Re:Pediatric Isolation of Stachybotrys From the Lung of a Child With Pulmonary H

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>

> Pediatrics 1999; 104: 964-966

> October, 1999

>

> Isolation of Stachybotrys From the Lung of a Child With Pulmonary

> Hemosiderosis

>

> AUTHOR: OKAN ELIDEMIR, MD, Pediatric Pulmonology Section, Baylor

College of

> Medicine, Houston, TX 77030; GIUSEPPE N. COLASURDO, MD, Division of

> Pediatric Pulmonary Medicine, University of Texas-Houston Medical

School,

> Houston, TX 77030; SUSAN N. ROSSMANN, MD, PHD, Department of

Pathology,

> Baylor College of Medicine, Houston, TX 77030; LELAND L. FAN, MD,

Pediatric

> Pulmonology Section, Baylor College of Medicine, Houston, TX 77030

>

> ABSTRACT. Recently, Stachybotrys atra, a toxigenic fungus, has been

> implicated as a potential cause of pulmonary

hemorrhage/hemosiderosis in

> infants living in water-damaged homes. Although epidemiologic

evidence

> supports this association, neither the organism nor its toxic

products has

> ever been recovered from humans. We report the first case in which

> Stachybotrys was isolated from the bronchoalveolar lavage fluid of

a child

> with pulmonary hemorrhage. Stachybotrys was also recovered from his

> water-damaged home. The patient recovered completely after his

immediate

> removal from the environment and subsequent cleaning of his home.

This case

> provides further evidence that this fungus is capable of causing

pulmonary

> hemorrhage in children.

>

> [stachybotrys, pulmonary hemorrhage, pulmonary hemosiderosis,

children,

> toxigenic fungi.]

>

> TEXT:

> ABBREVIATIONS. PH, pulmonary hemorrhage/hemosiderosis; BAL,

bronchoalveolar

> lavage; CFU, colony-forming units.

>

> Stachybotryotoxicosis is a disease of farm animals, particularly

of horses,

> caused by a fungus named Stachybotrys atra (S alternans, S

chartarum,

> synonyms). [n1,n2] Characteristic findings in the animal disease

include

> stomatitis, rhinitis, and conjunctivitis at the initial stage,

followed by

> thrombocytopenia, bleeding diathesis, and leukopenia. Affected

animals

> usually die with high fever, generalized infections, and bleeding.

In

> regions where equine stachybotryotoxicosis is enzootic,

individuals who

> handle fodder or sleep on straw mattresses frequently develop a

toxicosis,

> characterized by dermatitis, burning sensation in the nasal

passages, bloody

> nasal discharge, sore throat, cough, and tightness in the chest.

[n1-n3]

> Typically, symptoms of these patients improve within a couple of

weeks after

> termination of exposure. [n1-n3]

>

> Recent interest in Stachybotrys has focused on its potential

association

> with pulmonary hemorrhage (PH) in infants. Between January 1993

and December

> 1994, a geographic cluster of 10 infants with acute PH were

identified at a

> children's referral hospital in Cleveland, Ohio. [n4] An extensive

> epidemiologic evaluation done by a team from the Centers for

Disease Control

> and Prevention found an association between living in a water-

damaged house

> and PH. Subsequently, high spore counts of Stachybotrys were

discovered in 9

> of 10 of these infants' houses, and 5 infants had recurrence of

bleeding on

> return to their homes, thus implicating this fungus as a potential

agent in

> the pathogenesis of infantile PH. [n5] Although a definite cause-

and-effect

> relationship between Stachybotrys and PH has not been established,

the

> American Academy of Pediatrics' Committee on Environmental Health

recently

> recommended that infants under 1 year of age should avoid

chronically moldy,

> water-damaged environments, until more is known about the

pathogenesis of PH

> in infants. [n6] To our knowledge, Stachybotrys has not previously

been

> recovered from human tissues and/or body fluids. We report the

first case in

> which Stachybotrys was isolated from the bronchoalveolar lavage

(BAL) fluid

> of a child with progressive respiratory symptoms and PH.

>

> CASE REPORT

>

> A 7-year-old white boy was referred to a pediatric pulmonary

clinic for

> evaluation of chronic cough, recurrent pneumonias, and chronic

fatigue. He

> had been an active, healthy, growing child until 5 years of age,

when he

> developed pneumonia. During the next 14 months, he experienced

chronic,

> nonproductive cough accompanied by intermittent low-grade fever,

malaise,

> fatigue, and decreased appetite. No other significant symptoms were

> reported. Other family members were asymptomatic. The patient

lived with his

> parents in a 25-year-old farmhouse with a central gas heating

system. There

> were no smokers in the house. His physical examination was

remarkable for

> weight, 21 kg (10%); height, 121cm (25%); and late inspiratory

crackles over

> the left base.

