Attitudes of falsifications on
etiological diagnosis
Jung-Der Wang, MD, ScD
National Taiwan University College
of Public Health
National Taiwan University Hospital
Why take a refutational attitude?
A refutational attitude encourages one to
look for contradictions and alternatives.
 Human observational studies often invoke
many auxiliary hypotheses, which may
not be highly corroborated.
 Causal decision usually involves utility or
resource allocation.

Conjectures and falsifications on
etiological diagnosis

Jee SH, Wang JD, Sun CC, Chao YF. Prevalence of
probable kerosene dermatoses among ballbearing factory workers. Scand J Work Environ
Health 1985; 12:61-65. ]
 Jee SH, Chao KY, Sun CC, Wang JD. Outbreak of
contact dermatitis related to acticide EP paste in a
paint manufacturing factory. J Formosan Med
Assoc 1996; l95:628-631.
 Tsai SJ, Chang YC, Wang JD, Chou JH. Outbreak
of type A botulism caused by a commercial food
product in Taiwan: clinical and epidemiological
investigations. Chin Med J (Taipei) 1990; 46:43-8.
 Tang FC, Chu YJ, Wang LF, Wang JD. An outbreak
investigation of dermatosesamong people living in
Homei, Changhua. Chinese J Public Health 1997;
16(4):365-373. (in Chinese)
Outbreak of type A botulism caused
by a commercial food product in
Taiwan: clinical and epidemiological
investigations
 Shih-Jei
Tsai
 Yang-Chyuan Chang
 Jung-Der Wang
 Jih-Haw Chou
ABSTRACT

In that September 1986, we found 7
patients from a printing factory in ChangHwa city who developed an endemic
disease manifested by general malaise,
ptosis, double vision, dysarthria, and
proximal limb weakness, After clinical,
epidemiological, microbiological, and
toxicological investigations, an outbreak
of boutlism was comfirmed 2 weeks later,
Commercially canned peanuts made by an
unlicensed cannery were identified as the
vehicle of botulinum toxin transmission.

Antitoxin was given to 2 patients who needed
ventilator support. One of the 7 victims died from
medical complications and the remaining 6
patients recovered. Several administrative
problems exposed in this outbreak were the poor
governmental suprevision of canned food, the
inadequate quantities of “orphan drugs” stored
in this country, the inefficient system for
recalling the problem products, Since
commercially processed food is increasingly
popular with modernization, the possibility of
future botulism outbreaks should not be
overlooked.
Case No.
1
2
3
4
5
6
7
Age/Sex
52/F 15/M 28/M 15/M 15/M 17/M 17/M
Incubation period*(hr)
23
34
48
48
50
58
74
