Open access peer-reviewed chapter
Abstract
Brucellosis, one of the common zoonotic diseases all over the world, is still underdiagnosed. Under diagnosis is mostly due to certain concepts that should be revised especially in endemic areas. First of all, in endemic areas especially raw milk consuming communities, it is not logic to consider brucellosis only in certain occupations, while the whole community is exposed through utilization of non-pasteurized dairy products. Unawareness about the protean manifestations of brucellosis and its ability to affect almost every system in the body from heal to crown is another problem that needs orientation. Brucellosis now is one of the great imitators like SLE and TB. Chronic brucellosis can present by different manifestations even in the absence of fever and with low serum antibody titers. So, physicians in endemic areas should be aware by the usual and unusual presentations of brucellosis and should consider brucellosis in the differential diagnosis of almost every unexplained medical problem until proved otherwise.
Keywords
- fever
- osteoarticular
- brucella hepatitis
- brucella pancreatitis
- neurobrucellosis
- gonadal infection
- endocarditis
- and hematopoiesis
1. Introduction
Brucellosis is a common zoonotic disease. After routine screening of domestic livestock and application of animal vaccination programs, in industrialized countries, it became rare [1, 2].
In many endemic regions, about 500,000 incident cases of human brucellosis reported per year. Yet, because of the poor infrastructure and the inefficient notification systems, the true incidence is estimated to be 5,000,000 to 12,500,000 cases annually [3].
The variable and non-specific clinical presentations of brucellosis in human being yields great diagnostic difficulties [4].
The clinical picture has changed, in developing countries, because patients used to take antibiotics for any fever on their own initiative, or at the suggestion of the pharmacist. This has reduced the blood culture yield, making the diagnosis of brucellosis more difficult [5].
The course of the disease, may be:
Chronic brucellosis, usually present by psychoneurosis, sweating, and weight loss. Fever is not a must, and the agglutinins may be undetected; So, it resembles chronic fatigue syndrome. Localization can be seen in tissues, like bone, joints, cerebrospinal fluid, liver, kidneys, spleen, or skin. Localization may be the main presentation of systemic infection or may be the only manifestation of a chronic infection [4, 5].
Because of its non-specific clinical features, slow growth rate in the blood culture, and the complexity of its serodiagnosis, the timely and accurate diagnosis of human brucellosis is still challenging [7]. In the coming pages we will review the clinical presentation of brucellosis in different body systems.
2. Review of the body systems
2.1 Musculoskeletal and rheumatologic manifestations of brucellosis
The most common complication of brucellosis is reported to be osteoarticular involvement. It can mimic rheumatologic diseases. This may cause misdiagnosis and lead to malpractice [8].
Sacroiliitis, spondylitis, arthritis, osteomyelitis, tenosynovitis, and bursitis all were reported. The spine is the usual targeted site in the elderly, while in young the sacroiliac joints and knee arthritis predominate [9].
Gotuzzo et al. [10] retrospectively analyzed 304 cases of brucellosis. Articular manifestations were detected in 33.8% of patients. The most frequent pattern was sacroiliitis, then peripheral arthritis, manifested either as a single large lower extremity joint or as an asymmetric pauciarthritis. Mixed arthritis was a combination of the first two. Spondylitis was the least common, and significantly with more prolonged duration of symptoms (chronic course), affecting elder than young, with less frequent fever and malaise. It also tends to be destructive [10].
Mimicking rheumatic disorders was not only on the clinical level but also increased rates of positive RF (Rheumatoid Factor), anti-CCP; and decreased 25OHD levels in brucella seropositive patients were reported. So, in endemic areas it was recommended to consider brucellosis in the differential diagnosis of patients with rheumatologic manifestations even in the presence of autoimmune markers [8].
Spinal brucellosis is defined as involvement of the vertebral column, interspinal spaces and/or paraspinal areas (Figure 1) [11].
Figure 1.
Magnetic resonance imaging (MRI) of the lumbar spine revealed findings consistent with circumscribed spinal brucellosis complicated by lumbar spondylodiscitis, epidural abscess and large right-sided paraspinal abscess extended from L4 to the sacrum.
