|Year : 2018 | Volume
| Issue : 3 | Page : 145-148
Brucellosis associated with transient myelodysplastic features
Khalid Al-Hashmi1, Fahad H Al-Ghafri1, Anil Pathare2
1 Department of Medicine, Armed Forces Hospital, Al-Khoudh, Oman
2 Department of Hematology, Sultan Qaboos University Hospital, Al-Khoudh, Oman
|Date of Submission||06-Mar-2018|
|Date of Acceptance||30-May-2018|
|Date of Web Publication||3-Dec-2018|
Hematology, and Medical Oncology, Armed Forces Hospital/Sultan Qaboos University, 7063 code 111, Seeb, CPO
Source of Support: None, Conflict of Interest: None
This case demonstrates transient dysplasia in two cell lines associated with brucellosis infection which completely resolved upon treatment. Brucellosis is an important public health problem in the Middle Eastern and Mediterranean cultures, where animal husbandry including cattle grazing is an integral part of daily life in rural areas. This is the first report to our knowledge of brucellosis causing transient myelodysplasia in a brucella endemic area.
Keywords: brucellosis, myelodysplasia, transient
|How to cite this article:|
Al-Hashmi K, Al-Ghafri FH, Pathare A. Brucellosis associated with transient myelodysplastic features. Egypt J Haematol 2018;43:145-8
|How to cite this URL:|
Al-Hashmi K, Al-Ghafri FH, Pathare A. Brucellosis associated with transient myelodysplastic features. Egypt J Haematol [serial online] 2018 [cited 2020 Jan 23];43:145-8. Available from: http://www.ehj.eg.net/text.asp?2018/43/3/145/246781
| Introduction|| |
Brucellosis More Details is a zoonotic infection with a wide range of hematological findings including anemia, leukopenia, thrombocytopenia, pancytopenia, and/or disseminated intravascular coagulation ,,,,. The most common findings in the bone marrow examination were hemophagocytosis and granulomas ,. Hypoplasia was rarely reported in the medical literature, whereas myelodysplastic syndrome (MDS) and myelofibrosis have been seen to be associated in a case that presented with brucellosis ,,. In addition, there were case reports of underlying hematological malignancies that co-occurred with Brucella More Details infection ,,. Herein, we present a patient with brucella infection, who developed transient bone marrow dysplasia that normalized following successful treatment of the underlying infection.
| Case report|| |
A 27-year-old patient known to have thyroglossal cyst for the past 3 years was admitted to our hospital with a 2-week history of fever and increasing neck swelling. There was no history of travel or contact with sick patients, but he gave a history of consuming raw camel milk, a practice prevalent in the Dhofar region of Oman. On physical examination, he was pale and febrile, with a tender thyroglossal cyst and hepatosplenomegaly. There was no associated lymphadenopathy.
The initial blood investigations showed hemoglobin of 8.9 g/dl, white cell count of 2.0×109/l, with an absolute neutrophil count (ANC) of 1.4×109/l, platelet count of 154×109/l and reticulocytes of 1%. His liver function tests showed mild transaminitis (alanine aminotransferase 110 IU/l and aspartate aminotransferase 140 IU/l) with normal bilirubin and alkaline phosphatase. Serum folate and vitamin B12 were within normal reference ranges. Lactic dehydrogenase (LDH) was elevated (994 U/l). His coagulation studies [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels] were normal. The inflammatory markers were elevated including serum ferritin (11 648 ng/ml), erythrocyte sedimentation rate (54 mm/h), and C-reactive protein (CRP) (108 mg/l). The serological tests for HIV, hepatitis C virus, hepatitis B surface antigen, anti-hepatitis B core antigen, and anti-hepatitis B surface antigen were negative. The cytomegalovirus IgG and Epstein–Barr virus IgG were positive, but in both cases IgM was negative. Antinuclear antibody was negative.
