flaw as the cause for

either a building-related illness or a sick building syndrome.• Crisis building

Skk building where repeated industrial hygiene surveys have failed to localize aceuse for Ill-defined symptoms that precipitates a crisis of concern in the involvedemployees. Such buildings are frequently evacuated.

(Adaptedfrom Bardana EJ. Building-related Illness in occupational asthma, Eds: Bardena EJ,MontanaroA O'Hollaren IvTT Philadelphia: Hantey& Belfus, 1992337-54).

chemical sensitivity."13-1* This reviewwill, focus on the available sciendficinformation on "sick building syn-drome" and proposes an approach tothe evaluation of nonspecific building-associated complaints for cliniciansconfronted with this problem.

TERMINOLOGYAlthough air pollution in the setting ofheavy industry bas been well recog-nized for many centuries, indoor airquality issues in large commercialbuildings and their worker occupantsare relatively new developments inmedicine.15 The terminology that hasarisen in this area has become some-what confusing. The author's defini-

dona of commonly employed renns aresummarized in Table 1." It should bepointed out that there continues to besome disagreement as to the use andapplication of these labels. In evaluat-ing problem buildings, investigatorshave identified a variety of buildinp-related illnesses that are clearly attrib-utable to the building?." These includesuch diagnoses as hypersensitivitypneumonitis, humidifier fever, build-ing-related asthma, toxic pneumonitisor organic dust toxic syndrome, a va-riety of infectious syndromes (eg. Le-gionnaire's disease, Pontiac fever. Q-fever. tuberculosis), building-relateddermatitis and ocular symptoms andrare intoxication syndromes, eg, mis-

J

ProW*m tunning*20.30%

JBuikrmg ntoat

»ine*« •5-10*

J

Commtrdtlbuildings

I

IdiopothK touiWtny- jrttotemwt •-

1D-2S*

iBuilding* withouf

tdcntiNod problems •70-60%

!Undetectedprobtom* •10-20%

IHe»HhybuUdingf50-70%

Figure I.Schematic depiction of the dynamic continuum within commercial building stock focusedon the degradation of building performance (adopted from reference *22. with permission).

use of pesticides or other intoxi-cants.16-" These building-related ill-nesses have clinical case definitionsand can be diagnosed by objectivelymeasurable signs of illness. There islittle controversy related to these ill-nesses and they will not be dealt wihfurther in this review.

On the other hand, there has been anincreasing tendency to describe .symp-toms that appear or are perceived to berelated lo the air quality of a building,but which exhaustive studies fail iocorrelate with any identifiable problemin the building, ft is this group of tran-sient symptoms thai has composed thesymptom complex called "side build-ing syndrome" upon which this reviewwill concentrate.

Even those who utilize the lerrn"sick building syndrome"concede thatall investigators and scientific journalsdiscussing this issue have a great re-sponsibility to Hafino terminologyclearly."1-" One of the critical issuesoften lost in distinguishing building-related illness such as Legkmaire'sdisease and "sick building syndrome"is that the former biologically definedinfection may persist even after an af-flicted individual is removed from thebuilding, whereas the symptoms of"sick building syndrome" shouldquickly abate upon leaving the build-ing." It is often this distinction thatmotivates a number of unconventional,providers to seek linkage with otherequally con trovers JaJ diagnoses to jus-tify the persistence of symptoms.70 Indoing this one loses even the ill-de-fined parameters of this toraisntsymptom complex.

EPIDEMIOLOGICCONSIDERATIONSThe prevalence of "sick building syn-drome" remains largely unknown.Case definition for this symptom com-plex remains very arbitrary since thereare no biologic martens lo define itprecisely. It has bceri indicated thatthis is partly attributable to inadequateanalytical methods, and psrrjy relatedto the nonspeciflcity of many "sickbuilding syndrome" symptoms."Burge has observed that in the inves-

284 ANNALS OF ALLERGY. ASTHMA. & IMMUNOLOGY

tipiioi* conducted thus far there(doesnoi appear <° be one group of 'sickbuildings and a separate group of un-aflcfieU buildings." Rather, there is acontinuum of problems from onebuilding to another.31 In this respect,Woods has hypothesized a dynamiccontinuum within commercial buildingstock focused on the degradation ofbuilding performance (Fig J)-a Fur-thermore, most studies of this issuehave utilized a self-report instrument,and there is neither a standard ques-tionnaire nor a general consensus onihc range of symptoms that are appro-priate for inclusion.53

The National Institute of Occupa-lionul Safety and Health conducted nu-merous investigation? over the pastscvcr.il decades. By 1991 over 600 in-door air quality studies bad been per-formed as pan of the health hazardprogram."04 It has been estimatedne.-irly a third of buildings world-widehave some problems with their heat-ing, ventilation, and air conditioningsystem precipitating worker com-pliiints. Jn 1989 the Honeywell Corpo-ration conducted a random telephone.survey of 600 of its office workers.Twenty percent perceived their workproduct hampered by poor indoor airquality.1'1

