Endometriosis as a Differential Diagnosis in a 17-Year-Old Patient with Low Back and Radicular Pain: A Case Report

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I would like to thank the Editors of Women for the opportunity to review this manuscript. The topic is clinically relevant and timely, addressing an important issue in women’s health. Below, I provide specific comments aimed at improving the clarity, scientific rigor, and clinical relevance of the article.

General Comments:

• The manuscript lacks affiliation information.

• References are not numbered, which makes it difficult to follow citations and verify sources.

Introduction:

• The statement “During menstruation, the ectopic endometrial tissue also bleeds, but since the blood has no way of being expelled, it causes pain [2]” oversimplifies the complex pathophysiology of endometriosis-associated pain. Please elaborate.

• The sentence “However, endometriosis is often misdiagnosed, as its symptoms are frequently dismissed or normalized [2]” provides only one explanation. Misdiagnosis may also result from the nonspecific nature of symptoms, lack of awareness, and limitations in diagnostic methods etc. Please expand this discussion.

• The Introduction could be more concise. For instance, the final paragraph largely repeats points made earlier (with the exception of the mention of low back pain).

Case Presentation:

• Please specify the onset of symptoms such as dysmenorrhea and dyspareunia.

• Which combined oral contraceptive (COC) was prescribed? Was it administered cyclically or continuously?

Discussion:

• The second paragraph repeats information from the Case Presentation and should be removed.

• Please include a discussion on the role of hormonal treatment. It is important to highlight that, according to the latest ESHRE guidelines, histological confirmation of endometriosis is no longer required to initiate hormonal therapy. This is especially relevant for young patients.

• The discussion would benefit from a more in-depth consideration of appropriate hormonal management. For reference, you may consult this recent narrative review: doi: 10.3390/ph18040588; PMID: 40284023; PMCID: PMC12030075.

• Please expand on the prevalence and significance of endometriosis in adolescence, and the need for timely diagnosis and management.

Summary:
This case report addresses a clinically important topic. Although it does not present novel findings, it draws attention to three key aspects:

1. The occurrence of endometriosis with severe symptoms in adolescence,

2. The value of a multidisciplinary approach, and

3. The importance of selecting the appropriate hormonal treatment.

Recommendation:
Major revision is recommended. Please refer to the comments above.

Author Response

Comment 1 general: The manuscript lacks affiliation information. References are not numbered, which makes it difficult to follow citations and verify sources.

Response 1: affiliation are now included. References are now numbered.

Comment 2 Introduction:

Response 2: 

1. Endometriotic cells exhibit a high survival potential and their activity outside the perineum is due to several key factors; this include the expression of anti-apoptotic genes, immune evasion characterized by impaired natural killer (NK) cell activity [²], uncontrolled angiogenesis and hormonal imbalances, particularly estrogen dominance and resistance to progesterone. In addition, inflammation plays a crucial role, with activated macrophages contributing to nerve sensitization and releasing elevated levels of cytokines associated with pain [^1,2,5]. Another source of pain arises from the fact that ectopic endometrial tissue behaves like normal endometrium, therefore, during menstruation this tissue also bleeds, but since the blood has no way of being expelled, it leads to pain [⁶].
2. The absence of pathognomonic symptoms significantly contributes to delayed or missed diagnoses [⁵]. Moreover, the condition may remain clinically silent for prolonged periods, further complicating timely detection and management [⁵]. [...] The delay in diagnosis is also due to the lack of non-invasive methods for its detection.
3. Introduction has been modified.

Comment 3 case presentation: 

Response 3 

1. the patient reported a history of dysmenorrhea since menarche, which occurred at age 11,  and dyspareunia since the onset of sexual activity.
2. She had been continuously on oral contraceptives for approximately one year, with a pill that contained nomegestrol acetate (a progestin) and estradiol (an estrogen)

Comment 4 discussion

Response 4

1. The second paragraph has been removed
2. Currently, the gold standard for the treatment of endometriosis is hormone therapy, as the condition is estrogen dependent. Hormonal treatment can be started in young women when endometriosis is suspected, even prior to surgical confirmation [²⁹]. This treatment has demonstrated excellent results in reduction in symptoms, particularly pain, without influencing disease progression. Various types of hormone therapies are available and should be selected based on the individual characteristics of each patient. Continuous hormone therapy has been shown to be more effective than cyclic regimens [²⁹]. Combined oral contraceptives are typically used as first-line therapy, as they help stabilize hormone levels and reduce prostaglandin production. Oral progestins are also used for long-term management due to their low incidence of side effects and their anti-inflammatory effect and consequently pain reduction. However, caution is advised when prescribing oral progestins to adolescents, as they may cause temporary reductions in bone density. Gonadotropin-releasing hormone (GnRH) are limited to short-term use because of significant side effects, including hot flashes and bone loss, particularly at higher doses [^29,43]. When hormone therapy is unsuccessful, surgical intervention becomes necessary. 
3. see point 2.
4. Early detection of endometriosis is crucial, particularly in adolescents, despite the diagnostic challenges. Endometriosis in adolescents with pelvic pain is very common [⁴⁰], often presenting with varied and nonspecific symptoms, which contributes to its frequent under-recognition [²⁴]. Prompt diagnosis is essential to prevent disease progression and reduce the risk of future infertility. [⁴¹]

