Spirochetes, Mycobacteria & Atypicals
Serologies, rashes, and RIPE from syphilis to RMSF
Spirochetes and syphilis
BLT. Spirochetes are thin spiral bacteria best seen by darkfield microscopy: Borrelia (big enough to see with Giemsa stain on light microscopy), Leptospira, and Treponema (too thin for light microscopy).
Treponema pallidum. It cannot be cultured, so primary lesions are examined by darkfield microscopy and later stages are diagnosed by serology. Untreated infection moves through defined stages:
- PrimaryPainless chancre at the inoculation site
- SecondaryDisseminated maculopapular rash including palms and soles; condylomata lata; lymphadenopathy
- LatentAsymptomatic but seropositive
- TertiaryGummas; ascending aortic aneurysm from vasa vasorum endarteritis; neurosyphilis
Neurosyphilis. Tabes dorsalis (dorsal column loss with sensory ataxia), the Argyll Robertson pupil (accommodates but does not react to light, nicknamed the "prostitute pupil"), and general paresis.
Congenital syphilis. Saber shins, saddle nose, Hutchinson teeth, mulberry molars, and the Hutchinson triad of notched teeth, interstitial keratitis, and deafness. Penicillin G treats every stage; treating the pregnant mother prevents congenital infection. A Jarisch-Herxheimer reaction (fever, chills, myalgias within hours of the first dose) reflects products released from dying spirochetes.
| Feature | Nontreponemal (VDRL, RPR) | Treponemal (FTA-ABS, TP-PA) |
|---|---|---|
| Role | Cheap screen | Confirmation |
| Specificity | False positives: Viruses (mono, hepatitis), Drugs, Rheumatic fever/RA, Lupus/Leprosy | More specific |
| After treatment | Titers fall; used to follow response | Stay positive for life |
| Early disease | May be negative in early primary syphilis | FTA-ABS turns positive earliest; most sensitive in primary syphilis |
Lyme disease and leptospirosis
Lyme disease. Borrelia burgdorferi is transmitted by the Ixodes tick (mouse reservoir; deer maintain the tick), classically in the Northeast. The same tick can also transmit Babesia and Anaplasma.
- Stage 1 (early localized): erythema migrans, an expanding target rash, often with flu-like symptoms.
- Stage 2 (early disseminated): facial nerve palsy (sometimes bilateral), AV heart block, migratory arthralgias.
- Stage 3 (late): chronic arthritis of large joints and encephalopathy.
BAKE a Lyme pie: Bell palsy, Arthritis, Karditis, Erythema migrans. Treat early disease with doxycycline and cardiac or neurologic disease with ceftriaxone.
Leptospirosis. Leptospira interrogans (question-mark shaped) is acquired from water contaminated by animal urine; think surfers and the tropics. It causes a flu-like illness with conjunctival suffusion, photophobia, and myalgias. The severe form, Weil disease, adds jaundice, azotemia from renal failure, and hemorrhage.
Mycobacteria: tuberculosis and leprosy
Mycobacterium tuberculosis. An obligate aerobe whose mycolic acid-rich wall makes it acid-fast. Cord factor (trehalose dimycolate) is the key virulence factor: it activates macrophages, promotes granuloma formation, and induces TNF-α; sulfatides inhibit phagolysosome fusion. The Th1/IFN-γ (type IV) response builds caseating granulomas: central caseous necrosis ringed by epithelioid macrophages and Langhans giant cells.
Primary vs reactivation. Primary infection forms a Ghon complex (a subpleural lung focus plus hilar lymph node) that usually heals. Reactivation, typically when immunity wanes, produces cavitating lesions in the apices, where oxygen tension is highest.
Testing. The PPD skin test is a type IV reaction; it is falsely negative with anergy (HIV, sarcoidosis, steroids) and can be falsely positive after BCG. Interferon-γ release assays (IGRA) are unaffected by prior BCG vaccination.
| Drug | Mechanism | Key toxicity |
|---|---|---|
| Rifampin | Inhibits bacterial DNA-dependent RNA polymerase | Orange body fluids; CYP450 inducer; hepatotoxic |
| Isoniazid | Blocks mycolic acid synthesis (activated by bacterial catalase-peroxidase) | Neuropathy from B6 depletion (give pyridoxine); hepatotoxic |
| Pyrazinamide | Uncertain; active in acidic phagolysosomes | Hepatotoxic; hyperuricemia |
| Ethambutol | Inhibits arabinosyltransferase (cell wall synthesis) | Optic neuritis with red-green color loss |
Leprosy. M. leprae cannot be cultured, grows in armadillos, and prefers cool tissues (skin and superficial nerves). The host's T-cell response determines the form. Tuberculoid (paucibacillary) leprosy reflects a strong Th1 response: few bacilli, a few well-defined hypoesthetic plaques, and a positive lepromin test. Lepromatous (multibacillary) leprosy reflects a weak, Th2-skewed response: many bacilli, diffuse symmetric lesions, leonine facies, and a negative lepromin test. Treat with dapsone plus rifampin, adding clofazimine for multibacillary disease.
Atypical pneumonias and Chlamydia
Mycoplasma pneumoniae. No cell wall (its membrane contains cholesterol), so it is invisible on Gram stain and β-lactams are useless. It causes "walking pneumonia" in young adults, college students, and military recruits, with diffuse interstitial infiltrates that look worse than the patient. Cold agglutinins (IgM anti-I) can cause hemolysis. It grows on Eaton agar. Treat with a macrolide, doxycycline, or a fluoroquinolone.
Chlamydia trachomatis. An obligate intracellular bacterium that cannot make its own ATP. The elementary body is the infectious form that Enters the cell; it becomes the reticulate body, which Replicates. Serovars:
- A–C: trachoma, a chronic conjunctivitis that leads to blindness.
- D–K: urethritis, cervicitis, and neonatal conjunctivitis and pneumonia.
- L1–L3: lymphogranuloma venereum.
Treat with azithromycin or doxycycline. Related species, C. pneumoniae and C. psittaci (from birds), cause atypical pneumonia.
Legionella pneumophila. A gram-negative rod that stains poorly with Gram stain (use a silver stain) and grows on charcoal yeast extract agar with cysteine and iron. It is inhaled from water sources such as air conditioners and cooling towers, not spread person to person. Legionnaires disease is a severe pneumonia with high fever, diarrhea, confusion, and hyponatremia; Pontiac fever is the mild flu-like form. Diagnose with the urine antigen test; treat with a macrolide or fluoroquinolone.
Rickettsia: Rocky Mountain spotted fever
RMSF. Rickettsia rickettsii, an obligate intracellular bacterium carried by the Dermacentor tick, infects vascular endothelium. The rash starts on the wrists and ankles, involves the palms and soles, and spreads centrally, with fever and headache. Most cases occur in the southeastern US. Treat with doxycycline, even in young children.
Typhus contrast. Endemic (flea-borne) and epidemic (louse-borne) typhus produce a rash that starts centrally and spares the palms and soles.
Rickettsii on the wRists; typhus rashes on the Trunk. Palm-and-sole rashes: Coxsackie A (hand-foot-mouth disease), RMSF, and secondary syphilis.