A number of large multi-buildingstudies covering thousands of officew'.irkers have been conducted in NorthAmerica, the United Kingdom, andI .'...-...*.» Ztt-i* A « :~.j:*...«a*l AU^tra n.trwI'WIkl^W, y"W jLlJt*t**U*\*l* M W V « * < ^«»w

liunnaires were noi standardized inthese investigations making any com-purisons problematic. As well, theseMudic.s depended on self-reportedsymptoms and subjective estimates ofbuilding condirions,«i^liy air, dustyc'.tndiiions. fresh paint odor, etc." Thevalidity of these observations and ab-sence of confirmation by objectivemeasurements bns been n source ofsignificant criticism. The most com-mon independent health factors identi-fied in these Urge cross sectional stud-ies of "sick building" workers aresummarized in Table 2- There are noetiniparable data for these independenthealth factors in unaffected buildings.''Tic Environmental Protection Agen-

Tabte 2, Independent Health FactorsIdentified by Respondents toQuestionnaires Related to "Sic* BuildingSyndrome"

• Upper respiratory symptomsRhlnontieaNasal congestionSneezingSinus congestion

• Throat symptomsSorenessHoarsenessDry ness

• Lower respiratory symptomsCoughWheezingDyspneaChest tightness

• Ocular/cutaneous symptomsDryness(toftTearingBlurred visionSoreness/burningProblems Wfti contact lenses

• GeneralFBtigue/drowslnessChills/feverNausea

• MuscutosketetalMyalgiaCervical spasmLumbosacral spasm/painNumbness in hands/wristsPolyarthrelgia

• NeurologicHeadacheReduced memoryDifficulty in concentratingDepressionTension/nervousness

Modified and adapted from references *32and #35, with permission.

cy's BASE program suggests, how-ever, that symptom frequencies in adozen buildings selected at randomwere often lower by a factor of two ormore." The only finding common 10the multiple studies performed to dalewag the increased .symptom rates re-ported by females.*1"3- Even this ob-servation elicits debate because it maysimply reflect workplace disparities,ie, lower pay scale, assignment of me-nial tasks. unaliractive workspace,etc.3*

ECONOMIC REPERCUSQONSAlthough symptoms related 10 indoorpollution may seem trivia;, it is asso-ciated with e disproportionate expen-diture of both financial and manpowerresources. The economic impact of thisproblem can easily be overlooked inthe absence of a clear understanding ofbow widespread the problem is. Thenumhcr of incriminated buildings andtheir occupants is estimated lo be sub-stantial. In the United States, Woodshas estimated these numbers to he be-tween 800.000 and l,200,000commer-cial buildings with between 30 to 70million exposed o"~* pants.37 For ex-ample, if approximately half of EnvjJronmental Protection Agency's em-ployees reported headache fur theprevious week with a duration of twodays, this" corresponds to 5,000 head-aches/wk among 5000 employees, or aquarter of a million headaches peryear. If the cost of a headache is esti-mated to vary between $1.50 andS8.00,?* then the cost <£ buijding-re-lated headaches to the EavironmcntalProtection Agency as an organizationcould be valued at between $375-000and $2 million.36 If one adds the cost ofworkers' compensation actions and. insome instances, litigation against ar-chitects, building managers, employersand landlords, the cost of this problemcan reach astronomic proportions.'-1-4

PRECIPITATING FACTORS IN"SICK BU1LDCNG SYNDROME"My own experience as well as that ofyihcr investigators in the area of "sickbuilding syndrome" indicates there arethree major reasons associated with theunset of complaints in building occu-pants. They are (J) rapid new buildinpoccupancy, (2) building renovation,and (3) water or moisture incursionwith subsequent microbial contamina-tion. The most common precipicocwr isassociated with the initiation of exten-sive office building renovation thai isconducted during nmirmi work hourswith incomplete isolation of the con-struction are*, and with little or noadjustment of the ventilation rate-Painting, sheetrocking. plasicring, andcarpeting result in a variety of cherai-

U)I.UME 79. OCTOBER. ISX»7 285

cal emissions thai may adversely im-pact nearby employees. Airborne par-ticulate and volatile chemicalcontaminants are (he most frequentlyreported contaminants in.buildings un-dergoing renovation."-" Volatile or-ganic compounds in indoor air arisefrom a wide variety of building mate-rials, cleaners, office products and ma-chines, paints and furnishings. Exam-ples of typical volatile organiccompounds found in office buildingsinclude xylene, chloroform, etbyJben-z«n.e, chlorobenzcnc, styrene, and tri-chloroethylene. Volatile organic com-pounds frequently have annoyingodors and their presence in tiie settingof significant renovation or new build-ing occupancy is estimated at 70% to80%.

