We present four cases of atypical presentations of tuberculosis: TB meningitis with secondary myelofibrosis, tuberculous prostatic abscess, tuberculous aortitis, and tuberculous midline neck swelling.
Keywords: Atypical, presentation, tuberculosis
|How to cite this article:
Ganesh K, Faizal B, Oomen AT, Rao G, Pillai M. Clinical conundrums: Atypical presentations of tuberculosis. Ann Trop Med Public Health 2017;10:234-7
|How to cite this URL:
Ganesh K, Faizal B, Oomen AT, Rao G, Pillai M. Clinical conundrums: Atypical presentations of tuberculosis. Ann Trop Med Public Health [serial online] 2017 [cited 2017 Jul 15];10:234-7. Available from: https://www.atmph.org/text.asp?2017/10/1/234/205535
India has a high burden of tuberculosis (TB). The World Health Organization (WHO) statistics for 2014 give an estimated incidence of 2.2 million cases of TB for India of a global incidence of 9 million. The estimated TB prevalence figure for 2014 is 2.5 million. It is estimated that about 40% of the Indian population is infected with TB bacteria, the vast majority of whom have latent rather than active TB. TB can present in various ways. We present four cases of atypical presentations of TB to illustrate the public health hazard and the importance of keeping this disease in mind even today.
A 40-year-old male was admitted with a 4-day history of high-grade fever, headache, mild drowsiness, and disorientation. He had had one to two febrile episodes per month for the past 4–5 months. On clinical examination, the patient was conscious and mildly disoriented. He had pallor, tachycardia (102 per min), fever (102 °F), hepatosplenomegaly, neck stiffness, and positive signs of meningeal irritation. Investigations revealed pancytopenia (hemoglobin [Hb] 7.5g/dl, with normal mean corpuscular volume and mean corpuscular Hb, and a total count of 2.2 K/Ul with normal differential count, platelets 62.8 K/Ul) with low reticulocyte production index and normal liver and renal function tests. Chest x-ray, ECG- Electrocardiogram, CT- Computed Tomography brain, and blood sugars were normal. CSF- Cerebrospinal Fluid examination was suggestive of tubercular meningitis (583 cells, 95% mononuclear, CSF glucose 34 mg/dl, CSF protein 223 mg/dl). CSF cultures were sterile and AFB- Acid fast Bacilli and fungal smears were negative. USG- Ultrasound abdomen confirmed hepatosplenomegaly. Mantoux was positive. Evaluation of pancytopenia revealed normal peripheral smear and myelofibrosis with granulomas consistent with TB in the bone marrow. A final diagnosis of TB meningitis with secondary tubercular myelofibrosis was made.
A 69-year-old male presented with a 3-week history of generalized weakness, loss of weight and appetite, and nausea. There was also a feeling of incomplete evacuation of urine and passage of narrow stream of urine, with no hematuria, dysuria, fever, or bowel symptoms. Clinical examination revealed pallor. Vitals and rest of the systemic examination was normal. Routine investigations showed anemia with low MCV- Mean Corpuscular volume and MCH- Mean Corpuscular Hemoglobin (Hb 7.29 g/dl, MCV 66.6 fl, MCH 21.6 pg), high ESR- Erythrocyte Sedimentation Rate (52 mm/first hour), deranged renal function (serum creatinine 3.7 mg/dl, urea 100 mg/dl), and 2+ proteinuria and 3+ blood in urine. Peripheral smear showed microcytic hypochromic anemia. ECG, chest x-ray, and blood sugars were normal. A USG of abdomen showed hydronephrosis of both kidneys, with a prostate size of 40 cm3 and postvoid residue of 230 cm3. PSA- Prostate Specific antigen was 3.1 U/l and urine and blood cultures were sterile. A diagnosis of obstructive uropathy and moderate renal failure due to benign prostatic enlargement was made. He underwent transurethral resection of the prostate. Biopsy revealed multiple caseating granulomas suggestive of TB. A final diagnosis of tubercular prostatic abscess was made.
A 52-year-old male with diabetes, hypertension, and dyslipidemia presented with generalized fatigue and lethargy. Clinical examination was unremarkable. Investigations revealed moderate anemia (Hb 10 g/dl), elevated inflammatory markers (CRP- C-reactive protein 65), hypoalbuminemia (albumin 2.4), and mild conjugated hyperbilirubinemia. Renal functions, platelet and WBC- White Blood Cell count, coagulation parameters, thyroid function, and electrolytes were within normal limits. Routine chest x-ray and electrocardiogram were normal. Blood and urine cultures were sterile. A routine ultrasound of abdomen revealed a saccular aneurysm from abdominal aorta and features of early chronic liver disease. CT abdomen and an MDCT- Multidetector Computed Tomography angiogram revealed a wide necked saccular aneurysm from the infrarenal abdominal aorta, a suspicious peri-aneurysmal soft-tissue leak and a left psoas abscess/hematoma. An MRI- Magnetic Resonance Imaging spine was normal. Mantoux test was strongly positive. Patient underwent suture ligation of infrarenal abdominal aorta with axillobifemoral bypass from right axillary artery. After stabilization for a few days, patient developed back pain. Repeat MDCT aortogram revealed an increase in the size of the aneurysm, with increase in the psoas collection and new collections at the anastomotic site and lumbar triangle. Embolization and coiling was done. Biopsy of the aortic wall revealed caseating granulomatous inflammation consistent with TB. He developed massive hematemesis and hypotension. An urgent aortogram revealed an aortic-jejunal fistula, which was closed with a patent ductus arteriosus (PDA) closure device. He was started on ATT- Anti tubercular therapy. The final diagnosis was tuberculous aortitis.
