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Clinical Infection & Immunity

Case Report

Volume 5, Number 2, June 2020, pages 41-44

Miliary Tuberculosis Presenting as Pyrexia of Unknown Origin in a Health Care Worker

Pyrexia of unknown origin (PUO) also known as fever of unknown origin (FUO) is a condition that has tested the clinical acumen of many a physician. The myriad conditions that present as PUO [1] and the absence of any leading clinical clues make it a challenge for any doctor. Investigating a case of PUO requires extensive knowledge across different specialties of medical science. The first proper definition of PUO was described in medical literature by Petersdorf and Beeson in 1961 [2]. In this paper the authors set a cutoff of 3 weeks for a fever to be labeled as PUO with no diagnosis made after 1 week of inpatient investigation. A revised criterion was proposed by Durack and Street in 1991 [3]. Despite variations in definition the critical concept of PUO remains the same: significant fever that has lasted for longer than an acute self-limiting illness would be expected to last and which has not been identified despite reasonable investigations in a realistic time frame [4, 5].

It is well known that health care workers (HCWs) are at high risk of contracting infectious diseases [6]. The threat of infection with blood-borne pathogens is greater among HCWs than in the general populace because of the risk of occupational exposure to blood and body fluids [7]. Emerging infectious diseases particularly air-borne ones as severe acute respiratory syndrome (SARS), H5/N1 avian influenza and H1/N1 swine influenza pose a significant health hazard to HCWs [8]. The increased risk of tuberculosis (TB) among HCWs is also well documented [9].

A case of miliary TB presenting as PUO in an HCW has not been reported in indexed literature. Herein we report such a case.

A 31-year-old lady presented to the out-patient department (OP) with complaints of “on and off” fever of more than 2-week duration. The fever was more severe towards the evening and was associated with night sweats, dry cough and myalgia. Though not documented objectively she felt that she was losing weight and was also having loss of appetite since the last few weeks. She was a nurse by profession and had been working in the same hospital for several years. During her career she had taken care of different patients including those in infectious disease, general medical and surgical wards. She could not remember having been exposed to blood or other fluids and neither was there any history of needle stick injury. General examination was unremarkable; there was no jaundice, no significant peripheral lymph node enlargement nor any dermatological signs of infective endocarditis. Vitals were within normal limits. Systemic examination was unremarkable except for a mild, soft splenomegaly.

Hemogram was normal except for a mild leucopenia. Blood picture/peripheral smear did not show any abnormal cells or any hemoparasites. Erythrocyte sedimentation rate (ESR) was mildly elevated (32 mm/h; normal: up to 15 mm/h). Liver enzymes were also elevated: serum glutamate pyruvate transaminase (SGPT) was 218 U/L (normal: 9 - 52 U/L), serum glutamate oxaloacetate transaminase (SGOT) 277 U/L (normal: 14 - 36 U/L) and alkaline phosphatase (ALP) 149 U/L (normal: 38 - 126 U/L). Lactate dehydrogenase (LDH) was also elevated (LDH: 1,570 U/L, normal: 313 - 618 U/L). Chest X-ray showed the presence of miliary mottling predominantly visible in the perihilar regions (Fig. 1). This was followed up with a contrast enhanced computed tomography (CECT) study of the thorax which revealed the presence of innumerable miliary nodules scattered throughout both lungs (Fig. 2). Abdomen ultrasonogram (USG) confirmed the presence of splenomegaly. Bone marrow study was also done which showed the presence of epithelioid cells (Fig. 3) and granulomas (collection of epithelioid cells) (Fig. 4). However, polymerase chain reaction (PCR) testing on the bone marrow sample was negative for TB. Though sputum production was scanty, early morning samples were tested on four consecutive days for acid-fast bacilli but the test was inconclusive.

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Figure 1. Chest X-ray showing presence of miliary mottling predominantly visible in the perihilar regions.

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Figure 2. CECT of the thorax showing presence of innumerable miliary nodules scattered throughout both lungs. CECT: contrast enhanced computed tomography.

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Figure 3. Bone marrow showing presence of epithelioid cells.

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Figure 4. Bone marrow showing presence of granulomas.

As part of the workup of PUO, the following tests were also done (keeping in mind the clinical and epidemiological settings to which the patient belonged): blood and sputum culture, peripheral smear for malarial parasite, echocardiogram, human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV), Weil-Felix test, Paul-Bunnel test, Widal test, Toxoplasma immunoglobin M (IgM), Brucella IgM, Epstein-Barr virus (EBV) IgM and antinuclear antibody (ANA). All these tests were negative. Since the only clinical clue in addition to the fever was splenomegaly, investigations were also done in this direction. Malaria, infective endocarditis, viral hepatitis, HIV, infectious mononucleosis and hematological malignancies were ruled out. Considering the fact that the patient was a medical personnel with a “typical history” of loss of weight and evening rise of temperature and chest X-ray showing miliary mottling, TB was high in the list of differential diagnosis. This suspicion was reinforced with computed tomography of the chest and later the bone marrow study.