ScvcraJ reviews and a number ofinvestigations have incriminated vola-tile organic compounds in office build-ings as a cause of annoyance and/orirritation to the eyes and mucous mem-brane of the respiratory tract.*0-4* It isnot yet scientifically known whetherexposure to low level concentrations ofvolatile organic compounds has anysignificant adverse health effects. It isclear that certain odors are attributableto volatile organic compounds; how-ever, whether or not they cause or con-tribute to the nonspecific symptoms

outlined in Table 2 has yet 10 be estab-lished/5 Levels of volatile organiccompounds in the indoor environmentare attest alxegs well below thresh-old limit value standards published bythe American Conference of Govern-mental Industrial Hygienists. Il is al-most impossible to calculate the cumu-lative effect of total, volatile organiccompounds when one considers thepotential synergistic effect of airborneparticulate and other possible pollut-ants.49 Where ventilation rales meet OKexceed the requirements of the Amer-ican Conference of Governmental In-dustrial Hygienists; standard 62-1989,the total volatile organic compoundsare usually less than 1 mg/nv1 and con-centrations of individual volatile or-ganic compouads are well below (lessthan J %) any recognized occupationalexposure standard.45

In addition to building renovation,rapid new building occupancy isequally likely to induce annoyanceand/or irritative complaints in exposedworkers. The reasons are very similarLO those noted above wj th building ren-ovation, The same contamination withdusts and volatile organic compoundsoccurs when newly constructed build-ings are not left to "air out" and me-ticulously cleaned prior to occupancy.

In instances where emissions frymconstruction materials are nor the ini-tiaJ trigger of symptoms, the next mostacmncnly encountered problem is re-lated either to a poorly maintainedstructure, or one that was poorly yr>defectively constructed with resultantintrusion of water and contaminationwith microbial and fungal growth. Thismay be more problematic in certaingeographic locations where warmertemperatures and high relative humid-ity result in condensation problems inair conditioned structures, In general.older buildings are more susceptible tomoisture problems than newer build-ings. Obvious fungal growth usuallyprecipitates health concerns among of-fice occupants. This results in the typ-ical "moldy" or "mildew" odor thataccompanies such contamination.However, there is a paucity of scien-tific information upon which buildingengineers, industrial hygicnists and in-volved clinicians can make soundjudgements. There are no generally ac-cepted numerical guidelines that spec-ify "safe" exposure limits. More im-portantly, there are no establishedstandard)) as lo what airborne levelsconstitute a definite health hazard.Similarly, there arc no environmentalcriteria for deciding whether a mea-sured airborne level of ftngi or bacte-ria is a ride factor for bypersensiu'vjtypneumonitis or other defined respira-tory disorders." Analytical results ofair sampling for microorganisms ateuseful in identifying indoor sites wherefungi may be accumulating and ampli-fying. The same analytical results can-not, however, be used to predict orinvoke adverse health effects.

Figure 2. Pntential clinical sequelae associated with fungal conuiminauon of 9 building. SBS = sickbuilding syndrome. MCS * multiple chemical sensitivity, and ABPA = allergic bronchopulmoniiry

CLINICAL SEQUELAEASSOCIATED WITHMICROBIAL OVERGROWTHThere are a variety of clinical Out-comes that may be associated with mi-crobial growth in a building (Fig 2).

Annoyance ReactionsAnnoyance reactions occur in individ-uals who possess a heightened sense ofolfactory awareness. Odor perceptioninvolves the most ftmdameiltal of

286 ANNALS OF ALLERGY. ASTHMA. & IMMUNOLOGY

sense*. Eton a phylogenetic stand-point, it may be the oldest of the per-ceptual systems and is known to k—valve the limbic system of the brainwhJch is the seat of emotions in hu-mans and other animals.51 The abilityto tolerate a variety of non-irritating,but. undesirable odors, is dependent ona variety of genetic and acquired fac-tors lhal affect olfartim. These factorsmay include the presence of allergic ornonallergic rhinjtjs, infectious sinus-itis, nasal and paranasal polyposis. to-bacco use, and nasal instillation ofover-the-counter, prescription and il-licil drugs, among otters. The percep-tion of an undesirable odor is one ofthe principal heralding complaints ininstances of "sick buildiag syndrome."Frequently, a strong emotional re-sponse is voiced by occupants, and of-len. the complaints may continue de-spite remediation of the source. Aswell, the emotional response of occu-pants of ten seems out of proportion tothe identified problem.5' This often be-comes a difficult issue to solve, and acostly experience for the buildingowner or manager.*1-0 The source ofrepugnant odors in "sick building syn-drome" is frequently associated withthe "mildew" or 'Yousty"odor of fun-gal growth which represents fungaj-specific volatile organic compounds.

Irrhaiionol SymptomsAlthough conventional wisdom has at-tributed the transient, nonspecific irri-tation of mucous membranes or respi-ratory tract to volatile organiccompounds in office buildings, there isa paucity of scientific data substantiat-ing this assertion/5-*1 It is possible thatother factors-wlatuig-toJoial particu-lates. relative rumdLty, and tempera-lure may play a role in these nonspe-cific symptoms.

