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Evaluation/Workup

Epidemiology

• 10 million active TB cases worldwide, < 10 thousand in US
• GU TB seen in 2-20% patients, more prevalent in non-Euro/Anglocentric countries
• 3rd most common TB manifestation after pleural and lymphatic

GU TB Spread

• Hematogenous: most common, most commonly to kidneys and epididymis
• Retrograde: may be secondary to BCG usage (0.9% total BCG usage)
• Continguous spread: TB can spread via adjacent organs and does not "respect" normal anatomic boundaries, can form fistulae
• Direct inoculation: extremely rare, can spread from infected persons or bodily fluids, patients can spread to new organs through their own infected fluids

Manifestations

• Constitutional: fever, weight loss, night sweats, malaise present in < 20%
• LUTS: up to 50% have dysuria only, 50% have frequency/urgency, 33% have hematuria/flank pain
• Kidney: seen in up to 80% GU TB, granulomas can develop into abscesses, chronic pylonephritis, papillary necrosis, cutaneous sinus tracts, may result in autonephrectomy (seen in 33% GU TB)
• Ureter: usually descending infection, granuloma formation leads to scarring/strictures, can lead to renal failure from obstruction
• Bladder: patchy cystitis, ulcerations, dome affected more than trigone, bladder may contract down to volumes 20-100mL (thimble bladder)
• Epididymis: second most common site, involved in 10-55% GU TB, bilateral infection in 34%, may appear swollen/hardened on exam, up to 50% have posterior scrotal sinus tract, can cause vas nodular scarring, can spread to testis and cause orchitis, 5% develop hydrocele
• Prostate: seen in 22-49% GU TB, can be peripheral/asymptomatic (if hematogenous spread) or prostatitis (if urinary spread), suspect in chronic prostatitis despite antibiotics
• Seminal vesicle: can cause infertility and may be presenting symptom of GU TB, may cause hematospermia and rarely abscesses
• Urethra: seen in 2-4.5% GU TB, can lead to urethroscrotal fistulae
• Penis: can develop inflamed papule/plaque (lupus vulgaris), may have palpable granulomas in cavernous bodies and urethra, can be rapidly necrosing with poor prognosis (orificial TB), can be penile glandular papules (papulonecrotic tuberculid)

Diagnosis

• Urinary AFB culture: gold standard, first morning void is most concentrated, collect 3-5 on consecutive days for best diagnosis, culture growth can take 3-6 weeks, may be able to detect colony growth at 10 days
• NAAT: can detect within 1-2 days, but less sensitivte on non-pulmonary specimens
• Tissue biopsy demonstrates caseating granulomas, diagnostic in appropriate clinical context
• Screening tests (PPD, IGRA) do not differentiate between latent TB, active TB, or prior vaccination
• KUB: may show renal calcifications (present in > 50%), papillary necrosis, atrophic kidney with calcifications lining each renal lobe (pathognomonic for end-stage TB), calficiations elsewhere in GU tract
• CTU/IVP/MRU: demonstrates calyceal erosions (moth-eaten appearance), filling defects, phantom calyces (infundibular stenosis leads to failed contrast excretion), rigid ureter (pipestem), hydronephrosis, sharply angulated UPJ (Kerr's kink)
• Cystoscopy: findings mistaken for malignancy, biopsy recommended for diagnosis
• Other tests: obtain CXR, HIV, HBV, HCV, A1c, blood/sputum cultures, CBC, BMP

First Line Therapies

Drug	Dosing	Side effects
Isoniazid	5mg/kg (300mg) daily 15mg/kg (900mg) 3x weekly	Hepatotoxicity Peripheral neuropathy
Rifampin	10mg/kg (600mg) daily 10mg/kg (600mg) 3x weekly	Hepatotoxicity Pruritis Flulike symptoms
Pyrazinamide (weight-based dosing)	1000-2000mg daily 1500-3000mg 3x weekly	Arthralgia Hepatotoxicity Pruritus/Rash GI Symptoms Hyperuricemia
Ethambutol (weight-based dosing)	800-1600mg daily 1200-2400mg 3x weekly	Decreased visual acuity Red/green color changes Optic neuritis

Treatment tips

• Timing:6mo treatment total, 2mo with RIPE then 4mo with INH + rifampin
• Vitamin B6: prescribe with INH to decrease risk of neuropathy
• Second-line therapies: use if TB are resistant or side effects develop from first-line therapies
• Surveillance labs: check monthly LFTs, abstain from EtOH
• Second line drugs: streptomycin, capreomycin, amikacin, kanamycin, cycloserine, ethionamide, levofloxacin, moxifloxacin, paraASA, linezolid, bedaquiline

Surgical management

• Up to 55% with require some form of surgical therapy
• Obstruction: stent placement successful ~40% patients, 1+ PCNs may be needed if renal scarring prevents adequate drainage, fistula can develop after PCN removal
• Nephrectomy: may be necessary for resistant HTN, persistent pain, or infections, retroperitoneal approach may be needed due to severe scarring
• Ureteral obstruction: individualized approach, endoscopic management usually fails, may have lengthy strictures
• Bladder augment vs diversion: recommended for contracted poorly functional bladders

Malakoplakia

• Pathophysiology: disordered macrophage function leading to incomplete resolution of bacterial infection, Michaelis-Gutmann bodies are pathognomonic (seen on histology), also von Hansemann cells present (large monocytes w/ foamy cytoplasm)
• Bladder: presents with dysuria/hematuria, yellow/brown plaque seen on cystoscopy, can usually treat with TURBT and antibiotics
• Upper tract presents with fever and flank pain, imaging shows solid mass, usually requires nephrectomy