Re: croft 3 stages

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Stages of Mycotoxicosis: For Inhalation of Mycotoxin

The three Stages (1-3) ranging from lower to higher severity of

poisoning were modified according to exposure via the air as opposed

to ingestion already established (Forgacs et al., 1962; Joffe, 1971).

A separate Stage of convalescence occurs when a patient is completely

removed from the contaminated premises and the source of mycotoxin or

mold spores.

Stage 1: The primary changes are in the brain, respiratory and immune

systems, mucus membranes and gastrointestinal tract. Signs and

symptoms may include burning sensation in the mouth, tongue, throat,

palate, esophagus, and stomach, which is a result of the action of

the toxin on the mucous membranes and skin in the exposed areas.

Moist areas of the body armpits, under breasts, belt line and groin

are more sensitive or first affected. Patients may report burning

within the eyes, ears and nose. Patients also reported that their

tongues felt swollen and stiff. Mucosa of the oral cavity may be

hyperemic. Mild gingivitis, stomatitis, glositis, and esophagitis

developed. Inflammation, in addition to gastric and (small and large)

intestinal mucosal, resulted in vomiting, diarrhea and abdominal

pain. Excessive salivation, headache, dizziness, weakness, fatigue

and tachycardia were also present.

There may be fever and sweating. The respiratory system develops

burning sensations and congestion. Severe exposure to mycotoxin

within the lungs may lead to congestion, edema and failure, due to

caustic action. Body temperature remains normal and controllable by

the patient. The poisoning appears and disappears relatively quickly

in this Stage with the exception of, lungs and central nervous

system. Initially (Stage 1), the patient's symptoms are very

uncomfortable or painful. As the poisoning continues and the patient

progress toward Stage 2, he or she becomes accustomed to the presence

of the mycotoxin and a quiescent period follows due to lack of nerve

sensation. Depending on exposure levels, the first Stage may last

from 3 - 9 days. In scoring the 50 signs and symptoms listed in

Tables-1 and 2, an average score range of 20-45 represents Stage 1.

Stage 2: This Stage is often called the latent Stage or incubation

period because the patient feels apprehensive, but is capable of

normal activity in the beginning of this Stage. Every organ of the

body is affected by degeneration and necrosis with continued

exposure. The primary target organs for an individual become evident

over time, due to biological variation. These are disturbances in the

central and autonomic nervous systems resulting in headaches, mental

depression, loss of short-term memory, loss of problem-solving

ability, various neuropsychiatric manifestations, meningism, severe

malaise and fatigue, narcolepsy, loss of temperature control,

hyperesthesia or numbness of body areas, and cerebellar dysfunction

including hypotonia, attitude and gait, dysmetria, asthenia, vertigo,

disturbances of speech, and loss of balance (Best, 1961). Spinal cord

degeneration may also be observed in gait and reflex abnormalities,

such as the ability to drive vehicles, ride bicycles or pass sobriety

tests (inability to tolerate ethyl alcohol). Attention deficient

disorder may be observed in children. Various systems may include:

Eyes: visual disturbances, floating objects, light sensitive, lack

of tears, burning and itching. Ears: burning, itching, and loss of

hearing. Immune and hematopoietic: progressive loss of white and red

cells including a decrease of platelets and hemoglobin, and high

susceptibility to bacterial, mycotic and viral infections,

debilitating chemical and allergies. Gastrointestinal: metallic taste

in mouth, tooth loss, gum problems, stomatitis, sores in gums and

throat, nausea, vomiting, diarrhea or constipation, excessive

flatulence, abdominal distention, hepatitis, pancreatitis, and

diabetes mellitus. Respiratory: burning and bleeding from nasal

membranes, respiratory difficulty, asthma, extreme susceptibility to

cold, flu and pneumonia. Skin: thinning of hair on head, burning on

face, rashes, irritation, and edema. Renal: proteinuria, possible

hematuria. Reproductive: irregular ovarian cycles, increased

menstrual flow, fibroid growths in uterus, cystic development in

mammary glands, and tumors of mammary and prostate glands.

Musculoskeletal: somatitis, muscle weakness, spasms, cramps, joint

pain, enlargement of joints in hand, and clubbing of fingers.

Cardiovascular: chest pain, palpitations, ruptures of atrial walls,

myocardial infection and aneurysm of arteries.

The skin and mucous membranes may be icteric, pupils dilated, the

pulse soft and labile, and blood pressure may decrease or increase.