Systemic symptoms
Dizziness
+
+
+
+
+
+
+
General malaise
+
+
+
+
+
+
+
Gastrointestinal symptoms
Nausea/Vomiting
+
+
+
Abdominal pain
+
+
Diarrhea
+
Autonomic symptom
Dryness of mouth
Dysuria
Blurred vision
+
+
+
+
+
+
+
+
+
+
-
-
-
Neuromuscular symptoms
Diplopia
Ptosis
Dysarthria/dypshagia
Limb weakness
Respiratory distress
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
+
+
+
+
-
+
-
+
-
+
+
Died
+
+
-
-
-
-
-
Ventilator support
Antitoxin therapy
Outcome
Reco- Reco- Reco- Reco- Reco- Reco-
Figure Amplitude potentiation of CAMP
after isometric contraction for 15 seconds
Figure Electrodecremental response to repetitive
stimulation at a rate of 2.5 Hz and amplitude
potentiation with disappearance of electrodecremental responseafter iso metric contraction
(stimulation at the right Erb’s point and pick-up at
the right deltoid)
Clustering of cases with sudden
onset of bilateral weakness of
extremities with respiratory
paralysis in a printing shop
Conjectures
H1: Acute solvent poisoning
H2: n-hexane induced Polyneuropathy
H3: Acrylamide or methyl butylketone
induced polyneuropathy
Hn-2: Other upper motor neuron disease
Hn-1: Other lower motor neuron diseases:
Guillain-Barre Syndrome
Hn: Neuromuscular junction disease
1)Myasthenia gravis
2)Drug or toxin induced
3)Botulism
→ Rare clustering in space & time.
→ Rare clustering in space & time and
neostimine test (+)
→ History of medication, or spider or snake
bites
→ Clostridium botulinum(+) and toxin (+)
Deductions
H1→Consciousness disturbance
H2→Impaired NCVs
H3→Impaired NCVs
-------------------------------Hn-2→Consciousness disturbance and/or
involuntary movement
Hn-1→Impaired NCVs Guillain-Barre
Syndrome
Hn(1)→Myasthenia gravis or syndrome
Hn(2)→Drug or toxin induced
Hn(3)→Botulism
Observations and measurements
All affected workers had clear consciousness
throughout.
NCV was intact.
No involuntary movement.
Neostigmine test ().
No history of specific drug usage or animal
bites.
Culture showed Clostridium botulinum and
toxin in Canned peanuts.
Data analysis
Eating breakfast on Sept. 25-26 was
shown to be associated with the
appearance of symptoms.
Refutations
H1, H2,…Hn(1), Hn(2) were all excluded as
the diagnosis.
Future refutation attempts
Eliminated the canned peanuts, and no
more new cases occurred.
Data analysis
Eating breakfast
Yes
No Total
Botulism
Yes
7
0
7
No
7
25
32
Prevalence of probable kerosene
dermatoses among ball-bearing
factory workers.
Shiou-Hwa Jee, MD
 Jung-Der Wang, MD, ScD
 Chee-Ching Sun, MD
 Yung-Fa Chao, MD

