Is Allergy to Titanium Bone Fixation Plates a Problem?

Round 1

Reviewer 1 Report

The authors aimed to answer the question whether titanium devices used in the treatment of fractures in the craniofacial region can cause allergic reactions. The study comprised 50 subjects treated  surgically for maxillofacial injuries with the use of titanium composite devices. In addition, allergic tests were performed by the patch method.

The study covers some issues that have been overlooked in other similar topics. The structure of the manuscript appears adequate and well divided in the sections. Overall, the manuscript was written in good English and easy to understand and follow. Some of the comments that would improve the overall quality of the study are:

1-) Introduction section: Please better describe the aim of the work;

2-) Inclusion/exclusion criteria: will be useful for the readers to group the same in a table, removing from the text.

3-) Add limitation of the study in the discussion section;

4-) Conclusion Section: This paragraph required a general revision to eliminate redundant sentences and to add some "take-home message";

5-) Please also check typos thorough the text.

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate the time and effort that you dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions to the revised manuscript. Those changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

The authors aimed to answer the question whether titanium devices used in the treatment of fractures in the craniofacial region can cause allergic reactions. The study comprised 50 subjects treated  surgically for maxillofacial injuries with the use of titanium composite devices. In addition, allergic tests were performed by the patch method.

The study covers some issues that have been overlooked in other similar topics. The structure of the manuscript appears adequate and well divided in the sections. Overall, the manuscript was written in good English and easy to understand and follow. Some of the comments that would improve the overall quality of the study are:

1-) Introduction section: Please better describe the aim of the work;

The aim has been emphasized in introduction.

2-) Inclusion/exclusion criteria: will be useful for the readers to group the same in a table, removing from the text.

We provided the table.

3-) Add limitation of the study in the discussion section;

The limitations have been discussed now.

4-) Conclusion Section: This paragraph required a general revision to eliminate redundant sentences and to add some "take-home message";

Conclusion is rewritten.

5-) Please also check typos thorough the text.

Reviewer 2:

Point 01

The following sentences need at least one reference each, in order to back up their statements, otherwise they would be mere assumptions made by the authors:

“Allergic reaction usually occurs from minutes up to 72 hours after repeated contact with an allergen.”

“Despite allergic contact dermatitis (ACD) rarely constitutes severe medical condition it may seriously decrease the quality of life.”

“Manifestations of ACD include regional skin and mucosal lesions which may by accompanied by asthmatic conditions.”

“Manifestations of Allergic Contact Stomatitis (ACS) include erythematous plaques, vesiculation, ulceration, hyperkeratosis or lichenoid reactions which are frequently accompanied by subjective symptoms such as burning sensation or itchiness, pain, and edema.”

“Seldom the lesions extend beyond the oral cavity involving the facial skin and rest of the body resembling the ACD.”

“Many of the materials used in medicine, both metallic and non-metallic, are considered to be associated with elevated risk of allergy. Chromium, nickel, palladium, copper, acrylic compounds are known potential allergens.”

“Titanium, used widely in dentistry, craniofacial surgery, and orthopedics, was considered fully biocompatible.”

“However, the frequency of reported allergic reactions to titanium increases.”

“Usually in medical applications Grade IV titanium is used, which is composed of titanium, iron, carbon, oxygen, and nitrogen. Also, titanium alloys containing vanadium, nickel, aluminum, molybdenum, thallium, and niobium.”

“Titanium use is in medicine is increasing therefore practitioners of different specialties approach the patients equipped with titanium implants in everyday practice.”

“Nowadays the open reduction and internal fixation (ORIF) with the aid of titanium hardware is the gold standard for maxillofacial fractures treatment.”

“There is lack of evidence regarding the influence of allergic reactions to titanium on the bone fracture healing process.”

“As a result of advancements in casting and metallurgy and chemical industry development the titanium is more often present in paints, dyes, photocatalysts and other ordinary items.”

“This combined with the more frequent use of titanium in medicine can increase the incidence of titanium allergic reactions.”

 The introduction has been rewritten with proper references.

Point 02

The authors need to write the aims of the study at the end of the Introduction.

The aims were added.

Point 03

“In 8 cases there was prior contact with allergen, in 42 cases there was potential contact.”

What do the authors mean by “potential contact”?

The term was changed to more precise.

Point 04

The Discussion is a patch of short literature reviews about different sub-subjects on allergy, without any discussion about the findings of the study.

The section was changed.

Point 05

“In world literature only a few reports about allergic reactions caused by osteosynthesis elements are known. On contrary titanium use is extremely common in modern medicine. This leads to a conclusion that allergic reactions reports should be regarded incidental.”

