Attitudes of falsifications on Attitudes of falsifications on etiological diagnosisetiological diagnosis

Jung-Der Wang, MD, ScD

National Taiwan University College of Public Health

National Taiwan University Hospital

Why take a refutational attitude?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 Conjectures and falsifications on etiological diagnosisetiological diagnosis

Jee SH, Wang JD, Sun CC, Chao YF. Prevalence of probable kerosene dermatoses among ball-bearing 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 Outbreak of type A botulism caused by a commercial food product in by a commercial food product in

Taiwan: clinical and epidemiological Taiwan: clinical and epidemiological investigationsinvestigations

Shih-Jei TsaiYang-Chyuan ChangJung-Der WangJih-Haw Chou

ABSTRACTABSTRACTIn that September 1986, we found 7

patients from a printing factory in Chang-Hwa 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 7Age/Sex 52/F 15/M 28/M 15/M 15/M 17/M 17/MIncubation period*(hr) 23 34 48 48 50 58 74Systemic 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

+++++

+++++

+++++

++++-

++++-

---+-

---+-

Ventilator support + + - - - - -Antitoxin therapy + + - - - - -Outcome Died Reco-

veredReco-vered

Reco-vered

Reco-vered

Reco-vered

Reco-vered

Figure Amplitude potentiation of CAMP Figure Amplitude potentiation of CAMP after isometric contraction for 15 secondsafter isometric contraction for 15 seconds

Figure Electrodecremental response to repetitive Figure Electrodecremental response to repetitive stimulation at a rate of 2.5 Hz and amplitude stimulation at a rate of 2.5 Hz and amplitude potentiation with disappearance of electrodecre-potentiation with disappearance of electrodecre-mental responseafter iso metric contraction mental responseafter iso metric contraction (stimulation at the right Erb’s point and pick-up at (stimulation at the right Erb’s point and pick-up at the right deltoid)the right deltoid)

Clustering of cases with sudden Clustering of cases with sudden onset ofonset of bilateral weakness of bilateral weakness of

extremities with respiratory extremities with respiratory paralysisparalysis in a printing shop in a printing shop ConjecturesConjecturesH1: 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 SyndromeHn: Neuromuscular junction disease

1)Myasthenia gravis2)Drug or toxin induced3)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 (+)

DeductionsDeductions

H1→Consciousness disturbance

H2→Impaired NCVs

H3→Impaired NCVs

--------------------------------Hn-2→Consciousness disturbance and/or

involuntary movementHn-1→Impaired NCVs Guillain-Barre

SyndromeHn(1)→Myasthenia gravis or syndrome

Hn(2)→Drug or toxin induced 

Hn(3)→Botulism

Observations and measurementsObservations 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 analysisData analysisEating breakfast on Sept. 25-26 was shown to be associated with the appearance of symptoms.

RefutationsH1, H2,…Hn(1), Hn(2) were all excluded as the

diagnosis.

Future refutation attemptsEliminated the canned peanuts, and no more new cases occurred.

Data analysisData analysis

Eating breakfastEating breakfast Yes No TotalYes No TotalBotulismBotulism Yes 7 0 Yes 7 0 77

No 7 25 No 7 25 3232

Prevalence of probable kerosene Prevalence of probable kerosene dermatoses among ball-bearing dermatoses among ball-bearing

factory workers.factory workers.

Shiou-Hwa Jee, MDJung-Der Wang, MD, ScDChee-Ching Sun, MDYung-Fa Chao, MD

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 zipper-manufacturing workers with a similar age distribution, educational background, and income.

ABSTRACTABSTRACT

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 chi-square 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.

IntroductionIntroductionIn 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 dermatosisKerosene dermatosis

Figure 1. Structure of a typical ball-bearingFigure 1. Structure of a typical ball-bearing

Insertion of balls into ringsInsertion of balls into rings

Insertion of balls into ringsInsertion of balls into rings

Both hands exposed to keroseneBoth hands exposed to kerosene

Figure 2. The work process. Workers in Figure 2. The work process. Workers in processes B and C are heavily exposed; processes B and C are heavily exposed; those in processes A, D, and E are lightly those in processes A, D, and E are lightly exposed.exposed.

Exposed group Reference groupNumber of workers 79 263Sex Female Female

Age (years) Range 16-26 15-29 Mean 18.9 20.2 SD 1.9 3.7Monthly income NT$7,000a NT$7,000a

Educational level Elementary school only, in most cases

Elementary school only, in most cases

Major contactantsb Kerosene, steel Plastics, textilesMinor contactantsc Antirust oil Scissors, Iubricants

Table Characteristics of the exposed (ball-bearing factory) Table Characteristics of the exposed (ball-bearing factory) and reference (zipper manufacturing company) groups.and reference (zipper manufacturing company) groups.

a NT$ stands for new Taiwan dollars. NT$7,000 is equivalent to USD 200.b Any substances to which the workers were heavily exposed daily.c Substances to which the workers were lightly and only occasionally exposed.

Age(years)

Exposed group Reference group

Number of workers

examined

Percentage with

dermatoses

Number of workers

examined

Percentage with

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 2. Age-specific prevalence rates of Table 2. Age-specific prevalence rates of dermatoses among the exposed (ball-bearing dermatoses among the exposed (ball-bearing factory) and reference (zipper manufacturing factory) and reference (zipper manufacturing company) groups.company) groups.