A 59-year-old female presented with history of painless neck swelling for past 3 months. There was no fever, weight loss, or constitutional or pressure symptoms. Examination was normal apart from the midline swelling. Chest x-ray showed a mass lesion in the left apical region. A CT neck and CT chest showed minimally enhancing lesion in the anterior mediastinum on the left side, with central hypodense areas extending from thyroid gland to pulmonary artery on the left side encasing the vessels. There were no significant mediastinal lymph nodes or lung nodules. Initial possibilities considered were necrotic lymph node, thymoma and primary lung malignancy. She underwent midline sternotomy and complete excision of the mass. Biopsy showed extensive areas of caseation and multiple epithelioid granulomata with giant cell reaction consistent with TB. There was no evidence of malignancy. Patient was started on anti-tuberculous treatment and showed complete recovery.
An association between TB and myeloproliferative disorders has been described since the 1940s. Studies have shown that the frequency of TB may be higher in patients of myeloproliferative disorders like myelofibrosis and chronic myeloid leukemia., The mechanism of this association is debatable, although TGF-β has been implicated. TGF-β levels are elevated in the bone marrow and peripheral circulation of patients with myelofibrosis,, In TB, monocytes synthesize TGF-β, which is expressed in Langerhans giant cells and epithelioid cells in tuberculous pulmonary granulomas and in monocytes of patients with active TB.
Among the myeloproliferative syndromes, the association between TB and myelofibrosis has been rare. There are reports linking TB to myelofibrosis.,,,Earlier associations that have been documented are splenic TB with myelofibrosis and a case of TB meningitis and pancytopenia due to macrophage activation. Various hematological abnormalities like anemia of different types, pancytopenia, leucoerythroblastic anemia, leukemoid reaction, rarely dissemination intravascular coagulation (DIC- Disseminated Intravascular Coagulation), and myelofibrosis have been described in TB. To our knowledge, this is the first case report linking TB meningitis to a secondary myelofibrosis due to TB.
Genitourinary TB forms 10–14% of extrapulmonary TB, among which prostatic TB is uncommon and usually found incidentally during transurethral resection of the prostate. The implicated risk factors usually include hematogenous spread and prolonged steroid use, immunosuppressive therapy, diseases that impair cell-mediated immunity, and diseases with poor immune mechanisms. Association with malignancy and PSA levels is unclear, although there has been a report of coexisting prostatic TB and carcinoma prostate. Prostatic TB has been described in immunocompromised patients. Our patient was a case of obstructive uropathy due to suspected benign prostatic hypertrophy and whose biopsy revealed TB of the prostate.
Aortitis is an inflammation of the aorta. Most causes of aortitis are noninfectious. Infectious causes of aortitis are rarer. Commonest organisms are Salmonella More Details and staphylococcal species along with mycobacterium TB and treponema pallidum.,, Tuberculous aortitis may occur due to direct seeding of the thoracic aorta from adjacent infected tissues such as infected lymph nodes or lung lesions or by miliary spread. The epidemiology of aortitis is poorly characterized. Establishing the diagnosis early is critical because this condition is associated with a high rate of rupture and subsequent mortality if left untreated.,,,,, The diagnosis is very difficult to establish because this disorder is rare and can mimic Takayasu arteritis. Thus, tuberculous aortitis should be ruled out in patients with atypical aneurysms, pleural effusions, lymphadenitis, cavitary lung lesions, and immunosuppressed states before starting glucocorticoids., Our patient had an incidentally detected aneurysm that was shown to be consistent with TB. However, he did not show evidence of disseminated TB. He developed massive hematemesis due to an aorto-jejunal fistula, which has been described in tuberculous aortitis (mainly aorto-duodenal fistulas).,, In our knowledge, closure using a PDA closure device is the first reported case.
Midline neck swellings mainly comprise of thyroid swellings, throat and lymph nodes. Studies with pathological correlation have shown goiter and squamous cell carcinoma to be common benign and malignant lesions, respectively. TB may rarely present as a midline swelling with a connection to an underlying lung mass, as shown in our case. Complete excision showed that the mass was a necrotic lymph node. It may mimic more sinister lesions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Dyke SC, Some cases of aleukia or aplastic anemia associated with thrombopaenia. Lancet 1924;1:1048-51.
Morrow LB, Anderson RE. Active tuberculosis in leukemia. Malignant lymphoma and myelofibrosis. Arch Pathol 1965;79:484-93.
