para>May need to culture samples from infected adult contact because samples can be difficult to obtain in children ‚
Diagnostic Procedures/Other
- See "Tuberculosis. " ¯
- Collect samples for AFB/culture/NAAT. Sampling fluids from multiple sites greatly improves yield:
- Sputum culture positive in 62% (smear in 33%)
- Bronchoalveolar lavage (BAL) culture positive in 55% (smear in 27%)
- Gastric aspirate culture positive in nearly 100% (smear in 43%)
- CSF culture positive in 60% (smear in 8%)
- Biopsy organs based on symptoms.
Test Interpretation
- Caseating granulomas on biopsy (typically liver)
- Acute type: microabscesses; neutrophilic response
- Can see mycotic aneurysms if disease affects aorta
- TB pericarditis diagnosed by pericardial biopsy
TREATMENT
- Diagnosis is often hampered by low clinical suspicion, which delays collection of appropriate fluid/tissue samples for AFB smear and culture.
- Empiric therapy is often indicated, as early initiation of therapy reduces morbidity and mortality.
- Duration of therapy for all forms of TB should be tailored to each individual patient: Those with miliary TB are likely to be at the extremes of age, have a higher incidence of underlying disease, and a larger organismal burden. Thus, it is often appropriate to extend the duration of therapy beyond minimum recommendations.
GENERAL MEASURES
- Respiratory isolation if pulmonary disease; TB mask when out of hospital room or in contact with others at home (if deemed contagious)
- Attention to good nutrition is important. Many miliary TB patients are debilitated, and malnutrition weakens the immune system.
MEDICATION
- All drug regimens similar to those for general TB.
- Adherence is important to prevent drug resistance; directly observed therapy (DOT) recommended for nondaily regimens. DOT may not, however, be superior to self-administration (8)[A].
- Regimens <6 months have an unacceptably high rate of relapse. For a regimen to be maximally effective, it must include rifampin throughout the 6 months and pyrazinamide throughout the first 2 months (9).
- DOT regimens with observed therapy 3 times per week are effective, the WHO does not recommend twice weekly regimens (9).
- Response to treatment in patients with evidence of pulmonary TB should be evaluated by checking sputum smear at completion of initial phase. For patients with military TB, the initial phase may not yet be complete at 2 months " ”must assess and decide whether to continue or change drugs. If sputum is positive at 2 months, but the patient is better clinically, continue with current treatment and assess sputum at 3 months. If sputum remains positive at 3 months, full testing for drug resistance is indicated (9).
First Line
- Regimen 1 (preferred) (8)[A]
- Initial phase: isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) once daily for 8 weeks
- Continuation phase: INH/RIF daily for 18 weeks
- Regimen 2 (acceptable alternative) (8)[B]
- Initial phase: INH/RIF/PZA/EMB 3 times per week for 8 weeks
- Continuation phase: INH/RIF 3 times per week for 18 weeks
- Dosing for daily regimen (9) (for alternate dosing less frequently than daily, see "Tuberculosis " ¯)
- INH: adult 4 to 6 mg/kg/day (max 300 mg); pediatric 7 to 15 mg/kg/day (max 300 mg)
- RIF: adult 8 to 12 mg/kg/day (max 600 mg); pediatric 10 to 20 mg/kg/day (max 600 mg)
- PZA: adults 20 to 30 mg/kg/day (max 2,000 mg); pediatric 30 to 40 mg/kg/day (max 2000 mg)
- EMB: adults 15 to 20 mg/kg/day (max 1,600 mg): pediatric: 15 to 25 mg/kg/day (max 1,000 mg)
- Contraindications
- RIF: avoid if patient taking antiretrovirals
- EMB: may cause optic neuritis; avoid unless patient is old enough to cooperate for visual acuity and color testing.
- Precautions
- INH, RIF, PZA: may cause hepatitis; caution if liver disease
- RIF: colors urine, tears, and secretions orange; can stain contact lenses
- INH: peripheral neuritis and hypersensitivity possible; treat with pyridoxine.