In the absence of specific chemicalsor mixtures of chemicals, ic has beensuggested that indoor microbial con-tamination could account for a portionor the observed symptoms.55'59 Indoorair contains a variety of bacterial andfungal species.5*-39 Certain cell wallconstituents, particularly bacteria) en-

D, glucans, and othw proteases

have been observed to possess bothinflammatory and adjuvant proper-ties.60-*2 In this respect, it is of interestthat Michel and associates recentlydemonstrated that subjects sensitizedto housedust mite develop severeasthma when simultaneously exposedto housedust containing high concen-trations of endotoxjn.*3 This supportsthe theory that mite allergy (or otherallergens) act as an initialing environ-mental factor, whereas endotoxin actsa? a triggering mechanism for increas-ing the seventy of ihe basic disease.

At the present time there arc verylimited scientific data related to thedetection of endotoxin, glucans, orother microbial constituents in officesettings. A great deal more work willbe required before meir roles, if any,can be determined with any accuracyin building-related illness.62

SensitizarivnSensitization is a highly unlikelyHBCTHnism to explain synptoros inmost cases of "sick building syn-drome." The symptom complex of sickbuilding syndrome often developsacutely in individuals who have noneof the hallmarks of allergic disease. Aswell, (here arc relatively few chemicalswith (he capacity of inducing dc novoimmune hypersensitivity. Althoughsignificant levels or" dust and microor-ganisms have been found in publicbuildings,144^ it is more likely thatthese constituents contribute to symp-tomatology by either mechanical irri-tation, or by reactivity wfcfti volatileorganic compounds associated withmicroorganisms, than by de novo sen-sitization.*'

In addition Jo IgEr specific inecha-nrans, hypersensitivity pneumonic)snaf result from Exposure to moder-ately heavy concentrations of micro-organisms.06 The true incidence ofbuilding-related Bypersensitiviry pneu-monia's is not known. There is a pau-city of scientific data related to ibeactual dyse of bacterial or fungal ami-*gen required for either sensitization ordevetopmentof oven symptoms. I can-not overemphasize that the mere pres-ence of an airborne microbial contam-

inant cannot be directly identified witha disease process in an occupant unlessthere is additional, evidence linking an•himrrilogic response to a specificbuilding contaminant (as opposed roanalternative exposure, eg, home, bam,vehicle, ±5).

Respiraiory InfectionsRespiratory infections with commonpathogens such as viruses (eg, influ-enza, measles, common colds) andbacteria (eg, Legionnaire's disease. Qfever, tuberculosis) are certainly trans-missible by indoor air and have beenreported moficebuildings.*7'** Only afew fungal species, however, can causeinfections in otherwise healthy individ-uals (eg, Coccidioides immitis, His-toplasma capsulation, Cryptococcusneofnrmans). These are common tosoil and the last two also occur in birddroppings that may contaminate air in-take systems of buildings." Other fun-gal infections usually occur in the set-ting of patients wirb significant defectsin cell-mediated immunity,'" and havebeen reported JJD association wiflafaulty heating, ventilation and air coc-ditioning systems,7'-73 eg, dissemi-nated aspergillosis.

ToxicosisToxicosis results from chemical toxinsthai are generated by viable organisms.The irritant responses to endotoxin andglucans have been discussed above.Endotoxin has also been associatedwith the development of "organic dusttoxjc syndrome." The severity ofsymptoms in this condition appears tocorrelate with the number of grim-negative bacteria or endotoxin in theenvironment.7'' Symptom generallycommence four 10 eight hours afterexposure and include malaise, myal-gia-dyspnea, cough, headache, andnausea. It differs from hypersensicwrypneumonitis in that no prior sensitiza-fcjan is required, chest radiograph isgenerally normal, and dircnic sequelaedo not occur." Symptoms usually sub-side in hours and tolerance often de-velops despite continued exposure.The latter may be lost over weekendsor vacations with reappearance upon

79. OCTOBER. 1997 287

re-exposure, ie, "Monday nnmingmisery." This conditiai has been re-fened W under a variety of labels in-cluding humidifier fever, grain fever.toxic dust syndrome, etc."

Mycotoxicosis as a poten.ti.aj causecf "sick building syndrome.' remainsessentially undocumented. It would bea consideration only in instances offlorid contamination. Recently therehas been increased concern abouthomes water-damaged as a result offlooding. This would rarely be a prob-lem in a conunercial building setting.