Spondylitis or vertebral osteomyelitis is inflammation and infection of vertebrae. It may affect lumbar (60%), sacral (19%) and cervical vertebrae (12%) [12]. Spondylodiscitis (simultaneous inflammation of vertebrae and disc) and discitis (intervertebral disc infected without spondylitis) were also reported [13].
To diagnose vertebral involvement during brucellosis, routine clinical and laboratory assessments are not always sufficient. More advanced imaging techniques such as bone scintigraphy, computed tomography (CT), or magnetic resonance imaging (MRI) are required [14]. Predominant lymphocyte infiltration, new bone formation, epitheloid granuloma lesions on the ventral sides of the vertebral bodies, no, or very mild, vertebral body deformation, no abnormal paraspinal soft tissue signal, no intraosseous or paraspinal abscesses, and thin and irregular abscess walls, all these features (histopathological and MRI) are more suggestive of brucella spondylitis than pyogenic or the more destructive tuberculous varieties [15]. Osteomyelitis or destructive arthritis were encountered in few cases. The lumbosacral region is the most frequently involved region, while the thoracic and cervical regions were less likely to be affected [16].
On the other hand, the midthoracic spine, vertebral destruction with gibbus deformity, disk collapse, and paraspinal abscesses all were more frequent with tuberculous spondylitis [17].
Definite diagnosis of brucellosis is established by clinical manifestations and the isolation of brucella species from blood or bone marrow cultures. In the absence of bacteriologic confirmation, a positive serology for brucella is needed for definite diagnosis [15].
In comparison with spondylarthritis, Wang et al. [18] found that, the average disease duration of brucellosis patients was shorter than that of spondylarthritis patients, especially for the axial forms (5 months vs. 87 months, P = 0.001). History of animal contact (59.09%) and more frequent elevation of temperature, should alert physicians to consider brucellosis. In addition, low back pain (LBP) of brucellosis patients was generally less improved with exercise. The pain presented as persistent LBP, and was associated with higher rate of walking difficulties. Myalgia was another major musculoskeletal manifestation and seen in nearly half (45.45%) of brucellosis patients. Additionally, HLA-B27 was usually negative in cases with brucellosis [18].
Apart from the spinal affection, the sacroiliac (SI) joints are the most commonly reported especially in acute brucellosis and may be associated with spinal brucellosis. Patients may present with hip or low back pain, mimics acute low back pain of lumbar disc herniation and the back pain may radiate into thigh however, chronic sacroiliitis is associated with chronic back pain [7]. Both unilateral and bilateral affection were reported [19]. Sacroiliitis was also simultaneously seen with dactylitis, olecranon bursitis, humerus osteomyelitis and iliac muscle abscess, and with other systemic diseases, like endocarditis, pyelonephritis and thyroiditis [20, 21, 22, 23].
Peripheral skeleton involvement is less frequent than vertebral among patients with brucellosis. Arthralgia, enthesopathy, osteomyelitis, arthritis, bursitis, tendonitis, and tenosynovitis (Figures 2 and 3) [24] were all reported. Knee (Figures 4 and 5) [25], hip, and ankle joints are among the most common peripheral regions affected. Shoulders, wrists, elbows, interphalangeal and sternoclavicular joints may also be involved [13].
Figure 2.
Isolated diffuse thickening of the left hand without any arthralgia.
Figure 3.
Tenosynovitis of the flexor tendon sheaths, synovitis of the intercarpal, and 2–3 metacarpophalangeal joints and medullary bone marrow edema of the capitatum were detected in the magnetic resonance imaging of the hand in
Figure 4.
X-ray images showed multiple cystic low density areas (blue circle) of distal right femur and proximal tibia (a, b). PDWI (proton density weighted image) sequence of MRI showed effusion and synovial thickening of the right knee joint, and subchondral bone marrow edema (blue circle) of the distal femur and proximal tibia (c–e). Post-treatment X-ray images showed the low density area was significantly reduced (f, g). Post-treatment PDWI sequence of magnetic resonance images indicated the high signal area of bone marrow edema had disappeared (h–j).
Figure 5.
Results of the synovial aspiration from the inflammed knee in
In addition, brucellosis, in endemic areas should be in the differential diagnosis of some soft tissue syndromes like bursitis and plantar fasciitis [26, 27].