Comment 5 summary

Response 5

Reviewer 2 Report

Comments and Suggestions for Authors

This case presents an important reminder of the need for a thorough differential diagnosis in adolescents and young adults, particularly as they transition through puberty. The clinical picture reinforces the complexity of overlapping symptoms during this developmental stage and underscores the need for vigilance in distinguishing between physiological and pathological presentations.

 

I would like to raise a broader point about extending similar diagnostic considerations to children who have reached puberty or begun menarche, as early-onset symptoms may often be misattributed to hormonal changes rather than investigated further.

 

To strengthen the case, it would have been valuable to include data on the patient’s diet, exercise habits, and mood or psychosocial wellbeing. These factors can significantly influence clinical presentation and may have provided further context for the diagnosis, management approach, or potential differential considerations also family history.

Comments on the Quality of English Language

Fine. 

Author Response

Comment 1 I would like to raise a broader point about extending similar diagnostic considerations...

Response 1 An example of lack of correct diagnosis could be Polycystic ovary syndrome (PCOS),that is one of the most common endocrine disorders in women of reproductive age, after menarche. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS.

Meczekalski B, Niwczyk O, Kostrzak A, Maciejewska-Jeske M, Bala G, Szeliga A. PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment. J Clin Med. 2023 Feb 3;12(3):1221. doi: 10.3390/jcm12031221. PMID: 36769869; PMCID: PMC9918268.

Comment 2 To strengthen the case, it would have been valuable to include data on the patient’s diet, exercise habits, and mood or psychosocial wellbeing...

Response 2 The patient led an active lifestyle; she attended school regularly and she went to the gym and she went swimming; she also had healthy eating habits and a regular diet. 

Reviewer 3 Report

Comments and Suggestions for Authors

General assessment

This case report talks about a teenage girl who had endometriosis that showed up as lower back and nerve pain—something doctors don’t usually expect. It shows how important it is for healthcare providers to think about all possible causes when young patients have ongoing muscle or joint pain, especially if regular treatments like physiotherapy don’t help. The report is clearly written and tells the patient’s story well, but it could be better if it gave more details about how the diagnosis was made, what the nerve tests showed, and how the patient responded to treatment. Overall, it’s a strong and helpful report that just needs a few small changes to make it even clearer and more useful.

 

Major Comments
1. The diagnosis of endometriosis is a key moment in this case, but the report does not explain clearly how this diagnosis was made. It would be helpful to include more details about what tests or procedures were done at the specialist clinic. For example, did they use imaging tests like an MRI or ultrasound? Was a laparoscopy (a minor surgery used to look inside the abdomen) performed to confirm the diagnosis? What did the physical examination show? Including this information would make the case more complete and give doctors a better understanding of how endometriosis can be identified, especially when it shows up in unusual ways like back or nerve pain. This would also help other healthcare providers recognize similar cases in their own practice.

 

2. I also noticed an inconsistency with the references. In the main text, the references are numbered (e.g., 1, 2, 3), but in the reference list at the end, they are listed by the authors' names instead of corresponding numbers. This creates confusion because the reader expects to see the numbered references match the citations in the text. To improve clarity and consistency, the reference list should be formatted to match the citation style used in the text, either by using numbers or by reformatting the in-text citations to match the author-date format, depending on the preferred citation style (such as APA, Vancouver, etc.). This will make it easier for readers to follow and verify the sources.

 

Minor Comments

1. Grammatical/Language/Clarity: I observed several grammatical and stylistic issues throughout the manuscript. For instance, in the abstract section, line 4, the phrase "in presence of" is used. This could be improved by changing it to "in the presence of," which is more grammatically correct and sounds smoother. These small language adjustments will help improve the overall clarity and readability of the manuscript. Additionally, there are other similar instances where minor grammatical corrections could enhance the flow of the text and make it easier for readers to follow the ideas. Addressing these language issues will strengthen the manuscript and ensure it maintains a professional tone throughout.
2. In the case presentation, you mention that the patient "was evaluated by an Orthopaedic Manipulative Physical Therapist (OMPT) due to intense and disabling lower back pain." While this is accurate, I believe it would be more impactful and easier for a broader audience to understand if you take a moment to elaborate on what "Orthopaedic Manipulative Physical Therapist" means. Providing a brief explanation of OMPT, including what the role of this specialist is and how their approach differs from other types of physical therapy, would enhance the clarity of the case for readers who may not be familiar with the term. A few sentences explaining the techniques or methods used by OMPTs, such as manual therapy or joint mobilizations, could make the presentation more accessible and informative for both clinical and non-clinical readers.

