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Clinical Analysis: 38-Year-Old Male with Evening Rise of Temperature

Decoding the Presenting Complaints

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Most Likely Diagnosis: BRUCELLOSIS (Undulant Fever)

"Two features recognized in the nineteenth century distinguish brucellosis from other tropical fevers, such as typhoid and malaria: (1) the fever of brucellosis shows an undulating pattern...persists for weeks...followed by relapse; (2) the fever of brucellosis is associated with musculoskeletal symptoms and signs in about one-half of all patients."

• Harrison's Principles of Internal Medicine 22E (2025)

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Why Each Feature Fits

• Brucellosis is nicknamed undulant fever because of its remittent, wave-like fever pattern - often peaking in the evenings with drenching night sweats.
• Fever > 39.4°C occurs in 95% of patients; a relative bradycardia (pulse-temperature dissociation) may also be present.

• Osteoarticular involvement occurs in ~40% of cases.
• Sacroiliitis is the most common acute presentation; lumbar spondylitis/spondylodiscitis in the lumbar area is the next most frequent.
• In endemic areas, a man with fever + difficulty walking is suspected to have brucellosis until proven otherwise.
• Goldman-Cecil notes: "Among osteoarticular complications, sacroiliitis is the most common acute presentation."

• Ocular pain and blurring of vision occur in a subset of patients, representing either direct orbital/ocular brucellosis or part of neurobrucellosis.
• Up to 10% of men develop epididymo-orchitis; similarly, genitourinary and neurological spread is well documented.

• Neurobrucellosis affects the CNS/peripheral nervous system including cranial nerves, causing sensorineural hearing loss and tinnitus.
• Any cranial nerve may be affected; vestibulo-cochlear involvement causes tinnitus, vertigo, and ear pain.

• Oropharyngeal route is a recognized entry point (consumption of unpasteurized dairy, soft cheeses).
• Lymphadenopathy (cervical, axillary) is present in ~14% of patients, and oropharyngeal/gingival lesions reflect hematogenous seeding or local entry.

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Differential Diagnosis to Consider

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Key History Questions to Ask

1. Occupation: Farmer, veterinarian, abattoir/slaughterhouse worker, laboratory worker?
2. Diet: Unpasteurized milk, soft goat/sheep cheese (feta, brie), raw/undercooked meat?
3. Travel: Endemic area (Middle East, Mediterranean, Central Asia, Sub-Saharan Africa, Latin America)?
4. Animal contact: Cattle, sheep, goats, camels, swine, dogs?
5. Similar illness in family members (documented in ~50% of household cases in endemic areas)?

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Investigations

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Treatment

• Doxycycline 100 mg BD x 6 weeks + Rifampicin 600-900 mg OD x 6 weeks

• Doxycycline + Streptomycin (or Gentamicin) IM for initial 2-3 weeks, then switch to doxycycline + rifampicin to complete 3-6 months

"With early antimicrobial therapy, brucellosis is usually cured, and cases of relapsing brucellosis, chronic brucellosis, or localized complications are rare."

• Goldman-Cecil Medicine

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Red Flags Requiring Urgent Evaluation

• Focal neurological signs (neurobrucellosis - can cause meningitis, encephalitis)
• Cardiac involvement (Brucella endocarditis - rare but high mortality)
• Severe thrombocytopenia or pancytopenia
• Spinal cord compression signs

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• Harrison's Principles of Internal Medicine 22E (2025), Chapter 174: Brucellosis
• Goldman-Cecil Medicine, Chapter 286: Brucellosis
• Medical Microbiology 9e, Clinical Case 29.3

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Management of Brucellosis - Step-by-Step

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STEP 1: CLINICAL ASSESSMENT & RISK STRATIFICATION

• Occupational exposure: farmer, veterinarian, abattoir worker, lab personnel?
• Dietary: unpasteurized milk, soft goat/sheep cheese, undercooked meat?
• Travel to endemic area (Middle East, Mediterranean, South Asia, Africa)?
• Duration of symptoms (determines acute vs subacute vs chronic classification)

This patient has features suggestive of both spondylitis (back/waist pain) and possible neurobrucellosis (tinnitus + periorbital pain) - this classifies him as COMPLICATED brucellosis, requiring longer therapy.

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STEP 2: INVESTIGATIONS

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STEP 3: ANTIMICROBIAL THERAPY

A. Uncomplicated Acute Brucellosis (for reference)

• Doxycycline 100 mg PO BD x 6 weeks + Streptomycin 1 g IM OD x 2-3 weeks

• Doxycycline 100 mg PO BD x 6 weeks + Rifampicin 600-900 mg PO OD x 6 weeks

• Doxycycline 200 mg/day x 6 weeks + Gentamicin 3-5 mg/kg/day IM x 1-2 weeks

B. Complicated Brucellosis - Spondylitis / Sacroiliitis (this patient)

• Duration extended to 3 months minimum
• Triple regimen: Doxycycline + Rifampicin + initial Aminoglycoside (Gentamicin x 2 weeks)
• Monitor MRI spine for response

C. Neurobrucellosis (if confirmed by CSF/MRI)

• Duration 3-6 months
• Doxycycline 200 mg/day + Rifampicin 600-900 mg/day + TMP-SMX (co-trimoxazole) for 6+ weeks
• Can add Ceftriaxone 2 g IV q12h x 6 weeks (substitutes for one oral agent - better CNS penetration)
• Steroids may be considered in severe neurobrucellosis with inflammation

"Focal neurologic disease due to Brucella requires prolonged treatment for 3-6 months, usually with ceftriaxone supplementation of a standard two-drug regimen." - Harrison's 22E

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STEP 4: SUPPORTIVE MANAGEMENT

• Analgesics / NSAIDs for musculoskeletal pain (back, sacroiliac joints)
• Bed rest in the acute phase; gradual mobilization
• Spinal immobilization/bracing if significant spondylodiscitis on MRI
• Physiotherapy for back pain rehabilitation after acute phase settles
• Neurology referral if confirmed neurobrucellosis
• Orthopedics referral if spinal abscess (paravertebral/psoas) requiring surgical drainage

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STEP 5: MONITORING & FOLLOW-UP

• Return of fever, sweats, malaise
• Rising SAT titres
• Positive blood culture
• Treat relapse with the same or alternative two-drug regimen for a full 6 weeks

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STEP 6: PREVENT COMPLICATIONS & SPECIAL SITUATIONS

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STEP 7: INFECTION CONTROL & PREVENTION

• Notify public health authorities (notifiable disease in many countries)
• Identify source of infection (animal contact, food source)
• Screen family members and occupational contacts
• Avoid unpasteurized dairy products going forward
• Protective equipment if occupational exposure continues

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Summary Drug Chart for This Patient

"Complex or focal disease may necessitate ≥3 months of therapy. Adherence is very important - poor adherence underlies almost all cases of apparent treatment failure." - Harrison's 22E

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