Miliary tuberculosis: A new look at an old foe

Abstract

Miliary tuberculosis (TB), is a fatal form of disseminated TB characterized by tiny tubercles evident on gross pathology similar to innumerable millet seeds in size and appearance. Global HIV/AIDS pandemic and increasing use of immunosuppressive drugs have altered the epidemiology of miliary TB. Keeping in mind its protean manifestations, clinicians should have a low threshold for suspecting miliary TB. Careful physical examination should focus on identifying organ system involvement early, particularly TB meningitis, as this has therapeutic significance. Fundus examination for detecting choroid tubercles can help in early diagnosis as their presence is pathognomonic of miliary TB. Imaging modalities help in recognizing the miliary pattern, define the extent of organ system involvement and facilitate image guided fine-needle aspiration cytology or biopsy from various organ sites. Sputum or BAL fluid examination, pleural, pericardial, peritoneal fluid and cerebrospinal fluid studies, fine needle aspiration cytology or biopsy of the lymph nodes, needle biopsy of the liver, bone marrow aspiration and biopsy, testing of body fluids must be carried out. GeneXpert MTB/RIF, line probe assay, mycobacterial culture and drug-susceptibility testing must be carried out as appropriate and feasible. Treatment of miliary TB should be started at the earliest as this can be life saving. Response to first-line anti-TB drugs is good. Screening and monitoring for complications like acute respiratory distress syndrome (ARDS), adverse drug reactions like drug-induced liver injury, drug-drug interactions, especially in patients co-infected with HIV/AIDS, are warranted. Sparse data are available from randomized controlled trials regarding optimum regimen and duration of anti-TB treatment.

Keywords: Complications; Diagnosis; Human immunodeficiency virus; Miliary tuberculosis; Treatment.

Fig. 1

Chest radiograph (postero-anterior view) (A) and chest CT (lung window) (B) showing classical miliary pattern. The nodules (<2 mm) evident in miliary tuberculosis resemble the grains of pearl millet (Pennisetum typhoides, bajra) (C).

Fig. 2

Ophthalmoscopic picture showing choroid tubercles (arrows). (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)

Fig. 3

Clinical photograph of a HIV-seropositive patient who also had poorly controlled type 2 diabetes mellitus with miliary TB showing papulonodular cutaneous lesions over the face HIV = human immunodeficiency virus; TB = tuberculosis. Kind courtesy: Professor D.R. Reddy, Department of Dermatology, Venereology and Leprosy, Teerthanker Mahaveer Medical College & Research Centre, Moradabad, Uttar Pradesh, India.

Fig. 4

Algorithm for the diagnostic work-up of a patient with suspected miliary TB. The clinical and imaging diagnostic work-up should also aim at accurately assessing the extent of extrapulmonary involvement to facilitate monitoring and ensure adequate duration of treatment. All laboratory testing, especially, antituberculosis drug-susceptibility testing must be carried out in quality assured, periodically accredited laboratories. * Often used in children. † FNAC/excision biopsy. ‡ Radiologically guided FNAC/biopsy. § Mediastinoscopic/video-assisted thoracoscopic surgery, biopsy. || Laparoscopic biopsy. Useful in advanced HIV infection. TB = tuberculosis; TST = tuberculin skin test; IGRA = interferon-γ release assays; HRCT = high resolution computed tomography; CECT = contrast enhanced computed tomography; MRI = magnetic resonance imaging; FNAC = fine needle aspiration cytology; HIV = human immunodeficiency virus; AFB = acid-fast bacilli; L–J = Lowenstein–Jensen medium; DST = drug-susceptibility testing; MGIT = mycobacterial growth inhibitor tube; BACTEC = radiometric culture method; PCR = polymerase chain reaction; GeneExpert MTB/RIF = GeneXpert MTB/RIF assay (Cepheid, Sunnyvale, CA); LPA = line probe assay Adapted and reproduced with permission from Sharma et al. .

Fig. 5

Chest radiograph (postero-anterior view) (A) and CT chest (lung window) (B) showing classical miliary pattern. CT chest (mediastinal window) (C) of the same patient also shows pre-vascular and mediastinal lymph nodes (arrows) CT (lung window). CT abdomen (D) of the same patient showing intrabdominal lymphadenopathy (asterisk). Bronchoalvelolar fluid GeneXpert MTB/RIF detected Mycobacterium tuberculosis; there was no rifampicin resistance. CT = computed tomography.

Fig. 6

Organ system involvement in military TB. PET maximum intensity projection image (A) showing abnormal tracer accumulation in the lung fields. Axial CT of the same patient showing randomly distributed miliary nodules in both lungs. Axial ¹⁸FDG PET-CT fused image showing the FDG uptake in the nodules. PET = positron emission tomography; CT = computer tomography; ¹⁸FDG-PET CT = ¹⁸F labeled 2-deoxy-Dglucose positron emission tomography-computed tomography. Kind courtesy: Dr Madhavi Tripathy, Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Fig. 7

Algorithm for treatment of miliary TB. The anti-retroviral treatment recommendations in miliary TB patients co-infected with HIV are based on Refs. , . TB = tuberculosis; HIV = human immunodeficiency virus; + = seropositive; − = seronegative; ART = antiretroviral treatment; IRIS = immune reconstitution inflammatory syndrome; DILI = anti-TB drug-induced liver injury; EFV = efavirenz; NNRTI = non-nucleoside reverse transcriptase inhibitors. Adapted and reproduced with permission from Sharma et al. .