- PZA: may increase uric acid; unclear safety during pregnancy (8)[C]
- Significant possible interactions: Rifamycins alter level of phenytoin, antivirals, and other drugs metabolized by liver and may inactivate birth control pills (recommend a barrier method).
Second Line
- Rifabutin (Mycobutin): daily or twice weekly: adult 5 mg/kg, maximum 300 mg
- Rifapentine (Priftin): for continuation phase only. Adults: 600 mg once weekly, given with INH; not effective if HIV positive
- Corticosteroids: only with concurrent anti-TB therapy, and only for TB meningitis, pericarditis, or severe miliary disease; corticosteroids reduce fluid reaccumulation in pericarditis; no mortality benefit
- Streptomycin: caution: ototoxic and nephrotoxic; do not use in pregnancy.
- Several aminoglycosides and fluoroquinolones are effective against TB.
ISSUES FOR REFERRAL
- Infectious disease specialist, particularly for patients on antiretrovirals because doses may need adjusting.
- Expert consultation available FREE " ”from Curry International TB Center (877) 390-6682
- Notify public health authorities.
Pregnancy Considerations
Streptomycin cannot be used in pregnancy. But active TB should be treated. INH, rifampin, and ethambutol are each known to cross the placenta, but none are known to be teratogenic.
‚
SURGERY/OTHER PROCEDURES
- Location- and patient-specific
- Medical treatment unresponsiveness may rarely require surgical intervention; there is some evidence for the role of surgical therapy in select cases of drug-resistant TB.
INPATIENT CONSIDERATIONS
Place initially in isolation/negative-pressure room. Miliary TB is somewhat less contagious than other forms of TB. If patient lives at home with someone at increased risk of acquiring TB (e.g., HIV infection), then keep hospitalized until several consecutive sputum smears are negative and the patient is improved clinically. ‚
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- General TB follow-up; most states require department of public health notification.
- Identify and test any close contacts.
Patient Monitoring
See "Tuberculosis. " ¯ ‚
DIET
Some evidence suggests that high-cholesterol diet accelerates sterilization of sputum in pulmonary TB patients. In all patients, it is important to attend to specific malnutrition correction. ‚
PATIENT EDUCATION
As for general TB ‚
PROGNOSIS
- Mortality: untreated, approaching 100%; 16 " “38% on average; with early and appropriate treatment, <10%
- Nutritional deficit (assessed by four measures: very low BMI, low serum albumin and cholesterol, and lymphocytopenia) is an independent risk factor for acute respiratory failure in miliary TB (10).
- Relapse rate: <5% with adequate, DOT
COMPLICATIONS
- ARDS with refractory hypoxemia can occur.
- Multidrug-resistant TB is rare in the United States but increasing elsewhere.
REFERENCES
11 World Health Organization. Global tuberculosis report 2015. Geneva, Switzerland: World Health Organization; 2015. http://www.who.int/tb/publications/global_report/en/. Accessed 2015.22 Colditz ‚ GA, Brewer ‚ TF, Berkey ‚ CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271(9):698 " “702.33 Pereira ‚ SM, Dantas ‚ OM, Ximenes ‚ R, et al. BCG vaccine against tuberculosis: its protective effect and vaccination policies [in Portuguese]. Rev Saude Publica. 2007;41(Suppl 1):59 " “66.44 Mazurek ‚ GH, Jereb ‚ J, Vernon ‚ A, et al. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis intection " ”United States, 2010. MMWR Recomm Rep. 2010;59(RR-5):1 " “25.55 Hong ‚ SI, Lee ‚ YM, Park ‚ KH, et al. Is the sensitivity of the QuantiFERON-TB Gold In-Tube Test lower than that of T-SPOT.TB in patients with miliary tuberculosis? Clin Infect Dis. 2014;59(1):142.66 World Health Organization. Using the Xpert MTB/RIF assay to detect pulmonary and extrapulmonary tuberculosis and rifampicin resistance in adults and children. Expert Group Meeting Report: World Health Organization; 2013.77 Lee ‚ J, Lim ‚ JK, Seo ‚ H, et al. Clinical relevance of ground glass opacity in 105 patients with miliary tuberculosis. Respir Med. 2014;108(6):924 " “930.88 Volmink ‚ J, Garner ‚ P. Directly observed therapy for treating tuberculosis. Cochrane Database Syst Rev. 2007;(4):CD003343.99 TB CARE I. International Standards for Tuberculosis Care. 3rd ed. TB CARE I: The Hague; 2014.1010 Kim ‚ DK, Kim ‚ HJ, Kwon ‚ SY, et al. Nutritional deficit as a negative prognostic factor in patients with miliary tuberculosis. Eur Respir J. 2008;32(4):1031 " “1036.
