Inflammatory diseases of the scrotum: clinical guidelines

List of Abbreviations

HIV – human immunodeficiency virus.

WHO – World Health Organization.

ICD-10 – International Classification of Diseases 10th Revision.

PCR – polymerase chain reaction.

US – ultrasound.

NAAT – nucleic acid amplification test.

STI – sexually transmitted infection.

UTI – urinary tract infection.

LUTS – lower urinary tract symptoms.

AFB – acid-fast bacilli.

DNA – deoxyribonucleic acid

РКИ – randomized controlled trial

CDU – color Doppler ultrasonography.

Terms and Definitions

Epididymitis is inflammation of the epididymis that develops most frequently due to ascending spread of infection from the urethra or via hematogenous spread as a complication of infectious diseases.

Orchitis is inflammation of the testicular parenchyma.

Epididymo-orchitis is inflammation of the epididymis and testicle that develops most frequently due to ascending spread of infection from the urethra or via hematogenous spread as a complication of infectious diseases.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Epididymitis is inflammation of the epididymis that develops most frequently due to ascending spread of infection from the urethra or via hematogenous spread as a complication of infectious diseases [1].

Orchitis is inflammation of the testicular parenchyma.

Often, with ascending infection, simultaneous involvement of both the epididymis and the testicle itself occurs. In such cases, the condition is described as epididymo-orchitis.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Epididymitis is typically caused by the migration of pathogens from the urethra or urinary bladder, which can be identified using appropriate diagnostics in 90% of patients.

The predominant isolated pathogens are C. trachomatis and N. gonorrhoeae [2]. Men with urinary tract anomalies, recent or recurrent urinary tract infections, urinary tract obstruction, or recent surgery and/or endoscopic urinary tract therapies leading to bacteriuria are at a higher risk of epididymitis caused by enteric bacteria, Enterobacteriaceae (usually E. coli) [2,3].

Mumps virus should be suspected in the presence of viral prodromal symptoms and salivary gland enlargement.

Tuberculous epididymitis typically presents as chronic epididymitis in high-risk groups, such as immunocompromised men and individuals from high-prevalence countries.

Hematogenous orchitis occurs in mumps and brucellosis, typhoid fever, influenza, and streptococcal infections.

1.3 Epidemiology of the Disease or Condition

Epididymitis is a common condition with an incidence rate ranging from 25 to 65 cases per 10,000 adult males per year [4].

1.4 Features of Coding the Disease or Condition

N49.2 – Inflammatory disorders of scrotum

N45.0 – Orchitis, epididymitis and epididymo-orchitis with abscess (testicular and epididymal abscess)

N45.9 – Orchitis, epididymitis and epididymo-orchitis without mention of abscess

1.5 Classification of the disease or condition

Depending on the localization of the process, unilateral and bilateral epididymo-orchitis are distinguished.

Acute (lasting up to 6 weeks) and chronic (lasting more than 6 weeks) epididymo-orchitis are distinguished [5].

Based on the etiological factor, infectious and non-infectious (e.g., trauma, cancer, autoimmune or idiopathic conditions) epididymo-orchitis are distinguished.

Based on the nature of the infectious agent, the following types of epididymo-orchitis are distinguished [6]:

• Chlamydial

• Mycoplasmal

• Trichomonal

• Bacterial

• Viral meningitis

• Gonococcal

• Tuberculous

1.6 Clinical presentation of the disease or condition

Acute epididymitis is clinically characterized by pain, swelling, and increased temperature of the epididymis, and the testes and scrotal skin may also be involved.

The acute form of epididymo-orchitis begins suddenly with rapidly progressive enlargement of the epididymis or testis itself, sharp pain in it, and a rise in body temperature up to 38-40 °C. Inflammation and edema extend to the testicular tunics and scrotum [7]. Pain may radiate to the inguinal region and sometimes to the lumbar region, markedly intensifying with movement. Urethral discharge or dysuria may also be observed [8]

Tuberculous epididymo-orchitis presents with a subacute/more chronic onset, painless/painful scrotal swelling, systemic symptoms, and thickening of the scrotal skin [9].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Introduction to the section. Diagnostics aims to: determine the localization and causative agent of the disease; rule out other conditions that may present with similar symptoms.

