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Summary Table

Category	Details
Risk Factors	Sexually active males under 35 (STI-related); males over 35 with urinary obstruction or recent urethral instrumentation; men who practice insertive anal intercourse; prepubertal boys with anatomic urinary tract abnormalities
Etiology	Under 35: Chlamydia trachomatis and Neisseria gonorrhoeae. Over 35: enteric gram-negative rods, most commonly Escherichia coli. Prepubertal: post-viral or anatomic abnormality
Patient Presentation	Gradual onset unilateral scrotal pain and swelling developing over days, often accompanied by dysuria, urinary frequency, or urethral discharge
Classic Physical Exam	Tender, swollen epididymis (posterior aspect of testis); positive Prehn sign (pain relief with testicular elevation); intact cremasteric reflex; possible reactive hydrocele; urethral discharge may be present
Key Diagnostic Results	Urinalysis: pyuria and bacteriuria. NAAT positive for Chlamydia or Gonorrhea (in younger patients). Doppler ultrasound: increased blood flow to the affected epididymis
Management	Under 35, STI suspected: Ceftriaxone 500 mg IM once + Doxycycline 100 mg PO BID for 10 days. Over 35 or enteric organism suspected: Levofloxacin 500 mg PO daily for 10 days. Supportive care: scrotal elevation, NSAIDs, ice
Keywords	"Gradual onset scrotal pain," "Prehn sign positive," "cremasteric reflex intact," "increased flow on Doppler," "tender posterior testis," "sexually active male with dysuria"

1. Pathophysiology

Epididymitis is an inflammatory condition of the epididymis, the coiled tubular structure located along the posterior surface of the testis responsible for sperm maturation and transport. Understanding the mechanism requires recognizing that this is fundamentally an ascending infection that reaches the epididymis via retrograde spread through the vas deferens from the urethra, prostate, or bladder.

In sexually active men under 35, the most common pathogens are the sexually transmitted organisms Chlamydia trachomatis and Neisseria gonorrhoeae. These organisms colonize the urethra and ascend through the ejaculatory ducts into the vas deferens, ultimately seeding the epididymis. This is why patients in this age group often present with concurrent urethritis (urethral discharge, dysuria) alongside their scrotal symptoms. The connection between the urethral infection and the epididymal inflammation is direct and anatomic.

In men over 35, the pathophysiology shifts. The predominant organisms are enteric gram-negative bacteria, especially E. coli, reflecting an underlying cause rooted in urinary tract pathology rather than sexual transmission. Conditions such as benign prostatic hyperplasia, urethral strictures, or recent urinary catheterization promote urinary stasis and bacterial colonization. These bacteria then reflux into the ejaculatory duct and ascend to the epididymis. This is also the mechanism in men who practice insertive anal intercourse, where coliform bacteria gain access to the urethra.

The inflammatory response in the epididymis produces the hallmark findings: swelling, warmth, erythema, and tenderness localized to the posterior aspect of the testis. Because this is an inflammatory (vasodilatory) process rather than a vascular occlusion, blood flow to the affected side is increased, not decreased. This is the critical physiologic distinction from testicular torsion, where twisting of the spermatic cord cuts off arterial supply and produces decreased or absent blood flow.

The positive Prehn sign (pain relief on elevation of the scrotum) is explained by the fact that elevation reduces venous congestion and edema in the inflamed epididymis. The cremasteric reflex remains intact because the spermatic cord and its neural pathways are structurally unaffected, unlike in torsion where the twisted cord disrupts reflex arcs.

2. Classification and Clinical Manifestation

Classification	Time Course	Typical Organism	Clinical Features
Acute Epididymitis	Symptoms present for less than 6 weeks	C. trachomatis, N. gonorrhoeae (under 35); E. coli (over 35)	Unilateral scrotal pain, swelling, erythema; dysuria; possible urethral discharge; fever in moderate to severe cases
Chronic Epididymitis	Symptoms present for 6 weeks or longer	Often no identifiable organism; may follow inadequately treated acute episode	Dull, persistent scrotal ache; epididymal induration; typically no systemic signs
Epididymo-orchitis	Acute, with extension of infection into the testis itself	Same organisms as acute epididymitis; Mumps virus in unvaccinated males	Diffuse testicular and epididymal swelling; testis becomes tender and enlarged; higher fever; may be difficult to distinguish from torsion clinically

