PART I

PATCH TESTING

1

Pathophysiology of Allergic and Irritant Contact Dermatitis

3

1.1

Introduction

3

1.2

Pathophysiology of Irritant and Allergic Skin Inflammation

3

1.2.1

Irritant and/or Allergic Chemicals

4

1.2.2

Skin Irritation: Activation of Innate Immunity

5

1.3

Skin Allergy: The Role of Specific Immunity

6

1.3.1

Antigen-Specific Immunity

6

1.3.2

Skin Allergy: Mechanisms of Action

6

1.3.3

Indirect Responsibility of Chemicals in Skin Irritation

7

1.4

Pathophysiology of Skin Inflammation: The Connection between Innate and Acquired Immunity

7

References

8

2

Diseases for Which Patch Testing Is Recommended: Patients Who Should Be Investigated

2.1

Allergic Contact Dermatitis

11

2.1.1

Clinical Signs and Symptoms

11

2.1.2

Histopathological Features

11

2.2

Allergic Contact Dermatitis Syndrome

14

2.2.1

Stage 1 of ACDS

14

2.2.2

Stage 2 of ACDS

17

2.2.3

Stage 3 of ACDS

19

2.3

Allergic Contact Dermatitis Versus Irritant Contact Dermatitis: Criteria for Differential Diagnosis

23

2.4

Other Skin Diseases in Which Patch Testing Is of Major Interest

23

2.5

Algorithmic Approach: Key Role of Patch Testing

25

2.6

Hand Dermatitis: Definition and Procedures Applied in Differential Diagnosis

25

2.6.1

Hand Dermatitis: Exogenous and Endogenous Factors

26

2.6.2

A Classification of Hand Dermatitis

26

2.6.3

Tools of Investigation

31

2.6.4

Hand Dermatitis: Some Examples of an Algorithmic Approach

31

2.6.5

Hand Eczema: A Controversial Issue

31

References

32

3

Patch Testing Methodology

35

3.1

Historical Background

35

3.2

Definition and Aims

36

3.2.1

Requirements for an Ideal Patch Testing Procedure

36

3.2.2

Is Patch Testing the “Gold Standard” to Investigate Patients with Allergic Contact Dermatitis?

37

3.3

Patch Test Units

37

3.3.1

Nonchamber Patch Tests

37

3.3.2

Chamber Patch Tests

37

3.3.3

Plastic Square Chambers

41

3.3.4

Reinforcement of Patch Test Units

45

3.4

A General Overview of Allergens

45

3.4.1

Allergens

45

3.4.2

Bioavailability of Allergens

47

3.4.3

Quality Control of Allergens

47

3.4.4

Appropriate Amounts of Petrolatum to Be Applied at Patch Testing

47

3.4.5

Appropriate Amounts of Liquids to Be Applied at Patch Testing

48

3.5

Specific Recommendations When Considering Patch Testing Patients

48

3.5.1

Patch Testing on Intact Skin Is Critical

48

3.5.2

Medicaments and Patch Testing

49

3.5.3

Pregnancy and Patch Testing

50

3.5.4

Patch Testing in Children

50

3.6

Application of Patch Tests on the Skin: Some Practical Suggestions

51

3.6.1

Test Sites

51

3.6.2

Removal of Hair

52

3.6.3

Degreasing of Test Site

52

3.6.4

Application of Test Strips

52

3.6.5

Instructions to Patients

52

3.7

Reading Time

52

3.7.1

Standard Patch Test Occlusion and Reading Time

53

3.7.2

Conventional Patch Test Reading Time

53

3.7.3

Reading at Day 2, Day 3, and Day 4

53

3.7.4

Reading at Day 7

53

3.7.5

Single Reading Versus Multiple Reading

54

3.7.6

Day 3 Versus Day 4 Reading

54

3.7.7

One-Day Occlusion Versus Two-Day Occlusion

54

3.7.8

Marking the Skin

54

3.7.9

Positive Control

55

3.7.10

Immediate Urticarial Reactions to Some Allergens

55

3.8

Reading and Scoring Patch Test Results

56

3.8.1

Scoring Codes According to the 1CDRG

56

3.8.2

Proposal for Modified Scoring Codes of Positive Patch Test Reactions, According to ESCD and EECDRG

57

3.8.3

Rating Patch Test Reactions Based on Digital Images

57

3.8.4

Bioengineering Methods for Evaluating Skin Irritation and Allergic Reactions. A Comparison with Visual Scoring

