Environmental and Occupational Risk Factors Possibly Identified for

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Environmental and Occupational Risk Factors Possibly Identified for

Sarcoidosis CME

News Author: Laurie Barclay, MD

CME Author: Vega, MD, FAAFP

http://www.medscape.com/viewarticle/496208

Disclosures

To earn CME credit, read the news brief along with the CME

information that follows and answer the post test questions.

Release Date: December 17, 2004; Valid for credit through December

17, 2005

Credits Available

Physicians - up to 0.25 AMA PRA category 1 continuing physician

education credits

Dec. 17, 2004 — A case-control study published in the Dec. 15 issue

of the American Journal of Respiratory & Critical Care Medicine

suggests environmental and occupational risk factors for sarcoidosis.

" The prevailing view suggests that sarcoidosis occurs as the

consequence of exposure to one or more environmental agents

interacting with genetic factors, " write Lee S. Newman, MD, MA, from

the National Jewish Medical and Research Center and University of

Colorado Health Sciences Center in Denver, Colorado, and

colleagues. " Previous investigators have suggested that

environmental exposures to microbial agents may prove causative

because of their infectious and/or antigenic properties. "

At 10 centers, the investigators recruited and interviewed 706

patients newly diagnosed as having sarcoidosis and an equal number

of age-, race-, and sex-matched control subjects, using

questionnaires regarding occupational and nonoccupational exposures.

Univariable analyses demonstrated positive associations between

sarcoidosis and agricultural employment (odds ratio [OR], 1.46;

confidence interval [CI], 1.13-1.89), work exposure to insecticides

(OR, 1.52; CI, 1.14-2.04), and work environment containing mold or

mildew with possible exposure to microbial bioaerosols (OR, 1.61;

CI, 1.13-2.31).

Compared with control subjects, those with sarcoidosis were less

likely to have a history of ever smoking cigarettes (OR, 0.62; CI,

0.50-0.77). Multivariable modeling suggested increased sarcoidosis

risk for work in areas with musty odors (OR, 1.62; CI, 1.24-2.11)

and for occupational exposure to insecticides (OR, 1.61; CI, 1.13-

2.28), and a decreased OR related to ever smoking cigarettes (OR,

0.65; CI, 0.51-0.82).

" The study did not identify a single, predominant cause of

sarcoidosis, " the authors write. " We identified several exposures

associated with sarcoidosis risk, including insecticides,

agricultural employment, and microbial bioaerosols. "

Study limitations include potentially missing risk factors not

considered in questionnaire design, the possibility that some of the

statistically significant results may have occurred due to chance

alone, possible ascertainment bias, failure of many potential

control subjects to participate in the study, differential

information bias, and recall bias.

" Sarcoidosis is considered to be a hypersensitivity disorder, in

which an antigen induces a T cell-mediated cellular immune response.

As a result, it is possible that the etiologic agent or agents may

initiate disease at very low doses of exposure, " the authors

conclude. " Efforts should be directed at integrating exposure data

with our emerging understanding of other sarcoidosis risk modifiers

such as tobacco use, genetics, and familial aggregation. "

Two of the authors report a financial relationship with Centocor.

Am J Respir Crit Care Med. 2004;170:1324-1330

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

Identify the differential diagnosis of sarcoidosis based on clinical

and pathologic features.

Describe environmental and occupational exposures that can increase

the risk of developing sarcoidosis.

Clinical Context

Sarcoidosis is thought to be the result of an antigen-specific cell-

mediated immune response, and the authors of the current study note

that sarcoidosis can be difficult to distinguish in terms of

clinical and histologic clues from other disease states associated

with antigen exposure. These antigen-related disorders include

chronic beryllium disease, hypersensitivity pneumonitis due to

inhaled antigens, and fungal and mycobacterial antigen-induced

granulomatous lung disease.

An increased risk of sarcoidosis has been associated with those

working in multiple occupations, including firefighting and health

care, and environmental exposures to mold or agricultural products.

Because the significance of these possible risk factors remains

controversial, the authors of the current study performed a

multicenter case-control examination of patients with sarcoidosis.

Study Highlights

Ten centers participated in the study. Subjects with sarcoidosis

were included if they had tissue confirmation of noncaseating

granulomas on biopsy within 6 months of study enrollment, clinical

signs and symptoms of sarcoidosis, and if they were older than 18

years. Subjects with tuberculosis were excluded, as were most

patients with a history of beryllium exposure.

Control subjects were recruited by randomized dialing of telephone

numbers.

All participants received questionnaires regarding specific jobs,

hobbies, and exposures at home and work. They were interviewed

regarding all jobs held within the previous 6 months, and smoking

status was ascertained.

736 patients with sarcoidosis were recruited into the study, and

they were compared with 706 controls. 64% of cases were women, and

53% of all subjects were white. 44% of participants were black. The

median age of cases was 42.1 years.

On univariable analysis, occupations associated with an increased

risk of sarcoidosis included agricultural employment, physician,

jobs involving raising birds, automotive manufacturing, and middle

and secondary school teacher.

Exposures more frequently associated with sarcoidosis included

insecticides, pesticides, mold and mildew, and musty odors. All of

these exposures were related to the subject's occupation, but the

use of home central air conditioning was also associated with an

increased risk of sarcoidosis.

Location in urban vs rural areas did not affect the risk of

sarcoidosis, and other health care workers besides physicians did

not have an increased risk of disease.

A reduced risk of sarcoidosis was associated with either active or

passive smoking, and subjects with occupations that limited exposure

to other people, such as motor vehicle operator or computer

programmer, were also at reduced risk of sarcoidosis.

Multivariable analysis confirmed most of the univariable conclusions

of the study. In the multivariable model, the occupation of

physician was no longer associated with an increased risk of

sarcoidosis.

The authors did not confirm previous reports of an increased risk of

sarcoidosis related to exposure to wood dust, metals, silica, or

talc. They also did not demonstrate that employment as a firefighter

or in the U.S. Navy was associated with sarcoidosis, although the

researchers note that their study may not have been adequately

powered to appropriately analyze these possible risk factors.

Pearls for Practice

Sarcoidosis can be mistaken on clinical and pathologic findings for

exposure diseases such as hypersensitivity pneumonitis, chronic

beryllium disease, and mycobacterial and fungal granulomatous

disease.

The current study found an increased risk of sarcoidosis associated

with agricultural employment and exposure to pesticides, but smoking

conferred protection against the development of sarcoidosis.