Reactive intestinal dysfunction syndrome (RIDS) caused by chemical exposures

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Reactive intestinal dysfunction syndrome (RIDS) caused by chemical

exposures.

Archives of Environmental Health

9-1-98

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IN 1985, et al.[1] introduced a new disorder in their study entitled

" RADS: Case Reports of Persistent Airways Hyper-reactivity Following High

Level Irritant Exposures. " Reactive Airway Dysfunction Syndrome was

characterized by its rapid onset, specific relationship to a single

environmental exposure, and the apparent lack of an allergic or immunologic

etiology. In addition, there was no documented preexisting respiratory

illness, and the respiratory symptoms and airway hyperreactivity persisted

for at least 4 y after the initial incident. In their report, et al.

suggested that acute high-level irritant exposures may produce an asthmalike

syndrome in some individuals, with long- term sequelae of chronic airway

disease.

Meggs and Cleveland[2] reported that a measured increase in nasal

upper-airway resistance occurred in 10 patients who had known chemical

exposures and persistent multiple-chemical sensitivity. They reported that

these patients suffered from an upper-airways syndrome analogous to RADS and

termed it RUDS for Reactive Upper-Airway Dysfunction Syndrome. Although they

did not know the appropriate physiologic parameters for this reactivity,

they suggested that nasal airway resistance be studied and that inflammatory

cells and mediators be measured in nasal washings.

In this article, we describe eight patients who presented with acute onset

of abdominal distress characterized by severe bloating or edema of the

abdomen. Other systemic signs and symptoms occurred, but the intensity and

severity of the gastrointestinal distress was so marked that they clearly

suggested a recognizable pattern or syndrome. The cases were similar to the

other previously described occupational and/or environmental clinical

syndromes, RADS and RUDS, suggesting that other organs could be affected

similarly. In this article, we add the third R, which we term Reactive

Intestinal Dysfunction Syndrome (RIDS), to the recognized syndromes of RADS

and RUDS. Clinical experience with occupationally and environmentally

triggered patients reveals the smooth-muscle-lined urinary tract can also be

a reactive responding organ; however, to our knowledge, this has never been

described.

Clinical differentiation between RIDS and gastrointestinal

hypersensitivity- -a recognized disorder caused by an immunologic

hyperresponsiveness of the gastrointestinal tract to specific antigens--may

be difficult. Both conditions may have identical symptoms (e.g., nausea,

vomiting, abdominal pain, bloating, diarrhea, constipation, flatulence,

variety of extra-intestinal symptoms), and these symptoms are heterogeneous

from patient to patient.

An overview of our eight cases of RIDS demonstrated that, like RADS and

RUDS, another organ system can be reactive following acute chemical

exposures, and hyperresponsiveness can persist for years after the initial

exposure. Six of our eight cases were related occupationally, and all cases

had extra-intestinal symptoms that specifically included respiratory

problems, fatigue, and neurocognitive dysfunction.

Presentation of Cases

Case 1. We present this case first because it was only after he was seen

that we realized we were seeing something very special and, in retrospect,

we had seen other very distended patients but had not recognized their

significance.

G.W. was a 64-y-old male long-distance hauler of tank trucks, which

contained all kinds of chemicals. Frequently he was soaked with spills from

his cargo. In September 1988, while he was hauling a load of alleged

food-grade paraffin, he had a blowout on the road that resulted in an 8.5-h

wait in his cab while the tanker underwent repairs. Within 1 h of the

blowout, he developed an acute racking cough, pounding headache, and itchy

throat. Coughing continued for a day and a half. Within 40 h of the event,

swelling initially occurred in his feet, followed by his hands, and,

finally, his abdomen. He was treated in an emergency room and was able to

haul his tanker home, but he was in severe distress. He had no history of

any similar occurrence. Angioedema persisted along with marked abdominal

bloating, belching, heartburn, rectal itching, and gas. The bloating was so

severe that it resulted in shortness of breath and chest pain. His abdomen

remained chronically swollen and hard.

Physical examination revealed a hard and markedly protuberant abdomen.

Laboratory evaluation revealed abnormal liver function consistent with

hepatotoxic injury and the following abnormal immunologic markers: elevated

CD 26 cells; decreased T-suppressor cells; decreased natural killer cell;

and three autoimmune markers (i.e., antinuclear antibody, anti-smooth-muscle

antibody, and antithyroid antibody). These patterns were consistent with

immunotoxicity.[3]

G.W. was seen 1 yr after exposure, and he continued to manifest the

earlier-described gastrointestinal distress, which intensified along with

fatigue, weakness, arthralgia, and irritability following multiple chemical

exposures.