Criteria for establishing the diagnosis/condition: The diagnosis of epididymo-orchitis is established based on characteristic symptoms, ultrasound signs of inflammation in the epididymis and/or testis, and the detection of pathogenic microorganisms in the first portion of urine, ejaculate, or urethral swab.

Comments: spermatic cord torsion (testicular torsion) is a crucial differential diagnosis regardless of the patient's age. Testicular torsion is more characteristic of the following situations:

· Patient younger than 20 years (though it can occur at any age)

· Severe sudden pain (developing within a few hours)

· Preliminary tests do not show urethritis or a likely urinary tract infection [10,11].

Differential diagnosis must be performed with other vascular disorders, as well as trauma to the testis and epididymis.

2.1 Complaints and Anamnesis

Comments: historically, STIs were considered the predominant cause of epididymitis in the < 35 age group, and enteric pathogens in the > 35 age group. Evidence supporting this approach is limited, and age and sexual history are insufficient for selecting antibacterial therapy [1]

2.2 Physical Examination

Comments: upon examination of the scrotum, loss of scrotal skin rugosity, hyperemia, and tenderness on palpation may be noted.

2.3 Laboratory Diagnostics

Comments: the first morning portion of urine or a urethral swab is best used for analysis. The method of choice is NAAT [13].

Comments: standard urine culture has low sensitivity for the main etiological microorganisms. However, the presence of nitrites and leukocyte esterase may indicate a UTI in patients with concomitant LUTS. At the same time, it must be taken into account that a normal urinalysis and negative urine culture do not exclude the diagnosis of epididymo-orchitis [16,17].

Comments: identification of Mycobacterium tuberculosis in urine using PCR is a highly sensitive and specific diagnostic method for urogenital tuberculosis. Compared to culture, PCR showed a sensitivity of 95.6% and a specificity of 98.1% [18,19]. Compared to bacteriological, histological, or clinical-radiological diagnosis, it demonstrated a sensitivity of 94.3% and a specificity of 85.7% [20]. Nevertheless, despite the potential role of PCR in the diagnosis of urogenital tuberculosis, there is currently no evidence supporting the diagnosis of this condition without confirmation by microbiological methods [21]. If necessary, prostatic secretion, ejaculate, discharge from a draining scrotal fistula, as well as fine-needle aspiration biopsy samples should be examined using microscopy, AFB culture, and NAAT.

Comments: given that a sexually transmitted pathogen is the leading cause of epididymo-orchitis, from the standpoint of public health and secondary prevention of STIs, the diagnosis of viral and bacterial infections can increase early-stage detection rates [22].

2.4 Instrumental Diagnostics

Comments: scrotal ultrasound is more reliable for diagnosing acute epididymitis than laboratory workup alone [23], and the method can be useful for differential diagnosis and ruling out other pathologies [24]. On grayscale ultrasound, the epididymis will appear enlarged and heterogeneous; a reactive hydrocele or pyocele may be present. However, these are secondary signs in the diagnosis of acute epididymitis. Color Doppler ultrasound (CDU) will show increased blood flow on the affected side. It should be noted that the mere presence of increased epididymal blood flow is not sufficient; rather, it should

2.5 Other Procedures

Not applicable.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. Conservative management

Comments: empirical antimicrobial therapy should be chosen taking into account the most likely pathogen and the degree of penetration into the inflamed epididymis, and may need to be modified in accordance with local pathogen susceptibility and local guidelines. As a rule, systemic antibacterial drugs should initially be chosen taking into account the potential impact on both C. trachomatis and Enterobacteriaceae [27, 28]. Men with suspected or confirmed STIs should be re-examined 14 days after completion of treatment to test for cure and ensure contact tracing and treatment in accordance with local guidelines. Four guidelines based on systematic reviews were identified regarding this recommendation [29–33].

