A 25 Year Old Man Presents With Cough, Low grade fever And Night sweats For 3 Weeks

A 25 -year-old man from the third world country presents to his doctor with a persistent cough for 3 weeks, low grade fever, and night sweats. His chest x-ray  is shown above. The X ray shows mediastinal and right hilar lymphadenopathy and right upper lobe consolidation concerning
for primary tuberculosis (shown by arrows).
The patient's sputum is sent for acid-fast bacillus (AFB) stain and cultures, and the results show acid-fast bacilli consistent with Mycobacterium species.
While culture results are pending, the patient is started on 4 antituberculosis drugs. Fortunately, the sputum  culture result shows pan susceptible Mycobacterium tuberculosis, and his treatment is continued.

Case Discussion:

Tuberculosis:
Introduction: Tuberculosis (TB) is a bacterial infection caused by Mycobacterium . tuberculosis, an
obligate intracellular pathogen that is aerobic, acid fast, and non encapsulated.
TB primarily involves the lungs, although other organs are involved in one-third of cases.

More than 8 million cases occur annually around the world, with nearly 2 million TB-related deaths.  95% of TB deaths occur in low- and middle-income countries.

Risk Factors: Risk factors for infection or progression to active TB include:

• Populations who are at risk to overcrowding and malnutrition.
• HIV
• Immunocompromised states (e.g., cancer, treatment with tumor necrosis factor antagonists)
• Chronic diseases such as diabetes mellitus  or chronic renal failure/hemodialysis
• Malignancy.
• Genetic susceptibility.
• Injection drug users
• Smoking
• Personnel who work or live in high-risk settings (e.g., prisons, long-term care facilities, and hospitals).
• Adult women (ratio 2:1 adult man).
• Older age (both infection and progression).
• Children younger than 4 years of age who are exposed to high-risk individuals.
• Recent infection

Clinical Features: 

• The disease may be asymptomatic in some patients.
• TB can affect any organ system.

Manifestation of active TB can be classified as pulmonary or extrapulmonary.

Pulmonary:

• Early nonspecific signs and symptoms: fever, night sweats, fatigue, anorexia, weight loss.

• Later nonproductive cough (lasting 2 to 3 weeks) or cough with purulent sputum.

• Patients with extensive disease may develop dyspnea or acute respiratory distress syndrome.

• Physical examination findings also nonspecific with crackles or rhonchi.

Extrapulmonary TB, caused by hematogenous spread, occurs in the following order of frequency:

• Lymph nodes: painless swelling of cervical and supraclavicular nodes (scrofula) 

• Pleura: pleural effusion with exudates.

• Genitourinary tract: may cause urethral stricture, kidney damage or infertility (in women, affects the fallopian tubes and endometrium).

• Bones and joints: pain in the spine (Pott disease), hips, or knees.

• Other less common sites are meninges, peritoneum, intestines, skin, eye, ear, and pericardium.

• TB of the skin (scrofuloderma) shows ulcerations of the skin in the inguinal or cervical region along

with lymphadenopathy.

Diagnosis:

1. Tuberculin skin test (TST) with purified protein derivative (PPD) is not useful in diagnosing

active TB but is used to detect latent infection in exposed or high-risk individuals. A positive test is 10 mm induration at the inoculation site or 5 mm induration in a patient who is immunocompromised; evaluated in 48 to 72 hours after test placement.

2. Acid-fast bacilli may be seen on acid-fast staining from sputum or pleural or peritoneal fluid  They may also be seen upon staining tissue from fine-needle aspiration or biopsy of lymph nodes or other tissues.

3. Definitive diagnosis is based on culture of sputum (3 sets of samples collected 8 to 24 hours apart), urine (3 morning specimens—positive in 90% with urinary tract infection), or from tissue or bone biopsy using automated liquid culture systems. M. tuberculosis is slow growing and may take 4 to 8 weeks to identify.

4. Chest x-ray (CXR) is the diagnostic test of choice and classically shows upper lobe infiltrates with cavitation and/or lymphadenopathy. 

5. Other patterns of TB seen on CXR include a solitary nodule (Ghon complex) and diffuse infiltrates that may represent bronchogenic spread. 

6. In disseminated (miliary) TB, innumerable tiny nodules are seen throughout both lungs on CXR and CT. 

7, Histology reveals granulomas with caseating necrosis.

Differential Diagnosis: Because any pattern on CXR may be seen with active TB, the differential
diagnosis includes:
• Bacterial or viral pneumonia—Sputum or blood culture may reveal the infecting organism, and the patient will usually respond to antibacterial drugs and/or time.
• Fungal respiratory infections—These patients usually have a history of travel to or living in an area where histoplasmosis or coccidiomycosis is endemic.
• Acute histoplasmosis is usually asymptomatic or causes only mild symptoms and CXR typically shows hilar adenopathy with or without pneumonitis ; patients with chronic pulmonary histoplasmosis have gradually increasing cough, weight loss, and night sweats, and CXR shows uni- or bilateral fibronodular, apical infiltrates; positive serology or culture, immunodiffusion test, or
lung biopsy can be diagnostic.
• Coccidiomycosis has similar clinical features to TB and CXR may show infiltrate, hilar adenopathy, and pleural effusion; serologic tests are useful in the diagnosis.
• Sarcoidosis—No TB contacts, dyspnea and cough, hilar adenopathy on CXR, skin lesions help differentiate along with serum angiotensinconverting enzyme level or biopsy. Pathology shows noncaseating granulomata .

Management: 

For adult patients with active TB there are 4 major drugs used for treatment. The first line anti-TB medications should be administered together; split dosing should be avoided. Review the patient’s current medications to avoid drug interactions. A few combination medications are available but are more costly.
The following regimen is suggested by the American Thoracic Society, Infectious Diseases Society
of America, and the Centers for Disease Control and Prevention:

Two-month initial treatment phase with all 4 medications

• isoniazid 5 mg/kg daily [maximum 300 mg] ;
• rifampin  10 mg/kg daily  [maximum 600 mg]
• pyrazinamide 20 to 25 mg/kg daily [maximum 2 g]  
• ethambutol  5 to 20 mg/kg daily . 

Four-month continuation phase with isoniazid (INH) and rifampin; treatment is extended to 7 months for patients with cavitary pulmonary TB who remain sputum-positive after initial treatment or if pregnant.

The World Health Organization 2010 recommendations agree with continuing rifampin for 6 months and emphasize the importance of drug sensitivity testing to guide individual patient management