Vol 43 # 3 September 2011 - Kma.org.kw

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210 Complications of Brucellosis in Adults: An Experience from a State Hospital ... September 2011 The clinical manifestation of brucellosis is very great, ranging from asymptomatic infection to serious debilitating disease. Organ involvement can be assigned as focal involvement or as a complication. For the most part, brucellosis is a systemic infection that can involve any organ of the body [1] . The most common systems affected are the locomotor, gastrointestinal, genitourinary, hematologic, cardiovascular, respiratory, and central nervous systems [5,6] . Symptoms are nonspecific and may include fever, arthralgia, myalgia, chills, sweats, headache, and fatigue [14] . However, routine laboratory data reported in most studies have been of little diagnostic value [3,12] . Complications of brucellosis are a major medical problem in countries where brucellosis is still endemic, as in our region of southeastern Anatolia in Turkey. Osteoarticular involvement with a prevalence varying from 5.2 to 69% is the most common frequent complication of brucellosis [3,4,10,11,15-18] . The enormous range between reports in the literature may be due to characteristics of the study populations, the radio-diagnostic methods used, and the different diagnostic criteria employed. Brucellosis may also affect the musculoskeletal system at any site [4,14] . We observed osteoarticular involvement in 33.8% of 78 patients. As can be seen in Table 3, we found that the most commonly affected site was the sacroiliac joint, a finding in agreement with those recently reported by some authors [10, 11,18,19] . In this study, unilateral sacroiliitis (n = 8, 72%) was very common and it is similar to that reported by Geyik et al [14] and Calmenero et al [20] . However, Tasova et al [21] found a high rate of bilateral sacroiliitis (60%). Peripheral arthritis, especially presenting as monoarthritis, is the predominant involvement in some brucellosis series, and large joints such as the hips, knees and ankles are the most frequently affected [3,19,20] . In this study, peripheral arthritis was the second most frequent type of osteoarticular involvement, although the rate (34.6%) was higher than the Calmenero et al study(12%) [20] . On the other hand, the incidence of spondylitis reported in the literature varies significantly, ranging from 6% to greater than 50% [3,20,21] . In the present study, the rate of spondylitis was 7.8%. Hematological alterations in brucellosis are common, but they rarely constitute a true complication and resolve promptly with treatment [3] . The hematological manifestations of brucellosis include anemia, leucopenia, thrombocytopenia and clotting disorders [8] . Anemia in patients with brucellosis results from alteration in iron metabolism secondary to infection, hypersplenism, bleeding, and bone marrow suppression or autoimmune hemolysis [22] . The incidence of anemia has been reported as 44 to 74% in adult series in brucellosis [8,23] . This ratio was 55%, 56% and 54.6% cases in studies by Akdeniz et al [24] , Dilek et al [8] and Aygen et al [23] respectively. In our group, incidence of anemia was 44.2% and it is similar to the other studies. Earlier literature has emphasized the characteristic picture of a normal or reduced leukocyte count with relative or absolute lymphocytosis in patients with brucellosis [8, 22] . Leukopenia has been found to occur in 30 - 68% of the reported cases [22] . In this study, 80% of the patients had a normal leukocyte count and 14.3% has leucopenia. Leucopenia was detected 7.7%, 16% and 52% cases in the Aygen et al [23] , Gur et al [3] and Dilek et al [8] studies, respectively. The cause of leucopenia seems to be multifactorial. Thrombocytopenia is less common, having been reported in only 1 - 8% of cases, and it is rarely severe enough to cause bleeding [18] . Although the mechanism of the thrombocytopenia in brucellosis is not yet entirely known, it may be hypersplenism, bone marrow suppression due to septicemia, hemophagocytosis, granulomas and peripheral immune destruction of thrombocytes [8] . Thrombocytopenia was detected in 33.8% of patients in this study and it is higher than reported by Akdeniz et al [24] (26%) and Dilek et al [8] (14%). Pancytopenia has been described as between 3 - 21% in patients with brucellosis in the published series [8,22] . In this study, the incidence of pancytopenia was 2.6% and it is similar to that reported by Ertek et al[ 18] and Gur et al [3] . On the other hand, Sarı et al [25] reported the rate as 14.9%. In the present study, cutaneous complications were the third most frequent (3.9%). Cutaneous lesions occur in approximately 1 - 17% of patients with brucellosis [3,4,10,11,15-18] . Patients exhibit non-specific skin symptoms, such as erythema, papules, petechiae, urticaria, impetigo, eczematous rash, erythema nodosum, subcutaneous abscess, and cutaneous vasculitis [5] . Cutaneous findings in this study were similar to other reported studies [18,26,27] . It is important to emphasize that cutaneous lesions are not specific to brucellosis and may be seen in a variety of other dermatologic diseases caused by many agents. Genitourinary involvement occurs in 2 - 40% of patients with brucellosis [3] . In this study, 2.6% (n = 2, epididymo-orchitis and abortion) out of 78 patients had genitourinary complications. In men, various genitourinary infections including epididymo-orchitis, prostatitis, cystitis, pyelonephritis, interstitial nephritis, exudative glomerulonephritis, renal and testicular abscess, and seminal vasculitis have been attributed to brucellosis [6] . The most frequent genitourinary complication of brucellosis is epididymo-orchitis, affecting 2 - 20% of males with brucellosis [6, 28] . Although the prognosis of brucellar epididymoorchitis, as in our patient, is usually good, delay in diagnosis or inappropriate management may result in serious complication, such as testicular abscess, which may require orchiectomy [29] . It is well known that the effect of Brucella infection on pregnancy is no