Case 2. J.R., a 48-y-old naval shipyard worker, presented for the first time

with a constellation of signs and symptoms, including nausea, vomiting,

diarrhea, indigestion, and excessive bloating. She also complained of

flu-like symptoms, fatigue, weakness, and headache. The problems began 1 mo

after she began work at a different facility at the shipyard, where she had

been employed as a production controller of ships for the previous 15 y. She

noticed that she always felt " better " when she was away from the new

building and felt " worse " upon reentry.

J.R. was seen again many months later when she developed acute respiratory

distress on exposure to paint at her worksite. This episode required

treatment with adrenalin and oxygen. Subsequently, she developed multiple

episodes of reactive upper-airway dysfunction in response to exposures to

many unrelated chemicals, but especially following exposures to paints,

perfumes, and tobacco smoke. She was placed on disability because of these

recurrent episodes.

This case was particularly interesting because she initially developed RIDS,

which then spread to RUDS. Four years later, she continued to be disabled by

her reactive disease to chemical exposures, characterized by onset of the

following: cough, laryngeal spasm, difficult breathing, hoarseness to

aphonia, unilateral headache of migraine intensity, bedridden fatigue

lasting hours to days, nausea, vomiting, diarrhea, and bloating. The

significance of her reactive intestinal syndrome was not realized until

several of the other patients had been seen.

Case 3. D.S.C., a 39-y-old white woman, was employed as an assembly- line

worker for an automotive parts company. Her work included exposure to epoxy,

trichloroethylene, methylene chloride, triphenylmethane, isocyanates, and

lacquer.

She developed the following symptoms almost immediately after beginning

work: abdominal distention, lightheadedness, dizziness, fatigue, and

weakness. Subsequently, she lost 12.7 kg (28 lb), her tongue split and

burned, and she had sensations of being constantly cold.

She spent 3 mo in the coil department, after which she was placed in a job

that involved less exposures to the earlier-mentioned chemicals; although

her symptoms persisted, they were diminished. Upon return to her original

work, her abdomen became distended again. She developed vertigo. She lost

consciousness; became confused; began stuttering; developed a sore mouth;

and had constipation to obstipation of 3-wk duration, and this condition did

not respond to laxatives or enemas. A diagnosis of a " spastic colon " was

made by a gastroenterologist. The patient took a 6-mo medical leave from

work, the result of which was noted improvement in abdominal distress;

however, the fatigue and weakness persisted.

Upon return to work, abdominal distress, vertigo, tinnitus, and mental

confusion reoccurred. During the workday, she felt that she had to defecate

and had abdominal cramps but never had any bowel movements. She developed a

persistent and chronic hyperresponsiveness of her gastrointestinal tract,

with marked abdominal distention to multiple chemical exposures (e.g.,

perfumes, fragrances, cleaning agents). She could not tolerate the

workplace, and she was forced to leave on disability. She continues to

manifest abdominal distention, along with the other described signs and

symptoms in response to exposures to multiple unrelated volatile and odorous

chemicals.

Case 4. R.L., a 33-y-old male landscaper, developed onset of nausea,

abdominal cramps, and numbness after he worked for several months with the

herbicide, Fenocil. He had a major toxic exposure when he accidentally

sprayed the herbicide into his mouth and onto his face. He became sicker

with each exposure, with progression of nausea, fatigue, stomatitis,

anorexia, and weight loss.

With each exposure to herbicide, he developed acute achiness, tremors,

fatigue, sweats, and nausea. Medical evaluation revealed abnormal liver

function, absent evidence of hepatitis A, B, C, or CMV. He was diagnosed

with chemical hepatitis. He subsequently became markedly chemically

sensitive, with a the following distinct pattern of reactivity upon exposure

to multiple chemicals: (a) onset of Reactive Upper Airway Dysfunction

Syndrome, with choking, voice cracking, throat mucous, and overt cacosmia;

( within 1-min of exposure, occurrence of an explosive watery, painful

diarrhea, followed by weakness and lightheadness, all of which forced him to

lie down; © chest tightness accompanied by difficult breathing and cough,

developing into RADS; (d) mental confusion; (e) swelling of feet with

associated knee pain and frozen thighs; and (f) weakness, which occurred for

weeks, although the RUDS, RIDS, and RADS were of shorter duration.

Case 5. M.P., a 53-y-old woman, worked as a cashier in a food supermarket.

