Thrombocytopenia in Brucellosis: DISCUSSION

Brucellosis is a systemic disease in which any organ or body system can be involved. The symptoms are nonspecific; however, the majority complain of fever, sweats, malaise, anorexia, headache, arthralgia and backache. Although brucellosis has been controlled or eradicated in many developed countries, it still remains a health problem in developing countries. As no characteristic constellation of symptoms and signs exists, the diagnosis may be readily missed. The nonspecific antibiotic usage also lowered the rate of positive blood cultures and led to difficulties in the diagnostic work-up.

Hematological abnormalities of brucellosis have been reported in the literature. The incidence of thrombocytopenia was reported in the range of 2.4-33%. Akdeniz et al. reported 8% of isolated thrombocytopenia (platelets <150 x 107L) in 233 patients with brucellosis, but clinically detectable bleeding (epistaxis, gross hematuria, cutaneous petechiae) was seen in only three (1% of) cases, which were all mild. On the other hand, Galanakis et al. reported 6% of thrombocytopenia, with no isolated case, in 52 patients with childhood brucellosis who did not have extremely low platelet counts on admission (range: 95-150 x 107L). Moreover, isolated thrombocytopenia was also not encountered in al-Eissa’s study, which reported 5% of thrombocytopenia (range: 4-126 x 109/L) in a total of 110 children with brucellosis. Gur et al. described 2.4% of thrombocytopenia, with no isolated case, in a retrospective analysis of 283 adult patients from southeastern Turkey.

The etiology of thrombocytopenia in brucellosis remains obscure. Multiple possible mechanisms to clarify the pathogenesis of thrombocytopenia include hypersplenism, bone marrow suppression, disseminated intravascular coagulation, direct damage to platelets by viruses and bacteria, hemophago-cytosis, granulomas and immune-mediated. Patients with septic thrombocytopenia were found to have elevated platelet-associated IgG levels in the range of 52-82%. The platelet damage is caused by the splenic destruction of immune complex-coated platelets. The mechanism of thrombocytopenia for our patient is possibly related to brucellosis-induced immune peripheral destruction of platelets by antiplatelet antibodies, since the patient initially responded to steroid (Generic Deltasone a steroid drug) treatment.

The presented patient was initially misdiagnosed as ITP. Moreover, thrombocytopenia was improved after four days of standard dose of methylpred-nisolone treatment supporting our initial diagnosis. However, the treatment changed to antibrucellosis therapy after culturing B. abortus both in the blood and bone marrow. In our previous report, however, thrombocytopenia was resistant to eight days of high-dose steroid treatment. Both patients’ findings seem to be contradictory to each other; however, the presented patient would have possibly relapsed in the first two weeks after the steroid treatment unless the antibrucellosis treatment has been initiated. Benecos et al. reported an eight-year-old boy with complaints of epistaxis and buccal bleeding who initially responded to steroid and gammaglobulin treatment for the first two weeks but relapsed immediately afterwards. The presented patient was diagnosed as brucellosis on the fifth day, and antibrucellosis treatment was commenced before relapsing of thrombocytopenia. Gurkan et al. reported a brucellosis case that was initially diagnosed as ITP and received high-dose corticosteroid treatment (is a corticosteroid. Treating allergies, arthritis, breathing problems, certain blood disorders, collagen diseases) accordingly. The platelet count was only increased to 13.3 x 107L from 3.6 x 107L on day five. In our patient, a prompt rise of platelet count was observed after the steroid treatment supporting our view of ITP. Young et al. reported an apparent response to corticosteroids by the majority of patients with brucella-induced immune-mediated thrombocytopenia. Gurkan et al. also recommended a short-term trial of high-dose corticosteroid treatment (Pulmicort canadian contains budesonide which is a corticosteroid) to patients with brucellosis-induced thrombocytopenia. However, unless there is a response to steroid treatment in 3-5 days, it is of no use to extend the treatment period. The similarity between the pathogenesis of ITP and infection-induced, immune-mediated thrombocytopenia makes the rationale for using corticosteroid treatment (Brand Temovate is a corticosteroid used to reduce itching, redness). However, at the same time, the therapy should also be directed to the underlying infection. In patients at high risk of bleeding due to brucella-induced, immune-mediated thrombocytopenia, synchronous commencement of steroid and antibrucellosis treatment should be applied.

The presence of fever challenges the diagnosis of ITP. Ail infectious etiology should be sought immediately in those cases with ITP and fever. Not only the presence of fever during hospitalization but also a fever history prior to hospitalization were also found to be important in patients with provisional diagnosis of ITP. The fever indirectly tells us the underlying possible immune mechanism rather than ITP.

In the diagnosis of brucellosis, bone marrow cultures were found to be significantly more sensitive than cultures of the blood (92% vs. 70%, respectively), and the time to detection was shorter for bone marrow cultures. In the presented patient, blood and bone marrow cultures were taken as the patient was hospitalized with a history of fever. Both the bone marrow and blood cultures were found to have positivity for brucellosis on the fifth day.

In their excellent review regarding the thrombocytopenic purpura in brucellosis, Young et al. reviewed 41 cases of brucellosis complicated by thrombocytopenia severe enough to cause purpura and mucosal bleeding. The principal sites of mucosal hemorrhage included epistaxis (69%), gingivorrhea (44%) and hematuria (64%). However, in our patient, no mucosal bleeding was detected. In addition, 31 out of 41 reported patients (72%) were found to receive steroid for periods of up to eight weeks. Thirty-nine patients (90.7%) were found to be survived, and antimicrobial therapy with or without steroids led to rapid resolution of thrombocytopenia. In addition to the literature review by Young et al, there are several brucellosis-induced thrombocytopenic patients receiving intravenous gammaglobulin, steroids and/or antibrucellosis treatment. While thrombocytopenia is a component of pancytopenia in first four cases, the others had isolated thrombocytopenia. However, the interesting point in the presented patient is the acute response of isolated thrombocytopenia to corticosteroid treatment (Canadian Beclovent is a corticosteroid for treating respiratory problems) similar to cases of ITP. The diagnosis of infection-induced immune thrombocytopenia was put forward only after the positive cultures of bone marrow and blood cultures revealed brucellosis.

The patient was discharged from the hospital 10 days later in good health on rifampicin and doxycy-cline therapy. The follow-up of the patient revealed normal hematological findings together with a progressive reduction in the titer of the agglutination test for brucella. In conclusion, brucella infection may cause severe thrombocytopenia, mimicking a primary hematological disease, that is reversible after appropriate antimicrobial therapy. In rare cases, thrombocytopenia can be severe; therefore, prompt recognition of this complication and aggressive therapy are essential. In cases of brucellosis-induced, immune thrombocytopenic purpura, a short-term standard dose of corticosteroid treatment (Tabletes Temovate is a corticosteroid used to reduce itching, redness) might be an alternative and additional treatment as an urgent approach for thrombocytopenia while initiating antibrucellosis treatment. Further studies should also be carried out to demonstrate the benefits of corticosteroid treatment (Pulmicort drug contains budesonide which is a corticosteroid) for brucellosis as an additional treatment to antibrucellosis therapy.

Category: Health

Tags: brucellosis, corticosteroid, fever, thrombocytopenia