Glandular tularemia is a form of tularemia caused by Francisella tularensis characterized by isolated regional lymphadenopathy without a detectable skin ulcer, typically acquired via tick bites, handling infected animals, or animal bites. [1-2] It represents approximately 14–25% of tularemia cases in the US. [3-4] The glandular form is essentially ulceroglandular tularemia in which the skin lesion is inconspicuous or has healed by the time of presentation. [1-2]
The following figure illustrates the modes of acquisition and clinical manifestations of tularemia:
1. History
- Key HPI questions: Onset and duration of lymph node swelling; location of adenopathy; associated fever, chills, headache, malaise, myalgias [1-2][6]
- Exposure history is critical: Recent tick bites, deerfly bites, mosquito bites; handling rabbits, hares, rodents, or their carcasses; contact with domestic cats (can transmit via bites/scratches); hunting, skinning, or butchering wild game [1][7-8]
- Timing: Incubation period typically 3–5 days (range 1–14 days); patients seek care after a median of 3 days of illness [2-3]
- Symptom characterization: Tender, enlarging lymph node(s) in the region draining the inoculation site (inguinal/femoral for lower extremity tick bites; axillary for upper extremity exposure; cervical for oropharyngeal route) [1][7]
- Important negatives: No visible skin ulcer or eschar (distinguishes glandular from ulceroglandular); no pharyngitis (distinguishes from oropharyngeal); no conjunctivitis (distinguishes from oculoglandular) [2]
2. Alarm Features
- High fever (>39°C) with systemic toxicity — suggests possible progression to typhoidal or pneumonic form [2][9]
- Rapidly enlarging, fluctuant lymph nodes — ~30% of patients develop lymph node suppuration [2][10]
- Respiratory symptoms (cough, dyspnea, chest pain) — raises concern for pneumonic tularemia via hematogenous spread [2][11]
- Neurological changes (confusion, stupor) — may indicate typhoidal form or meningitis [2]
- Immunocompromised status — associated with worse prognosis and unusual/severe manifestations [2][6]
- Failure to improve on beta-lactam antibiotics — a classic clinical clue to tularemia [10][12]
3. Medications
- First-line for mild-moderate glandular tularemia:
- Ciprofloxacin 500 mg PO BID or levofloxacin 500 mg PO daily for 10–14 days [1][13]
- Doxycycline 100 mg PO BID for 14–21 days (higher relapse rate ~10–15% vs ~5–10% with fluoroquinolones) [2][10]
- First-line for severe disease:
- Gentamicin 5 mg/kg/day IV divided q8h (adjust for renal function) for 10 days [1][14]
- Streptomycin 30 mg/kg/day IM divided q12h (max 2 g/day) for 10 days [1][14]
- Step-down: Parenteral aminoglycoside until clinical improvement, then transition to oral fluoroquinolone or doxycycline to complete 10–14 days [1][15]
- Contraindicated/ineffective: Beta-lactams (intrinsic resistance), most macrolides, anti-TB agents [1][10]
- Special populations: Fluoroquinolones and doxycycline are now designated first-line for outbreaks per 2025 CDC recommendations; gentamicin preferred in pregnant women with severe disease [2][13]
4. Diet
- No specific dietary triggers or restrictions
- Adequate hydration during febrile illness
- Avoid consumption of untreated water from natural sources (wells, springs, streams) in endemic areas — a known transmission route [2][5]
- Ensure thorough cooking of wild game meat [2]
5. Review of Systems
- Constitutional: Fever, chills, night sweats, fatigue, malaise, anorexia, weight loss [2][6]
- Musculoskeletal: Myalgias, arthralgias [2]
- Skin: Any skin lesion, ulcer, or eschar (may be subtle or healed) [1]
- Respiratory: Cough, dyspnea, pleuritic chest pain (screen for pneumonic involvement) [6]
- GI: Sore throat, nausea, vomiting, diarrhea, abdominal pain [6]
- Ophthalmologic: Eye pain, redness, photophobia (rule out oculoglandular form) [6]
- Neurologic: Headache, confusion (screen for meningitis/typhoidal form) [2]
6. Collateral History and Family History
- Occupational exposure: Hunters, trappers, farmers, landscapers, veterinarians, laboratory workers at highest risk [7-8]
- Recreational exposure: Hiking, camping, outdoor activities in endemic areas (south-central US — Arkansas, Missouri, Oklahoma; also Northern Hemisphere broadly) [3][7]
- Household contacts: Other family members with similar symptoms may suggest a common exposure source (e.g., shared animal contact, tick-infested environment) [2]
- Pet history: Cat ownership — domestic cats can transmit F. tularensis via bites or scratches [1][16]
- No person-to-person transmission — standard precautions are adequate [15]
- Family history is generally not relevant (no hereditary predisposition)