57

3.8.5

Remarks About Reading and Scoring Patch Test Results

58

3.9

Irritant Patch Test Reactions

60

3.10

False-Positive Patch Test Reactions

63

3.11

False-Negative Patch Test Reactions

63

3.12

Compound Allergy

65

3.13

Cross-Sensitization, Concomitant Sensitization, and Polysensitization

65

3.13.1

Cross-Sensitization

65

3.13.2

Concomitant Sensitization

66

3.13.3

Polysensitization

66

3.14

Unwanted Adverse Reactions of Patch Testing

66

3.14.1

Patch Test Sensitization (“Active Sensitization”)

68

3.14.2

Excited Skin Syndrome (“Angry Back”)

68

3.15

Patch Test Readings in Different Ethnic Populations

69

3.15.1

Patch Test Reading in Oriental Populations

69

3.15.2

Patch Test Reading in Black Populations

70

3.16

Patch Testing Techniques in Different Climatic Environments

71

3.16.1

Temperate Climates

72

3.16.2

Tropical Climates

72

3.16.3

Patch Testing Procedures in the Tropics

72

3.17

Is Self-assessment of Allergic Contact Dermatitis by Patients Recommendable?

73

3.17.1

Self-assessment by Questionnaires

73

3.17.2

Self-readings of Patch Tests by Patients

73

References

74

4

Baseline Series of Patch Tests

79

4.1

Historical Background

79

4.2

Advantages and Disadvantages of Using a Baseline Series of Patch Tests

79

4.2.1

Advantages

79

4.2.2

Disadvantages

80

4.3

Three Major Baseline Series Used Worldwide

80

4.4

“Mixes” of Baseline Series

83

4.5

ICDRG-Revised International Minimal Baseline Series of Patch Tests

83

4.6

Concise Information About Allergens Included in the Updated 2011 Minimal Baseline Series of the ICDRG

86

4.7

Concise Information on Other Common Allergens Included in the Updated 2011 Minimal Baseline Series of the ICDRC

90

4.8

Additional Series of Patch Tests

91

References

91

5

Photopatch Testing

95

5.1

Definition and Aims

95

5.2

Photoallergic Contact Dermatitis

95

5.3

Photoallergic Contact Dermatitis Versus Airborne Allergic Contact Dermatitis: Criteria for Differential Diagnosis

97

5.4

Photoallergic Drug Eruptions

98

5.5

Photopatch Testing Methodology

98

5.6

Light Sources

99

5.7

Proposal for a Photopatch Test Series

100

References

100

6

TRUE Test System

103

6.1

Introduction

103

6.2

TRUE Test System

103

6.3

More Practical Information About the Technology of TRUE Test

104

6.4

Regulatory Information

106

6.5

Standard TRUE Test Series

106

6.6

New Additions

109

6.7

Methodology of Use

109

6.8

Additional Practical Information

110

References

110

7

Additional Testing Procedures and Spot Tests

113

7.1

Strip Patch Test

113

7.2

Open Test

113

7.3

Semi-open Test

114

7.4

Repeated Open Application Test

116

7.5

Testing Procedures with Unknown Substances

117

7.5.1

Strategy

118

7.5.2

Steps Required Prior to Any Testing Procedure

119

7.5.3

Testing Procedures with Solid Products and Extracts

119

7.5.4

Testing Procedures with Cosmetics and Other Related Products

121

7.6

Oral Provocation Test (Oral Challenge)

121

7.7

Other Investigations

122

7.7.1

pH Measurement

122

7.7.2

Spot Tests

122

7.7.3

Chemical Analysis

126

7.8

Additional Remarks About Chemistry and Immunology in Relationship with Allergic Contact Dermatitis

127

References

127

8

Clinical Relevance of Patch Test Reactions

129

8.1

Introduction

129

8.2

General Principles

129

8.3

Past and Current Relevance

130

8.4

Scoring System

130

8.5

Strategies

131

8.5.1

Clinical History

131

8.5.2

Environmental Evaluation

132

8.5.3

Further Correlations

134

8.5.4

Additional Investigations

134

8.6

Suggestions for Improved Evidence-Based Diagnosis of Relevance

135

8.7

Additional Remark

135

References

136

9

Atopy Patch Tests

137

9.1

Introduction

137

9.2

Summary of the Pathophysiology of Atopic Dermatitis

137

9.2.1

Influence of Age

138

9.3

Principles and Usage of Atopy Patch Tests

138

9.4

Technical Aspects of Atopy Patch Tests

138

9.4.1

Materials: Allergens, Vehicles and Controls

138

9.4.2

Prior Precautions

140

9.4.3

Procedure and Reading of Atopy Patch Tests

140

9.5

Side Effects

141

9.6

Interpretation of Results

141

9.6.1

Sensitivity, Specificity and Reproducibility of Atopy Patch Tests

141

9.6.2

Clinical Relevance of Atopy Patch Tests

142

9.7

Conclusion

142

References

143

PART II

PRICK TESTING

10

Spectrum of Diseases for Which Prick Testing and Open (Non-prick) Testing Are Recommended: Patients Who Should Be Investigated