None of this is a conclusion of your study. Stick to the findings your study in order to write the conclusion.

The conclusions have been changed.

Point 06

“In our study it was found that titanium fixing elements as well as titanium dental implants do not cause allergic skin reactions.”

Dental implants?!?! I thought that your study was about bone fixation plates.

The conclusions have been rewritten.

Reviewer 3:

Introduction

This investigation is a paper that presents information for researchers in the field of allergy to titanium of dental implants. Titanium, used widely in implant dentistry, and maxilofacial surgery, was considered fully biocompatible. However, the frequency of reported allergic reactions to titanium increases. This afirmation is not showed in this section with evidence scientific by experimental and clinical studies. In fact, in this section only a reference is showed. The authors should include in the section recent studies of theses aspects of allergy in titanium devices.

Also, the aim of the study are not included.

The introduction was rewritten and the aim has been emphasized.

Materials and methods.

This section is not adequated. This study was designed to analyze the different the allergy among patients treated by itianum devices and control patients. The size of two samples is very diferent. The method for allergy assessment based in International Contact Dermatitis Research Group (ICDRG) recommendations is not referenced in the text.

The ICDGR scoring explanation has been added.

Results.

The allergic reaction is triggered when the repeated exposure happens. In 8 cases there was prior contact with allergen, in 42 cases there was potential contact. None of the patients was allergic to titanium or its compounds. Only one patient had positive patch test for silver nitrate.

Surgical complications and allergy symptoms are presented togheter in one table. This presentation is incorrect because suggests confussion of findings.

The table bas been corrected.

Discussion

Most of this section must be changed to introduction. The authors not presented a discussion of the clinical findings of the study.

The parts of text were moved to introduction and the discussion has been rewritten.

Conclusions.

This section is not adequated according to the paper. The first two lines are aspects of introduction. The conclusions only must be related with main aspects of the paper.

 The conclusions section is rewrtitten.

References. This section must be revised. Some references are written with capital letters. Only 6 references (18.7%) are of the last 5 years.

 New references added.

Conclusively, the study is not ready for publication 

Author Response File: Author Response.pdf

Reviewer 2 Report

Point 01

The following sentences need at least one reference each, in order to back up their statements, otherwise they would be mere assumptions made by the authors:

“Allergic reaction usually occurs from minutes up to 72 hours after repeated contact with an allergen.”

“Despite allergic contact dermatitis (ACD) rarely constitutes severe medical condition it may seriously decrease the quality of life.”

“Manifestations of ACD include regional skin and mucosal lesions which may by accompanied by asthmatic conditions.”

“Manifestations of Allergic Contact Stomatitis (ACS) include erythematous plaques, vesiculation, ulceration, hyperkeratosis or lichenoid reactions which are frequently accompanied by subjective symptoms such as burning sensation or itchiness, pain, and edema.”

“Seldom the lesions extend beyond the oral cavity involving the facial skin and rest of the body resembling the ACD.”

“Many of the materials used in medicine, both metallic and non-metallic, are considered to be associated with elevated risk of allergy. Chromium, nickel, palladium, copper, acrylic compounds are known potential allergens.”

“Titanium, used widely in dentistry, craniofacial surgery, and orthopedics, was considered fully biocompatible.”

“However, the frequency of reported allergic reactions to titanium increases.”

“Usually in medical applications Grade IV titanium is used, which is composed of titanium, iron, carbon, oxygen, and nitrogen. Also, titanium alloys containing vanadium, nickel, aluminum, molybdenum, thallium, and niobium.”

“Titanium use is in medicine is increasing therefore practitioners of different specialties approach the patients equipped with titanium implants in everyday practice.”

“Nowadays the open reduction and internal fixation (ORIF) with the aid of titanium hardware is the gold standard for maxillofacial fractures treatment.”

“There is lack of evidence regarding the influence of allergic reactions to titanium on the bone fracture healing process.”

“As a result of advancements in casting and metallurgy and chemical industry development the titanium is more often present in paints, dyes, photocatalysts and other ordinary items.”

“This combined with the more frequent use of titanium in medicine can increase the incidence of titanium allergic reactions.”

Point 02

The authors need to write the aims of the study at the end of the Introduction.

Point 03

“In 8 cases there was prior contact with allergen, in 42 cases there was potential contact.”

What do the authors mean by “potential contact”?

Point 04

The Discussion is a patch of short literature reviews about different sub-subjects on allergy, without any discussion about the findings of the study.