By Etiology

Age Group	Likely Etiology	Associated Findings
Prepubertal boys	Post-viral inflammation; anatomic urinary tract abnormality (e.g., ectopic ureter, posterior urethral valves)	Evaluate for structural anomalies; urine culture often negative; consider voiding cystourethrogram
Sexually active, under 35	C. trachomatis, N. gonorrhoeae	Urethral discharge, history of unprotected sexual contact, partner with STI symptoms
Over 35 or recent instrumentation	E. coli, other enteric gram-negatives	History of BPH, catheterization, or urologic procedure; urinary symptoms predominate
Men practicing insertive anal intercourse (any age)	Enteric organisms (E. coli, other coliforms), plus STI organisms	Dual coverage may be required (ceftriaxone + fluoroquinolone)

3. Diagnostic Workup

Test	Role	Expected Finding
Urinalysis with microscopy	Best initial screening test	Pyuria (>10 WBC per high-power field), bacteriuria
Urine Gram stain	Rapid identification of organism type	Gram-negative rods suggest enteric bacteria; gram-negative diplococci suggest N. gonorrhoeae
NAAT (Nucleic Acid Amplification Test)	Gold standard for identifying STI pathogens	Positive for C. trachomatis and/or N. gonorrhoeae from urethral swab or first-void urine
Urine culture	Identifies enteric organisms and guides antibiotic sensitivity	Positive for E. coli or other coliforms in older patients
Color Doppler ultrasound of the scrotum	Most accurate test for distinguishing epididymitis from torsion	Increased blood flow to the affected epididymis; epididymal enlargement and edema; possible reactive hydrocele
CBC	Supportive, not diagnostic	Leukocytosis with left shift in moderate to severe cases

The workup begins with a urinalysis, which serves as the best initial screening test. Finding pyuria (white blood cells in the urine) strongly supports an infectious inflammatory etiology and helps differentiate epididymitis from non-infectious causes of scrotal pain. A urine Gram stain can provide rapid preliminary information about the type of organism: the presence of gram-negative intracellular diplococci points toward gonococcal infection, while gram-negative rods suggest enteric bacteria.

For patients under 35 or those with risk factors for sexually transmitted infection, a NAAT from either a urethral swab or first-void urine specimen is the gold standard for confirming Chlamydia and Gonorrhea. This test has superior sensitivity and should be ordered in all cases where STI is suspected, even if the Gram stain is negative. In older patients or those with urinary tract risk factors, a urine culture with sensitivities is more informative and guides targeted antibiotic therapy.

When there is any clinical uncertainty about whether the patient has epididymitis versus testicular torsion, a Color Doppler ultrasound of the scrotum is the most accurate imaging study. The critical finding is the pattern of blood flow:

Condition	Doppler Finding
Epididymitis	Increased blood flow (hyperemia)
Testicular torsion	Decreased or absent blood flow

This single imaging distinction is among the most tested concepts in this differential. However, if torsion is strongly suspected on clinical grounds (sudden onset, absent cremasteric reflex, high-riding testis), imaging should not delay surgical exploration. Torsion is a clinical diagnosis when the presentation is classic, and the window for testicular salvage is narrow (ideally under 6 hours).

4. Management and Treatment

Clinical Scenario	Antibiotic Regimen	Duration
STI likely (under 35, sexually active)	Ceftriaxone 500 mg IM single dose + Doxycycline 100 mg PO twice daily	Doxycycline for 10 days
Enteric organism likely (over 35, BPH, instrumentation)	Levofloxacin 500 mg PO once daily	10 days
Both STI and enteric organisms possible (insertive anal intercourse)	Ceftriaxone 500 mg IM single dose + Levofloxacin 500 mg PO once daily	Levofloxacin for 10 days
Supportive measures (all patients)	Scrotal elevation, ice packs, NSAIDs for pain	As needed

Acute stabilization begins with empiric antibiotic therapy tailored to the most likely organism based on the patient's age and risk factors. You do not wait for culture results before starting treatment.

For the sexually active male under 35, the regimen targets Chlamydia and Gonorrhea simultaneously. Ceftriaxone 500 mg is given as a single intramuscular injection to cover N. gonorrhoeae (including most resistant strains), and Doxycycline 100 mg twice daily for 10 days covers C. trachomatis. If the patient weighs 150 kg or more, the ceftriaxone dose increases to 1 g IM. All sexual partners from the preceding 60 days should be evaluated, tested, and treated presumptively.

For men over 35 or those with risk factors for enteric organisms, Levofloxacin 500 mg orally once daily for 10 days is the standard regimen. An alternative is Ofloxacin 300 mg orally twice daily for 10 days. These fluoroquinolones provide excellent coverage against E. coli and other gram-negative enteric pathogens.