Heavily exposed groupa

Heavily exposed groupb

Total

N %c N %c N %c

Workers with dermatoses 31 91 35 78 66 84

Erythema 24 70 27 60 51 65 Eczema 7 21 5 11 12 15

Defatting dermatitis --- 0 3 7 3 4Workers without dermatoses 3 9 10 22 13 16

Total of workers examined 34 100 45 100 79 100

Table 3. Results of the dermatologic examination of Table 3. Results of the dermatologic examination of the hands with kerosene exposure.the hands with kerosene exposure.

a Workers exposed to kerosene in processes B and C for >5 h daily.b 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%.

Outbreak of contact dermatitis Outbreak of contact dermatitis related to acticide EP paste in a related to acticide EP paste in a

paint manufacturing factorypaint manufacturing factory

Shiou- Hwa JeeKun-Yu ChaoChee- Ching SunJung- Der Wang

ABSTRACTABSTRACTAn 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- 4-isothiazolin-3-one is the likely cause of the dermatitis.

IntroductionIntroduction 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 Dermatitis at a paint manufacturing plantmanufacturing plant

(a) Erythematous (a) Erythematous and edematous and edematous

band-form plaques band-form plaques and round blotches and round blotches

on forearm. (b) on forearm. (b) Irregularly shaped Irregularly shaped erythematous and erythematous and

edematous plaques edematous plaques disseminated on disseminated on

both flexor both flexor forearms.forearms.

Dermatitis Dermatitis caused by caused by

isothiazolinoneisothiazolinone

Isothiazolinone dermatitisIsothiazolinone dermatitis

Liquid dispensing of paintLiquid dispensing of paint with with containercontainer

Isothiazolinone Isothiazolinone dermatitis :dermatitis :

Loading and Loading and mixing of paintmixing of paint

Occupational exposure Contact dermatitis

Totalp

value

Yes No

Raw materials handling groups

Liquid dispensing group 4 0 4 0.0029* Powder dispensing group 0 3 3

Dispersion groups

Loading and mixing group ＃ 4 1§ 4 0.0048*

Resin dispensing and quality control group 0 5 5

Total 8 9 17 0.003+

Table 1 . Frequency of contact dermatitis and Table 1 . Frequency of contact dermatitis and occupational exposures among workers at the raw occupational exposures among workers at the raw material department of a paint manufacturing plant.material department of a paint manufacturing plant.

* Fisher’s exact test, two-tailed. +Mantel-Haenszel summary chi-square.§ Gloves worn.

Patch tests on guinea pigs (GP) with Patch tests on guinea pigs (GP) with Acticide EP (A1-A16) paste and methyl 2-Acticide EP (A1-A16) paste and methyl 2-

benzimidazole carbamate (M1-M16)benzimidazole carbamate (M1-M16)

Pathology of isothiazolinone Pathology of isothiazolinone dermatitis with necrosis & induration dermatitis with necrosis & induration

An outbreak investigation of An outbreak investigation of dermatoses among people living in dermatoses among people living in

Homei, Changhua countyHomei, Changhua county

Feng-Cheng TangYu- Ten ChuLi- Fang WangJung- Der Wang

ABSTRACTABSTRACTThe 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 Plate The administrative areas of Homei town, Changhua countytown, Changhua county

Dermatoses found at Homei town Dermatoses found at Homei town

Dermatoses found at Homei Town Dermatoses found at Homei Town suspected to be related to incineratorsuspected to be related to incinerator

Plate The distribution map of dermatoses Plate The distribution map of dermatoses

cases due to insect bites in Lisheng Licases due to insect bites in Lisheng Li

Table Description of dermatoses in study Table Description of dermatoses in study populationpopulation

Adult Children Male Female Date of onset (in 1993) Cases

　 　 　 　 Jul Aug Sep Else NA 　

Insect bites 17 2 7 12 4 11 3 0 1 19

Lichen urticatus/ eczema/erythema*

9 2 8 3 1 7 1 1 1 11

Scabies 2 4 3 3 2 3 1 0 0 6

Pruritus 4 1 2 3 0 0 1 1 3 5

Hyperpigmentation 0 2 1 1 1 1 0 0 0 2

Seborrheic dermatitis

3 0 3 0 1 0 0 0 2 3

Fungal infection 2 0 0 2 1 0 1 0 0 2

Urticaria 2 0 0 2 0 2 0 0 0 2

Erythema 1 0 1 0 0 0 0 0 1 1

Eczema 3 1 2 2 2 2 0 0 0 4

Purpura 1 0 0 1 0 0 0 1 0 1

Lichen simplex chronicus

0 1 1 0 0 0 0 0 1 1

Total 44 13 28 29 12 26 7 3 9 57*Dermatologist supposed those skin disorders probably were caused by insect bites but without suitable treatment

Table The status of family clusters in Table The status of family clusters in

relation to the prevalence of insect bitesrelation to the prevalence of insect bites Male adult Female

adultChildren OR x2

value

Dermatoses Cluster

(+)

Cluster

(-)

cluster

(+)

cluster

(-)

Cluster

(+)

Cluster

(-)

Insect bites+ 12 1 12 1 4 0 12

Else

disorders#

3 2 2 3 1 0 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 Table The industries were located at

Lisheng Li in Homei town, Changhua countyLisheng Li in Homei town, Changhua county Industries NoBasic Metal Industries 6Fabricated Metal Products Manufacturing 5Plastic Products Manufacturing 4Non-metallic Mineral Products Manufacturing 1Transport Equipment Manufacturing and Repairing 1Pulp, Paper and Paper Products Manufacturing 1Retail Sale of Used Merchandise Stores 1Animal Husbandry 1Knit Fabric Mills 1Platemaking 1Out of business/ Moving away/ Not available 7Total 29