Point 05

“In world literature only a few reports about allergic reactions caused by osteosynthesis elements are known. On contrary titanium use is extremely common in modern medicine. This leads to a conclusion that allergic reactions reports should be regarded incidental.”

None of this is a conclusion of your study. Stick to the findings your study in order to write the conclusion.

Point 06

“In our study it was found that titanium fixing elements as well as titanium dental implants do not cause allergic skin reactions.”

Dental implants?!?! I thought that your study was about bone fixation plates.

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate the time and effort that you dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions to the revised manuscript. Those changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

The authors aimed to answer the question whether titanium devices used in the treatment of fractures in the craniofacial region can cause allergic reactions. The study comprised 50 subjects treated  surgically for maxillofacial injuries with the use of titanium composite devices. In addition, allergic tests were performed by the patch method.

The study covers some issues that have been overlooked in other similar topics. The structure of the manuscript appears adequate and well divided in the sections. Overall, the manuscript was written in good English and easy to understand and follow. Some of the comments that would improve the overall quality of the study are:

1-) Introduction section: Please better describe the aim of the work;

The aim has been emphasized in introduction.

2-) Inclusion/exclusion criteria: will be useful for the readers to group the same in a table, removing from the text.

We provided the table.

3-) Add limitation of the study in the discussion section;

The limitations have been discussed now.

4-) Conclusion Section: This paragraph required a general revision to eliminate redundant sentences and to add some "take-home message";

Conclusion is rewritten.

5-) Please also check typos thorough the text.

Reviewer 2:

Point 01

The following sentences need at least one reference each, in order to back up their statements, otherwise they would be mere assumptions made by the authors:

“Allergic reaction usually occurs from minutes up to 72 hours after repeated contact with an allergen.”

“Despite allergic contact dermatitis (ACD) rarely constitutes severe medical condition it may seriously decrease the quality of life.”

“Manifestations of ACD include regional skin and mucosal lesions which may by accompanied by asthmatic conditions.”

“Manifestations of Allergic Contact Stomatitis (ACS) include erythematous plaques, vesiculation, ulceration, hyperkeratosis or lichenoid reactions which are frequently accompanied by subjective symptoms such as burning sensation or itchiness, pain, and edema.”

“Seldom the lesions extend beyond the oral cavity involving the facial skin and rest of the body resembling the ACD.”

“Many of the materials used in medicine, both metallic and non-metallic, are considered to be associated with elevated risk of allergy. Chromium, nickel, palladium, copper, acrylic compounds are known potential allergens.”

“Titanium, used widely in dentistry, craniofacial surgery, and orthopedics, was considered fully biocompatible.”

“However, the frequency of reported allergic reactions to titanium increases.”

“Usually in medical applications Grade IV titanium is used, which is composed of titanium, iron, carbon, oxygen, and nitrogen. Also, titanium alloys containing vanadium, nickel, aluminum, molybdenum, thallium, and niobium.”

“Titanium use is in medicine is increasing therefore practitioners of different specialties approach the patients equipped with titanium implants in everyday practice.”

“Nowadays the open reduction and internal fixation (ORIF) with the aid of titanium hardware is the gold standard for maxillofacial fractures treatment.”

“There is lack of evidence regarding the influence of allergic reactions to titanium on the bone fracture healing process.”

“As a result of advancements in casting and metallurgy and chemical industry development the titanium is more often present in paints, dyes, photocatalysts and other ordinary items.”

“This combined with the more frequent use of titanium in medicine can increase the incidence of titanium allergic reactions.”

 The introduction has been rewritten with proper references.

Point 02

The authors need to write the aims of the study at the end of the Introduction.

The aims were added.

Point 03

“In 8 cases there was prior contact with allergen, in 42 cases there was potential contact.”

What do the authors mean by “potential contact”?

The term was changed to more precise.

Point 04

The Discussion is a patch of short literature reviews about different sub-subjects on allergy, without any discussion about the findings of the study.

The section was changed.

Point 05

“In world literature only a few reports about allergic reactions caused by osteosynthesis elements are known. On contrary titanium use is extremely common in modern medicine. This leads to a conclusion that allergic reactions reports should be regarded incidental.”

None of this is a conclusion of your study. Stick to the findings your study in order to write the conclusion.

The conclusions have been changed.

Point 06

“In our study it was found that titanium fixing elements as well as titanium dental implants do not cause allergic skin reactions.”

Dental implants?!?! I thought that your study was about bone fixation plates.

The conclusions have been rewritten.