>

> Chest radiograph and computed tomography of the chest demonstrated

left

> lower lobe consolidation. Pertinent laboratory findings included

hemoglobin,

> 9.2 g/dL; hematocrit, 28%; mean corpuscular volume, 72 mu L. There

was no

> evidence of hemolysis in the peripheral blood smear. Serum

erythrocyte

> sedimentation rate, blood urea nitrogen, creatinine,

immunoglobulins and

> immunoglobulin G subclasses, alpha-1-antitrypsin, urinalysis,

sweat test,

> and barium swallow were normal. BAL fluid showed a moderate number

of

> hemosiderin-laden macrophages (26%) and grew S atra (Fig 1) in

> Sabouraud-dextrose agar medium. Multiple surface cultures from the

> bronchoscopy suite and mycology laboratory were negative for this

organism.

>

> On further questioning, we learned that the family moved into the

farmhouse

> shortly before the patient's symptoms began. This house suffered

from severe

> flood damage and was being reconstructed in stages by the family.

We

> investigated the house and immediately detected a strong moldy

odor on

> entering. Beneath the bathroom sink, next to patient's bedroom,

> approximately 2 m<2> of the wallpaper was densely covered with

black-colored

> mold. Multiple cultures from this area and other surfaces of the

house grew

> S atra. Aspergillus and Penicillium species were also recovered in

a culture

> obtained from a living room surface. The family cleaned the house

according

> to Centers for Disease Control and Prevention guidelines, and for

2 months,

> the patient relocated to his grandmother's house, which had no

history of

> water damage. Within 1 month, the patient's appetite improved, his

cough

> resolved, and his weight increased 2 kg. Ten months later, he

remains

> symptom-free, and his activity level is back to normal.

>

> DISCUSSION

>

> S atra is a common saprophyte, known to grow well on cellulose-

rich, damp

> material, such as moist wallpaper or straw, in a black-colored,

sooty layer.

> [n3] Under experimental conditions, about two-thirds of the

isolates of this

> fungus produce mycotoxins called satratoxins [n7-n9] and include

some of the

> most toxic macrocyclic trichothecenes. [n8,n10] Trichothecene

toxins are

> strong inhibitors of protein synthesis. [n10] Effects of systemic

exposure

> to trichothecene mycotoxins have been well-studied in a variety of

> laboratory and farm animals and include skin and mucus membrane

irritation,

> lymphocyte depletion and a hemorrhagic syndrome. [n11,n12]

Inhalation of

> satratoxins by laboratory animals has produced a dose-dependent

toxigenic

> effect. [n12] In lungs of mice and swine, inhaled toxins caused

similar

> morphologic changes, mainly characterized by intraalveolar and

interstitial

> inflammation and hemorrhagic exudate in the alveolar lumina,

indicative of

> alveolar and vascular epithelial injury. [n11,n12] In addition to

the amount

> of S atra spores inhaled, the toxicity of the strain selected was

another

> determinant of the degree of lung injury. In one study of mice

exposed to a

> less toxic strain, the pulmonary inflammatory response was much

less severe.

> [n12] From these animal studies, two conclusions can be drawn: 1)

> satratoxins, when inhaled, can cause pulmonary alveolar and

vascular injury

> leading to hemorrhagic inflammation in the lungs; and 2) the

degree of this

> inflammation is dependent on both the amount of spores inhaled and

the

> strain of S atra.

>

> There is recent epidemiologic evidence to support a role for S

atra in the

> cause of infantile PH. Montana et al [n4] described a cluster of

10 infants

> with PH, who were more likely than control infants to live in

water-damaged

> homes. In 5 of these infants, pulmonary hemorrhage recurred after

discharge

> from the hospital and return to their homes. In a subsequent

study, the same

> investigators found that the mean concentration of S atra was

higher in the

> homes of infants with PH than control infants (in the air, 43

colony-forming

> units [CFU]/m<3> vs 4 CFU/m<3>; on surfaces: 20 X 10<6> CFU/m<3>

vs 0.007 X

> 10<6> CFU/m<3>). [n5] However, it must be emphasized that the

spores and

> organisms were not found in the patients. Therefore, an actual

> cause-and-effect relationship between S atra and PH has not been

> definitively established. [n5,n6,n13,n14]

>

> The presence of hemosiderin-laden macrophages in BAL fluid reflects

> intrapulmonary bleeding. [n15] Microcytic anemia secondary to

depletion of

> body iron stores is usually present in patients with PH. [n15,n16]

The

> findings of recurrent respiratory symptoms and pulmonary

infiltrates,

> microcytic anemia, and hemosiderin-laden macrophages in the BAL

fluid

> confirmed the diagnosis of PH in our patient.

>

> S atra is not a common indoor mold in North American homes.