Bursitis could be the presenting feature of brucellosis. Brucella bursitis usually lacks local inflammatory signs and fever [28]. Most patients have prolonged symptoms from few months to many years with the exception of few cases presented acutely. Culturing the bursal aspirate usually prove the diagnosis. Serological detection of brucella infection via standard tube agglutination (STA) test has been reported to exhibit a sensitivity of 84.6%. However, lacking a detectable immune response has been frequently recognized in patients with localized disease [29].
2.2 Gastrointestinal manifestations of brucellosis
Ingestion of non-pasteurized milk and/or raw animal products are the main sources for infection in endemic areas. So, gastrointestinal (GI)manifestations of brucellosis are variable from mild chronic symptoms up to emergency presentation in rare cases [30].
Upper GI manifestations like anorexia. Nauseas and vomiting are frequently reported up to hematemesis in rare cases associated with thrombocytopenia [31].
Abdominal pain with different clinical modalities and different underlying lesions has been reported in association with brucellosis e.g. abdominal visceral pain due to hepatitis [32], cholecystitis [33], terminal ileitis, colitis [34, 35] and occasionally oophoritis in females [36] has been described in the literature.
Acute abdominal pain due to acute pancreatitis [37], and acute bowel ischemia secondary to brucella induced vasculitis has been also reported [38]. Abdominal pain due to inflammatory peritonitis is another possibility which may occur in patients with liver cirrhosis (spontaneous bacterial peritonitis)or rarely as a direct peritoneal infection without cirrhosis [39]. Pain is not only visceral, but also abdominal wall pain in combination with fever and severe low back pain has been reported [40].
Lower GI symptoms like chronic diarrhea may also be a feature of brucellosis and so in endemic areas, it should be ruled out before immunosuppressive therapy in cases diagnosed as IBD (inflammatory bowel disease) [41].
Hepatic and splenic involvement with both hepatomegaly and splenomegaly are frequently encountered in brucellosis. Hepatomegaly may be documented in 15–20% of cases. Meanwhile, derangement of liver biochemistry is usually minor. Granulomatous hepatitis, diffuse hepatitis without granuloma, focal necrosis and rarely liver abscess (brucelloma) have been rarely reported [42]. Radiologically, two main patterns were recognized; solitary abscesses involving liver (Figure 6) and multiple smaller abscesses, with frequent splenic affection, and absence of calcifications characterize the second pattern [43, 44].
Figure 6.
A liver abscess is seen on contrast CT in a patient with brucellosis.
Brucella can stimulate collagen deposition, leading to scar formation, chronic fibrosis or cirrhosis. On the other hand, it is possible that brucellosis can trigger decompensation, in pre-existing cirrhosis [45].
2.3 Cardiovascular manifestations of brucellosis
Cardiovascular complications of brucellosis may include endocarditis, pericarditis and mycotic aneurysms involving the brain, aorta, and other vessels [46].
Cardiac affection is generally rare accounting for less than 2% of patients with brucellosis, yet frequently fatal. The incidence of endocarditis due to brucellosis ranges from 0.7 to 10.9% of endocarditis cases worldwide, mainly in Mediterranean countries.
Brucella endocarditis is a life-threatening infection accounting for the majority of mortality related to brucellosis (80%) [47]. Mortality from brucella endocarditis was found to be increased 47-fold in presence of associated pericardial effusion and 25-fold in association with congestive heart failure that developed after brucella endocarditis [46].
Almost 75% of brucella endocarditis involves the aortic valve (Figure 7) [48]. It may lead to abscess formation in the aortic root. The mitral valve is less frequently affected unless diseased. Pre-existing valve disease predisposes to valve involvement. Prosthetic valve endocarditis due to brucellosis has also been reported [49].
Figure 7.
A transthoracic echocardiogram performed on a patient with brucellosis: The white arrows point to the thickened aortic valves. This thickening is secondary to vegetations.
Diagnosis of brucella endocarditis requires a high index of suspicion especially in endemic areas, in cases with history of Contact with livestock and endocarditis with negative blood cultures [50].