Stachybotrys chartarum (curd) andits toxic metabolites (satratoxins) havebeen linked to life-threatening pulmo-nary hemorrhage in a cluster of teninfants in Cleveland.7* AQ. ten werehospitalized and pibnciazy hemor-rhages recurred in five infants shortlyafter discharge finn hospital. Informalsurveillance for pulmonary hemor-rhage by the Centers for Disease Con-trol and Prevention following theCleveland report uncovered an addi-tional 32 cases in Chio and 47 casesamong infants in the rest of the coun-try.77 Unfortunately, in the latter re-ports investigators wens unable to doany confirmatory studies. There ap-pears to be a synergistic effect betweenexposure to £ charturum and the pres-ence of tobacco smoke.78'" Thus far allreported cases io humans have oc-curred in inf>r*« less than 1 year ofage.79

Although there have been reports ofStachybotrys-induced disease in farmworkers handling heavily contami-nated hay, (be absence of appropriateconfirmatory studies makes the linkagetenuous.10 Similar concerns surroundthe report by Croft et al regardirtg-a—Chicago family with a heraorrbagjc al-veolitis presumed to be related to tri-chotheeene toxicosis." Johanning et alreported on the results of a question-naire survey among 53 New York of-fice workers who were exposed to fun-gaj contaminants as a result of waterincursion from a faulty storm drain.*2

Although these authors conclude thatwader symptoms and subtle immuno-logicchanges in the complainants werethe result of exposure to toxigenic 5.

c/wrrcrum and other fungi, there is nodirect scientific evidence substantiat-ing this asserticn. There are no con-fumed cases of Stachybotrys-inducedhcmorrbagic alveolitis in adults.7* Ithas been speculated that infants anancKB susceptible because their lungsare developing rapidly.79 This usuallyoccurs in the setting of very significantwater damage. It is highly doubtfulthat this organism plays a significantrole in the induction of what has beencharacterized as "sick building syn-drome." Aflaioxin from Aspergillusflavus is a mycotoxin associated withincreased cancer risk, but an unlikelyparticipant in the nonspecific symp-toms associated wjth "sick buildingsyndrome."

j&ss Psychogenic IllnessPsychogeruc and social factors play asignificant role in the evolution ofmany cases of "sick building syn-drome." There are insufficient scien-tific data to state how often this occurs.The origin of the problem developsfirm an initiaj lack of scientific infor-mation, dissemination of misinforma-tioi, or providers who unequivocallydiagnose an evolving pathologic statethat has not been scientifically demon-strated.*3 Frequently, the media add tothe confusion. Unfortunately, the usecf "sick building syndrome" as a sur-rogate €or a bonafide diagnosis con-tributes little to clarify the clinical sit-uation. With the suggestion of"dangerous" microbial aerosols in theworkplace, patients understandably be-come concerned about their long-termhealth. Inappropriate belief spstsnsmay become entrenched in situationswhere office-workers are frustrated intheir attempts to correct a perceivedproblem and ignored by their employ-ers and physicians.1*

In my experience analyzing in-stances of "Sick building syndrome"there Frequently is ari evolution tochronic complaints from wbat origi-nated as transient building-relatedsymptoms. Frqucnrly. the spectrum ofodors or irritants precipitating symp-toms expands without plausible ratio-nale. There are no physiologic reasons

for this transition, but it must be rec-ognized that when this occurs, thesynpton complex no longer repre-sents what has been traditionally re-ferred to as "sick building syndrone."In tins respect, some patients may findthe theories of clinical ecology com-forting and useful, and as a matter ofcourse are also labeled as having %"-tiple chemical sensitivity." ft thispoint they have acquired twopseudodiagnostic labels defined onlyby nonspecific symptoms and con-founded by a confusing nomenclatureand considerable scientific contro-versy. Hence, the adage vf this re-view . . ."a wolf in sheep's doBnng."In effect, many individuals who foliarin this transition can be said to suffer aform of toxic agoraphobia usually trig-gered by an odor or the pT '̂liTi ofan exposure, ie. a form of cacosmia orparosmia. Kurt believes this symptomcomplex is analogous to the manifes-tations of panic disorder as defined byDSM-rV-R,** This belief is supportedby two recent investigations. KM

ASSOCIATION OF "SICKBUILDING SYNDROME" WITHOTHER CONTROVERSIALDIAGNOSESTraditionally the symptom complex of"sick building syndrome" has impliedthe development of transient annoy-ance and/or im'tationaJ symptom thatare temporally related to a building ora specific area of a building. The keyissue lending credibility to this "diag-nosis" has always been the strikingtemporality of symptoms within thebuilding. Symptoms regress upon exit-ing the building and resume upon re-turning. The obvious solution io anysuch patient bas been to change thework station to an alternative site. Inthose affected patients where such so-lutions appear to be elusive, there is agradual evoJutjon to a permanence ofsymptoms beyond tte envelope of thebuilding. The reaacn for this subtletransform ation is not always evident.Because many of these patients k-come engaged in one form or anotherof legal action (eg, Workers' Compen-sation, Americans mfti Disabilities

28* ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY

Sick Building8yndn>fl»

Fatigue (BO)Confusion (20)UriablMyfZO)Eye Irritation (90)Headache (100)

fatigue (93)Memoiy Loss (77)Confusion (73)IrtteWKytST)HW<J»Che (67)

Memory Lots (90)Confusion (90)

Firtgue (100)Memory Low (63)Contort*) (64)IrrittbiOty (50)Headache (83)

Kiturc 3. Similarity rfcore pympiom? in four controversial disorders frequently associated with onemother i adapted Mid modified from references #12, 18, and 87. used with penmssioi). MCS = multiplechemical sensitivity.