I noticed that the first sentence in the treatment section starts with a lowercase letter. Specifically, the line "since the first session of physiotherapy, education of the patient was performed" should begin with a capital letter, as it is the start of a new sentence. Proper capitalization at the beginning of sentences is an important part of maintaining correct grammar and professional writing standards. I recommend correcting this to: "Since the first session of physiotherapy, education of the patient was performed." This small adjustment will improve the manuscript's overall clarity and adherence to standard writing conventions.

Author Response

Comment 1

Response 1: transvaginal ultrasound revealed endometriotic tissue on the uterosacral ligament that led to an adjustment in her hormonal therapy

Comment 2 

Response 2: references are now numbered correctly

Comment 3

Response 3: we have corrected the grammar and linguistic issues that we found.

Comment 4

Response 4: A OMPT is a specialized physiotherapist in the “management of neuro-musculoskeletal conditions, based on clinical reasoning, using highly specific treatment approaches including manual techniques and therapeutic exercises” 

OMPT Definition. https://www.ifompt.org/About+IFOMPT/OMPT+Definition.html 

Reviewer 4 Report

Comments and Suggestions for Authors

In this article, "Endometriosis as a DifferentialDiagnosis in a 17‐Year‐Old Patient withLow Back and Radicular Pain: A CaseReport" Vergara et al. presents the case of an adolescent girl diagnosed with endometriosis based on her musculoskeletal symptoms, including "lumbar and radicular pain."

This is a well-structured and detailed clinical case. Please see my comments below: 

Abstrac:t

• I recommend adding a sentence highlighting the clinical novelty or differential contribution of the case at the end of the abstract.

Discussion:

• The discussion could benefit from a more explicit comparison with other similar cases described in the literature, especially in adolescent population.
• The discussion should expand a little more and highlight in more detail the novelty of this case.

Language and style

• Revise style to eliminate slight redundancies (e.g., repeated use of “the patient reported...”), repeated use of cause ("...causes pain [2]. The exact cause of endometriosis remains unclear...")
• Missing some capital letters: Treatment section, " since the first session of physiotherapy.."

 

Author Response

Comment 1 abstract

Response 1: This case report highlights the importance of differential diagnosis in patients with LBP, as endometriosis can present not only in older women but also in younger patients, including those already being on oral contraceptives. Therefore, even outside of a preconception context, clinicians should remain aware of the possibility of endometriosis, despite it being less common.

Comment 2 discussion

Response 2 To date, no similar cases have been reported in the literature, highlighting the novelty of our case within the current scientific landscape. Nonetheless, existing studies do emphasize the association between endometriosis and LBP, as well as the need for a multimodal approach that includes medical support, physiotherapy, consideration of pain pathophysiology and potential genetic predisposition 

Artacho-Cordón F, Salinas-Asensio MDM, Galiano-Castillo N, Ocón-Hernández O, Peinado FM, Mundo-López A, Lozano-Lozano M, Álvarez-Salvago F, Arroyo-Morales M, Fernández-Lao C, Cantarero-Villanueva I. Effect of a Multimodal Supervised Therapeutic Exercise Program on Quality of Life, Pain, and Lumbopelvic Impairments in Women With Endometriosis Unresponsive to Conventional Therapy: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2023 Nov;104(11):1785-1795. doi: 10.1016/j.apmr.2023.06.020. Epub 2023 Jul 17. PMID: 37467936.

Shokri P, Zahmatyar M, Falah Tafti M, Fathy M, Rezaei Tolzali M, Ghaffari Jolfayi A, Nejadghaderi SA, Sullman MJM, Kolahi AA, Safiri S. Non-spinal low back pain: Global epidemiology, trends, and risk factors. Health Sci Rep. 2023 Sep 4;6(9):e1533. doi: 10.1002/hsr2.1533. PMID: 37674621; PMCID: PMC10477419.

