Diagnostic dilemmas have always been an integral part of medicine, but the saga between TB and sarcoidosis is never-ending, especially in a country like ours.The traditional evaluation based on clinical and radiological investigations depictoverlapping features, adding to the confusion.Histopathology, once the age old saviour has shown itslimitations. Microbiological diagnosis confirmatory for TB, is time consuming. Adding to the despair is the managementbeingcontrastingfor the two,hence differentiating the two is imperative.

Multisystemic involvement favours sarcoidosis with lung and intrathoracic lymph node being most commonly involved,followed by skin, eyes, joints, CNS, heart and liver.Constitutional symptoms and dyspnoea are overlapping for the two.Following manifestations clinch the diagnosis for sarcoidosis -Lofgren syndrome, Heerfordt syndrome, lupus pernio, uveitis, optic neuritis, VII nerve palsy, treatment responsive renal failure, treatment response cardiomyopathy,spontaneous ventricular tachycardia, atrioventricular block, nephrocalcinosis with hypercalcemia.

Chest imaging highlighting pleural effusions, empyema, miliary mottling, thick walled cavitatory lesions, centrilobular nodules with tree-in-bud appearance,consolidation with ipsilateral lymphadenopathy with central necrosis and peripheral rim enhancement favours TB, whereas perilymphatic nodules in bilateral upper,right middle and linguar lobe,bilateral peribronchovascular infiltrates with upper and middle lobe predominance, bilateral symmetrical hilar and right paratracheal lymphadenopathy without central hypodensity favours sarcoidosis.

Gallium-67 scan showing the classical ‘Lamda sign’(increased blood flow in bilateral paratracheal and hilar lymph nodes) and ‘Panda sign’(uptake in bilateral parotid and lacrimal gland)together are highly specific for sarcoidosis.

Lymph node sampling is a major aid in differentiating these granulomatous mimickers- where once presence of necrosis would stamp the patient with TB, but recent studies show central fibrinoid necrosis is seen in 20% of sarcoidosis patient and non necrotising granulomas can be seen in 24% of TB patients. Giant cells showing intracytoplasmic inclusion bodies-Schwann bodies, asteroid bodies,blue bodies of calcium oxalate are considered charactersitic for sarcoidosis.

Diagnostic invasive procedures via bronchoscopylike Endoscopic ultrasound guided transbronchial nodal aspiration(EU-TBNA), EU guided fine needle aspiration(EU-FNA), Transbronchial lung biopsy(TBLB) and bronchoalveolar fluid analysis help in increasing the yield for diagnosis and differentiating the two.BAL fluid CD4:CD8 lymphocytes>3.5:1 is observed 50-60% sarcoidosis patients but is not very specific.

The negativity of Tuberculin Skin Testing(TST) can help in distinguishing sarcoidosis from TB with negative predictive value(NPV) of 86%, except of immunocompromised patients. According to WHO systematic review, both TST and IGRAs have low positive predictive value in high-TB burden areas but both have high negative predictive value in all settings with no  significant differences in value being 99.6% &99.4% respectively.Hence both are equal in NPVfor distinguishing between pulmonary sarcoidosis and TB.

Molecular techniques for detecting TB like real time polymerase chain reaction(RT-PCR) result in rapid detection of TB compared to TB cultures, which have a turn around time of 6 weeks. RT-PCR has shown a good performance in distinguishing between sarcoidosis and TB if the MTB genome copies were 1.14 x 10³ copies per ml. Further automation like Xpert MTB/RIF assay has tur around time of 2 hours.SAT-TB(Simultaenous amplification and testing method for Mycobactrium tuberculosis rRNA) uses EU-TBNA samples to distinguish between sputum negative activeTB from sarcoidosis with inactive TB containing dead MTB-DNA.LAMP(Loop-mediated isothermal amplification) is suitable for developing countries. Comparing the competency of multiple NAAT based assay in detecting MTB reveals that SAT-TB(96%) has the highest sensitivity followed by LAMP and Xpert MTB/RIF whereas the highest specificity is for Xpert MTB/RIF(98%) followed by LAMP and SAT-TB.

Multitargeted PCRhelp in detecting extrapulmonary TB with IS6110, MPB64 and protein b being specific for tubercular uveitis. Further overexpression of IL-17RC on CD8 T cells by PCR in peripheral blood was associated with ocular sarcoidosis.

Experimental research reveals the difference of immune complexes for ESAT-6/SFP-10 antigen in vitro with dynamic light scattering helps in distinguishing sarcoidosis from TB with diagnostic performance of 92.2%. Sarcoidosis once considered Th1 mediated disease,has shown to have IL-17A from Th17 cells mediated role in induction & maintenance of disease. Lung based molecular markers showed overexpression of Extracellular matrix(ECM) organization markers like MMP-8 in TB, whereas there is over represenatation of genes in arachidonic acid pathway-PLA2G6, PLA2G7, AKR1C1, LTA4H and PTGER4 in sarcoidosis.All these studies need further evaluation to establish their diagnostic role.

In India, it is a dictum to rule out TB actively before stamping the patient as sarcoidosis. Clinical spectrum, subtle radiological differences, widespread and rampant availability of bronchoscopy facilities and the inclusion of NAAT based assays in national programmes has aided in ending this saga. But there is no denying thatmany a time patients receive atherapeutic trial of anti-tubercular therapy before initiating steroids for sarcoidosis in a country like ours.

REFERENCES:

1.Sodsri et.al. Pulmonary sarcoidosis diagnosis in TB-endemic area.J Thoracic Dis 2023;15(10):5760-5772

2.Talwar D et al. Pulmonary sarcoidosis. Indian J Rheumatol 2021;16:S47-57

3.Esmaeil M et al. Common feature of tuberculosis and sarcoidosis. International Journal of Mycobacteriology 2016; S240-S241