ACL Fair Housing Amendments Act,Toxic Tort Litigation, etc), ffie conceptof a sen-limited symptom complex isnever as forbearing as a condition thathas permanence and is all encompass-ing. Vl< Accordingly, one occasionallyobserves a tendency to lode "sickbuilding syndrome" with the develop-ment a i other chronic disorders, manyc£ which suffer a similar paucity ofbiologic markers and an absence ofan effective therapeutic intervention."Disability among such patients isconsiderable.

"Multiple chemical sensitivity" isfrequently invoked as the natural out-come of "sick building sprhrne."The latter serves as the environmentaltrigger for "multiple chemical sensitiv-hy."2" Core symptoms of these pro-period symptom complexes are simi-lar. ie. skin and/or mucous membrane

T headache.cognitive impairment, etc11'*'7 (Fig 3).Symptoms are not the result of tissuedamage rhat can be observed or mea-sured by physical examination or lab-oratory studies.""90 Once the transitioni-1. established, the patient feels justifiedin the expression of chronic synplonsfur which there is little hope of anyeffective therapeutic intervention.*1"93

Previous studies of patients with "mul-liple chemical sensitivity" have ob-

served that 69% to 86% claimed totaldisability.9'-*3

In selected patients with "sick build-ing syndrome" or "multiple chemicalsensitivity" there is a furtherproclivityto associate with other ill-defined,chronic disorders with overlappingsymptoms. These include chronic fa-tigue syndrome and fj.bromyalfia.87 Ithas been proposed that chronic fatiguesyndrome and fibromyalgia are simi-lar, if aor identical disorders.9*95 Allthese conditions share a preponderancecf female patients wirh similar meanages at presentation, marital status, ed-ucational level, employment rai£, andduration of illness (Fig S)."*-93 Re-cently, there have also been claims as-sociatangthe "chemical" basis of "mul-tiple chemical sensitivity" with theinduction of porphyria.** This pur-ported association is based principallyonfresults fromVsingJe reference lab-oratory utilizing a fundamentallyflawed assay .firerythrocyte copropor-phyrin oxidase.*6

Based on these observations, the cli-nician should be extremely cautiousabout accepting or applying "sickbuilding syndrome" as a bunafide di-agnosis. This frequently triggers a di-agnostic domino effect leading to anunintended clinical outcome. Just as arecent panel of The World Health Or-

ganisation has recommended a newname, "idiopathic environmental intol-erance," to stress the fact that environ-mental chemicals have not beenproven to cause "multiple chemicalsensitivity" synptons,! would submitthat a better name for "sick, buildingsyndrome" would be "idiopathicbuild-ing intolerance" to remove any illusionof a bonafjde illness.

APPROACH TO PATENTSWITH IDIOEKEHICBrjIIDINSINTOLERANCEBuilding-associated illness often pre-sents a major diagnostic challenge tothe clinician. The patient often arriveswith deeply entrenched perceptions re-garding the absolute Linkage of theirsynptons to poor air quality in tteirwork environment. Three major pit-falls arise in the evaluation of possibleattribution of any sjnptcm complex toa particular workplace, domicile orproduct. These are (l)faUure to recog-nize an explanatory preexisting medi-caL disorder, (2) failure to diagnose onunderlying condition masquerading as"sick building syndrome, "and (3) in-appropriate patient advocacy in the ab-sence of credible scientific substantia-tion. In evaluating any patient withsuch problems I recommend a strati-fied approach beginning with a com-prehensive history and physical exam-ination to eliminate the first twopjtfalb. In obtaining the medical his-tory, it is essential that attention begiven to the details of the patients'workplace and non-workplace expo-sores. Frequently, one sees a reason-ably complete description of the work-place and its exposures without similarattention to the home, avocations, so-ciaj habits, recreational activities, typeof vehicle driven, etc. Supplementationof the madicBl history with an exten-sive questionnaire that can be checkedat the time of examination can be ex-tremely useful"1 As well, the examinermust make every effort to obtain asmany previous medica! records as ispossible.