In 1960, Perry and Belter published their interesting study included 44 patients died from fatal brucellosis and they concluded that, the usual cause of death during brucellosis was endocarditis. In some instances myocarditis and pericarditis were evident. Most patients die from valve deformity and congestive heart failure rather than from sepsis or embolism. Tissue examination revealed micro-abscesses within valve cusps, the destruction of the commissures, and the nodular, calcific nature of the deformity indicate that this is a chronic bacterial endocarditis. There was nothing in the lesions to suggest a hypersensitivity reaction; and eosinophils were lacking [51]. Mortality drops from 32.7% in the medical treatment only group, to 6.7% when surgery is combined to the medical treatment [52]. Fibrosis, hyalinization, and calcification were more frequently seen in brucella endocarditis than endocarditis caused by other bacteria. Most patients died because of valve deformity and congestive heart failure, which were hard to treat with medicine only [53].
Patients should be followed up by an infectious disease specialist in the first 6 months after surgery, during which the risk of relapse is high. After 6 months, a continued follow-up with a cardiologist is more appropriate [54]. In almost 40% of the cases blood culture came negative. So, the diagnosis of brucella prosthetic valve endocarditis and its complications is mainly echocardiographic. Despite occasional recovery with antibiotics alone, adding surgery to medical treatment is the most efficient therapeutic approach, yielding significant decrease in mortality [55].
Idiopathic pericardial effusion or myocarditis, even in the absence of concomitant endocarditis are other potential complications of brucellosis. Lacking of routine thorough echocardiographic studies in patients with brucellosis may explain the underestimation of isolated affection of pericardium or myocardium in the absence of concomitant endocarditis. So, in endemic areas, brucellosis should be considered in the differential diagnosis of disorders that affect the pericardium or myocardium even in the absence of concomitant endocarditis [56]. The occurrence of isolated myocarditis has been seen in endemic areas. Pulmonary edema and interstitial pneumonia due to brucella myocarditis, which was treated successfully has been reported by Jubber and associates in 1990 [57]. A 35-year-old female patient, found to have both myocarditis and pneumonia associated with effusion both pericardial and pleural was reported, with bilateral pleural thickening and pleural adhesion. Etiologically, next-generation sequencing, revealed brucella-related myocarditis and pneumonitis, with good response to anti- brucellosis antibiotics. When appropriate cultures are negative, next-generation sequencing to identify pathogens was recommended by the authors [58]. Timely diagnosis of brucella-related myocarditis and administration of appropriate antibiotic therapy can be life saving [59].
2.4 Haematologic manifestations of brucellosis
In the course of human brucellosis, anemia, leucopenia, thrombocytopenia and pancytopenia were all frequently reported [60]. In one series, anemia, leukopenia and thrombocytopenia were found in 74, 45, and 39.5% of cases respectively [61]. Associated increased and normal bone marrow cellularity ruled out bone marrow failure as a cause. The most common findings in the bone marrow evaluation were histiocytic hemophagocytosis and granulomas. Brucellosis was also, concurrently diagnosed with hematological malignancies in extremely rare cases in which the leukemic infiltrate was the cause of pancytopenia [62]. Hypersplenism, autoimmune hemolysis or alteration of iron metabolism secondary to infection are other possible mechanisms [63].
Brucellosis is unique in that it often manifests as a febrile pancytopenia in contrast to the leukocytosis and neutrophilia with bandemia that usually seen with bacteremia. Though, no specific hematological findings could be used to diagnose brucellosis. Yet, certain findings should alert the physician to the possibility of brucellosis especially in endemic areas e.g. Leukopenia with relative lymphocytosis [64], leucocytosis with relative lymphopenia [65], and eosinopenia that has been suggested as an early finding even before the serology became positive [66].
Brucellosis-induced cytopenia has no specific discriminating features from non-infectious etiologies, and therefore, brucellosis is frequently misdiagnosed as a primary hematologic disease or malignancy. However, with treatment of the underlying brucellosis hematologic manifestations usually resolves. So, brucellosis, should be in the differential diagnosis of any case of cytopenia, especially if living in, or exposed to, endemic areas [67].