According to

> Kozak et al, [n17] S atra is found in 2.9% of homes in California.

A study

> from eastern Canada [n18] found this mold in only 1 of 52 homes.

In another

> Canadian study [n19] approximately 280 species of molds were

recovered from

> dust particles collected in the living areas of 401 homes.

Stachybotrys was

> found in only 3 of them.

>

> Stachybotrys has not been previously reported to grow from human

tissues

> and/or body fluids. The identification of Stachybotrys throughout

our

> patient's house in conjunction with the failure to find potential

sources of

> contamination from the equipment used during and after

bronchoscopy suggests

> that the growth of this fungus from the BAL fluid represents

actual recovery

> from the patient. Although confirmation by lung biopsy would have

been

> helpful, biopsy could not be justified based on the patient's

clinical

> condition. Recovery of Stachybotrys from the same BAL fluid

containing

> hemosiderin-laden macrophages provides additional evidence that

this fungus

> is capable of causing pulmonary hemorrhage in humans, similar to

that found

> in animals.

>

> CONCLUSION

>

> In summary, we report the first isolation of S atra from the BAL

fluid of a

> child with PH. The isolation of the organism from the patient's

> water-damaged home and the resolution of symptoms after his move

to another

> home provide additional evidence that environmental exposure to S

atra was

> responsible for this patient's pulmonary disease. Although the

focus has

> previously been on S atra and infants with PH, our case

demonstrates that S

> atra is also associated with PH in older children. For infants

with PH, the

> American Academy of Pediatrics' Committee on Environmental Health

has

> recommended that pediatricians should obtain a thorough

environmental

> history with attention to molds and water damage in the home. [n6]

In areas

> where flooding and water damage are found, cleaning of the walls

and other

> water-damaged items with a solution of water mixed with chlorine is

> advocated. In light of this report, we would extend these

recommendations to

> include all children with PH.

>

> ACKNOWLEDGMENTS

>

> We thank Ruth A. Etzel, MD, PhD, and Jim H. White for their

valuable and

> thoughtful advice. We also thank Malloch for his help in

confirmation

> of the identity of Stachybotrys recovered from the patient. In

addition, we

> thank Yesenia and Mosely for their excellent

secretarial

> assistance.

>

> SUPPLEMENTARY INFORMATION: Received for publication Jan 19, 1999;

accepted

> Apr 5, 1999.

>

> Reprint requests to (L.L.F.) Texas Children's Hospital, Pediatric

Pulmonary

> Section, MC 3-2571, in Center, 6621 Fannin St, Houston, TX

77030.

> E-mail: lfan@...

>

> REFERENCES:

>

> [n1] Forgacs J. Stachybotryotoxicosis. In: Ciegler A, Kadis S, Ajl

SJ, eds.

> Microbial Toxins, VIII. New York, NY: Academic Press; 1972:95-128

>

> [n2] Drobotko VG. Stachybotryotoxicosis. A new disease of horses

and humans.

> Am Rev Soviet Med. 1945;2:238-242

>

> [n3] Hintikka EL. Human stachybotryotoxicosis. In: Wyllic TD,

Morehouse IG,

> eds. Mycoloxic Fungi, Mycotoxins, Mycotoxicoses, III. New York,

NY: Marcel

> Dekker Inc; 1978:87-89

>

> [n4] Montana E, Etzel RA, Allan T, Horgan TE, Dearborn DG.

Environmental

> risk factors associated with pediatric idiopathic pulmonary

hemorrhage and

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URL:

> http://www.pediatrics.org/cgi/content/full/99/1/e5

>

> [n5] Etzel RA, Montana E, Sorenson WG, Kullman GJ, Allan TM,

Dearborn DG.

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>

> [n6] American Academy of Pediatrics, Committee on Environmental

Health.

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>

> [n7] Korpinen EL, Uoti J. Studies on Stachybotrys alternens.

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>

> [n8] Bata A, Harrach B, Ujszasi K, Kis-Tamas A, Lasztity R.

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isolated in

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>

> [n9] Sorenson WG, Frazer DG, Jarvis BB, Simpson J, VA.

> Trichothecene mycotoxins in aerosolized conidia of Stachybotrys

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>

> [n10] Feinberg B, McLaughlin CS. Biochemical mechanism of action of

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>

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>

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>

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> Letter

>

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>

> [n15] Sherman JM, Winnie G, sen MJ, Abdul-Karim FW, Boat TF.

Time

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>

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>

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>

> [n19] Canada Mortgage and Housing Corporation. Moldy Houses: Why

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>

> GRAPHIC: Figure 1, Microscopic appearance of Stachybotrys atra

recovered

> from the BAL fluid of our patient (X500). Grouped phialides

bearing dark

> conidia are observed at the end of a rough conidiophore.

>