147

10.1

Contact Urticaria Syndrome

147

10.1.1

Clinical Symptoms and Stages of CUS

147

10.1.2

Etiology and Mechanisms of CUS

149

10.1.3

Contact Urticaria to Natural Rubber Latex

152

10.2

Protein Contact Dermatitis

153

References

156

11

Methodology of Open (Non-prick) Testing, Prick Testing, and Its Variants

159

11.1

Open (Non-prick) Testing

159

11.2

Prick Test: Technical Modalities and Reading

160

11.2.1

Technique of Puncture

160

11.2.2

Control Solutions

160

11.2.3

Reading Time

161

11.2.4

Reading Prick Test Results

162

11.2.5

Medicaments and Prick Testing

162

11.2.6

False-Negative Reactions

163

11.2.7

False-Positive Reactions

163

11.2.8

Prick Tests in Children and Babies

163

11.3

Prick-by-Prick Test

163

11.4

Scratch Test

163

11.5

Scratch-Chamber Test

164

11.6

Comparative Indications of Open (Non-prick) Testing, Prick Testing, and Other Related Tests

164

11.7

Intradermal Testing for Type 1 Hypersensitivity

164

11.8

Prick Testing: Allergens of Interest for Skin Problems

165

11.8.1

Latex

165

11.8.2

Airborne Environmental per Annum Allergens

166

11.8.3

Airborne Environmental Seasonal Allergens

166

11.8.4

Food Allergens (Trophallergens)

166

11.8.5

Occupational Allergens

167

11.8.6

Fungi

168

11.8.7

Miscellaneous (Immunological and/or Non-immunological) Urticariogens

168

References

169

PART III

TESTING IN CUTANEOUS SYSTEMIC IMMUNE-RELATED ADVERSE DRUG REACTIONS: INTEREST AND LIMITATIONS

12

Testing Procedures in Cutaneous Systemic Immune-Related Adverse Drug Reactions

173

12.1

General Considerations

173

12.2

Proposal of a Classification of CADR

175

12.3

Tools of Investigation in CADR

175

12.4

Histopathological Limitations in Diagnosis of a CADR

176

12.5

Patch Testing in CADR

177

12.5.1

Spectrum of CADRs for Which Patch Testing is Recommended

177

12.5.2

Spectrum of CADRs for Which Patch Testing Can Be Performed (Being Still Controversial)

178

12.5.3

Spectrum of CADRs for Which Patch Testing Is of No Interest

179

12.5.4

Guidelines in Drug Patch Testing: General Rules

179

12.5.5

Technical Aspects of Drug Patch Testing

180

12.5.6

Readings of Drug Patch Tests

183

12.5.7

False-Negative Patch Test Reactions

183

12.5.8

False-Positive Patch Test Reactions

183

12.6

Prick Testing in CADR

183

12.7

Intradermal Testing in CADR

184

12.8

Oral Provocation Test (Oral Challenge) in CADR

184

References

184

APPENDICES

187

Appendix A

Additional Series of Patch Tests

187

A.1

Introductory Remarks

187

A.2

Bakery Series

188

A.3

Corticosteroid Series

188

A.4

Cosmetic Series

191

A.5

Epoxy Resin Series

193

A.6

Hairdressing Series

193

A.7

Isocyanate Series

194

A.8

Metal Series

196

A.9

(Meth)Acrylates Series

196

A.10

Plastics and Glues Series

198

A.11

Rubber Additives Series

199

A.12

Textile Dyes and Finish Series

200

A.13

Other Series

202

References

206

Appendix B

The International Contact Dermatitis Research Group

207

B.1

Historical Background

207

B.2

Current Tasks and Strategy of the ICDRG

208

B.3

ICDRG Members

208

References

210

Appendix C

A List of Companies Producing and/or Distributing Patch and/or Prick Test Materials and/or Allergens

210

C.1

Introductory Remarks

210

C.2

List of Companies

210

Suggested Reading

213

Index

215