Laboratory tests for biologic mark-ers of building exposures are seldomhelpful, except in the case of environ.-

VOUUME 79. OCTOBER. 1997 289

mental tobacco smoke. More com-monly than not, laboratory studies areTOpg Jjkely lo assist in the elucidationof alternative disease processes. Theclinician should consider selecting rel-atively high yield, low cost tests (eg.complete blood count, chemistryscreen, screening computerized LO-mography of sinuses, selected allergyskin testing, putacnaiy function stud-ies, etc) before proceeding to more ex-pensive evaluations less likely to yielduseful information (eg, autoimmunescrology, airborne bacterial/mold de-terminations, toxicology screens, lym-phocyte surface marker studies, etc).9"

The appropriate use of consultantscan prove invaluable in the assessmentof building-associated symptoms. Forexample, collaboration with an otolar-yngoJogist 10 assess symptoms relating

Table 3. Diagnostic Groupings of MedicalConditions Commonly Confused withToxicity or HypersensWvrty 10 IndoorPollution

infectious diseasesAcute/chronic sinusitisPharyngitisTonsillitisBronchitis

Allergic/inflammatory disordersAllergic rhinitisBronchia) asthmaContact dermatitisIdiopathic urticaria/angloedemaHypereensrtivlty pneumonitisOrganic toxic dust syndrome

Nonallerglc respiratory disordersChronic serous otitis mediaEustachian tube dysfunctionNasaVparanasal polyposlsVocal cord polyps/nodulesGastroesophageal refluxRhinitis medicamerrtosaVocal cord dysfunction

MetabolicAoxJc conditionsThyroid dysfunctionDiabetes mellitusRecreational drug abuseRheumatic disordersPharmaceutical side effects

Psychiatric disordersGeneralized anxiety statesPenlc disorder/toxic agoraphobiaSocialization disorder

Modified from reference 097 with permis-skn.

to upper airway obstruction cr voicedisorders such as hoarseness, laryngi-tis, or persistent throat pain ascribed topoor air quality may lead to an alter-native diagnosis, eg, vocal cord dys-function. Similarly, referral to a der-matologist or psychiatrisr can proveinvaluable in shedding light on associ-ated cutaneous or cognitive problems.

The initial process of evaluationshould focus on the differential diag-nostic process, It is imperative to con-sider Ac common medical and psycho-logic conditions chat may present asperceived toxicity or hypersensitivitycaused by indoor pollution. Five gen-eral groups of disorders have beenidentified in patients who present withbuilding-related illness (Table 3).

Upon completion of this initialphase of differential diagnosis, the sec-ond step relates lo developing an as-sessment of the most likely cause forthe patient's complaints. ID this re-spect, collaboration with a knowledge-able industrial hygienist or buildingengineer is invaluable. When possibleand practical, the clinician should al-ways lake the opportunity to visit andinspect the building- A number of ex-cellent protocols have been developedas guidelines in the investigation ofindoor air quality. AD of these proto-cols share a flexible approach and em-phasize general observations over ac-tual measurements of pollutants.*2-*9-100

The major building-related issues thatshould be addressed can be dividedinto five major categories: (1) buildingage and design: (2) outdoor air quality;(3) heating, ventilation and air condi-tioning design and maintenance; (4)renovation: and (5) management phi-Josopby,2"""7 -

The third and final step involves thedistillation of available data into a sci-entifically based, easily understood de-scription of the likely pathogenic pro-cess. The author frequently relics onthe paradigm of annoyance reactions,transientimtatioi, sensitizotJon. infec-tion, toxicosis, or psychogenic illnessdescribed above (Eg 2). A careful a-tempt is made to explain the medicalimplications of these various alterna-tive* to the patient lucidly. At

several alternative mechanisms mayapply. The often used pscudodiagnosisof "sickbuilding syndrome" is avoidedentirely with the hope that the patientwill be reassured, and armed with ascientific medical perspective, proceedto cope with the issues at hand withoutadverse impact on their psychologicstability, their employment, or their ca-reer. In this respect, the physician oweseach patient his or her advocacy, burthis patronage must always be tem-pered by the overriding responsibilityto scientific veracity.

In summary, "sick building syn-drome" is a pseudodiagnosis com-posed of nonspecific, transient synp-tomS Without kllOWn biologic TttnJaaraIts application in the clinical settinginvites frequent subsequent linkage toother similar vague diagnoses associ-ated with chronic debility and lack ofeffective therapeutic interventions, eg."multiple chemical sensitivity,'1 fibro-myalgia, chronic fatigue syndrome,among others. Hence, the thrust of thisreview is to encourage the reader loavoid use of this term in favor of asimpler, descriptive diagnosis (eg,transient annoyance and/or irritation)or if this is not appealing, adopt thediagnostic label of "idiopathicbuildingintolerance" instead.

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Requests far reprints thould k addressed tu:

EmUJ Bardana. Jr. MDOregon Health Sciences UniversityDivision qf Allergy 4 Clinical tmmunalaxy1181 SWSam Jackson Park RtL PV 320Portland. OR97ZQ1

CME ExaminationNo 007-009Questions 1-20, Bardana EL I997;79:283-94.