Hemolysis, is another potential presentation of brucellosis, though rare yet, still brucellosis should be in the differential diagnosis as an underlying trigger for any case of hemolysis, especially those living in areas where brucellosis is endemic. Microangiopathic hemolytic anemia (MAHA) is the most common presentation (DIC, TTP and HUS) [8]. However, the literature revealed few reports about brucella presenting with Coombs-positive AIHA [68, 69].
In addition to DIC that can occur as a feature of sepsis in acute brucellosis venous or arterial thrombotic insults were rarely reported. The reported cases include abdominal artery thrombosis, popliteal artery aneurysm, deep vein thrombosis, portal vein thrombosis and cerebral vein thrombosis [70].
2.5 Skin manifestations in brucellosis
Patients may primarily present with cutaneous lesions in about 3–14% of cases with brucellosis in some series. Papulonodular lesions, erythema nodosum-like lesions, maculopapular eruptions, and contact urticaria were all frequently reported [71].
An inflammatory process in the dermis, such as perivascular and periadnexal lymphohistiocytic infiltrates and focal granulomatous lesions usually detected during histologic examination. These findings are similar to those found in the liver and bone marrow biopsies in brucellosis patients [72].
Vasculitic lesions, petechiae, purpura (in case of thrombocytopenia), liquefactive panniculitis, subcutaneous abscesses, chronic ulcerations, recurrent epidermal cyst, palmar erythema and livedo reticularis were rarely reported.
Such cutaneous lesions are not specific to brucellosis and so, brucellosis should be kept in mind in the differential diagnosis of such lesions especially in endemic areas and when the epidemiologic history of the patient is risky for such a zoonotic infection [71].
The cutaneous lesions were reported in every phase of the disease and regress with anti-brucella treatment. So, in acute brucellosis the presentation will be associated with fever, while fever may not be present in chronic brucellosis. Direct inoculation of the bacteria into the skin, deposition of immune complexes, hypersensitivity phenomena, and invasion of the skin via a hematogenous route are suggested scenarios for skin involvement in brucellosis. So, the clinician in endemic area should always keep in mind that a skin rash could represent a rare manifestation of this relatively common infectious disease [73].
The role of infectious diseases in urticaria (and angioedema) has been discussed for more than a century. Resolution of urticaria with eradication of the infection was clearly evident; however, a causal relationship with underlying or precipitating infection is difficult to establish. Among trigger factors, brucellosis should be in the differential diagnosis especially in endemic areas. Eradication of the infection could in fact lead to the resolution of urticaria [74].
2.6 Neurological manifestations of brucellosis (neurobrucellosis)
Nervous system involvement is either due to direct damage of nervous tissue or indirectly, via the production of endotoxins and immune response that are triggered by the presence of the bacteria in the human body [75]. The neurological presentation usually includes meningitis, meningoencephalitis, and encephalitis [76, 77]. Different varieties of meningovascular complications are also frequently described (mycotic aneurysms, ischemic strokes, and subarachnoid hemorrhages, etc.). Intracranial hypertension due to the arachnoid drainage system affection has been described [78]. Sensorineural hearing loss due to vestibulocochlear nerve affection is the commonest feature of cranial nerve involvement [79]. Spinal cord can also be affected; myelitis [80] and transverse myelitis [81] were reported. Spinal cord or spinal root compression can be the presentation of abscess or granuloma caused by neurobrucellosis [78].
Peripheral nervous system involvement occurs in 7% of neurobrucellosis [82]; Acute, subacute, and chronic polyradiculoneuropathies can occur. The clinical presentation may mimic Guillain-Barré Syndrome [82, 83].
Other complications, as psychiatric symptoms, are rare; the most commonly observed are depression, personality changes, euphoria, and psychosis [84].
Central nervous system involvement in brucellosis may be seen at every stage of the illness, even long after the convalescence phase. In some case reports from endemic area neurobrucellosis progresses gradually 3 months after the occurrence of the first symptom. Ataxia occurring months after the beginning of the first symptoms (post-infectious cerebellar ataxia) was also seen. So, clinicians should keep in mind that similar to tuberculosis, these manifestations may also develop due to brucellosis [79]. Epilepsy, is another suggested sequela [85, 86].