Le Bousse-Kerdilès MC, Martyré MC. Myelofibrosis: pathogenesis of myelofibrosis with myeloid metaplasia. French INSERM Research Network on Myelofibrosis with Myeloid Metaplasia. Springer Semin Immunopathol 1999;21:491-8.
Rameshwar P, Chang VT, Thacker UF, Gascón P. Systemic transforming growth factor-beta in patients with bone marrow fibrosis-pathophysiological implications. Am J Hematol 1998;59:133-42.
Hirsch CS, Yoneda T, Averill L, Ellner JJ, Toossi Z. Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-beta 1. J Infect Dis 1994;170:1229-37.
Hashim MS, Kordofani AY, el Dabi MA. Tuberculosis and myelofibrosis in children: a report. Ann Trop Paediatr 1997;17:61-5.
Toossi Z, Gogate P, Shiratsuchi H, Young T, Ellner JJ. Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions. J Immunol 1995;154:465-73.
Viallard JF, Parrens M, Boiron JM, Texier J, Mercie P, Pellegrin JL. Reversible myelofibrosis induced by tuberculosis. Clin Infect Dis 2002;34:1641-3.
Crail HW, Alt HL, Nadler WH. Myelofibrosis associated with tuberculosis: a report of four cases. Blood 1948;3:1426-4.
Tassies D, Cervantes F, Nicolás JM, Feliu E, Soriano E, Rozman C. Tuberculosis in chronic myeloproliferative syndromes: its incidence and principle characteristics in a series of 562 patients. Med Clin (Barc) 1991;96:321-3.
Andre J, Schwartz R, Dameshek W. Tuberculosis and myelosclerosis with myeloid metaplasia: report of three cases. JAMA 1961;178:1169-74.
Avasthi R, Mohanty D, Chaudhary SC, Mishra K. Disseminated tuberculosis: interesting hematological observations. J Assoc Phys. India 2010;58:243-4.
Gupta N, Mandal AK, Singh SK. Tuberculosis of the prostate and urethra: a review. Indian J Urol 2008;24:388-91.
Aji S, Alhassan S, Mashi. S, Imam. M. Tuberculosis of the Prostate Gland Masquerading Prostate Cancer: A Case Report, Open Journal of Urology, 2013;3: pp. 269-271.
Gebo KA. Prostatic tuberculosis in an HIV infected male. Sex Transm Infect 2002;78:147-8.
Gornik HL, Creager MA. Aortitis. Circulation 2008;117:3039-51.
Foote EA, Postier RG, Greenfield RA, Bronze MS. Infectious aortitis. Curr Treat Options Cardiovasc Med 2005;7:89-97.
Virmani R, Burke A. Nonatherosclerotic diseases of the aorta and miscellaneous disease of the main pulmonary arteries and large veins. In: Silver M, Gotlieb A, Schoen F, editors. Cardiovascular pathology 3rd ed. Philadelphia, PA: Churchill Livingstone;2001.pp. 107-37.
Bardin JA, Collins GM, Devin JB, Halasz NA, Nonaneurysmal suppurative aortitis. Arch Surg 1981;116:954-6.
Fernández Guerrero ML, Aguado JM, Arribas A, Lumbreras C, de Gorgolas M. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine (Baltimore) 2004;83:123-38.
Müller BT, Wegener OR, Grabitz K, Pillny M, Thomas L, Sandmann W. Mycotic aneurysms of the thoracic and abdominal aorta and iliac arteries: experience with anatomic and extra-anatomic repair in 33 cases. J Vasc Surg 2001;33:106-13.
Reddy DJ, Shepard AD, Evans JR, Wright DJ, Smith RF, Ernst CB. Management of infected aortoiliac aneurysms. Arch Surg 1991;126:873-9.
Gajaraj A, Victor S. Tuberculous aortoarteritis. Clin Radiol 1981;32:461-6.
Tsai TJ, Yu HC, Lai KH, Lo GH, Hsu PI, Fu TY. Primary aortoduodenal fistula caused by tuberculous aortitis presenting as recurrent massive gastrointestinal bleeding. J Formos Med Assoc 2008;107:77-83.
de Kruijf E. J. F. M, van Rijn A. B. B, Koelma IA, Kuijpers T. J. A, van ‘t Wout J. W. Tuberculous Aortitis with an Aortoduodenal Fistula Presenting as Recurrent Gastrointestinal Bleeding, Clin Infect Dis. 2000;31:841-2.
Popat V, Vora D, Shah H. Clinico-pathological correlation of neck lesions—a study of 103 cases. Internet J of Head and Neck Surg 2009;4:2.
Kasilingam SK. Tuberculosis presenting as mediastinal and lung mass radiologically: A case report. Trop Doct 2013;43:142-3.
Global Tuberculosis Control 2015. Geneva: WHO; 2015. http://www.who.int/tb/publications/global_report/. Available from: http://www.tbfacts.org/tb-statisticsindia/#sthash.2WI2AWrZ.dpuf.
Source of Support: None, Conflict of Interest: None