Brucellosis presenting as mediastinal lymphadenopathy with ...



Brucellosis presenting as mediastinal lymphadenopathy with raised ẞ2 microglobulin

Abstract

A 65 year old male with no significant past medical history presented with high grade continuous fever for the past one month. It was associated with rigors, chills and sweating. Clinical examination was unremarkable and routine screening for pyrexia was unrewarding. Contrast enhanced chest CT revealed mediastinal lymphadenopathy. Brucella serology by ELISA method was initially negative but later on in week 6th of illness it became highly positive with dilutional titers of 1:1280. Subsequently ẞ2 microglobulin levels were also high i.e 3570 i.u. The patient was treated with Inj Streptomycin 1gm/day, Cap Rifampcin 600 mg/day and Cap Doxycycline 100 mg bd. His symptoms resolved with in 2 weeks. He received drugs for 6 weeks and was followed for past 11 months. Presently he is stable and symptom free.

Key words: Brucellosis, ẞ2 Microglobulin, Lymphadenopathy

Case Report

An elderly male retired government official, resident of Kashmir, a state in northern India presented with high grade continuous fever of 102º F to 104º F for a months duration . The patient was evaluated at the secondary level care facility as a case of pyrexia without reaching any diagnosis. Later on the patient followed a consultant physician with more than 4 OPD visits. The most of diagnostic work up for the fever was inconclusive.

On initial contact with the patient, he was found to be anxious and sweaty. His temperature was 104º F, respiratory rate of 22 cycles/min, BP of 110/70mm Hg, and pulse of 88 beats/ min. He had mild pallor and splenic tip was palpable, rest of general and systemic examination was normal.

His Hemoglobin was 14.3 mg/dl, Total leucocyte count of, DLC of 52% polymorphs, 28% lymphocyte, 16% monocytes. Platelet count was 205 x 10/l. ESR was 48 mm/hr. The peripheral smear, liver functions, kidney functions were within normal range.CPK was 198 u/l and LDH was 156 u/l. Urine analysis, Electrocardiogram, Chest X-Ray, ultrasound of abdomen, blood culture and urine cultures were inconclusive. The serologic tests for Brucella, Typhoid, Toxoplasma, Rubella, Cytomegalovirus, Epstein Barr virus, Retrovirus, Hepatitis A to E, Syphilis was negative.

After one week of extensive investigations he persisted with drenching fever. Patient underwent Mantoux test, Echocardiography, Doppler ultrasound of lower limbs, stool for occult blood and prostate specific antigen tests. All of these investigations were normal. The patient was being managed symptomatically with paracetamol. Contrast enhanced CT chest, neck and abdomen was done. It was reported by radiologist to have mediastinal lymphadenopathy (Figure 1 & 2) with left axillary node and enlarged spleen (Figure 4).

The fever continued unabbating, small nodes appeared in left axilla and patient started to complain of backache. The patient was planned for mediastinoscopy and node sampling at National cancer centre. While awaiting the procedure, bone marrow was done this did not reveal any abnormal morphology of cells. Bone marrow culture was sterile. Bone marrow was negative for AFB stain as well as for AFB culture. The patient’s lower back ache worsened which prompted us to repeat brucella serology. It came 1:640 titer by ELISA method.

Meanwhile myeloma profile was done which was negative but ẞ2microglobulin was high 1760 iu. In 6th week of illness brucella ELISA serology was repeated and titres were 1:1280 and ẞ2 microglobulin levels had risen to 3540 iu.

Patient was started on injection Streptomycin 1gm/day, cap Rifampcin 600 mg/day. He showed defervesence of fever from day 9th of treatment. The patient became afebrile after 2 weeks of treatment. Injection streptomycin was stopped after 2 weeks and tab Doxycycline 100 mg bd was added to cap Rifampcin, the treatment was continued for 6 weeks. After 2 months patient underwent check contrast enhanced CT of chest which revealed resolution of mediastinal lymphadenopathy and left axillary node (fig 3). He had resolution of symptoms and was followed twice in past 11 months. He is doing well.

Discussion

Brucellosis is a common infection among those people who have a contact with the livestock. It is an occupational hazard for veterinarians, farmers and laboratory personnel. A broad spectrum of clinical manifestations can be seen, ranging from asymptomatic infection to multisystem involvement (1). Therefore, diagnosis can be difficult. The most common presentations of brucellosis are fever, rigors, chills, ill health, chronic fatigue, backache, headache, periorbital pain or loss of well-being.

These patients have shown to have anemia, pancytopenia, lymphadenopathy and spleenomegaly. Brucella can involve specific organ and cause organ specific syndromes like cardiac or neurobrucellosis. Brucellosis can cause complications such as spondylitis, sacroiliitis, osteomyelitis, endocarditis, epididymo-orchitis, meningitis, and encephalitis (1). Pertinent to mention that brucellosis may induce microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura, and hemolytic uremia syndrome (2).

