A. Definitions

1. Lymphangitis = Inflamed lymphatic channels
2. Lymphadenitis = Inflamed lymph nodes
3. Acute Lymphangitis
   1. Linear erythematous streaks extending from primary lesion
   2. Usually caused by streptococcal infections (usually Group A streptococcus)
   3. Staphylococcus aureus causes lymphadenitis (with less streaking from lesion)
4. Nodular Lymphangitis = Nodular subcutaneous swellings along involved lymphatic glands
5. Swelling, erythema, ± fever

B. Etiology of Chronic Lymphangitis / Lymphadenitis

1. Arthropod + animal vectors account for lymphadenitis in ~60% of patients
2. Sporothrix schenckii
   1. Often associated with gardening, rose thorn skin prick
   2. Fungal infection treated with itraconazole
3. Mycobacteria - "Scrofula"
   1. Mycobacterium marinum - lymphangitis
   2. Mycobacterium scrofulaceum and other atypicals (lymphadenitis)
4. Leishmania braziliensis
   1. Mainly only in Texas in the USA; South America and Central America, other places
   2. Usually plaques, papules, and nodules, restricted to skin ("oriental sore") [9]
   3. Visceral leishmaniasis (kala-azar) - fever, organomegaly, cytopenias, highly lethal
   4. Liposomal amphotericin B is effective in skin lesions, some visceral lesions [9]
5. Nocardia brasiliensis - often with frank pus
6. Others
   1. Francisella tularensis (see below)
   2. Plague - Yersinia pestis
   3. Cat scratch disease
   4. Anthrax - Baccilus anthracis
   5. L. venereum - chlamydia
   6. Rickettsial infection: such as scrub typhus, Ehrlichosis
   7. Kawasaki Disease
   8. Rat bite fever

C. Tularemia [2,3,6]

1. Organism
   1. Francisella tularensis (Types A and B, both found in North America and elsewhere)
   2. Gram negative, aerobic coccobaccilus
   3. Found in contaminated water or soil and transmitted by various organisms
   4. Also called "rabbit fever" or "deer fly fever"
   5. Ulceroglandular form most common; pneumonic tuleremia can occur also
2. Transmission
   1. Primarily by ticks (Dermacentor and Amblyomma) to humans,
   2. Carried by rabbits (rats or skunks) which are bitten by ticks
   3. Transmission from rabbit carcasses has been described
   4. Direct person to person transmission has not been documented
   5. Aerosolized transmission can cause tularemia pneumonia or systemic illness
   6. Pneumonic tularemia associated with brush cutting and lawn mowing reported [13]
3. Symptoms
   1. Painful, erythematous ulcer (60-80%) at site of initial skin lesion, and frank pus
   2. This form is called "typhoidal" or ulceroglandular
   3. Incubation 2-5 days with large tender, lymphadenopathy (lymphangitis may occur)
   4. Other symptoms include fever, chills, headache, cough, myalgia
   5. Uncommon meningitis, pericarditis, peritonitis have been reported
   6. May also present as an atypical pneumonia [5] or directly as systemic illness [10]
4. Diagnosis
   1. Differential diagnosis should include causes of lymphangitis
   2. Tuleremia is only major cause of large, tender lymph nodes with associated skin ulcer
   3. Confirmed with serum agglutination titers (acute only) >1:80 titer (requires 2 weeks)
   4. ELISA tests are under development
   5. Rarely positive on Gram stains or blood cultures
5. Treatment [10,12]
   1. Gentamcin 5mg/kg IV or IM once daily for 10-14 days is preferred treatment
   2. Alternative first line is streptomycin 15mg/kg q12 hours IM for10-14 days
   3. Chloramphenicol is less effective than the aminoglycosides
6. Prevention [10,12]
   1. Avoidence of exposure
   2. Vaccination of high risk populations with experimental vaccine (US Army)
   3. Doxycycline 100mg po bid or ciprofloxacin 500mg po bid begun after exposure and during incubation period may prevent disease
7. Mortality of untreated persons is 20-30%

D. Buboes

1. Means tender, enlarged lymph nodes (lymphadenitis)
2. Causes
   1. Syphilis - secondary infection
   2. Primary genital herpes simplex infection
   3. Plague
   4. Chancroid
   5. Lymphogranuloma venerium
   6. Granuloma inguinale (Donovanosis)
3. Chancroid
   1. Haemophilus ducreyi
   2. Gram negative coccobacillus, difficult to culture
   3. Uncommon in USA
   4. Initially, small papule or pustule, red lesions on genitalia, ulcerates then very painful
   5. Painful adenopathy, inguinal region, ~50% of cases
   6. Treatment: Erythromycin 500mg qid x 7d, Ceftriaxone 250mg x 1 IM
   7. Alternatives: Azithromycin x 2gm x 1 dose or Ciprofloxacin 500mg bid x 3d
   8. All sexual contacts should be treated
4. Lymphogranuloma Venerium (LGV)
   1. Caused by serotypes L1, L2, L3 of Chlamydia trachomatis
   2. Fewer than 1000 cases / year in USA
   3. Initial lesion after 7 day incubation, on genitalia
   4. May have papule, eroded or ulcerated nodule, herpetoform lesions, urethritis
   5. Bubos may develop and become fluctuant; may rupture
   6. 20% of patients present with enlarged lymph nodes; usually resolves in 2-3 months
   7. Diagnosis. by culture of C. trachomatis
   8. Treatment: Doxycycline 100mg bid x 21d, ? Azithromycin 2gm x 1
5. Granuloma Inguinale (Donovanosis)
   1. Calymmatobacterium granulomatis
   2. Gram negative rod, endemic to tropics; very rare in USA
   3. Incubation period usually ~30 (8-80) days
   4. Nodule progresses to Ulcerating papule then to friable granulation tissue
   5. Secondary anaerobic infection common
   6. Pseudo-bubos may form, are actually deep granulomas (lymphadenopathy does not occur)
   7. Rule out syphilis, amoebiasis
   8. Treatment is doxycycline, 100mg bid; alternative TMP/SMX, erythromycin

References

1. Sugar AM and Mattia AR. 1994. NEJM. 331(3):181 (Case Report)
2. Dennis DT, Inglesby TV, Henderson DA, et al. 2001. JAMA. 285(21):2763
3. Inglesby TV, Dennis DT, Henderson DA, et al. 2000. JAMA. 283(17):2281
4. Kostman JR and DiNubile MJ. 1993. Ann Intern Med. 118(11):883
5. Fredricks DN and Remington JS. 1996. Arch Intern Med. 156(18):2137
6. Franz DR, Jahrling PB, Friedlander AM, et al. 1997. JAMA. 278(5):399
7. Tenborg M, Davis B, Smith D, et al. 1997. MMWR. 46:617
8. Galimand M, Guiyoule A, Gerbaud G, et al. 1997. NEJM. 337(10):677
9. Montelius S, Maasho K, Pratlong F, et al. 1998. Lancet. 352(9138):1438 (Case Report)
10. Drugs and Vaccines Against Biological Weapons. 1999. Med Let. 41(1046):15
11. Ratsitorahina M, Chanteau S, Rahalison L, et al. 2000. Lancet. 355(9198):111
12. Drugs and Vaccines Against Biological Weapons. 2001. Med Let. 43(1115):88
13. Feldman KA, Enscore RE, Lathrop SL, et al. 2001. NEJM. 345(22):1601
14. Chanteau S, Sahalison L, Ralafiarisoa L, et al. 203. Lancet. 361(9353):211