What lab tests are recommended for a female patient with late latent syphilis, Hepatitis C (HCV) antibody positive, anemia, and new onset psychosis?

Comprehensive Laboratory Workup for Female Sex Worker with Late Latent Syphilis, HCV Antibody Positive, Anemia, and New Onset Psychosis

This patient requires immediate CSF examination to exclude neurosyphilis given her late latent syphilis diagnosis, followed by comprehensive screening for HIV, reactivation of HCV, causes of anemia, and metabolic/infectious contributors to psychosis. 1

Immediate Priority: Neurosyphilis Evaluation

A lumbar puncture must be performed for all patients with late latent syphilis (≥1 year duration) to exclude neurosyphilis, particularly when neuropsychiatric symptoms are present. 1

CSF Studies Required:

• CSF VDRL (sensitivity 49-87.5%, specificity 74-100% for neurosyphilis diagnosis) 1
• CSF cell count and protein (normal values: WBC <5 cells/mm³, protein <40 mg/dL in adults) 1
• CSF TPPA or FTA-ABS (if VDRL negative but clinical suspicion remains high) 1

HIV Testing (Mandatory)

All patients with syphilis must be tested for HIV infection. 1, 2

• HIV antibody/antigen combination test (4th generation) 1
• If positive, obtain CD4 count and HIV viral load (HIV-infected patients with late latent syphilis require CSF examination regardless of symptoms) 1, 2

Hepatitis C Reactivation Assessment

Despite negative HCV RNA last year, retest given the association between syphilis and HCV transmission in high-risk populations, plus new psychosis which can rarely occur with HCV. 3, 4

• HCV RNA quantitative PCR (to distinguish active infection from resolved infection, as HCV antibody remains positive for life) 1
• HCV genotype (if RNA positive, to guide potential treatment) 1
• Hepatic function panel: AST, ALT, alkaline phosphatase, total/direct bilirubin, albumin (syphilitic hepatitis can cause cholestatic injury) 5
• Prothrombin time/INR (assess synthetic liver function) 5

Anemia Workup

• Complete blood count with differential and platelet count 1
• Reticulocyte count (distinguish hypoproliferative from hemolytic anemia)
• Peripheral blood smear (evaluate for hemolysis, microangiopathy, or other morphologic abnormalities)
• Iron studies: serum iron, TIBC, ferritin, transferrin saturation
• Vitamin B12 and folate levels (common in high-risk populations)
• Direct Coombs test (DAT) (if hemolysis suspected) 6
• Indirect bilirubin, LDH, haptoglobin (if hemolysis suspected)

Psychosis Evaluation

Infectious/Metabolic Causes:

• Comprehensive metabolic panel: sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium 1
• Thyroid function tests: TSH, free T4 (thyroid dysfunction can cause psychosis)
• Rapid plasma reagin (RPR) titer (confirm current syphilis activity; fourfold change is clinically significant) 1, 2
• Urinalysis and urine drug screen (substance-induced psychosis is common in this population)

Neurosyphilis-Related (if CSF obtained):

• CSF studies as listed above 1

Additional Sexually Transmitted Infection Screening

All patients with syphilis should be screened for other STIs given high co-infection rates. 1, 3, 4

• Gonorrhea and Chlamydia NAAT from cervical/vaginal, pharyngeal, and rectal sites (based on sexual practices) 1
• Hepatitis B surface antigen (HBsAg), total anti-HBc, anti-HBs (6.8% prevalence in high-risk populations with syphilis) 7
• Trichomonas testing (wet mount or NAAT) 1

Baseline Monitoring for Syphilis Treatment

• Baseline RPR titer (use same test method for all future monitoring; RPR and VDRL are not interchangeable) 1, 2
• Pregnancy test (treatment differs in pregnancy; penicillin desensitization required if allergic) 1, 2

Follow-Up Serologic Monitoring Schedule

For late latent syphilis, recheck RPR at 6,12,18, and 24 months after treatment completion. 2

• Treatment success is defined as fourfold decline in RPR titer within 12-24 months 2
• If HIV-positive, monitor every 3 months instead of every 6 months (at 3,6,9,12,18, and 24 months) 2

Critical Pitfalls to Avoid

• Do not skip CSF examination in late latent syphilis with neuropsychiatric symptoms – neurosyphilis requires different treatment (aqueous penicillin G 18-24 million units/day IV for 10-14 days vs. benzathine penicillin G 2.4 million units IM weekly × 3 weeks) 1, 2
• Do not assume HCV is cleared based on last year's negative RNA – reinfection rates are high in sex workers, and acute HCV can present with neuropsychiatric symptoms 8, 3, 4
• Do not use treponemal tests (FTA-ABS, TP-PA) to monitor treatment response – these remain positive for life regardless of cure 2
• Do not compare RPR and VDRL titers interchangeably – only 29% of sera have concordant titers between these tests 1
• Do not delay treatment pending all results – benzathine penicillin G 2.4 million units IM weekly × 3 weeks should be initiated immediately for late latent syphilis unless neurosyphilis is confirmed 1, 2