Reviewer 3:

Introduction

This investigation is a paper that presents information for researchers in the field of allergy to titanium of dental implants. Titanium, used widely in implant dentistry, and maxilofacial surgery, was considered fully biocompatible. However, the frequency of reported allergic reactions to titanium increases. This afirmation is not showed in this section with evidence scientific by experimental and clinical studies. In fact, in this section only a reference is showed. The authors should include in the section recent studies of theses aspects of allergy in titanium devices.

Also, the aim of the study are not included.

The introduction was rewritten and the aim has been emphasized.

Materials and methods.

This section is not adequated. This study was designed to analyze the different the allergy among patients treated by itianum devices and control patients. The size of two samples is very diferent. The method for allergy assessment based in International Contact Dermatitis Research Group (ICDRG) recommendations is not referenced in the text.

The ICDGR scoring explanation has been added.

Results.

The allergic reaction is triggered when the repeated exposure happens. In 8 cases there was prior contact with allergen, in 42 cases there was potential contact. None of the patients was allergic to titanium or its compounds. Only one patient had positive patch test for silver nitrate.

Surgical complications and allergy symptoms are presented togheter in one table. This presentation is incorrect because suggests confussion of findings.

The table bas been corrected.

Discussion

Most of this section must be changed to introduction. The authors not presented a discussion of the clinical findings of the study.

The parts of text were moved to introduction and the discussion has been rewritten.

Conclusions.

This section is not adequated according to the paper. The first two lines are aspects of introduction. The conclusions only must be related with main aspects of the paper.

 The conclusions section is rewrtitten.

References. This section must be revised. Some references are written with capital letters. Only 6 references (18.7%) are of the last 5 years.

 New references added.

Conclusively, the study is not ready for publication 

Author Response File: Author Response.pdf

Reviewer 3 Report

Abstract. This section is adequated and show the summary of the paper.

Introduction.

This investigation is a paper that presents information for researchers in the field of allergy to titanium of dental implants. Titanium, used widely in implant dentistry, and maxilofacial surgery, was considered fully biocompatible. However, the frequency of reported allergic reactions to titanium increases. This afirmation is not showed in this section with evidence scientific by experimental and clinical studies. In fact, in this section only a reference is showed. The authors should include in the section recent studies of theses aspects of allergy in titanium devices.

Also, the aim of the study are not included.

Materials and methods.

This section is not adequated. This study was designed to analyze the different the allergy among patients treated by itianum devices and control patients. The size of two samples is very diferent. The method for allergy assessment based in International Contact Dermatitis Research Group (ICDRG) recommendations is not referenced in the text.

Results.

The allergic reaction is triggered when the repeated exposure happens. In 8 cases there was prior contact with allergen, in 42 cases there was potential contact. None of the patients was allergic to titanium or its compounds. Only one patient had positive patch test for silver nitrate.

Surgical complications and allergy symptoms are presented togheter in one table. This presentation is incorrect because suggests confussion of findings.

Discussion

Most of this section must be changed to introduction. The authors not presented a discussion of the clinical findings of the study.

Conclusions.

This section is not adequated according to the paper. The first two lines are aspects of introduction. The conclusions only must be related with main aspects of the paper.

References. This section must be revised. Some references are written with capital letters. Only 6 references (18.7%) are of the last 5 years.

Conclusively, the study is not ready for publication 

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate the time and effort that you dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions to the revised manuscript. Those changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

The authors aimed to answer the question whether titanium devices used in the treatment of fractures in the craniofacial region can cause allergic reactions. The study comprised 50 subjects treated  surgically for maxillofacial injuries with the use of titanium composite devices. In addition, allergic tests were performed by the patch method.

The study covers some issues that have been overlooked in other similar topics. The structure of the manuscript appears adequate and well divided in the sections. Overall, the manuscript was written in good English and easy to understand and follow. Some of the comments that would improve the overall quality of the study are:

1-) Introduction section: Please better describe the aim of the work;

The aim has been emphasized in introduction.

2-) Inclusion/exclusion criteria: will be useful for the readers to group the same in a table, removing from the text.

We provided the table.

3-) Add limitation of the study in the discussion section;

The limitations have been discussed now.

4-) Conclusion Section: This paragraph required a general revision to eliminate redundant sentences and to add some "take-home message";

Conclusion is rewritten.

5-) Please also check typos thorough the text.

Reviewer 2:

Point 01

The following sentences need at least one reference each, in order to back up their statements, otherwise they would be mere assumptions made by the authors:

“Allergic reaction usually occurs from minutes up to 72 hours after repeated contact with an allergen.”

