Case Report: Concomitant presence of two STIs in a male patient

Background The spirochaete Treponema pallidum subsp. pallidum, which causes the infectious disease syphilis, can be spread through sexual contact or perinatal transmission. In recent years, cases of syphilis have increased, especially among individuals engaging in behaviour that makes them more vulnerable (condomless sex and multiple sexual partners). Condylomata acuminata (external genital warts) is one of the most common viral sexually transmitted infections (STIs). Individuals who are behaviourally vulnerable are also highly prone to two or more STIs. Our case exemplifies the occurrence of two STIs in a young man who was behaviourally vulnerable to acquiring STIs. Case We report a case of a 21-year-old year old heterosexual man presenting with concomitant primary syphilis and genital warts. He presented with a painless genital ulcer and warty growths on his glans penis. Examination showed a painless indurated ulcer and multiple genital warts. Serology was positive for quantitative Venereal disease research laboratory test (1:16 titre). The patient was diagnosed with two concomitant STIs. He was treated as per the latest Centers for Disease Control and Prevention (CDC) guidelines for primary syphilis and podophyllin resin for genital warts. After four weeks, the genital ulcer showed complete healing and there was a significant reduction of genital warts. Conclusions Individuals with multiple sexual partners engaging in sexual activity without the use of prevention tools are at a greater chance of acquiring two or more STIs. To reduce concomitant transmission, preventive measures against genital ulcer diseases like syphilis, herpes, and chancroid, such as early identification and treatment, and condom distribution, must be strengthened as part of national STI prevention. Patients with two or more STIs should be followed regularly to assess the progress of infection and should be offered timely medical treatment.


Introduction
Genital ulcer diseases (GUDs) are breaks in the skin and mucosal continuity in the genital and perigenital region, usually resulting from sexually transmitted infections (STIs).Syphilis is a multisystemic, multistage, chronic illness with a varied prognosis and myriad of clinical presentations. 1 Anogenital warts, are also called condyloma acuminata, are one of the most common STIs in the developed world, with a frequency of 2.4 infections per 1,000 people per year. 2,3Individuals engaging in behaviour that makes them more vulnerable (sex without the use of prevention tools and multiple sexual partners) are at increased likelihood of acquiring two or more STIs.Presence of one STI increases the likelihood for acquiring another STI and our case exemplifies the aforementioned phenomenon.Our case presented with two concomitant STIs, one being bacterial and the other being viral in aetiology.

Case report
A 21-year-old male resident of Central India studying at a local college presented to the Dermatology Outpatient Department of the Datta Meghe Institute of Higher Education and Research affiliated tertiary care teaching hospital at Sawangi, Wardha, Maharashtra with complaints of a painless genital ulcer and warty growths on his penis.He reported that the warty lesions had been present for the past two months and the ulcerative lesion appeared three weeks ago.Detailed sexual history revealed regular, penile-vaginal intercourse without the use of prevention tools with sex workers (SWs) for the past six months in his home town, with the last occurrence being approximately four weeks before he presented to our hospital.His general physical examination was within normal limits.There was no history of burning micturition and pus discharge through the urethra.There was a single, painless, indurated ulcer of 3Â3 cm in size with rolled edges and minimal discharge on the penis at the coronal sulcus (Figure 1).Glans penis showed cauliflower floretlike growths on the coronal sulcus and sub-preputial area of the penis (Figure 2).There was no regional lymphadenopathy.Detailed muco-cutaneous examination of the oral cavity, perianal area and palms and soles were normal.The quantitative Venereal Disease Research Laboratories (VDRL) test was reactive in the titre of 1:16, however the test for treponema pallidum haemagglutination (TPHA) was non-reactive.Serological tests for hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV) were negative.On the basis of sexual history, temporal relation, clinical examination and serology, we made a diagnosis of concomitant STIs of primary syphilis and genital warts.
We treated the patient with office-based topical application of podophyllin resin (20% w/v) in benzoin (10% w/v) on the genital warts, while the surrounding healthy skin area was protected with petrolatum.Applications were carried out every 10 days until complete clearance of warty lesions.Primary syphilis was treated with a two intramuscular injection of benzathine penicillin (2.4 million units, 1.2 million units in each buttock) after the sensitivity test.Contact tracing is being attempted for the sexual partners for the past three months.On a follow-up visit, the lesion of primary syphilis and genital warts had completely resolved (Figure 3).