His blood film showed leukoerythroblastic picture with the presence of reactive lymphocytes. The bone marrow aspirate showed a hypercellular marrow for age with dysplasia involving the erythroid, myeloid, and megakaryocytic lineages (>10% of cells in each) ([Figure 1] and [Figure 2]a and b). The blast count was less than 5% and ring sideroblasts were not identified on an iron stain. The bone marrow biopsy showed dysplastic megakaryocytes with separated nuclear lobes. Repeated blood cultures were sterile. Imaging studies showed normal chest radiograph and ultrasound of the thyroglossal cyst demonstrated cystic lesion filled with moving echoes/debris, which may indicate the infective process. Ultrasound of the abdomen confirmed the presence of hepatosplenomegaly. Initially he was started on augmentin and clindamycin and was subsequently treated with tazocin when his fevers did not resolve.
|Figure 1 Initial bone marrow aspirate showing dysplasia in megakaryocytes.|
Click here to view
|Figure 2 (a, b) Initial bone marrow aspirate documenting dysplastic erythroid and myeloid series.|
Click here to view
The agglutination test for brucella was positive on the 10th day at a titer of 1 : 1280. The patient was thereafter managed with amikacin (15 mg/kg) intravenously for 2 weeks, oral rifampicin (450 mg) for 6 weeks, and doxycycline 100 mg twice daily for 6 weeks. The patient became afebrile within 5 days after starting this therapy. His hematological parameters improved within 2 weeks with a hemoglobin level of 10 g/dl, white cell count of 4.0×109/l, ANC of 1.6×109/l, and platelet count of 370×109/l. As there was significant dysplasia observed on the initial bone marrow during active infection, a repeat examination was performed 3 months after completion of treatment which showed normal trilineage hemotopoiesis ([Figure 3]).
| Discussion|| |
Brucellosis has a wide clinical spectrum of presentation , and has been associated with several hematological abnormalities, including anemia, leucopenia, thrombocytopenia, and pancytopenia ,,,. The bone marrow findings that have been previously described are hemophagocytosis, granulomas, and rarely hypoplasia ,,,. In our case, we document bone marrow dysplasia seen at initial presentation, which resolved completely after treatment of the underlying brucella infection.
To our knowledge, this is the first case of transient myelodysplasia associated with brucellosis. The initial bone marrow showed dysplasia in erythroid and megakaryocytic lineages. There was no evidence of hemophagocytosis. The bone marrow biopsy also showed dysplastic megakaryocytes, but did not show any granulomas or myelofibrosis. Furthermore, the bone marrow repeated 3 months following effective treatment of brucella infection was completely normal.
Serology is the preferred method for the diagnosis of brucellosis when bacterial isolation is not possible, as culture of the organism is difficult. In regions endemic to brucellosis, such as ours, the agglutination test is used as the principal test and should be interpreted in the light of local prevalence of the antigen in the exposed population. Hence, when brucellosis is suspected in patients with negative cultures, rising agglutinin titers over 1 : 160 are considered diagnostic . On the other hand, blood culture is the gold standard in the diagnosis of brucellosis. The sensitivity of blood culture depends on several factors, such as previous use of antibiotics and phase of the disease. Bone marrow cultures may provide higher sensitivity, yield faster culture times, and may be superior to blood cultures when evaluating patients with previous antibiotic use . In our case, blood cultures were negative probably due to the early use of broad-spectrum antibiotics.
The mechanism of transient myelodysplasia is not clear. Cytopenias in infections are usually secondary to marrow hyperplasia, hypersplenism, or as a result of direct inhibition of bone marrow by the invasive pathogen (brucella, in this case) or release of inhibitory substances that inhibit hematopoiesis ,,. It is believed that the release of inflammatory cytokines like transforming growth factor (TGF-β) could play a role in the clinical manifestations and hematological changes reported in the literature . However, mutations in the TGF-β producer phenotype could also influence the clinical outcome of patients infected with brucella .