Rahmioglu N, Mortlock S, Ghiasi M, Møller PL, Stefansdottir L, Galarneau G, Turman C, Danning R, Law MH, Sapkota Y, Christofidou P, Skarp S, Giri A, Banasik K, Krassowski M, Lepamets M, Marciniak B, Nõukas M, Perro D, Sliz E, Sobalska-Kwapis M, Thorleifsson G, Topbas-Selcuki NF, Vitonis A, Westergaard D, Arnadottir R, Burgdorf KS, Campbell A, Cheuk CSK, Clementi C, Cook J, De Vivo I, DiVasta A, Dorien O, Donoghue JF, Edwards T, Fontanillas P, Fung JN, Geirsson RT, Girling JE, Harkki P, Harris HR, Healey M, Heikinheimo O, Holdsworth-Carson S, Hostettler IC, Houlden H, Houshdaran S, Irwin JC, Jarvelin MR, Kamatani Y, Kennedy SH, Kepka E, Kettunen J, Kubo M, Kulig B, Kurra V, Laivuori H, Laufer MR, Lindgren CM, MacGregor S, Mangino M, Martin NG, Matalliotaki C, Matalliotakis M, Murray AD, Ndungu A, Nezhat C, Olsen CM, Opoku-Anane J, Padmanabhan S, Paranjpe M, Peters M, Polak G, Porteous DJ, Rabban J, Rexrode KM, Romanowicz H, Saare M, Saavalainen L, Schork AJ, Sen S, Shafrir AL, Siewierska-Górska A, Słomka M, Smith BH, Smolarz B, Szaflik T, Szyłło K, Takahashi A, Terry KL, Tomassetti C, Treloar SA, Vanhie A, Vincent K, Vo KC, Werring DJ, Zeggini E, Zervou MI; DBDS Genomic Consortium; FinnGen Study; FinnGen Endometriosis Taskforce; Celmatix Research Team; 23andMe Research Team; Adachi S, Buring JE, Ridker PM, D'Hooghe T, Goulielmos GN, Hapangama DK, Hayward C, Horne AW, Low SK, Martikainen H, Chasman DI, Rogers PAW, Saunders PT, Sirota M, Spector T, Strapagiel D, Tung JY, Whiteman DC, Giudice LC, Velez-Edwards DR, Uimari O, Kraft P, Salumets A, Nyholt DR, Mägi R, Stefansson K, Becker CM, Yurttas-Beim P, Steinthorsdottir V, Nyegaard M, Missmer SA, Montgomery GW, Morris AP, Zondervan KT. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023 Mar;55(3):423-436. doi: 10.1038/s41588-023-01323-z. Epub 2023 Mar 13. PMID: 36914876; PMCID: PMC10042257.

Comment 3 language

Response 3: we revised style and language

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I have no further comments. 

Author Response

Introduction: you can find the changes about pathophysiology in page 2, line 47-55; the explanation about misdiagnosis can be find in page 2 line 58-71, page 2 line 89-91, page 3 line 110-11 and line 112-117. 
Case Presentation: You can find the specification about the onset of symptoms in page 4, line 157-159; the discussion about COC in page 4, line 164-167.
Discussion: Second paragraph has been deleted; the discussion about hormonal treatment can be find in pages 6-7, line 256-273; the discussion about the significance in adolescents can be find in page 6, line 242-248. 

Reviewer 3 Report

Comments and Suggestions for Authors

This case report provides a valuable and well-documented account of adolescent endometriosis presenting as low back and radicular pain. It is clearly written, clinically relevant, and supported by proper citations/literature, and guidelines. The multidisciplinary approach and the physiotherapist’s role are well emphasized. The manuscript meets the standards for publication. I recommend acceptance in its present form.

Author Response

Diagnosis: you can find description about the diagnosis in the patient in page 5 line 216-218.

OMPT definition: The definition about OMPT can be find in page 3 line 135-137.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors have uploaded a revised version without indicating the changes that were made.
I reiterate that the Discussion section should clearly state what this case contributes in comparison to previously published similar cases. These cases do exist; a simple PubMed search easily retrieves several examples, including:

• Cricco C, Daugenti A, Angilecchia D, Ceron D. Differential diagnosis of endometriosis in a patient with nonspecific low back pain: A case report. J Bodyw Mov Ther. 2021 Jul;27:227-232. doi: 10.1016/j.jbmt.2021.02.019. Epub 2021 Mar 5. PMID: 34391238.

• Troyer MR. Differential diagnosis of endometriosis in a young adult woman with nonspecific low back pain. Phys Ther. 2007 Jun;87(6):801-10. doi: 10.2522/ptj.20060141. Epub 2007 Apr 18. PMID: 17442838.

Furthermore, the English language still requires professional editing to meet the standards expected in a scientific publication

Comments on the Quality of English Language

The English language still requires professional editing to meet the standards expected in a scientific publication

Author Response

The abstract has been modified. 
You can find a comparison with other similar cases and the novelty of this case report in page 7, line 278-282.

Round 3

Reviewer 4 Report

Comments and Suggestions for Authors

The use of English continues to need review by a native speaker or specialist, although it has improved over previous revisions.

Added changes are still not noted in the text.