Patient was started on anti-TB therapy (ATT) as per Revised National Tuberculosis Control Program (RNTCP), a state-run TB control initiative of the government of India. She was also given a short course of steroids. As per the RNTCP program she took ATT for 6 months with periodic follow-up. During her follow-up liver enzymes were monitored along with chest X-ray.

Steroids were tapered and stopped over a course of 2 weeks. There was immediate defervescence and a “sense of well being” on starting treatment. This may be partly attributed to the steroids. But it continued even after the course of steroids was over. She was followed up for further 6 months after the treatment for TB was over and continued to be healthy. Intermittently she still attends our OP for common medical ailments (aches and pains, seasonal allergic rhinitis, etc) and remains healthy.

HCWs always face the hazard of contracting infectious diseases [6]. They are at increased risk of occupational exposure to blood and body fluids than the general population [7]. Also they are particularly prone to air-borne infections including TB [8, 9].

Considering the occupational risks involved miliary TB would be the first suspect in an HCW with fever and miliary mottling on the chest radiograph. Other causes of miliary mottling described include miliary carcinomatosis, varicella infection, disseminated histoplasmosis, silicosis and pneumoconiosis [10]; but these are less likely in an HCW for obvious reasons. As was the case with our patient elevation of liver enzymes (SGOT, SGPT and ALP) and LDH has been described in miliary TB [11, 12]. Though demonstration of acid-fast bacilli in sputum or bronchial washings can be considered as conclusive evidence for TB, this test has its limitations in miliary TB [13]. Demonstration of granuloma in bone marrow specimen and PCR testing in the same sample are welcome alternatives; however, they are also not 100% sensitive [13, 14]. In our patient sputum was negative for acid-fast bacilli. Bone marrow showed the presence of epithelioid granulomas; however, PCR was negative.

PUO will always remain a challenge to the treating physician. Understanding the challenges involved in the evaluation of such a condition by the patient because of the very nature of the illness and the duty of the treating physician to reinforce this and instill confidence in the patient is of paramount importance. It becomes all the more important when the patient is an HCW because he or she would be aware of the infections they are at risk of because of their occupation. By any measure the duty of all HCWs to follow universal precautions needs no better emphasis.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Informed Consent

The patient described in the case report had given informed consent for the case report to be published.

Author Contributions

AMI was involved in the selection of the case and wrote the manuscript. SP was involved in the case presentation. JSK and BMB interpreted the slides. All authors were involved in the discussion, revision and approval of the final manuscript.

Data Availability

All data and information regarding this manuscript are present within the text.

1. Beresford RW, Gosbell IB. Pyrexia of unknown origin: causes, investigation and management. Intern Med J. 2016;46(9):1011-1016.
   doi pubmed
2. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961;40:1-30.
   doi pubmed
3. Durack DT, Street AC. Fever of unknown origin - reexamined and redefined. Curr Clin Top Infect Dis. 1991;11:35-51.
4. De Kleijn EMH, Knockaert DC, van der Meer JWN. Fever of unknown origin: a new definition and proposal for diagnostic work-up. Eur J Intern Med. 2000;11:1-3.
   doi
5. Knockaert DC, Vanderschueren S, Blockmans D. Fever of unknown origin in adults: 40 years on. J Intern Med. 2003;253(3):263-275.
   doi pubmed
6. Sepkowitz KA, Eisenberg L. Occupational deaths among healthcare workers. Emerg Infect Dis. 2005;11(7):1003-1008.
   doi pubmed
7. Tarantola A, Abiteboul D, Rachline A. Infection risks following accidental exposure to blood or body fluids in health care workers: a review of pathogens transmitted in published cases. Am J Infect Control. 2006;34(6):367-375.
   doi pubmed
8. Nienhaus A, Kesavachandran C, Wendeler D, Haamann F, Dulon M. Infectious diseases in healthcare workers - an analysis of the standardised data set of a German compensation board. J Occup Med Toxicol. 2012;7(1):8.
   doi pubmed
9. Baussano I, Nunn P, Williams B, Pivetta E, Bugiani M, Scano F. Tuberculosis among health care workers. Emerg Infect Dis. 2011;17(3):488-494.
   doi pubmed
10. Tun NM, Mattoo V. Miliary mottling on chest X-ray: an unusual presentation of adenocarcinoma of the lung. Am J Med Sci. 2015;349(4):e4.
    doi pubmed
11. Hickey AJ, Gounder L, Moosa MY, Drain PK. A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection. BMC Infect Dis. 2015;15:209.
    doi pubmed
12. Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: a clinical approach. Am J Med. 2015;128(10):1138 e1131-1138 e1115.
    doi pubmed
13. Mert A, Bilir M, Tabak F, Ozaras R, Ozturk R, Senturk H, Aki H, et al. Miliary tuberculosis: clinical manifestations, diagnosis and outcome in 38 adults. Respirology. 2001;6(3):217-224.
    doi pubmed
14. Escobedo-Jaimes L, Cicero-Sabido R, Criales-Cortez JL, Ramirez E, Romero M, Rivero V, Islas F, et al. Evaluation of the polymerase chain reaction in the diagnosis of miliary tuberculosis in bone marrow smear. Int J Tuberc Lung Dis. 2003;7(6):580-586.

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