What is the appropriate work‑up for a male patient with acute distal penile pain described as a bee‑sting sensation without visible rash or erythema?

Workup for Acute Distal Penile Pain Without Visible Abnormalities

Begin with a focused history and physical examination to exclude urethritis, interstitial cystitis/bladder pain syndrome, and referred pain from the prostate or bladder, followed by urinalysis and urine culture as the essential initial laboratory tests. 1

Initial Clinical Assessment

Critical History Elements

• Pain characteristics: Document the exact location (tip of penis vs. shaft vs. base), quality (sharp, burning, stabbing), duration, and any triggers or relieving factors 1
• Urinary symptoms: Ask specifically about dysuria, frequency, urgency, hesitancy, incomplete emptying, and whether voiding relieves or worsens the pain 1
• Sexual history: Recent sexual activity, new partners, condom use, history of sexually transmitted infections, and whether pain occurs with ejaculation 1
• Trauma history: Any recent instrumentation (catheterization, cystoscopy), pelvic/perineal trauma, or straddle injuries 1
• Systemic symptoms: Fever, chills, hematuria, penile discharge, or constitutional symptoms 1
• Medical history: History of kidney stones, bladder conditions, prostatitis, or inflammatory conditions 1

Physical Examination Focus

• External genitalia: Carefully inspect the glans, urethral meatus, and entire penile shaft for subtle erythema, discharge, lesions, or tenderness that may not be immediately apparent 1
• Palpation: Gently palpate along the urethra from meatus to base to identify focal tenderness, masses, or induration 1
• Testicular examination: Assess both testicles for size, consistency, masses, and tenderness to exclude referred pain 1, 2
• Prostate examination: Digital rectal exam to assess for prostate tenderness, bogginess, or masses in men with distal penile pain 1
• Abdominal examination: Palpate suprapubic region for bladder distention or tenderness 1

Essential Laboratory Testing

First-Line Studies

• Urinalysis with microscopy: Essential to identify pyuria, hematuria, or crystals that may indicate infection, stones, or inflammatory conditions 1
• Urine culture: Mandatory even if urinalysis appears normal, as normal urinalysis does not exclude urethritis or bladder pathology 1, 2
• Urethral swab (if discharge present): Test for Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification testing 1

Additional Testing Based on Clinical Suspicion

• Post-void residual volume: Use bladder ultrasound or catheterization if obstructive symptoms are present to assess for urinary retention 1
• Uroflowmetry: Consider if voiding symptoms accompany the pain to evaluate for bladder outlet obstruction 1
• Urine cytology: If patient has smoking history or unexplained hematuria to screen for bladder malignancy 1

Differential Diagnosis Framework

Most Likely Diagnoses for Isolated Distal Penile Pain

Urethritis is a primary consideration when pain localizes to the penile tip, even without visible discharge 1. The pain may be described as burning or stinging and often worsens with urination. Many patients with urethritis deny pain and instead describe "pressure" or discomfort 1.

Interstitial cystitis/bladder pain syndrome (IC/BPS) should be strongly considered in men with distal penile pain, as pain at the tip of the penis is a characteristic location for this condition 1. The AUA guideline specifically notes that chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain in the perineum, suprapubic region, testicles, or tip of the penis 1. The distinction between IC/BPS and CP/CPPS in men can be challenging, as both conditions share overlapping features 1.

Referred pain from bladder or prostate pathology must be excluded, as the sensory innervation of the lower urinary tract can cause pain to be perceived distally 1.

Less Common but Important Considerations

• Urethral stricture or stenosis: May present with distal penile pain, particularly if associated with voiding difficulty 1
• Urethral calculus: Small stones lodged in the distal urethra can cause sharp, localized pain 1
• Meatal stenosis: Narrowing of the urethral opening can cause pain at the tip, especially during urination 1
• Penile malignancy: While typically presenting with visible lesions, early carcinoma in situ can occasionally present with pain before visible changes 1

Diagnostic Algorithm

Step 1: Rule Out Infection (Days 1-3)

1. Obtain urinalysis and urine culture immediately 1
2. If urinalysis shows pyuria or patient has risk factors for STI, obtain urethral swab for gonorrhea/chlamydia 1
3. If infection confirmed, treat appropriately and reassess in 2-3 weeks 1

Step 2: Assess for Bladder/Prostate Pathology (If Initial Tests Negative)

1. Measure post-void residual if obstructive symptoms present 1
2. Consider uroflowmetry if voiding dysfunction suspected 1
3. Perform careful digital rectal examination for prostate tenderness 1

Step 3: Consider IC/BPS or CP/CPPS (If Above Negative)

The diagnosis of IC/BPS should be strongly considered in men with pain, pressure, or discomfort perceived to be related to the bladder and associated with urinary frequency, nocturia, or an urgent desire to void 1. Key diagnostic features include:

• Pain that worsens with bladder filling or improves with urination 1
• Pain that worsens with specific foods or drinks 1
• Absence of infection or other identifiable pathology 1

Step 4: Advanced Evaluation (If Diagnosis Remains Unclear)

• Cystoscopy: Consider if hematuria present, symptoms persist despite treatment, or to evaluate for bladder lesions or urethral pathology 1
• Imaging: Generally not indicated unless hematuria, suspected stones, or concern for upper tract pathology 1
• Urodynamic studies: Reserved for selected patients with complex voiding symptoms 1

Critical Pitfalls to Avoid

Do not dismiss the complaint based on normal external examination alone 1. Many urologic conditions causing distal penile pain have no visible external findings, and the absence of erythema or rash does not exclude significant pathology.

Do not assume normal urinalysis excludes all pathology 1, 2. Urethritis, early IC/BPS, and other conditions may present with normal urinalysis.

Do not overlook the possibility of IC/BPS in men 1. While historically considered a female condition, IC/BPS occurs in men and frequently presents with distal penile pain as a primary symptom.

Recognize that patients may not use the word "pain" 1. Many describe their symptoms as "pressure," "discomfort," or "burning," so careful questioning about symptom quality is essential.

Consider that symptoms meeting criteria for both IC/BPS and CP/CPPS may coexist 1. In such cases, treatment can include therapies for both conditions.

When to Refer to Urology

• Persistent symptoms despite appropriate antibiotic therapy for confirmed infection 1
• Hematuria (microscopic or gross) requiring cystoscopic evaluation 1
• Suspected IC/BPS or CP/CPPS requiring specialized management 1
• Abnormal findings on imaging or concern for malignancy 1
• Voiding dysfunction with elevated post-void residual or abnormal uroflowmetry 1