7. Risk Factors
- Tick exposure — accounts for >50% of US cases (Dermacentor variabilis, D. andersoni, Amblyomma americanum) [3][7]
- Deerfly/horsefly bites — important vector in some regions (e.g., Wyoming) [17]
- Mosquito bites — common vector in Scandinavia and Finland [2]
- Direct animal contact — handling infected rabbits, hares, rodents, or their carcasses [7-8]
- Male sex, summer months — most cases occur in males during warm seasons when tick/insect exposure peaks [3][7]
- Geographic location: Endemic in south-central US, Northern Hemisphere broadly; re-emerging in Europe [7][9]
- Immunocompromised status — associated with more severe and atypical presentations [2][6]
8. Differential Diagnosis
- Cat scratch disease (Bartonella henselae) — regional lymphadenopathy, often with cat scratch/bite history; typically self-limited [18]
- Lymphoma — painless lymphadenopathy, B symptoms; tularemia can mimic malignancy on imaging and histopathology [11][19]
- Tuberculosis — chronic lymphadenopathy with caseating granulomas; tularemia histopathology can be indistinguishable [19]
- Sporotrichosis — lymphocutaneous nodular pattern following lymphatic drainage
- Staphylococcal/streptococcal lymphadenitis — typically responds to beta-lactams (failure to respond is a clue to tularemia) [12]
- Plague (Yersinia pestis) — bubonic form with painful inguinal/axillary adenopathy; epidemiologic context differs
- Non-tuberculous mycobacterial infection — chronic lymphadenopathy, especially cervical in children
- Toxoplasmosis — cervical lymphadenopathy, often asymptomatic; exposure to cats/undercooked meat
- Infectious mononucleosis — generalized lymphadenopathy, pharyngitis, fatigue
9. Past Medical History
- Prior tularemia episodes (reinfection is possible though uncommon)
- Immunocompromising conditions (HIV, transplant, immunosuppressive therapy) — associated with worse outcomes [2][6]
- Chronic kidney disease — requires aminoglycoside dose adjustment [1]
- History of beta-lactam treatment failure for presumed lymphadenitis — a classic clue [12]
10. Physical Exam
- Vital signs: Fever is nearly universal; tachycardia proportional to fever [2][6]
- Lymph node exam: Tender, enlarged regional lymph nodes — location depends on inoculation site (inguinal/femoral for tick bites on lower extremities; axillary for upper extremity; cervical less common in glandular form) [1][7]
- Nodes may be fluctuant if suppurated (~30% of cases) [2]
- Overlying erythema and warmth
- Skin: Thorough search for subtle or healing ulcer/eschar at inoculation site (may reclassify as ulceroglandular) [1]
- Tick search: Full-body skin exam for embedded ticks
- Pharynx: Normal in glandular form (pharyngitis suggests oropharyngeal form) [2]
- Eyes: Normal (conjunctivitis suggests oculoglandular form) [2]
- Lungs: Clear in isolated glandular form; crackles or decreased breath sounds suggest pneumonic involvement [6]
- Skin rashes: Erythema nodosum can occur as a complication [2]
11. Lab Studies
- Serology (primary diagnostic method):
- Microagglutination test (MAT) for IgM/IgG — most patients seroconvert 2–3 weeks after symptom onset [2][6]
- Paired acute and convalescent sera (2–3 weeks apart); 4-fold rise in titer is confirmatory [2]
- Single elevated titer is presumptive [2]
- PCR: Useful for early diagnosis from lymph node aspirates, wound swabs; more sensitive than culture [2]
- Culture: Lymph node aspirate or biopsy on cysteine-enriched media; blood cultures often negative; must alert the laboratory due to high risk of laboratory-acquired infection [1][6][15]
- General labs: CBC (may show leukocytosis or normal WBC), CRP/ESR (elevated), LFTs (may be mildly elevated in systemic disease) [4]
- Median time to diagnosis is 23.5 days in some series, highlighting the importance of clinical suspicion [12]
12. Imaging
- Ultrasound of lymph nodes: First-line to characterize adenopathy — assess for suppuration, abscess formation, conglomerate nodes [4]
- CT with contrast: Useful if deep lymphadenopathy suspected or to evaluate for abscess requiring drainage [4]
- Chest imaging: Not routinely needed in isolated glandular form; obtain if respiratory symptoms present to rule out pneumonic involvement [11][15]
- International Journal of Infectious Diseases + 1[11][20]
- PET/CT: Can show intensely hypermetabolic lesions mimicking malignancy — important pitfall [11]
- Imaging unnecessary in straightforward glandular tularemia with clear exposure history and positive serology
13. Special Tests
- Direct immunofluorescence assay (DFA) — can be performed on tissue specimens [6]