Because of the lack of pathognomonic signs and symptoms, clinical suspicion plays a key role in endemic areas. Compatible clinical picture as in (Figures 8 and 9) [87], inflammatory spinal fluid analysis and evidence of brucella infection in CSF or blood are the main clues to diagnose. CSF cultures being the reference standard for the diagnosis yet, are often negative. So, high titers of brucella antibodies in serum or CSF detected by various agglutination tests are still the most frequent supportive test for the diagnosis in practice [88].
Figure 8.
Clinical presentation of Neurobrucellosis (Part 1).
Figure 9.
Clinical presentation of Neurobrucellosis (Part 2).
2.7 Respiratory manifestations of brucellosis
Though pulmonary involvement is rare yet, in endemic areas, brucellosis should always be considered as a potential causative agent in patients with pulmonary symptoms [89].
The most frequent symptom of lung involvement is non-productive cough. Dry cough can be seen in 10 to 33% of patients. Respiratory airways are responsible for such symptoms in less than half of patients with abnormalities in the chest X-ray [90].
Objective features of respiratory involvement are only present in around 1% of patients however, some authors from endemic areas reported 7%. Pneumonia, bronchopneumonia, pleural effusion with a predominance of monocytic or lymphocytic infiltrates, and paroxysmal dry cough all were reported. Less frequently, empyema, granulomas and solitary nodules, interstitial pneumonia, hilar and paratracheal lymphadenopathy, and even pneumothorax have all been described [91, 92].
Neither clinical features nor chest radiography revealed specific findings in brucellosis with pulmonary involvement. Respiratory culture yield was very low, with none of sputum samples and only 10% of pleural effusion samples showing positive results in some series [93, 94].
Unless the clinicians identify epidemiologic risk and clinical features of brucellosis and then request specific serologic and culture methods to confirm the diagnosis, they will miss brucellosis as the underlying etiology.
A delay for about 1 month before the recognition of brucella pneumonia is usual, and concurrent rheumatologic symptoms are present in almost half of patients. Neutrophilia is uncommon, but many patients have mildly raised transaminase levels and thrombocytopenia. The clinician should request specific serologic and culture tests required for the diagnosis of brucella once clinically suspected [94].
2.8 Genitourinary manifestations of brucellosis
Approximately 2–20% of brucellosis cases involve the genitourinary system. Epididymo-orchitis or orchitis is the most common manifestation, followed by cystitis, tubo-ovarian abscess in females, and prostatitis in males [95]. Suggestive epidemiologic history, seasonal pattern in endemic areas, gradual onset, longer duration all are suggestive points in the history. Undulatory fever with periods of apyrexia, variable local features from minimal to florid inflammation, with no associated lower urinary tract symptoms and no serious leukocytosis in the blood picture, with failure of response to empiric antibiotics in a case of epidedimo-orchitis all will suggest brucella epidedimo-orchitis rather than non-specific epidedimo-orchitis. High clinical suspicion, together with imaging diagnostic tools and microbiologic studies contribute to the reduction of unnecessary orchiectomies [96].
Involvement of the prostate gland may mimic cancer [97] and also Tubo-Ovarian brucellosis in females may mimic ovarian tumors [36].
The hazards of the female reproductive system in patients with brucellosis include pregnancy disorders at various times, intrauterine fetal death, as well as endometritis, oophoritis, mastitis, placentitis, and causeless abortions [98]. Neither the serum agglutination titer, nor the clinical type of the disease show any correlation with the occurrence of abortion [99]. Mastitis and breast abscess due to brucellosis, though rare, is another reported hazard for women infected with brucellosis [100]. Again in areas where ingestion of unpasteurized milk and milk products is common brucellosis as a potential etiologic agent, should be considered for any breast mass or abscess [101].
Kidneys (glomerulonephritis, pyelonephritis) are rarely involved [102]. Hematuria, dysuria, and hydronephrosis are rare. Medical history of consumption of non-pasteurized dairy products is important for diagnosis, otherwise it may be overlooked easily [103].
2.9 Occular manifestations of brucellosis
Eye involvement may be serious with grave complications, so early consideration and recognition can lead to prompt treatment and might prevent blindness from severe ocular damage [104]. Uveitis, neuritis, optic neuritis, papilledema, keratitis, and more-diverse ocular and neurological presentations associated with brucellosis have been reported [105]. Ocular features might also involve dacryoadenitis, conjunctivitis, episcleritis, keratitis, iritis, iridocyclitis, neuroretinitis, retinitis, chorioiditis, panuveitis, pars planitis, and hyalitis [106].