REVISED Amendments from Version 1
There are some minor grammatical corrections in the manuscript.
Any further responses from the reviewers can be found at the end of the article Discussion Syphilis is a disease caused by the bacteria Treponema pallidum that has a myriad of clinical presentations and is referred to as a "great mimicker" in clinical medicine.5][6][7] Wu et al., 7 conducted a study where it was found that there is a higher prevalence of syphilis  among individuals living with HIV, especially among men who have sex with men.The presence of one STI increases the likelihood that the individual will acquire another STI.The presence of genital ulcer disease increases the risk of acquiring HIV due to mucosal damage and the pool of inflammatory cells at the site of ulcers. 7 a study by Kops et al., it was shown that there are higher chances of acquiring human papilloma virus (HPV) if an individual has an STI. 6A history of prior STI leads to decreased clearance of HPV load and provides an easy access for viral entry into the damaged epithelial barrier.The various factors associated with increased likelihood of concomitant STIs are smoking, substance use disorder and men having sex with men. 7e presence of concomitant STIs suggests the person is behaviourally vulnerable.Individuals with multiple STIs should be investigated for the presence of other venereal transmitted diseases, particularly HIV and hepatitis B virus infection, and appropriate laboratory work-up should be done to confirm the diagnosis.
The primary take-away lesson from our case is as follows: individuals with multiple sexual partners and involved in sexual activity without the use of prevention tools are at greater chance of acquiring two or more STIs.Attempts should be made to perform partner tracing of such cases and individuals should be offered counselling and appropriate medical management.Patients with two or more STIs should be followed regularly to assess the progress of infection and should be offered timely medical treatment.
2) Did you repeat the TPHA later to confirm the diagnosis or to see the disease development after treatment?Were any serological tests repeated during follow-up?

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes

Is the case presented with sufficient detail to be useful for other practitioners? Yes
Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Treponemes, treponematic diseases
We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Electra Nicolaidou
1st Department of Dermatology and Venereology, National and Kapodistrian University of Athens, Athens, Greece Thank you for answering most of my comments.The first comment, however, as well as the 6th, were not followed by changes in the text.The authors may want to explain to the readers why the used podophillin for the treatment of genital warts even though it is not the most appropiate treatment, according to the guidelines.

Is the case presented with sufficient detail to be useful for other practitioners? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: I am a dermatologist-venereologist with a special interest in sexually transmitted infections, psoriasis and vitiligo.

San Gallicano Dermatological Institute IRCCS, Rome, Italy
The paper, Concomitant presence of two STIs in a male patient, by Rusia K et al describes the case of a young heterosexual student who presents with two sexually transmitted infections at the same time as ghenital warts and syphilis.The AA underline how condylomatosis is very common in sexually active young people while the epidemiology of syphilis describes higher prevalence curves in MSM and people with HIV infection.The case is well described and documented, the diagnostic and therapeutic process well described.The message that emerges is that syphilis should always be considered in the presence of another STI such as condylomatosis, even if genital warts have notoriously a high incidence in the general population.The authors also highlight the importance of HIV testing and contact tracing in at risk patients.(Ref-1).According to the ECDC, a large proportion of syphilis diagnoses in 2022 has been reported in subjects aged 45 years or older.However, while data on increasing STI rates among men who have sex with men have been increasingly reported, a scarce attention has been paid to populations with a lower sexual risk, such as heterosexual individuals.
This paper considers the risk of syphilis in a heterosexual patient in line with the most recent epidemiological considerations.This is a well written case report of a patient presenting with two concomitant STIs, syphilis and genital warts, that were typical in clinical appearance and responded well to treatment.The case is well presented.My comments are as follows: 1)The patient was treated according to the CDC guidelines for syphilis, but these guidelines were not followed for the treatment of genital warts.These guidelines state that "podophyllin resin is no longer a recommended regimen because of the number of safer regimens available" and that "the area to which treatment is administered should not contain any open lesions, wounds of friable tissue".So, the authors may want to explain why they used this treatment for the genital warts, especially in a patient with an ulcer surrounding part of the warts.2)Abstract, Background: MSMs have high rates of syphilis because they often engage in behavior that makes them more vulnerable, so there is no need to refer to them separately.3) Abstract, Background: "be exposed to one or more STIs" could be changed to "two or more STIs" 4) Abstract, Case: "quantitative serological disease research laboratory test" could be changed to "quantitative Venereal disease research laboratory test" 5) Abstract, Conclusions: Human papillomavirus is not correctly spelled and it does not cause genital ulcer diseases 6) Introduction: Anogenital warts are also called condylomata acuminata (not condyloma acuminatum, which is singular number) 7) Case report: "Primary syphilis was treated with a single intramuscular injection..." It is actually two injections, not a single one, as it is correctly described by the authors in the brackets.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes Is the case presented with sufficient detail to be useful for other practitioners?Yes Competing Interests: No competing interests were disclosed.
Reviewer Expertise: I am a dermatologist-venereologist with a special interest in sexually transmitted infections, psoriasis and vitiligo.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Figure 1 .
Figure 1.A single clean ulcer on the coronal sulcus.

Figure 2 .
Figure 2. Whitish pink growth on the coronal sulcus.

Figure 3 .
Figure 3. Resolution of genital ulcer and wart after receiving single dose of injectable benzathine penicillin and after application of podophyllin resin at day 30.

Reviewer Report 03
July 2024 https://doi.org/10.5256/f1000research.167723.r290390© 2024 Nicolaidou E. This is an open access peer review report under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

References 1 .
STI cases on the rise across Europ.European Centre for Disease Prevention and Control.Reference Source Is the background of the case's history and progression described in sufficient detail?Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes Is the case presented with sufficient detail to be useful for other practitioners?Yes Competing Interests: No competing interests were disclosed.Reviewer Expertise: STIs I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.Reviewer Report 15 February 2024 https://doi.org/10.5256/f1000research.147742.r235347© 2024 Nicolaidou E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Electra Nicolaidou 1st Department of Dermatology and Venereology, National and Kapodistrian University of Athens, Athens, Greece