ABSTRACT
The objective of this study was to investigate
the prevalence rate of dermatoses among
workers in a ball-bearing factory and its
possible association with their exposure to
kerosene. Two groups of female workers
participated in the study. The first group
included 79 persons with major kerosene
exposure during work, while the second, a
reference group, was composed of 263 zippermanufacturing workers with a similar age
distribution, educational background, and
income.
Dermatologic examinations were used to prevalence
rate of hand dermatoses (erythema, scaling, and
eczema). In the exposed group 51 persons(65%) had
erythema with or without desquamation over the
interdigital spaces, 12 persons(15%) had eczematous
lesions, 3 persons (4%) had defatting dermatitis, and
only 13 persons (16%) were apparently asymptomatic.
In the reference grounp only one person had hand
eczema (<1%). The difference in the occurrence of
dermatoses between the two groups was significant
according to the Mantel-Haenszel summary chisquare test. Patch tests on five workers with
eczematous lesions revealed one to be sensitive to
mercury. The findings indicate that kerosene is skin
irritant. Antirust oil used on the ball-bearings may
also contribute to the irritant effect.
Introduction

In 1981, a ball-bearing factory in Taiwan
requested consultation concerning
dermatologic problems in their
assembling department, where workers
often complained of burning, pain, edema,
and blister formation on the hands. The
situation had been present since the
factory opened in 1966.
Kerosene dermatosis
Figure 1. Structure of a typical ball-bearing
Insertion of balls into rings
Insertion of balls into rings
Both hands exposed to kerosene
Figure 2. The work process. Workers in
processes B and C are heavily exposed;
those in processes A, D, and E are lightly
exposed.
Table Characteristics of the exposed (ball-bearing factory)
and reference (zipper manufacturing company) groups.
Number of workers
Sex
Age (years)
Range
Mean
SD
Monthly income
Educational level
Major contactantsb
Minor contactantsc
a
Exposed group
79
Female
Reference group
263
Female
16-26
18.9
1.9
15-29
20.2
3.7
NT$7,000a
Elementary
school only, in
most cases
Kerosene, steel
Antirust oil
NT$7,000a
Elementary school
only, in most cases
Plastics, textiles
Scissors, Iubricants
NT$ stands for new Taiwan dollars. NT$7,000 is equivalent to USD 200.
Any substances to which the workers were heavily exposed daily.
c
Substances to which the workers were lightly and only occasionally
exposed.
b
Table 2. Age-specific prevalence rates of
dermatoses among the exposed (ball-bearing
factory) and reference (zipper manufacturing
company) groups.
Exposed group
Age
(years)
Reference group
Number of Percentage Number of Percentage
workers
with
workers
with
examined dermatoses examined dermatoses
15-19
59
86
143
0
20-24
19
74
72
1
25-29
1
100
78
0
Total
79
84
263
1
Table 3. Results of the dermatologic examination of
the hands with kerosene exposure.
Heavily
exposed
groupa
Workers with
dermatoses
Erythema
Eczema
Defatting dermatitis
Workers without
dermatoses
Total of workers
examined
a
Heavily
exposed
groupb
Total
N
%c
N
%c
N
%c
31
91
35
78
66
84
24
7
---
70
21
0
27
5
3
60
11
7
51
12
3
65
15
4
3
9
10
22
13
16
34
100
45
100
79
100
Workers exposed to kerosene in processes B and C for >5 h daily.
Workers exposed to kerosene lightly and irregularly in processes A, D, and E.
c
Number of workers with or without dermatoses divided by number of workers
examined multiplied by 100%.
b
Outbreak of contact dermatitis
related to acticide EP paste in a
paint manufacturing factory
 Shiou-
Hwa Jee
 Kun-Yu Chao
 Chee- Ching Sun
 Jung- Der Wang
ABSTRACT
An outbreak of severe itching, erythematous and
edematous dermatitis over the extremities and
upper back developed in 8 of 17 workers in the raw
materials department of a paint manufacturing
factory. The outbreak occurred during a 2-month
period when Acticide EP paste (Thor Chemical,
Cheshire, UK) was used in place of Metatin as a
microbiocide (Acima Chemical, Buchs, Switzerland) .
To evaluate the frequency and the etiologic agent of
this outbreak, a plant walk-through, examination and
review of photographs of skin lesions followed by
statistical analysis for association between the
development of dermatitis and exposure to Acticide
paste were performed. Three guinea pigs were
subjected to patch tests comparing the
dermatotoxicity of Acticide EP and Metatin.
The results showed that 8 out of 17 workers (47%) suffered
from contact dermatitis during the 2-month period.
Stratification by occupational exposure further confirmed
the association between the development of dermatitis and
exposure to the Acticide paste. The dermatotoxicity test on
guinea pigs revealed the marked corrosive effect of the
paste and the absence of dermatotoxicity of Metatin. After
the removal of the paste from the raw material, there were no
new cases of contact dermatitis at the 6 month follow-up. We
conclude that Acticide EP paste was the responsible
offending agent. Because isothiazolinone derivatives are
well-known antigens and 2-n-octyl-4-isothiazolin-3-one is the
active ingredient in Acticide EP paste, 2-n-octyl- 4isothiazolin-3-one is the likely cause of the dermatitis.
Introduction