“Despite allergic contact dermatitis (ACD) rarely constitutes severe medical condition it may seriously decrease the quality of life.”

“Manifestations of ACD include regional skin and mucosal lesions which may by accompanied by asthmatic conditions.”

“Manifestations of Allergic Contact Stomatitis (ACS) include erythematous plaques, vesiculation, ulceration, hyperkeratosis or lichenoid reactions which are frequently accompanied by subjective symptoms such as burning sensation or itchiness, pain, and edema.”

“Seldom the lesions extend beyond the oral cavity involving the facial skin and rest of the body resembling the ACD.”

“Many of the materials used in medicine, both metallic and non-metallic, are considered to be associated with elevated risk of allergy. Chromium, nickel, palladium, copper, acrylic compounds are known potential allergens.”

“Titanium, used widely in dentistry, craniofacial surgery, and orthopedics, was considered fully biocompatible.”

“However, the frequency of reported allergic reactions to titanium increases.”

“Usually in medical applications Grade IV titanium is used, which is composed of titanium, iron, carbon, oxygen, and nitrogen. Also, titanium alloys containing vanadium, nickel, aluminum, molybdenum, thallium, and niobium.”

“Titanium use is in medicine is increasing therefore practitioners of different specialties approach the patients equipped with titanium implants in everyday practice.”

“Nowadays the open reduction and internal fixation (ORIF) with the aid of titanium hardware is the gold standard for maxillofacial fractures treatment.”

“There is lack of evidence regarding the influence of allergic reactions to titanium on the bone fracture healing process.”

“As a result of advancements in casting and metallurgy and chemical industry development the titanium is more often present in paints, dyes, photocatalysts and other ordinary items.”

“This combined with the more frequent use of titanium in medicine can increase the incidence of titanium allergic reactions.”

 The introduction has been rewritten with proper references.

Point 02

The authors need to write the aims of the study at the end of the Introduction.

The aims were added.

Point 03

“In 8 cases there was prior contact with allergen, in 42 cases there was potential contact.”

What do the authors mean by “potential contact”?

The term was changed to more precise.

Point 04

The Discussion is a patch of short literature reviews about different sub-subjects on allergy, without any discussion about the findings of the study.

The section was changed.

Point 05

“In world literature only a few reports about allergic reactions caused by osteosynthesis elements are known. On contrary titanium use is extremely common in modern medicine. This leads to a conclusion that allergic reactions reports should be regarded incidental.”

None of this is a conclusion of your study. Stick to the findings your study in order to write the conclusion.

The conclusions have been changed.

Point 06

“In our study it was found that titanium fixing elements as well as titanium dental implants do not cause allergic skin reactions.”

Dental implants?!?! I thought that your study was about bone fixation plates.

The conclusions have been rewritten.

Reviewer 3:

Introduction

This investigation is a paper that presents information for researchers in the field of allergy to titanium of dental implants. Titanium, used widely in implant dentistry, and maxilofacial surgery, was considered fully biocompatible. However, the frequency of reported allergic reactions to titanium increases. This afirmation is not showed in this section with evidence scientific by experimental and clinical studies. In fact, in this section only a reference is showed. The authors should include in the section recent studies of theses aspects of allergy in titanium devices.

Also, the aim of the study are not included.

The introduction was rewritten and the aim has been emphasized.

Materials and methods.

This section is not adequated. This study was designed to analyze the different the allergy among patients treated by itianum devices and control patients. The size of two samples is very diferent. The method for allergy assessment based in International Contact Dermatitis Research Group (ICDRG) recommendations is not referenced in the text.

The ICDGR scoring explanation has been added.

Results.

The allergic reaction is triggered when the repeated exposure happens. In 8 cases there was prior contact with allergen, in 42 cases there was potential contact. None of the patients was allergic to titanium or its compounds. Only one patient had positive patch test for silver nitrate.

Surgical complications and allergy symptoms are presented togheter in one table. This presentation is incorrect because suggests confussion of findings.

The table bas been corrected.

Discussion

Most of this section must be changed to introduction. The authors not presented a discussion of the clinical findings of the study.

The parts of text were moved to introduction and the discussion has been rewritten.

Conclusions.

This section is not adequated according to the paper. The first two lines are aspects of introduction. The conclusions only must be related with main aspects of the paper.

 The conclusions section is rewrtitten.

References. This section must be revised. Some references are written with capital letters. Only 6 references (18.7%) are of the last 5 years.

 New references added.

Conclusively, the study is not ready for publication 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The manuscript now seems to be suitable for publication.

Reviewer 3 Report

The review of the paper is correct