Fixed Drug Eruption Due to Doxycycline Postexposure Prophylaxis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

                                                                    

Although the report highlights doxycycline's increasing usage as postexposure prophylaxis (PEP) for sexually transmitted infections (STIs) and the emergence of fixed drug eruptions (FDE) as a notable adverse reaction it needs a clearer presentation and correction of certain aspects to improve its clarity and structure. Firstly, it should be more explicitly stated that fixed drug eruption (FDE) is a Type B adverse reaction, which is classified as a cutaneous drug reaction. This is important for understanding the nature of the adverse event in relation to the broader category of drug reactions.

Additionally, the pathogenic mechanisms of FDE should be briefly described to offer the reader a better understanding of how this reaction occurs and the possibility of cross-reactivity between different tetracyclines, as mentioned in the introduction.

The description of the case itself is somewhat unclear, especially regarding the chronology of events and the duration of doxycycline treatment. The timeline of when the patient began the treatment, how long the treatment lasted, when the lesions appeared, and how they progressed over time should be more clearly outlined to avoid confusion.

Furthermore, it is important to clarify whether an allergy work-up was performed, such as patch testing or drug provocation testing. This would help confirm the diagnosis and assess cross-reactivity with other tetracyclines. If such tests were not conducted, a stronger emphasis should be placed on the clinical presentation that supports the diagnosis of FDE.

 

 

 

Author Response

Thank you for your comments. 

We added your recommended text on Type B adverse reaction. It was inserted on line 71 of the attached file. "Fixed drug eruptions (FDE) are Type B adverse reactions, which is classified as a cutaneous drug reaction." 

The mechanism of FDE was included as recommended on line 72-77. 

"FDE are due to the migration and activation of CD8+ T cells in the epidermis. The resulting activation of the T cells induce cytokine (interferon-gamma and TNF-alpha) expression and adopt natural killer cell activity in addition to increasing expression of other cytotoxic molecules (cell surface molecule CD56, granzyme B, and perforin) in the epidermis.[12] These responses cause the epidermal necrosis seen in FDE." 

The chronology of the case was re-works to improve clarity. This can be see on line 115 to 211 of the attached document. 

The updated report includes an expanded clinical presentation paragraph found on line 178-184, and reasoning why at confirmation test was not done on lines 189-194.

 

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

1.     Overall a well written case report and ROL.

However-

The authors mention that ‘The patient stopped taking doxycycline, but the eruption has been slow to re solve. This starkly contrasts with other case reports, where eruptions become substantially better after discontinuing the causative agent.[12, 23]’

This statement is subjective, without providing exact  duration to recovery. Also FDEs may take days to weeks to resolve, the time to recovery is variable and  hyperpigmentation may persist even longer. (Yim S, Abu-Hilal M. Fixed Drug Eruption. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook-sae/chapter/B78.II.856.2.?rfmcm Accessed November 02, 2024.)

It is not clear whether in the index case it is the hyperpigmentation which is persisting.

2.     In the discussion, it seems the authors are suggesting restricting the use of doxycycline due to the potential to cause FDEs. This seems unreasonable as the authors themselves state that ‘The actual rate of fixed drug eruptions associated within the class of tetracyclines is unknown. Doxycycline has the fewest case reports of dermatological adverse effects among the tetracyclines’.

Definitely an increased awareness of avoiding re-use of any drug which has caused an FDE is required both among prescribers and patients, but a potential FDE, the incidence of which is unknown and probably rare as per the authors themselves, seems an inappropriate reason to avoid the use of a drug.

Author Response

Thank you for your comments. 

We updated the submission with your recommendations. We added your recommended text and reference, which can be seen on line 193-194.

We clarified that the hyperpigmentation persisted for greater than 6 months online 186-187.

In the discussion, we updated the language discussing the rate of FDE on line 451-453.