Comments: data from a large comparison group indicate that young age alone is not a sufficient prognostic factor for a sexually transmitted pathogen [1].

Comments: based on existing guidelines and expert group consensus, the antibacterial therapy regimens presented in Appendix A3 are recommended

3.2. Surgical treatment

Comments: surgical treatment - revision of the scrotal organs, may be required for drainage of abscesses or removal of tissue in case of destruction. A comparative cohort study showed that the absence of differentiation between the epididymis and testis on palpation and the presence of an abscess on ultrasound may predict the need for surgical intervention after initial treatment with antibiotics (systemic antibacterial agents) [33].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not provided for this category of patients.

5. Prevention and Dispensary Observation

Comments: a large C. trachomatis carriage screening study, including a randomly selected group of 5,000 men of whom 1,033 were tested, revealed no benefits in terms of reducing the risk of epididymitis over nine years of follow-up [34].

Comments: a cohort study showed that sperm parameters may be impaired during epididymitis, but recover after successful treatment [35].

6. Organization of Medical Care

Indications for planned hospitalization (admission to a day hospital):

1. Suspicion of tuberculosis or specific infection (if standard therapy is ineffective, granulomas or fistulae are present, or there is a history of tuberculosis).

Indications for emergency hospitalization:

1. Epididymal and/or testicular abscess or suspected abscess.

2. Severe general condition (pronounced intoxication, immunosuppression)

Indications for patient discharge from the hospital:

1. Completed surgical treatment of destructive forms of epididymitis/epididymo-orchitis, as well as resulting complications.

2. Improvement in the patient's condition (normalization of temperature, normalization of complete blood count, decrease in symptom severity)

7. Additional Information

For patients with confirmed or suspected epididymo-orchitis caused by sexually transmitted microorganisms (N. gonorrhoeae, C. trachomatis, or M. genitalium), all partners potentially at risk must be notified and examined. They should be screened for all major STIs (35) and treated with systemic antibiotics active against C. trachomatis (and N. gonorrhoeae or M. genitalium, if confirmed in the patient).

The lookback period for contact tracing is six months for confirmed C. trachomatis epididymo-orchitis, 60 days for confirmed N. gonorrhoeae epididymo-orchitis, and three months for confirmed M. genitalium epididymo-orchitis. In other cases considered to be STIs other than those specified above, the duration of the lookback period is arbitrary [36,37].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Apolikhin Oleg Ivanovich, MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Director of the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health. Member of the Presidium of the Russian Society of Urology (RSU), member of the European Association of Urology (EAU), Academician and Co-Chairman of the Committee of the European Academy of Andrology (EAA), member of the American Urological Association (AUA), member of the Royal Society of Medicine (RSM), member of the Société Internationale d'Urologie (SIU). There is no conflict of interest.

2. Krasnyak Stepan Sergeevich, Leading Research Scientist at the Department of Andrology and Human Reproduction, N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology, Executive Secretary of the Profile Commission on Men's Health of the Russian Ministry of Health, PhD. Member of the Russian Society of Urology (RSU), member of the Russian Association of Human Reproduction (RAHR), member of the European Academy of Andrology (EAA), member of the American Society of Andrology (ASA). There is no conflict of interest.

3. Khazan Petr Leonidovich, Senior Research Scientist at the Department of Inflammatory Diseases, N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health. Member of the Russian Society of Urology (RSU), member of the European Association of Urology (EAU). There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

- Urologist

- Medical students, residents, postgraduate students

 Table 1.Rating scale for levels of evidence (LoE) for diagnostic methods (diagnostic interventions)

Table 2.Level of Evidence (LoE) rating scale for preventive, therapeutic, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Rating scale for grades of recommendation (GoR) for methods of prevention, diagnosis, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1. Order of the Ministry of Health and Social Development of the Russian Federation No. 366n dated April 16, 2012, "On Approval of the Procedure for Providing Pediatric Care".