The body temperature does not exceed 38 degree C and the patient may

be afebrile, or chilled. Visible hemorrhagic spots may appear on the

skin. Thoughts of suicide may be prominent in the person's mind at

this time or anytime in Stage 2. Human bonding is very important for

survival.

Degeneration and hemorrhages of the vessels marks the transition from

the second to the third Stage of the disease and may not be

consistently observed. The degeneration of the vital organs including

serious respiratory insufficiency or asthma and CNS degeneration will

take the patient into Stage three along with development of necrotic

angina. If exposure continues, depending on exposure levels, Stage 2

may continue from weeks to months or even years until the symptoms of

the third Stage develop. Evaluating the 50 signs and symptoms (Table-

1 and 2) by assigning a score (0-least intense to 5-most intense or

severe) to each symptom, we have determined that an average score

range of 45-180 represents Stage 2.

Stage 3: Severe degeneration of the vital organs. The transition from

the second to the third Stage is sudden. In this Stage, the patient's

resistance is already low, and violent severe symptoms are present,

especially under the influence of stress, or associated with physical

exertion and fatigue. The first visible sign of this Stage may be

lung, brain or heart failure (heart attack), with or without the

appearance of petechial hemorrhage on the skin of the trunk, the

axillary and inguinal areas, the lateral surfaces of the arms and

thighs, the face and head, and in serious Cases, the chest. The

petechial hemorrhages vary from a few millimeters to a few

centimeters in diameter. There is increased capillary fragility and

any slight trauma may cause the hemorrhages to increase in size.

Aneurysms of the brain or aorta may be observed by angiography.

Hemorrhages may also be found on the mucous membranes of the mouth

and tongue, and on the soft palate and tonsils. There may be severe

interstitial thickening or scarring of the lungs, or respiratory

failure. Nasal, gastric and intestinal hemorrhages and hemorrhagic

diathesis may occur. Necrotic angina begins in the form of catarrhal

symptoms and necrotic changes soon appear in the mouth, throat, and

esophagus with difficulty and pain on swallowing. Severe degeneration

of the skin on the face, eyelids, and loss of lashes is also often

present.

Necrotic lesions may extend to the uvula, gums, buccal mucosa,

larynx, vocal cords, lungs, stomach, and intestines and other

internal organs such as the liver and kidneys and are usually

contaminated with a variety of avirulent bacteria. Bacteria infection

causes an unpleasant odor from the mouth due to the enzymatic

activity of bacteria on proteins. Areas of necrosis may also appear

on the lips and on the skin of the fingers, nose, jaws, and eyes.

Regional lymph nodes are frequently enlarged. Esophageal lesions may

occur and involvement of the epiglottis may cause laryngeal edema and

aphonia (loss of voice). Death may occur by strangulation.

Patients may suffer an acute parenchymatous hepatitis accompanied by

jaundice. Bronchopneumonia, pulmonary hemorrhages, and lung abscesses

are frequent complications. Tumors may develop of various organs,

including skin, urinary bladder, brain, mammary gland, bone, immune,

liver, prostate, possibly resulting in death. The most common cause

of death is brain failure due to both direct effects of the mycotoxin

on the central nervous system and indirect effects due to respiratory

failure or lack of oxygen to the brain caused by the severe caustic

inflammation (fibrinous exudation) reaction with the lung tissue,

rendering it non-functional. Again, using the scoring system

represented in Tables-1 and 2, an average score of greater or equal

180 represents Stage 3.

Stage of Convalescence: The course and duration of this Stage 3

depends on the intensity of the poisoning and complete removal of the

patient from the premises or source of mycotoxin. Therefore, the

duration of the recovery period is variable. There is considerable

cellular necrosis and scarring to all major organs of the body in

which cells will not regenerate, including the brain, spinal cord,

eyes, lung, heart, liver, pancreas, kidney, adrenal, and blood

vessels. If the disease is diagnosed during the first Stage,

hospitalization is usually unnecessary, but allergies and asthma

should be monitored closely. If the disease is diagnosed during the

second Stage and even at the transition from the second to third

Stages, early hospitalization may preserve the patient's life. If

however, the disease is only detected during the third Stage, death

cannot be prevented in most Cases.

1. Croft, W. A., Jastromski, B. M., Croft, A. L., and s, H.

A., " Clinical

Confirmation of Trichothecene Mycotoxicosis in Patients Urine " ,

In: Journal of

Environmental Biology 23(3), 301-320 (2002)

2. Forgacs, J., and W. T. Carll : Mycotoxicoses. In : Advances in

Veterinary

Science. Academic Press, New York and London, pp 273-372 (1962).