- Immunohistochemical staining — useful on biopsy specimens [6]
- Histopathology: Necrotizing granulomatous inflammation; rarely caseating granulomas (mimics TB) [19]
- No validated clinical scoring system exists for tularemia severity stratification
- Point-of-care: No rapid bedside test currently available; diagnosis relies on clinical suspicion and confirmatory serology/PCR
14. ECG
- ECG is not routinely indicated in glandular tularemia
- Myocarditis is a very rare complication — obtain ECG if chest pain, dyspnea, or signs of heart failure develop [16]
- Pericarditis and endocarditis have been reported but are exceedingly rare, typically in the setting of pneumonic or typhoidal forms [21-22]
- If obtained, look for: ST changes, conduction abnormalities, or low voltage suggesting pericardial effusion
15. Assessment
- Glandular tularemia is a localized, generally mild-to-moderate form of tularemia with isolated regional lymphadenopathy and no detectable skin ulcer [1-2]
- Typically presents with fever + tender regional adenopathy in a patient with relevant exposure history (tick bite, animal contact) [1][6]
- Median incubation 3 days; patients often present after several days of illness [3]
- Frequently initially misdiagnosed — median time to diagnosis ~23 days; beta-lactam failure is a key diagnostic clue [3][12]
- Complications: Lymph node suppuration (~30%), chronic course, rarely meningitis, soft tissue abscess, erythema nodosum [2][10]
- Mortality in glandular form is very low with appropriate treatment; overall US case fatality rate is ~2.3% (driven primarily by pneumonic/typhoidal forms) [23]
16. Treatment Plan
Initial management:
- Start empiric antibiotics as soon as tularemia is suspected — early treatment is the most important prognostic factor [2][10]
- Alert the microbiology laboratory if cultures are sent [1][6][15]
Mild-moderate glandular tularemia (outpatient):
- Ciprofloxacin 500 mg PO BID × 10–14 days, OR
- Levofloxacin 500 mg PO daily × 10–14 days, OR
- Doxycycline 100 mg PO BID × 14–21 days (higher relapse rate) [1-2][13]
Severe or complicated disease (inpatient):
- Gentamicin 5 mg/kg/day IV divided q8h × 10 days (adjust for renal function), OR
- Streptomycin 15 mg/kg IM q12h (max 2 g/day) × 10 days [1][14]
- Step down to oral fluoroquinolone or doxycycline once clinically improved [1]
Suppurative lymph nodes:
- Surgical drainage or excision may be required in ~23% of patients, particularly with abscess, necrosis, or conglomerate nodes [4][10]
- Antibiotic duration is typically longer in patients requiring drainage [4]
Postexposure prophylaxis (laboratory exposure):
17. Disposition
- Discharge criteria (most glandular tularemia): Hemodynamically stable, tolerating PO, no signs of systemic toxicity, reliable follow-up; can be managed as outpatient with oral fluoroquinolone or doxycycline [1][3]
- Admission criteria: High fever with systemic toxicity, inability to tolerate oral medications, suspected pneumonic or typhoidal progression, immunocompromised host, suppurative nodes requiring IV antibiotics or surgical drainage [2][9]
- Observation: Consider for patients with diagnostic uncertainty or borderline systemic illness
- Specialist consultation: Infectious disease consultation for confirmed or suspected cases; surgery if suppurative nodes require drainage; public health notification (tularemia is a nationally notifiable disease) [3][23]
18. Follow Up / Return Precautions
- Follow-up in 48–72 hours to assess clinical response to antibiotics; re-evaluate at 1–2 weeks [10]
- Convalescent serology at 2–3 weeks to confirm diagnosis [2][6]
- Return precautions — seek immediate care for:
- Worsening or new lymph node swelling, fluctuance, or drainage
- Persistent or worsening fever despite 48–72 hours of appropriate antibiotics
- New respiratory symptoms (cough, dyspnea, chest pain)
- Confusion, altered mental status
- Inability to tolerate oral medications
- Relapse: Treatment failures and relapses occur in 5–15% of cases, especially with delayed treatment (>2–3 weeks after onset) or bacteriostatic agents; patients should be counseled about this possibility [2][10]
- Expected recovery: Most patients with glandular tularemia treated early with appropriate antibiotics recover fully, though lymphadenopathy may take weeks to months to fully resolve [10][19]
- Prevention counseling: Tick avoidance measures (DEET, permethrin-treated clothing, tick checks), gloves when handling wild game, avoid untreated water sources in endemic areas [2][7]
References
1. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. — Stevens DL, Bisno AL, Chambers HF, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2014.
2. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. — Stevens DL, Bisno AL, Chambers HF, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2014.
3. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. — Stevens DL, Bisno AL, Chambers HF, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2014.
4. Tularaemia: Clinical Aspects in Europe. — Maurin M, Gyuranecz M. The Lancet. Infectious Diseases. 2016.
5. Tularaemia: Clinical Aspects in Europe. — Maurin M, Gyuranecz M. The Lancet. Infectious Diseases. 2016.
6. Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases. — Weber IB, Turabelidze G, Patrick S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2012.
7. Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases. — Weber IB, Turabelidze G, Patrick S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2012.
8. Evaluation of the Clinical Characteristics, Laboratory Parameters, and Antibiotic Treatment in Patients Diagnosed With Tularemia. — Çakır Kıymaz Y, Bolat S, Katırcı B, et al. Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2025.
9. Evaluation of the Clinical Characteristics, Laboratory Parameters, and Antibiotic Treatment in Patients Diagnosed With Tularemia. — Çakır Kıymaz Y, Bolat S, Katırcı B, et al. Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2025.
10. Going Down the Rabbit Hole. — Burdick KJ, Ealick W, Vargas Acevedo H, Sectish TC, Sandora TJ. The New England Journal of Medicine. 2024.
11. Going Down the Rabbit Hole. — Burdick KJ, Ealick W, Vargas Acevedo H, Sectish TC, Sandora TJ. The New England Journal of Medicine. 2024.
12. Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers Sixth Edition. — Nancy Shadick MD MPH, Nancy Maher MPH, Dennis Hoak MD United States Centers for Disease Control and Prevention (2022). 2022.
13. Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers Sixth Edition. — Nancy Shadick MD MPH, Nancy Maher MPH, Dennis Hoak MD United States Centers for Disease Control and Prevention (2022). 2022.
14. Tick-Borne Diseases in the United States. — Spach DH, Liles WC, Campbell GL, et al. The New England Journal of Medicine. 1993.
15. Tick-Borne Diseases in the United States. — Spach DH, Liles WC, Campbell GL, et al. The New England Journal of Medicine. 1993.
16. Multifaceted effects of F rancisella tularensis on human neutrophil function and lifespan. — Kinkead LC, Allen LA. Immunological Reviews. 2016.
17. Multifaceted effects of F rancisella tularensis on human neutrophil function and lifespan. — Kinkead LC, Allen LA. Immunological Reviews. 2016.
18. Tularemia for Clinicians: An Up-to-Date Review on Epidemiology, Diagnosis, Prevention and Treatment. — Antonello RM, Giacomelli A, Riccardi N. European Journal of Internal Medicine. 2025.
19. Tularemia for Clinicians: An Up-to-Date Review on Epidemiology, Diagnosis, Prevention and Treatment. — Antonello RM, Giacomelli A, Riccardi N. European Journal of Internal Medicine. 2025.
20. Tularemia Treatment: Experimental and Clinical Data. — Maurin M, Pondérand L, Hennebique A, et al. Frontiers in Microbiology. 2023.
21. Tularemia Treatment: Experimental and Clinical Data. — Maurin M, Pondérand L, Hennebique A, et al. Frontiers in Microbiology. 2023.
22. Pulmonary Tularemia: A Diagnosis Not to Overlook. — Zaghdoudi A, Robin F, Moulinie J, et al. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. 2026.