September 2011 KUWAIT MEDICAL JOURNAL 211 more than those of other bacterial infections [19] . While abortion was seen in 5% (n = 8) of our patients, a lower rate was reported by Memish et al [7] , Bukharie et al [10] and Kochar et al [16] studies. However, Kahn et al [30] reported that the incidence of spontaneous abortion in the first and second trimesters was 43%, and that of intrauterine fetal death in the third trimester was 2%, but this result needs to be evaluated with a prospective and controlled clinical study. Nervous system complications include meningitis, encephalitis, myelitis, radiculoneuritis, brain abscess, epidural abscess, demyelination syndromes and meningovascular syndromes [31] . These may occur at any stage of the disease [19] . The reported incidence of neurological complications ranges from zero to19.4% [3,4,10,11,15-18] . In the present study, the incidence was 1.3%, after a case with depression was excluded. Meningitis is the most frequent neurological complication, and it can be the presenting finding or it can occur late in the course of the disease [4] . A high cure rate can be achieved by treatment with triple combination in these diseases (tubercular meningitis, viral encephalitis, aseptic meningitis), which may otherwise have a high mortality and morbidity [3] . The prognosis of meningitis, as in our patient, is usually good. The most common disturbance in patients with brucellosis is depression. Although depression and mental inattention are common complaints in brucellosis, direct invasion of the central nervous system occurs in less than 5% of cases [3] . In the present study, the frequency of depression was low (1.3%). On the other hand, the frequency was 37.8% in the study by Savas et al [1] . Gastrointestinal symptoms, including anorexia, nausea, vomiting, diarrhea, abdominal pain, and gastrointestinal bleeding were reported [23] . Liver and spleen enlargement with mild non-specific elevation of liver enzyme levels can be detected in approximately 50% of all patients with brucellosis [32] . On the other hand, all cases with elevated liver enzymes should not be evaluated as liver involvement. Hepatic involvement has been reported in the literature at around 2 - 3% [3,5,18] . While hepatitis is common, it is usually subclinical, and jaundice is rare [10] . Lulu et al [33] reported 40% hepatic involvement in their study, namely 1% clinical hepatitis and 38.5% anicteric hepatitis. In our study, liver enzyme elevation was observed in 28 - 32% of cases and a diagnosis of clinical hepatitis was made in only 1.3% cases. Brucella is also a rare cause of liver abscess, acute cholecystitis, pancreatitis and spontaneous peritonitis [31] . Respiratory involvement in brucellosis may occur following inhalation of infectious aerosols, and possibly via bacteremic spread of the organisms to the lungs [34] . A variety of pulmonary manifestations have been documented in the literature, including bronchopneumonia, lung abscess, empyema, pleural effusion, granulomas, solitary nodules, hilar and paratracheal lymphadenopathy [35] . Pulmonary involvement was detected in < 1 - 5% cases [34] and pneumonia may sometimes be the sole presentation of brucellosis [35] . There was a patient with pneumonia in this study group, who was cured by standard antibiotic therapy. In brucellosis, the aim of the treatment regimen is to control the acute illness and to prevent both complications and relapses [14] . The successful treatment of brucellosis requires prolonged chemotherapy regimen with a combination of antibiotics [3] . Despite treatment including several antibiotic regimens, relapse is estimated to occur in 5 - 40% of patients with acute brucellosis in the following year, depending on antibiotic use, duration of treatment, and drug combination [5] . In this study, the patients were given various regimens. The treatment duration was based on organ involvement, CRP and ESR normalization. We did not treat with a single agent and thus our relapse rate was low (3.9%) during the one-year follow-up. CONCLUSION Brucellosis will continue to be a public health problem in countries where consumption of raw milk and / or its products and stockbreeding are widespread. The most frequent complication of brucellosis is osteoarticular, followed by hematological, cutaneous, genitourinary, nervous and other system complications. Since brucellosis is a preventable disease, knowledge and early diagnosis of the complications are especially important. Consequently, primary health care physicians in endemic regions must recognize that brucellosis is an infection which may involve almost any organ system and which may vary markedly in its clinical presentation. REFERENCES 1. Savas L, Onlen Y, Savas N, Yapar AF, Aydın M, Tugal O. Prospective evaluation of 140 patients with brucellosis in the southern region of Turkey. Infect Dis Clin Pract 2007; 15:83-88. 2. Mantur BG, Amarnath SK. Brucellosis in India-a review. J Biosci 2008; 33:539-547. 3. Gur A, Geyik MF, Dikici B, et al. Complications of brucellosis in different age groups: a study of 283 cases in southeastern Anatolia of Turkey. Yonsei Med J 2003; 44:33-44. 4. Kokoglu OF, Hosoglu S, Geyik MF, et al. Clinical and laboratory features of brucellosis in two university hospital in southeast Turkey. Trop Doct 2006; 36:49-51. 5. Buzgan T, Karahocagil MK, Irmak H, et al. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int J Infect Dis 2010; 14:e469-478.
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