Optic nerve involvement in brucellosis is part of neurobrucellosis and it usually involves both optic nerves [107]. Rarely, premacular hemorrhage may be seen in the context of brucella endocarditis [108].
Ophthalmic brucellosis may present by injection, blurred vision, eye pain, lacrimation, double vision, foreign body sensation, cotton-wool lesions, exudative retinal detachment, and retinal hemorrhage [106]. Diagnosis of ocular brucellosis mainly depends on culture and serology of blood and intraocular fluids [109].
A thorough ophthalmic examination for features of eye involvement, has been recommended in endemic areas for any case of brucellosis whether they have ophthalmic symptoms or not [106].
2.10 Other unusual presentations of brucellosis
In addition to systemic manifestations reported above, daily reports from endemic areas describe more unusual presentations of this endemic disease. Septic shock is one of the rare presentations of brucellosis [110]. Case reports about febrile neutropenia in patients with known malignancies proved to be another unusual presentation of brucellosis. SO, it should be considered in the differential diagnosis of febrile neutropenia in patients with cancer, particularly in endemic countries [111].
Infective thyroiditis due to brucellosis has been also noticed in endemic areas (Figure 10) [112]. So, the authors concluded that particularly in brucella-endemic regions, when mass formation on neck area is encountered, brucella induced abscess should be considered.
Figure 10.
Giant thyroid abscess related to postpartum brucella infection. On MRI, a cystic mass lesion, approximately 10.5 × 8.5 × 7 cm, thick-walled, slightly hyperintense on T1-oriented images, and hyperintense on T2-oriented images, with peripheral contrast following intra-venous contrasting material injection, containing thin septa, attracted attention.
Brucella infection of prosthetic devices includes breast implants [113]. Prosthetic joints, prosthetic heart valves, and one case of an infected pacemaker has been reported [114]. Spontaneous fracture due to brucella osteomyelitis is another unusual presentation [115].
Severe pharyngitis [116], abdominal; mesenteric and retroperitoneal lymphadenopathies, mimicking lymphoma has also, been reported. So in communities endemic in brucellosis; the diagnosis of brucellosis should be considered in any long duration fever even in the absence of a typical clinical presentation [117].
3. Summary and conclusion
The WHO has recognized brucellosis as one of the NZD (Neglected zoonotic Diseases).
Brucella infection is often not recognized due to failure of most of the health care givers to realize that; the classic acute febrile illness with non-specific symptoms, may yield a multisystem disease with localized suppurative complications in at least one third of cases.
Sticking to the traditional picture of the febrile illness in a farmer or a worker with direct exposure to animals stands behind failure to diagnose a lot of serious complicated brucella cases in the community.
A new look to this endemic disease is urgently needed, especially in endemic areas and raw milk consuming communities, taking in consideration the following points:
In communities known to be endemic in brucellosis and known to consume non-pasteurized milk (like, the middle east and Sud America); all the community are exposed, regardless of job, culture or socioeconomic status.
Considering brucellosis only in febrile patients is another pitfall especially in presence of positive epidemiologic history (residency or recent travel to endemic area or recent consumption of raw milk product). In chronic, localized or complicated brucellosis the temperature is usually normal i.e. absence of fever does not exclude brucellosis.
The characteristic symptom of brucellosis is that no characteristic symptom. So, oriented physician with high index of suspicion is vital for early screening, diagnosis and treatment.
Awareness about, the possible presentation of brucellosis that can face each physician in his specialty (e.g. The ear specialist about Brucellosis as a possible cause of sensory neural hearing loss & the ophthalmologist for brucellosis as a potential cause of uveitis, etc.) is mandatory.
To conclude: Brucellosis is an infectious disease with protean clinical presentation. Fever and musculoskeletal manifestations are the commonest clinical manifestations. The disease however can involve any organ, as mentioned above. Therefore, brucellosis should be considered in the differential diagnosis of any compatible clinical scenario, particularly in areas where brucellosis is endemic.
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