ADDITIONAL READING
Drugs for tuberculosis. Treat Guidel Med Lett. 2012;10(116):29 " “36; quiz 37 " “38. ‚
SEE ALSO
Tuberculosis; Tuberculosis, CNS ‚
CODES
ICD10
- A19.9 Miliary tuberculosis, unspecified
- A19.2 Acute miliary tuberculosis, unspecified
- A19.8 Other miliary tuberculosis
- A19.0 Acute miliary tuberculosis of a single specified site
- A19.1 Acute miliary tuberculosis of multiple sites
ICD9
- 018.90 Miliary tuberculosis, unspecified, unspecified
- 018.00 Acute miliary tuberculosis, unspecified
- 018.80 Other specified miliary tuberculosis, unspecified
- 018.92 Miliary tuberculosis, unspecified, bacteriological or histological examination unknown (at present)
- 018.82 Other specified miliary tuberculosis, bacteriological or histological examination unknown (at present)
- 018.96 Miliary tuberculosis, unspecified, tubercle bacilli not found by bacteriological or histological examination, but tuberculosis confirmed by other methods [inoculation of animals]
- 018.95 Miliary tuberculosis, unspecified, tubercle bacilli not found by bacteriological examination, but tuberculosis confirmed histologically
- 018.94 Miliary tuberculosis, unspecified, tubercle bacilli not found (in sputum) by microscopy, but found by bacterial culture
- 018.93 Miliary tuberculosis, unspecified, tubercle bacilli found (in sputum) by microscopy
- 018.91 Miliary tuberculosis, unspecified, bacteriological or histological examination not done
- 018.86 Other specified miliary tuberculosis, tubercle bacilli not found by bacteriological or histological examination, but tuberculosis confirmed by other methods [inoculation of animals]
- 018.85 Other specified miliary tuberculosis, tubercle bacilli not found by bacteriological examination, but tuberculosis confirmed histologically
- 018.83 Other specified miliary tuberculosis, tubercle bacilli found (in sputum) by microscopy
- 018.81 Other specified miliary tuberculosis, bacteriological or histological examination not done
- 018.06 Acute miliary tuberculosis, tubercle bacilli not found by bacteriological or histological examination, but tuberculosis confirmed by other methods [inoculation of animals]
- 018.05 Acute miliary tuberculosis, tubercle bacilli not found by bacteriological examination, but tuberculosis confirmed histologically
- 018.04 Acute miliary tuberculosis, tubercle bacilli not found (in sputum) by microscopy, but found by bacterial culture
- 018.03 Acute miliary tuberculosis, tubercle bacilli found (in sputum) by microscopy
- 018.02 Acute miliary tuberculosis, bacteriological or histological examination unknown (at present)
- 018.01 Acute miliary tuberculosis, bacteriological or histological examination not done
- 018.84 Other specified miliary tuberculosis, tubercle bacilli not found (in sputum) by microscopy, but found by bacterial culture
SNOMED
- Miliary tuberculosis (disorder)
- Acute miliary tuberculosis
- Chronic miliary tuberculosis
CLINICAL PEARLS
- The diagnosis of miliary TB requires a high degree of clinical suspicion. Empiric therapy is generally appropriate while awaiting confirmation of test results.
- Chest CT scan is more sensitive than CXR for detecting miliary disease in the lung; and GGO on CT is predictive of severity.
- PPD is positive in <40% of patients.
- IGRAs have higher sensitivity and specificity than PPD for diagnosis of miliary TB.
- When miliary TB is suspected, appropriate specimens from suspected sites of involvement must be obtained for histologic and nucleic acid amplification testing.