Unusually, vasculitis can be seen secondary to skin involvement (3). Renal involvement is rare but can result in acute renal failure (4). During the course of brucellosis, even disseminated intravascular coagulation (DIC) and shock may develop (5). Brucella bacteremia can cause abscess formation in the spleen, liver, or in other organs. Even soft tissue abscesses can occur (6-8). In rare clinical scenarios brucella may present as hemophagocytic lymphohisticytosis(9).

Our patient presented with pyrexia and initial brucella serology was negative. The CT chest revealed mediastinal lymphadenopathy with spleenomegaly and high levels of β 2 microglobulin, lymphoma came into differential diagnosis. As this patient developed backache and headache, repeat brucella serology was sent and titer came 1:640. This titer doubled in a weeks time. He was put on brucella treatment. He responded to the treatment with resolution of signs, symptoms and laboratory parameters.

β2 M, also known as β2-Microglobulin is a component of MHC class I molecules found expression in all nucleated cells (excludes red blood cells). The major function of MHC class I molecules is to display fragments of proteins from within the cell to T-cells and cells containing foreign proteins will be attacked.

β2M(β2-Microglobulin) is a low molecular weight protein. It was demonstrated that β2M(β2-Microglobulin) was localized in the membranes of nucleated cells and was found to be associated with HL-A antigens. β 2M(β2- Microglobulin) is present in free form in various body fluids and as a subunit of histocompatibility antigens on cell surfaces.(12) Commonly it is increased in renal failure, hematologic malignancies, HIV & AIDS, multiple myeloma, amylodosis and inflammatory conditions like ankylosing spondolitis.(9,10)

Patient took Inj streptomycin and Cap rifampcin for 2 weeks, he showed clinical defervesence of his symptoms within 2 weeks. On completion of his treatment he was clinically stable with resolution of nodes and decreasing titers of β2 microglobulin.

The patient was followed meticulously for past 11 months in our OPD for recurrence of fever or appearance of hemolymphoreticular abnormality.

The present case gives dimension to varied presentations of brucellosis. It gives us insight how patients can erroneously be subjected to invasive procedures before reemphasizing traditional causes of pyrexia of unknown origin (11). In particular brucellosis should be kept as a strong differential diagnosis of PUO in a endemic zone despite non encouraging serology results. We advocate serial serology testing should be performed before contemplating invasive procedures for establishing cause for PUO.

References

1. Sozen TH, Bruselloz, in Infectious Diseases and Microbiology. Topcu A, Soyletir G, and Doganay M, Eds.2002 pp 636–642, Oxford University Press, Istanbul, Turkey, 1st, 2nd edition.

2. Soker, Devecioglu C, Yaramis A, Ipek S, Ozbek M, Tuzun H. Microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure associated with acute brucellosis. International Pediatrics 2001; 16 ( 2): 105–108.

3. Ayaslioglu, Koçak M, and Bozdogan O. A case of brucellosis presenting with widespread maculopapular rash. American Journal of Dermatopathology 2009 ; 31 (7): 687–690.

4. Ceylan, Karahocagil MK, Soyoral Y et al. Renal involvement in Brucella infection Urology 2009 ; 73, (6): 1179–1183.

5. Akalın, Celen MK, Geyik MF, Kokoglu OF, Hosoglu S, and Ayaz C. Pancytopenia in case of acute Brucellosis. Turk Mikrobiyoloji Cemiyeti Dergisi. 2004 ;34 :67–69.

6. Williams RK and Crossley K. Acute and chronic hepatic involvement of brucellosis. Gastroenterology.1982 ; 83 (2) 455–458.

7. Akritidis, Tzivras M, Delladetsima I, Stefanaki S, Moutsopoulos HM, and Pappas G. The liver in brucellosis. Clinical Gastroenterology and Hepatology. 2007; 5(9):1109-1112.

8. Caliskan C, Barut S, Koseoglu D, Aytan H, and Demirturk F. Obturatory abscess and pelvic pain caused by Brucella melitensis. Mikrobiyoloji Bulteni. 2009; 43 (2) :325–329.

9.Gosh JB, Roy M, Bala A. Infection associated with hemophagocytic lymphohisticytosis trigerred by nosocomial infection. OMJ 2009; 24: 223-225.

10. Naseem. Splenic abscess secondary to Brucella melitensis. Journal of the College of Physicians and Surgeons Pakistan.2002;12 (8) :488–490.

11.Cokca F, Yilmaz-Bozkurt G,Azap A,Memikoglu O,Tekeli E.Meningoencephalitis, pancytopenia, pulmonary insufficiency and splenic abscess in a patient with brucellosis, Saudi Medical Journal 2006; 27 (4): 539–541.

12.Celik AD, Yulugkural Z, Kilincer C, Hamamcioglu MK, Kuloglu F, Akata F. Negative serology: could exclude the diagnosis of brucellosis? Rheumatol Int 2010.

13. Bethea M, Forman DT. Beta 2-microglobulin. Its significance and clinical usefulness. Ann Clin Lab Sci. 1990;20(3):163-8.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download