She had no known major chemical exposures. The syndrome of RIDS developed

following the occurrence of a fractured hip, during which time she was

exposed to multiple drugs and anesthetics. She had classical atopic allergy

with eczema, asthma, and perennial and seasonal rhinitis.

On exposure to multiple volatile chemicals, including rubber, polyurethane,

plastics, polyvinyl chloride (PVC) pipe, and new carpet, she developed an

urgency to defecate (without diarrhea) and acute chest and arm pains.

Symptoms attenuated in the presence of fresh air.

Case 6. G.P. was a 46-y-old press-room worker who had been exposed to

toluene for 14 y. In 1994, a new press was installed, but for approximately

1 y it had a malfunctioning solvent-recovery system. The press room in which

he worked had a toluene level of 300 ppm, and in his office the level was

240. (Sullivan and Krieger[4] reported the threshold limit value [TLV] of

toluene to be set at 100 ppm.) This worker also used to wash his hands in

toluene.

Soon after the press began malfunctioning, he developed headaches with

tinnitus, near fainting, weakness, slurred speech, difficulty pronouncing

words, impaired vision, impaired thinking, a " bad sinking feeling, " and

shaking. During these syncopal-like spells, his blood pressure and blood

glucose were reportedly normal. Subsequent to his occupational exposures, he

began having syncopal-like spells, even when he was not exposed at the

workplace, characterized by a " high " that was identical to when he breathed

toluene. These spells were associated with dizziness, pallor, weakness,

disorientation, nausea, and a flu-like feeling, with the final phase of

these reactions being characterized by explosive diarrhea. This worker had a

long history of irritable bowel syndrome, with relatively mild alternating

constipation and diarrhea, and the syndrome was seemingly unrelated to any

environmentally triggered exposure. The attacks, however, were precipitated

by any exertion that exceeded 3 or 4 min or by exposure to multiple volatile

chemicals. He also experienced asthma-like attacks (RADS) whenever he was

near a gas station.

Case 7. S.M. was a 51-y-old case manager at a nursing and rehabilitation

center. The interior of her house was sprayed with the organophosphates

chlorpyrifos and diazinon. Carpets in her house were so saturated with

pesticides that they took days to dry. After scrubbing the floors on her

hands and knees, she began experiencing stomach cramps. Approximately 3 wk

later, she experienced a sore bladder, kidney pain, extreme fatigue,

breathing problems (i.e., as if something was sitting on her chest), and

shortness of breath. Steam cleaning the carpets made her feel sicker.

A month after pesticide sprayings, she moved out of her house and into a

motel. A few days later, she returned to her house for 30 min, after which

time she experienced abdominal cramping and breathing problems. Two weeks

later, she was exposed to outgassing from a new carpet at work, and she

experienced nausea and vomiting. Pesticide spraying on lawns near her home

caused fatigue, chest pain, nausea, vomiting, diarrhea, and severe headache.

Four years after the events described, she still experiences respiratory

distress, nausea, vomiting, and diarrhea when she is exposed to low levels

of pesticides and other multiple chemicals. Although these responses are

consistent with the cholinergic reactions of cholinesterase inhibition, we

included her case because the reactive intestinal symptoms occur with

nonesterase inhibiting chemicals.

Case 8. M.J., a 57-y-old woman, was exposed to carbonless copy paper for

more than 10 y. When she was exposed to multiple chemical irritants, she

developed headache, bloating, diarrhea (occasionally explosive), personality

change with irritability, watery and runny eyes, and an overall feeling of

weakness--especially in her arms and legs--for about 24 h. Exposures that

elicited the most profound symptoms were carbonless paper, tobacco smoke,

air fresheners, gasoline, perfumes, and fabric softener.

Discussion

In a normally functioning body, more than 99% of all sensory information is

discarded by the brain as irrelevant and unimportant.[5] The nervous system

achieves this modulation by a complex network of synapses, which can both

facilitate and/or inhibit all or part of a sensory input. Some of this

modulation is done by neuropeptides, which are neurotransmitters produced

from neurons whose cell bodies lie in various sympathetic and

parasympathetic ganglia.[6] These neuropeptides include substance P,[7]

neuropeptide Y,[8-11] galanin,[12] calcitonin gene- related peptide,[13] and

vasoactive intestinal polypeptide.[14]

The receptors of these polymodal neuropeptides are sensitive to a variety of

stimuli, including noxious chemicals[6] and other environmental triggers;

given that they are common to both the respiratory and digestive tracts,

they may be responsible for producing these reactive disorders. Their signs

and symptoms can be described as a manifestation of dysautonomia that

results from a seemingly inappropriate autonomic nervous system function.