CME Test Questions

1. AJI the following diagnoses be-long in the category of building-related illnesses except:A. Hypersensitivity pneumonitisB. Humidifier feverC. TuberculosisD. Q feverE. Vocal cord dysfunction syn-

drome2. A building where studies have

failed to localize a cause for ill-defined symptoms in occupantswith resultant fear and eventualevacuation is termed a:A. tight building.B. problem building.C. crisis building.

~Dnroubled building. ~ "3. The estimated number of commer-

cial buildings with nalfunctLcningheating, ventilation and air condi-tioning systems is:A. 10%B. 25%C. 33%D. 50%E 65%

4. The approximate number of af-fected building occupants who

may be suffering adverse healtheffects due to poor indoor air qual-ity is:A. 2 million.B. 5 million.C. 10 million.D. 20 million.E. 50 million.

5. All of the following are precipita-tors of "sick building syndrome"except:A. Preparation <£ food or bever-

agesB. Occupancy of a new building

before final completionC. Renovation of any commercial

building during normal work-shift?

~D. Water or moisture incursion6. True statements related to indoor

levels of volatile organic com-pounds in commercial buildingsinclude all cf the following ex-ceptA. Associated with annoying

odorsB. Bnanate from paints, carpet

adhesives, plastering com-pounds . etc.

C. Are usually well below TLVstandards published by theAmerican Conference of Gov-ernmental Industrial Hygien-ists

D. Are usually less than 1% ofany recognized occupationalexposure standard

E. Arc definite respiratory irri-tants

7- Obvious mold growth in commer-cial ofice buildings is usually as-sociated with all of the followingexcept:A. Poor maintenance of the heat-

ing, ventilation, and air condi-tioning system

B. Intrusion of waterC. Typical "mildew" odorD. Health concerns among build-

ing occupantsE. Adverse health effects

8. All of the following oorxiitionsmay impact how a building occu-pant responds to an undesirableodor except:A. Allergic rhinitisB. Chronic sinusitisC. Cigarette smokingD. Cocaine abuse

VOLUME 79. OCTOBER 1997 293

E. Migraine headaches9. The source of the typical "mil-

dew" or "moldy" odor emanatingfrom fungal overgrowth is relatedto which constituents produced byfungi:A. EndotoxinB. ProteasesC. Volatile organic compoundsD. GlucansE. Mycotoxins

10- Fungal species associated vittisystemic infections in health indi-viduals include all of the feiLkw-ing except:A. Coccutioides imm'aisB. Histoplasma capsulatumC. Penidllium notationD. Crypiococcus neoformans

11. Organic dust toxic syndrome isusually caused by which of thefollowing:A. Thermoactinomyceies vulgarisB. EndotoxinC. Candida albicansD. Aspergillus flauusE. Stachyboirys chartarum (atra)

12. Aflatoxk is a carcinogenic nyco-toxin derived from which of thefollowing species?A. Aureobaaidium pullulansE. Alternaria tenuisC. Sitaphilus granariusD. Aspergillus flavusE. Merulius lacrymans

13. Building-related psychogenic ill-ness has its inception m aD of thefollowing except:

A. Preexisting atopic diseaseB. The lay mediaC MisinformationD. Lack of informationE Uninformed, alarmist provid-

ers14 r/iemcKt sigoificant trigger result-

ing in me development of toxicagoraphobia in sick building syn-drome is:A. An upper respiratory infectionB. Poor acoustical qualitiesC. Unacceptable room tempera-

turesD. Perception of some maiodorE. Inadetjuafe illumination

15. Conditions frequently associatedwith "sick building Syndrome"in-clude all of the following except:A. Multiple chemical sensitivityB. Chronic fatigue syndromeC. FibromyaJgiaD. PorphyriaE Polymyalgia rheumatica

16. Three nHJcrpttfells that should beconsidered before attribution ofany symptom complex to a build-ing include aD of the followingexcept:A. Age of the buildingB. Failure to recognize apreexist-

ing medical disorderC. Failure to diagnose a condition

masquerading as "side build-ing sjndrxne"

D. Inappropriate patient advocacy17. Historically, information about the

patient's workplace is as impor-

tant as information about which ofthe following:A. Private residenceB. Motor vehicle drivenC. AvocationsD. Social habitsE. HI of the above

18. An example cf a relatively highyield, low cost test in the evalua-tion of patients with building-re-lated symptoms include:A. Complete blood countB. Computerised tomography screen

of sinusesC. Pulmonary function studiesD. Selected allergy skin testsE. All of the above

19. In evaluating building-rettedcomplaints the clinician shouldmake every attempt to:A. Compare prevalence of symp-

tom in similar buildingsB. Examine fce rate of absentee-

ism in all occupantsC. Make a visit to the buildingD. Perform allergy testing in aU

occupants20. Which building-specific issue

should be considered h evaluatingthe adequacy of any building:A. ftniH-JTvj age and designB. Heating, ventilation and air

conditioning design and main-tenance

C. RenovationD. Management philosophyE. Ml of the above

ZSM ANNALS OF ALLERGY. ASTHMA. & IMMUNOLOGY