Thus far, it is accepted that anemia, leukopenia, thrombocytopenia, and pancytopenia are the hematological complications closely associated with concomitant brucella infection. MDS are clonal hematopoietic disorders, often manifested by karyotypic and/or molecular genetic aberrations. Li et al.  reported a patient with acute brucellosis and myelodysplastic syndrome that was revealed while investigating prolonged and persistent pancytopenia even after adequate treatment of brucella infection. That patient had MDS with excess blasts-1 (refractory anemia with excess blasts-1) and brucella infection is unlikely to be the underlying casual event linked to the genesis of MDS in this case. On the contrary, unlike the case reported by Li et al. , our patient’s initial bone marrow showed dysplasia in two cell lines that completely normalized following successful treatment of brucella infection.
| Conclusion|| |
Brucellosis is an important public health issue especially in endemic areas and when it is intertwined with local cultural practices. Moreover, it presents as pyrexia of unknown origin and initial tests are usually nondiagnostic. Furthermore, it can mimic almost any infectious or noninfectious condition, making it extremely difficult to diagnose it quickly, leading to complications, especially in endemic areas. The finding of transient myelodysplasia in our case warrants caution in interpreting dysplastic findings in the bone marrow of cytopenic patients presenting with brucella infection.
Financial support and sponsorship
NilConflicts of interest
There are no conflicts of interest.
| References|| |
Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV. The new global map of human brucellosis. Lancet Infect Dis
Scrimgeour EM, Mehta FR, Suleiman AJ. Infectious and tropical diseases in Oman: a review. Am J Trop Med Hyg
Erkurt MA, Sari I, Gül HC, Coskun O, Eyigün CP, Beyan C. The first documented case of brucellosis manifested with pancytopenia and capillary leak syndrome. Intern Med
Al-Eissa YA, Assuhaimi SA, al-Fawaz IM, Higgy KE, al-Nasser MN, al-Mobaireek KF. Pancytopenia in children with brucellosis: clinicalmanifestations and bone marrow findings. Acta Haematol
Karaman K, Akbayram S, Bayhan GI, Dogan M, Parlak M, Akbayram HT et al.
Hematologic Findings in Children With Brucellosis: Experiences of 622 Patients in Eastern Turkey. J Pediatr Hematol Oncol
Demir C, Karahocagil MK, Esen R, Atmaca M, Gönüllü H, Akdeniz H. Bone marrow biopsy findings in brucellosis patients with hematologic abnormalities. Chin Med J (Engl)
Erdem E, Yıldırmak Y, Günaydın N. Brucellosis presenting with pancytopenia due to hemophagocytic syndrome. Turk J Haematol
Yildirmak Y, Palanduz A, Telhan L, Arapoglu M, Kayaalp N. Bonemarrow hypoplasia during Brucella infection. J Pediatr Hematol Oncol
Bakri FG, Al-Bsoul NM, Magableh AY, Shehabi A, Tarawneh M, Al-Hadidy AM et al.
Brucellosis presenting as myelofibrosis: first case report. Int J Infect Dis
Li JJ, Sheng ZK, Tu S, Bi S, Shen XM, Sheng JF. Acute brucellosis with myelodysplastic syndrome presenting as pancytopenia and Fever of unknown origin. Med Princ Pract
Sari I, Altuntas F, Hacioglu S, Kocyigit I, Sevinc A, Sacar S et al.
A multicenter retrospective study defining the clinical and hematological manifestations of brucellosis and pancytopenia in a large series: Hematological malignancies, the unusual cause of pancytopenia in patients with brucellosis. Am J Hematol
Al-Anazi KA, Al-Jasser AM. Brucella bacteremia in patients withacute leukemia: a case series. J Med Case Rep
Barutca S, Sivri B. Brucellosis and hepatocellular carcinoma: just a coincidence? Am J Gastroenterol
Moyer NP, Holcomb LA, Hauslert WJ. Brucella. In: Balows A, editor. Manual of clinical microbiology
. Washington, DC: American Society for Microbiology. 1991. pp. 457–461.
Buzgan T, Karahocagil MK, Irmak H, Baran AI, Karsen H, Evirgen O, Akdeniz H. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int J Infect Dis
Akbulut H, Celik I, Akbulut A. Cytokine levels in patients withbrucellosis and their relations with the treatment. Indian J Med Microbiol
Rafiei A, Hajilooi M, Shakib RJ, Alavi SA. Transforming growthfactor-beta1 polymorphisms in patients with brucellosis: anassociation between codon 10 and 25 polymorphisms and brucellosis. Clin Microbiol Infect
[Figure 1], [Figure 2], [Figure 3]