In June 1992, the factory nurse of a paint
manufacturing plant noted an outbreak of skin
rashes during a 2-month period. She recorded
and photographed the rashes in the outbreak.
An occupational physician was notified at the
onset of this outbreak. A dermatologist was
consulted at the end of July 1992. The outbreak
manifested with burning and itching skin
lesions that erupted mainly on the arms and
legs of several workers in the raw materials
department.
Dermatitis at a paint
manufacturing plant
(a) Erythematous
and edematous
band-form plaques
and round blotches
on forearm. (b)
Irregularly shaped
erythematous and
edematous plaques
disseminated on
both flexor forearms.
Dermatitis
caused by
isothiazolinone
Isothiazolinone dermatitis
Liquid dispensing of paint with
container
Isothiazolinone
dermatitis :
Loading and
mixing of paint
Table 1 . Frequency of contact dermatitis and
occupational exposures among workers at the raw
material department of a paint manufacturing plant.
Occupational exposure
Contact
dermatitis
Raw materials handling groups
Liquid dispensing group
Powder dispensing group
Total
p
value
Yes
No
4
0
0
3
4
3
0.0029*
4
1§
4
0.0048*
0
5
5
8
9
17
Dispersion groups
Loading and mixing group
Resin dispensing and
quality control group
Total
＃
0.003+
* Fisher’s exact test, two-tailed. +Mantel-Haenszel summary chi-square.
§
Gloves worn.
Patch tests on guinea pigs (GP) with
Acticide EP (A1-A16) paste and methyl 2benzimidazole carbamate (M1-M16)
Pathology of isothiazolinone
dermatitis with necrosis & induration
An outbreak investigation of
dermatoses among people living in
Homei, Changhua county
 Feng-Cheng
 Yu-
Tang
Ten Chu
 Li- Fang Wang
 Jung- Der Wang
ABSTRACT
The objective of this study is to determine the
cause of an endemic outbreak of erythematous
lesions of skin among people living in Ho-Mei,
Chang-Hua county, Inhabitants with skin lesions
who lived in the prevalent area were asked to come
for dermatological examination. All volunteered
subjects were examined by at least one
dermatologist and one occupational physician and
interviewed with a structured questionnaire. 51
subjects with skin lesions were diagnosed among
78 subjects who came. 36 cases with insect bite was
the most prevalent diagnosis. Adults with insect
bites were found to be more frequent more than
children, and female and male were equal in
numbers. Victims usually developed the lesions of
insect bites in August and there was a significant
high tendency of family cluster.
In the walk-through survey to the surrounding
environment, we found that there were one
refuse incinerator and some factories
surrounding the prevalent area. However, the
furnace of the incinerator was about two
kilometers far from the endemic area and its
chimney was only 35 meters high. The
operations of all the other local factories
generally did not produce toxic air pollutants.
After implementing environmental sanitation
procedures to eradicate local insects including
mosquitoes, the skin lesions disappeared and
never recurred. We concluded the endemic
outbreak of the skin lesions was not associated
with air pollution, but probably caused by insect
bites.
Plate
The administrative areas of Homei
town, Changhua county
Dermatoses found at Homei town
Dermatoses found at Homei Town
suspected to be related to incinerator
Plate The distribution map of dermatoses
cases due to insect bites in Lisheng Li
Table
Description of dermatoses in study
population
Adult Children Male Female Date of onset (in 1993) Cases
Jul Aug Sep Else NA
7
17
2
12
4
11
3
0
1
19
Insect bites
8
9
2
3
1
7
1
1
1
11
Lichen urticatus/
eczema/erythema*
3
2
4
3
2
3
1
0
0
6
Scabies
2
4
1
3
0
0
1
1
3
5
Pruritus
1
0
2
1
1
1
0
0
0
2
Hyperpigmentation
3
3
0
0
1
0
0
0
2
3
Seborrheic
dermatitis
0
2
0
2
1
0
1
0
0
2
Fungal infection
0
2
0
2
0
2
0
0
0
2
Urticaria
1
1
0
0
0
0
0
0
1
1
Erythema
2
3
1
2
2
2
0
0
0
4
Eczema
0
1
0
1
0
0
0
1
0
1
Purpura
1
0
1
0
0
0
0
0
1
1
Lichen simplex
chronicus
28
44
13
29 12
26
7
3
9
57
Total
*Dermatologist supposed those skin disorders probably were caused by insect
bites but without suitable treatment
Table
The status of family clusters in
relation to the prevalence of insect bites
Male adult
Dermatoses
Insect bites+
Else
disorders#
Cluster Cluster
(+)
(-)
Female
adult
cluster
(+)
cluster
(-)
Children
OR x2
value
Cluster Cluster
(+)
(-)
12
1
12
1
4
0
3
2
2
3
1
0
12
1 6.6*
* Mantel-Haenszel test was used (p<0.05)
+ Including skin disorders caused by insect bites but without suitable
treatment
# Excluding the cases who were caused by insect bites, such as pruritus,
hyperpigmentation, seborrheic dermatitis, fungal infection, urticaria,
erythema, eczema, purpura, lichen simplex chronicus
Table The industries were located at
Lisheng Li in Homei town, Changhua county
Industries
Basic Metal Industries
Fabricated Metal Products Manufacturing
No
6
5
Plastic Products Manufacturing
Non-metallic Mineral Products Manufacturing
Transport Equipment Manufacturing and Repairing
4
1
1
Pulp, Paper and Paper Products Manufacturing
Retail Sale of Used Merchandise Stores
Animal Husbandry
Knit Fabric Mills
1
1
1
1
Platemaking
Out of business/ Moving away/ Not available
Total
1
7
29