Perhaps another explanation is that exposures to neurotoxins and irritants

may further aggravate damage, and the dysautonomia may, in fact, be a

physiologic mechanism designed to rid the body of further pollutants. For

example, congestion in RUDS reduces particle inhalation; bronchospasm and

cough in RADS reduces particle retention; and vomiting and diarrhea in RIDS

reduces pollutant retention.

Given that 95% of environmentally triggered disease involves the

neurovascular system (i.e., the autonomic nervous system that connects to

the vascular system[15]), the multisystem nature of these diseases is

understood easily. Based on our clinical observations and findings, we

conclude that this dysautonomia results from an inability of the body to

suppress or discard irrelevant sensory information when exposures are of a

low level, particularly when the body perceives it as injurious. This

opinion best describes at least one of the physiologic mechanisms involved

in the development and progression of chemical sensitivity and the reactive

organ dysfunction syndromes described.

Reactive Intestinal Dysfunction Syndrome may be to gastrointestinal

hypersensitivity what RADS is to asthma. The former is considered

nonimmunologic in origin, whereas investigators think the latter has

immunologic mechanisms. It is more likely, however, that their origins are

not mutually exclusive and that both mechanisms participate. Nonetheless, at

this time, for purposes of classification it may be best for us to describe

RIDS like RADS (as not classically immunologic in origin) and to use the

diagnosis of gastrointestinal hypersensitivity when a clear allergic

mechanism can be established.

A possible explanation for a combined immunologic and nonimmunologic

mechanism may be that of neurogenic switching, a hypothesis offered by

Meggs[16] (i.e., stimulation of inflammation at one site can lead to

inflammation at another site). Inasmuch as almost all of our cases were

triggered via the respiratory tract, neurogenic switching might explain the

subsequent triggering of the gastrointestinal tract as an alternative site.

We can readily appreciate that because of the relatively large surface areas

of both the lungs and the gut, both are especially vulnerable to the

environments to which they are exposed constantly.

Conclusion

To the previously described clinical syndromes, Reactive Airway Dysfunction

Syndrome (RADS) and Reactive Upper Airway Dysfunction Syndrome (RUDS), we

add the third R: Reactive Intestinal Dysfunction Syndrome (RIDS). The three

syndromes appear to have the following in common:

1. An initial high level or significant environmental or occupational

exposure to a chemical or irritant, resulting in an acute clinical illness;

2. Development of a persistent or chronic hyperresponsiveness to multiple

chemicals and irritants;

3. A nonimmununologic mechanism mediated through inflammatory mediators,

neuropeptides, and local tissue hyperresponsiveness for which an immune

mechanism may also play a role. Neurogenic switching may explain the

combined nonimmunologic and immunologic mechanisms; and

4. Their importance in producing disability from exposures to multiple

chemicals and/or irritant triggers found in most industrial and occupational

settings.

We emphasize that a careful and comprehensive history of the events

preceding the onset of these reactive disorders will often establish an

environmental or occupational etiology.

Submitted for publication May 30, 1997; revised; accepted for publication

January 28, 1998.

Requests for reprints should be sent to Allan D. Lieberman, M.D., Center for

Occupational and Environmental Medicine, 7510 Northforest Drive, North

ton, SC 29420-4297.

References

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[9.] Furness JB, Costa M, Emson PC, et al. Distribution, pathways and

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[10.] Ekblad E, Winther C, Ekman R, et al. Projections of peptide-

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[11.] H, Rudolph A, Gschmeissner S. Ultrastructural co-localization of

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[12.] Bedecs K, Berthold M, Bartfai T. Galanin--10 years with a

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[13.] CA, Nakashima M, Gittes GK, et al. Calcitonin gene-related

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[14.] Straub SG, Sharp GW. A wortmannin-sensitive signal transduction

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[15.] Rea WJ. Chemical Sensitivity. Boca Raton, FL: Publishers, 1992;

p 32, vol 1.

[16.] Meggs WJ. Neurogenic switching: a hypothesis for a mechanisms for

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CAROL M. BALDWIN Respiratory Sciences Center Departments of Medicine and

Psychology University of Arizona Tucson, Arizona

IRIS R. BELL Departments of Psychology, Psychiatry, and Family and Community

Medicine University of Arizona Tucson, Arizona and Department of Psychiatry

Tucson Veterans Affairs Medical Center Tucson, Arizona

Lieberman, Allan ; Craven, Ruth, Reactive intestinal dysfunction

syndrome (RIDS) caused by chemical exposures.., Vol. 53, Archives of

Environmental Health, 09-01-1998, pp 354(5).