For patients who practice insertive anal intercourse, dual coverage is necessary because both STI organisms and enteric bacteria may be responsible. The recommended combination is Ceftriaxone 500 mg IM once plus Levofloxacin 500 mg PO daily for 10 days.

Supportive care is important for symptom management in all patients. Scrotal elevation (using a towel roll or athletic supporter) reduces dependent edema. NSAIDs such as ibuprofen provide both analgesia and anti-inflammatory benefit. Ice packs applied intermittently help with swelling. Patients should avoid heavy lifting and sexual activity until symptoms resolve and antibiotic courses are completed.

Contraindications and cautions:

Doxycycline is contraindicated in pregnancy. If a pregnant patient's partner is being treated for epididymitis from a chlamydial source, alternative regimens for the partner may apply, but doxycycline remains the standard for the male patient himself.
Fluoroquinolones should be used cautiously in patients with a history of tendon disorders, QT prolongation, or myasthenia gravis. They are generally avoided in the pediatric population except when no alternative exists.
If the patient does not improve within 48 to 72 hours, re-evaluate the diagnosis. Consider abscess formation, incorrect organism coverage, or an alternative diagnosis such as testicular tumor.

Long-term follow-up: Patients with STI-related epididymitis should be tested for HIV and syphilis. A test of cure is recommended for gonococcal infections. Chronic or recurrent epididymitis in older men warrants evaluation for underlying urologic pathology (prostatic obstruction, stricture disease).

5. Differential Diagnosis and Distractors

Differential	Why It Is Similar	Key Discriminator
Testicular torsion	Also presents with acute unilateral scrotal pain in a young male	Torsion has sudden onset (often nocturnal), absent cremasteric reflex, high-riding testis with horizontal lie, and decreased/absent blood flow on Doppler. Epididymitis has gradual onset, intact cremasteric reflex, positive Prehn sign, and increased flow on Doppler.
Orchitis (mumps)	Presents with testicular pain and swelling, often in a young male	Mumps orchitis follows parotitis by 4 to 8 days, is often bilateral, and the patient typically has a history of incomplete vaccination. There is no urethral discharge or pyuria.
Testicular cancer	Presents as a scrotal mass in a young male	Testicular tumors are painless, firm, and do not transilluminate. Tumor markers (AFP, beta-hCG, LDH) may be elevated. There is no fever, no pyuria, and no urethral discharge.
Incarcerated inguinal hernia	Can cause acute scrotal or inguinal pain with swelling	The swelling extends into the inguinal canal, bowel sounds may be auscultated in the scrotum, and the patient often has nausea/vomiting or signs of obstruction. No pyuria or urethral findings.
Fournier gangrene	Scrotal pain, swelling, erythema, and fever	Fournier gangrene produces rapidly progressive necrosis with crepitus on palpation, dusky or gangrenous skin changes, and systemic toxicity disproportionate to exam findings. It is a surgical emergency.
Hydrocele	Scrotal swelling in a male	Hydroceles are painless, fluctuant, and transilluminate with a penlight. There is no tenderness, no fever, and no inflammatory findings.

6. Traps and High-Yield Pearls

The single most common way students get questions about epididymitis wrong is by confusing it with testicular torsion. Exam writers deliberately construct vignettes with overlapping features (young male, scrotal pain, unilateral swelling) and embed the discriminating details in subtle parts of the stem. The keys that point toward epididymitis over torsion are: gradual onset over hours to days (not sudden), intact cremasteric reflex, positive Prehn sign, the presence of dysuria or urethral discharge, and pyuria on urinalysis. If the vignette asks for an imaging study, the answer is Doppler ultrasound, and the distinguishing finding is increased versus decreased blood flow.

A second trap involves selecting the wrong antibiotic regimen. The exam expects you to match the treatment to the patient's age and sexual history. A 22-year-old with urethral discharge gets ceftriaxone plus doxycycline (STI coverage). A 60-year-old with a recent Foley catheter gets levofloxacin (enteric coverage). Choosing levofloxacin for the young STI patient, or doxycycline alone for the elderly patient, are both common errors.

A third tested concept is knowing when not to image. If a vignette describes sudden-onset scrotal pain with an absent cremasteric reflex and a high-riding testis in an adolescent, the next best step is immediate surgical exploration, not Doppler ultrasound. Imaging should not delay definitive treatment for torsion. The Doppler is reserved for cases where the clinical picture is ambiguous, which is exactly when epididymitis enters the differential.

The core competency being tested across questions on this topic is the ability to distinguish inflammatory from ischemic causes of acute scrotal pain, to select age-appropriate empiric therapy, and to recognize when imaging is appropriate versus when it would cause harmful delay.

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