23. Pulmonary Tularemia: A Diagnosis Not to Overlook. — Zaghdoudi A, Robin F, Moulinie J, et al. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. 2026.
24. Tularemia in Pediatric Patients: A Case Series and Review of the Literature. — Kossadoum RF, Baron A, Parizot M, et al. The Pediatric Infectious Disease Journal. 2025.
25. Tularemia in Pediatric Patients: A Case Series and Review of the Literature. — Kossadoum RF, Baron A, Parizot M, et al. The Pediatric Infectious Disease Journal. 2025.
26. Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response - United States, 2025. — Nelson CA, Meaney-Delman D, Fleck-Derderian S, Winberg J, Mead PS. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2025.
27. Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response - United States, 2025. — Nelson CA, Meaney-Delman D, Fleck-Derderian S, Winberg J, Mead PS. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2025.
28. Tularemia as a Biological Weapon: Medical and Public Health Management. — Dennis DT, Inglesby TV, Henderson DA, et al. The Journal of the American Medical Association. 2001.
29. Tularemia as a Biological Weapon: Medical and Public Health Management. — Dennis DT, Inglesby TV, Henderson DA, et al. The Journal of the American Medical Association. 2001.
30. Clinical Management of Potential Bioterrorism-Related Conditions. — Adalja AA, Toner E, Inglesby TV. The New England Journal of Medicine. 2015.
31. Clinical Management of Potential Bioterrorism-Related Conditions. — Adalja AA, Toner E, Inglesby TV. The New England Journal of Medicine. 2015.
32. Tularemia: An Experience of 13 Cases Including a Rare Myocarditis in a Referral Center in Eastern Switzerland (Central Europe) and a Review of the Literature. — Frischknecht M, Meier A, Mani B, et al. Infection. 2019.
33. Tularemia: An Experience of 13 Cases Including a Rare Myocarditis in a Referral Center in Eastern Switzerland (Central Europe) and a Review of the Literature. — Frischknecht M, Meier A, Mani B, et al. Infection. 2019.
34. Tularemia Transmitted by Insect Bites--Wyoming, 2001-2003. — MMWR. Morbidity and Mortality Weekly Report. 2005.
35. Tularemia Transmitted by Insect Bites--Wyoming, 2001-2003. — MMWR. Morbidity and Mortality Weekly Report. 2005.
36. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
37. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
38. A Clinical Pitfall in Caseating Necrotizing Granulomatous Lymphadenitis: Tularemia. — Özan Köse S, Erdem H, Köse ÖC, Yılmaz Ertürk F. Diagnostic Microbiology and Infectious Disease. 2025.
39. A Clinical Pitfall in Caseating Necrotizing Granulomatous Lymphadenitis: Tularemia. — Özan Köse S, Erdem H, Köse ÖC, Yılmaz Ertürk F. Diagnostic Microbiology and Infectious Disease. 2025.
40. Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones. — Widerström M, Mörtberg S, Magnusson M, Fjällström P, Johansson AF. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
41. Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones. — Widerström M, Mörtberg S, Magnusson M, Fjällström P, Johansson AF. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
42. ACCF/AHA/CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism Threats. Task Force III: Prevention and Control of Cardiovascular Complications of Emerging Infectious Diseases and Potential Biological Terrorism Agents and Diseases. — Cooper LT, Mensah GA, Baddour LM, et al. Journal of the American College of Cardiology. 2007.
43. ACCF/AHA/CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism Threats. Task Force III: Prevention and Control of Cardiovascular Complications of Emerging Infectious Diseases and Potential Biological Terrorism Agents and Diseases. — Cooper LT, Mensah GA, Baddour LM, et al. Journal of the American College of Cardiology. 2007.
44. ACCF/AHA/CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism Threats. Task Force I: Direct Cardiovascular Implications of Emerging Infectious Diseases and Biological Terrorism Threats. — Baddour LM, Zheng ZJ, Labarthe DR, O'Connor S. Journal of the American College of Cardiology. 2007.
45. ACCF/AHA/CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism Threats. Task Force I: Direct Cardiovascular Implications of Emerging Infectious Diseases and Biological Terrorism Threats. — Baddour LM, Zheng ZJ, Labarthe DR, O'Connor S. Journal of the American College of Cardiology. 2007.
46. Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021. — Wu HJ, Bostic TD, Horiuchi K, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
47. Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021. — Wu HJ, Bostic TD, Horiuchi K, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.