What is the differential diagnosis for chlamydia?

Differential Diagnosis for Chlamydia

When evaluating a patient with suspected chlamydia, the differential diagnosis must include other sexually transmitted infections (gonorrhea, trichomoniasis, mycoplasma), non-infectious urogenital conditions (urinary tract infections, bacterial vaginosis), and complications of untreated chlamydia itself (pelvic inflammatory disease, epididymitis, reactive arthritis).

Primary Differential Considerations by Clinical Presentation

For Urethritis and Dysuria

• Gonorrhea is the most critical differential, as it presents with similar urethral discharge and dysuria in both men and women, and co-infection occurs frequently 1
• Nongonococcal urethritis from Ureaplasma urealyticum should be considered, as this organism causes clinically indistinguishable symptoms from chlamydia 2
• Urinary tract infections from typical uropathogens (E. coli, Klebsiella) must be excluded, particularly in women presenting with dysuria and pyuria but sterile urine cultures (acute dysuria-pyuria syndrome) 3
• Mycoplasma genitalium causes urethritis that is clinically identical to chlamydial infection 1

For Vaginal Discharge in Women

• Bacterial vaginosis presents with abnormal vaginal discharge but typically has a different character (thin, gray, fishy odor) compared to chlamydial cervicitis 3
• Trichomoniasis causes vaginal discharge and dysuria, making it a key differential diagnosis 1
• Cervicitis from other causes including gonorrhea and herpes simplex virus should be considered when evaluating abnormal vaginal discharge 3

For Pelvic Inflammatory Disease (PID)

• Polymicrobial PID involving anaerobes, gram-negative rods, and other organisms must be considered, as chlamydia is isolated from only 5-50% of women with PID symptoms 4
• Gonococcal PID is a critical differential, as 30% of women with dual gonococcal and chlamydial infections who were treated only for gonorrhea developed salpingitis 4
• Appendicitis must be excluded in women presenting with lower abdominal pain 4
• Ectopic pregnancy is essential to rule out in women of reproductive age with abdominal pain 4
• Endometriosis can present with chronic pelvic pain similar to sequelae of chlamydial infection 4

For Epididymitis in Men

• Gonococcal epididymitis presents identically to chlamydial epididymitis in sexually active young men 5
• Urinary tract pathogens (E. coli, Pseudomonas) cause epididymitis in older men or those with urinary tract abnormalities 5
• Testicular torsion must be urgently excluded in men presenting with acute testicular pain 5

For Reactive Arthritis

• Post-enteric reactive arthritis from Salmonella, Shigella, Campylobacter, or Yersinia presents with similar inflammatory arthritis 1-4 weeks after infection 6
• Gonococcal arthritis (disseminated gonococcal infection) should be considered in sexually active young adults with new-onset inflammatory arthritis 6
• Other seronegative spondyloarthropathies including psoriatic arthritis and ankylosing spondylitis may present similarly 6

For Rectal Infections

• Gonococcal proctitis is clinically indistinguishable from chlamydial proctitis in those engaging in receptive anal intercourse 3
• Herpes simplex proctitis causes rectal pain and discharge 3
• Inflammatory bowel disease should be considered in patients with chronic proctocolitis symptoms 3

For Conjunctivitis

• Gonococcal conjunctivitis is a critical differential requiring urgent treatment to prevent corneal perforation 3
• Viral conjunctivitis (adenovirus) is more common but typically bilateral and associated with upper respiratory symptoms 3
• Bacterial conjunctivitis from typical pathogens (Staphylococcus, Streptococcus) presents similarly 3
• In neonates, chlamydia is the most common cause of neonatal conjunctivitis, but gonococcal and chemical conjunctivitis must be excluded 3

Key Clinical Pitfalls

• Asymptomatic infection is the norm: Over 80% of chlamydial infections are asymptomatic, meaning the absence of symptoms does not exclude the diagnosis 7
• Co-infection with gonorrhea is common: Always test for both organisms simultaneously, as treatment for one does not cover the other 1
• Mild or nonspecific symptoms: Many women with tubal infection have symptoms too mild or nonspecific to prompt treatment, leading to unrecognized PID and subsequent infertility 4
• Partner notification is essential: Failure to treat partners leads to reinfection and continued transmission 8

Diagnostic Approach

• Nucleic acid amplification testing (NAAT) is the most sensitive and specific test for chlamydia and should be used for diagnosis 1
• Test for gonorrhea simultaneously using NAAT from the same specimen 1
• Consider testing multiple sites: urethra, cervix, rectum, and pharynx based on sexual practices 3
• Screen high-risk populations: all sexually active women under 25 years, pregnant women, and those with multiple partners 5