2. Order of the Russian Ministry of Health No. 203n dated April 14, 2025, "On Approval of Criteria for Assessing the Quality of Medical Care".

3. Drug information: State Register of Medicines: https://grls.rosminzdrav.ru

4. Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Health Protection in the Russian Federation".

5. International Statistical Classification of Diseases and Related Health Problems (ICD-10).

6. Order of the Russian Ministry of Health No. 205n dated May 2, 2023, "On Approval of the Nomenclature of Positions of Medical Workers and Pharmaceutical Workers".

7. Order of the Ministry of Health and Social Development of the Russian Federation No. 541n dated July 23, 2010, "On Approval of the Unified Qualification Handbook of Positions of Managers, Specialists, and Employees, Section 'Qualification Characteristics of Healthcare Worker Positions'".

8. Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Fundamentals of Health Protection in the Russian Federation' Regarding Clinical Practice Guidelines".

9. Order of the Russian Ministry of Health No. 103n dated February 28, 2019, "On Approval of the Procedure and Timelines for the Development of Clinical Practice Guidelines, Their Revision, the Standard Template of Clinical Practice Guidelines, and Requirements for Their Structure, Composition, and Scientific Validity of Information Included Therein".

10. Order of the Russian Ministry of Health No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services".

11. Order of the Ministry of Health of the Russian Federation No. 1094n dated November 24, 2021, "On Approval of the Procedure for Prescribing Medicinal Products, Prescription Form Templates for Medicinal Products, the Procedure for Issuing, Recording, and Storing Said Forms, Prescription Form Templates Containing Prescriptions for Narcotic Drugs or Psychotropic Substances, the Procedure for Their Manufacture, Distribution, Registration, Record-Keeping, and Storage, as Well as the Rules for Issuing Prescription Forms, Including in the Form of Electronic Documents".

Recommended antibiotic regimens [30–32]:

1. For men with acute epididymitis at low risk for gonorrhea (e.g., no discharge):

A. Fluoroquinolones active against C. trachomatis – levofloxacin**, 500 mg orally once daily for ten to fourteen days*

OR

B. Doxycycline** 200 mg initial dose orally, followed by 100 mg twice daily for ten to fourteen days* plus an antibiotic (systemic antibacterial agents) active against Enterobacterales⁺ for ten to fourteen days*

2. For men with suspected acute gonococcal epididymitis:

A. Ceftriaxone** 1000 mg intramuscularly as a single dose plus doxycycline** 200 mg initial dose orally, followed by 100 mg twice daily for ten to fourteen days*

3. For sexually inactive men with acute – levofloxacin 500 mg orally once daily for ten to fourteen days*

*Depending on pathogen identification and clinical response.

⁺ Men with severe infection requiring hospitalization will require parenteral administration, intravenously or intramuscularly.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Epididymo-orchitis is inflammation of the epididymis and the testis itself. This condition can be caused by various factors, including infections, trauma, or other causes.

Symptoms of epididymo-orchitis:

· testicular pain;

· swelling and enlargement of the testis;

· discomfort during urination;

· urethral discharge;

· fever.

If you notice such symptoms, you must consult a doctor for diagnosis and treatment.

Diagnosis of epididymo-orchitis includes a physical examination, urine and blood tests, and scrotal ultrasound (ultrasonography).

Treatment of epididymo-orchitis depends on its cause. It may include antibiotics (systemic antibacterial drugs) for bacterial infection, anti-inflammatory and analgesic therapy, and other methods. In some cases, surgical intervention may be required.

It is important to follow the doctor's recommendations and avoid self-medication, as this can lead to complications.

To prevent epididymo-orchitis, it is necessary to maintain personal hygiene, avoid casual sexual contacts, timely treat infectious diseases, and consult a doctor when symptoms appear.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Rating scales, questionnaires, and other assessment tools are not used.