Case+3+Discussion

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Xray appearance: -reticulonodular infiltrate distributed fairly uniformly throughout the lungs -coalescence of nodules -‘snowstorm’ appearance -cardiomegaly -elevated right hemidiaphragm

Bedside echo: -subxyphoid view with most anterior chamber the RV, posterior to that the largest chamber the LV -mild to moderate sized pericardial effusion present -normal chamber sizes -Of note: when teaching ultrasound internationally, it is standard that instruction should be according to cardiology echo guidelines with probe marker on the right side of the screen. Hence the image may be backward from what many of you have learned, however, if there is any desire to teach, comfortable with 'standard' echo view should be achieved.

Provisional Diagnosis: Miliary tuberculosis

Discussion: In the 1700s a form of fatal disseminated tuberculosis was termed ‘miliary tuberculosis’ due to the resemblance on gross pathologic examination of small nodules in the interstitial spaces of the lungs to various sizes of millet seeds. Now known to represent lympho-hematogenous spread of mycobacteria, miliary tuberculosis is used contemporarily to denote all forms of progressive, widely disseminated disease. Though associated most often with the classic radiographic findings as described above, reportedly only 2/3 of patients diagnosed with military TB display such a 'miliary' pattern.

Tuberculosis in sub-saharan Africa has been a recognized top 10 cause of mortality for decades due to the high prevalence of immunodeficiency, dense population in context of communicable disease, and poverty leading to communicability, lack of education, and lack of resources to control an otherwise very controllable disease. With the rollout of DOTS in the 1990s, case recognition jumped greatly as contact was made with TB contacts. Despite persistent improvements in diagnosis (such as ‘Gene-xpert’ offering PCR detection of Mycobacterium in samples within 2 hrs) and case following (improved resources), the inpatient TB wards remain filled with the publicly reported Malawian case total of 23000 (2010) almost certainly an under-representation of the true burden of disease due to persistent under-diagnosis.

A few quick learning points about miliary TB: predominantly affects adolescents/young adults, elderly, HIV pos, and males. In immunocompetent individuals such as our patient miliary TB represents < 2% of TB cases worldwide. Diagnosis is notoriously difficult as patients are, as in the case of our patient, often ‘smear negative’ (bacteriologically negative through gene xpert or AFB micro) due to lack of granulomatous disease. However, though the bacilli may not always be found in sputum in miliary TB, presence of lung interstitial disease can cause dry cough and dyspnea/tachypnea as such on this case. A myriad of other symptoms can exist in the context of disseminated disease, but most generally patients describe the classic night sweats, weight loss, and fevers suggesting systemic infectious illness. Of note, BCG vaccination given in many 3rd world countries has been shown to be most efficacious in preventing TB meningitis and miliary TB.

The diagnosis of miliary TB (or any TB for that matter) in this resource poor setting is derived from putting together the puzzle of history, bacteriology, other supporting labwork, and imaging. Firstly, from the history we see a pattern of persistent symptoms despite reasonable treatment for both gram pos and atypical PNA. In addition, patient described those classic ‘B’ symptoms of night sweats and weight loss over a chronic 5 month time period. Bacteriologically, though miliary TB in severe forms can be sputum positive, our negative status does not rule out and in fact somewhat supports the diagnosis. Supporting labwork suggests systemic disease with a pancytopenia suggesting bone marrow infiltration. Finally, the patient’s chest xray above is certainly suspicious, combined with a pericardial effusion (causing observed cardiomegaly) seen in disseminated disease.

Medicine is so fascinating as being contextual: change the context to CCRMC (with no travel history, not homeless, and never incarcerated), TB would certainly be on the differential, but so would also histo, cocci, CA!!, sarcoidosis, amyloidosis, etc… (there is a long list on uptodate of b/l diffuse nodular infiltrate causing pathology). In fact some of the nodules on this gentleman’s xray are certainly larger than 3mm which is seen in less than 10% of miliary TB cases (typically 2mm or smaller). But there are no bronchoscopy capabilities here, and the reality of medicine in this resource poor setting is often trial of therapy. Statistically, with the burden of disease in this context, this is TB until this gentleman demonstrates persistent symptoms despite 2-4 weeks of TB therapy. So now we watch and wait as the patient initiates RHZE, and enrolls in the national TB program for DOTS. Diagnosis for the national TB program? "Smear-negative TB."