Musculoskeleta l Manifestat ions of Brucellosis: A Study of 90 Cases in Israel

Nurit Zaks, Shaul Sukenik, Michael Alkan, Daniel Flusser,

Lily Neumann, and Dan Buskila

Rheumatological manifestations are frequently reported in patients with brucel- losis. In a retrospective study of 90 patients diagnosed with brucellosis over a period of 18 years, 83 (92%) patients were Bedouins, 55 of whom (61%} reported ingestion of unpasteurized goat milk and goat milk products. The male/female ratio was 1:1, and the adult to child ratio was 3:2. The mean age of the patients was 25 years (range, 1-72 years). Rheumatological manifestations (myalgia, arthralgia, and arthritis) were reported in more than half of the patients. These manifestations started on days 3 and 4 of the disease and were mild to moderate in severity. Myalagia was evident in 49 (54%) patients and was more common in adults than in children (67% versus 37%; P < .01) and in men (67%) than in women (42%; P < .01). Arthralgia was the most common musculoskeletal manifestation, found in 55 (61%) patients, and occurred more often in children than in adults (74% versus 52%; P < .05). Arthritis was detected in 37 (41%) patients. The hip and knee joints were the most common sites of arthritis (31% each) followed by sacroiliac involvement (17%) and shoulder or spine involvement (5% each). Arthritis was also more common in children (63% versus 29%; P < .01). The prevalence of arthritis was similar in men and women. Cure was achieved in all patients after antibiotic therapy. Copyright © 1995 by W.B. Saunders Company

INDEX WORDS: Brucellosis; musculoskeletal manifestations; arthritis; infection.

B rucellosis is a zoonotic disease with world- wide distribution caused by a gram nega-

tive rod named by Bruce in 1887.1 Four species of brucella are now known: Brucella melitensis is the most pathogenic and is responsible for most of the worldwide morbidity, especially in devel- oping countries. Goats are the common source of the disease. Brucella abortus is common in cattle and found in central Europe and North America. In humans it causes a milder disease. Brucella suis and Brucella canis have only infre- quently been reported in humans. 2,3 The disease is acquired mainly by ingestion of unpasteurized milk or milk products of infected animals but also by inhalation or direct contact via skin abrasions.

Even though it has been more than 100 years since the organism was isolated, brucellosis remains a major health problem of approxi- mately half a million new cases a year, causing also a heavy economic and verterinary burden. 2 Brucellosis is endemic in Latin America, 4 in the Mediterranean, 5 and in the near east. 64 Its

incidence has been steadily increasing in Isra- el's neighboring countries in the last decades. This trend may be attributed to a true increase in the number of patients or to a greater awareness on the part of medical personnel to

From the Depa1¢ment of Medicine and Epidemiology Unit, Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel.

Nurit Zaks, MD: Intern in Internal Medicine, Soroka Medical Center," Shaul Sukenik, MD: Professor of Medicine, Head of Department of Medicine "D, "Soroka Medical Center; Michael Alkan, MD: Professor of Medicine, Head of Infec- tious Diseases, Institute, Soroka Medical Center; Daniel Flusser, MD: Lecturer in Internal Medicine, Department of Medicine "D, "' Soroka Medical Center; Lily Neumann, PhD: Associate Professor, Head of Epidemiology Unit, Faculty of Health Sciences, Ben-Gurion University; Dan Buskila, MD: Associate Professor, Head of Rheumatology Unit, Soroka Medical Center.

Address reprint requests to Prof Dan Buskila, Department of Medicine B Soroka Medical Center, F.O.B. 151, Beer Sheva, Israel 84101.

Copyright © 1995 by W.B. Saunders Company 0049-0172/95/2502-000355. 00/0

Seminars in Arthritis and Rheumatism, Vo125, No 2 (October), 1995: pp 97-102 97

98 ZAKS ET AL

the disease. It should be noted, however, that in the United States it has been estimated that there are 26 undiagnosed cases per every diag- nosed one. 9

Brucellosis is a multisystem disease that mani- fests most commonly as fever of unknown origin with other systemic symptoms and signs (diapho- resis, lymphadenopathy, anorexia, malaise, fa- tigue) but also causes localized processes such as pancarditis, glomerulonephritis, orchitis, and arthritis. Musculoskeletal involvement in brucel- losis was first reported by Kennedy in 1904. l° Over the years an increasing number of reports have described musculoskeletal manifestations of brucellosis, emphasizing the importance of rheumatological findings in this disease. Among these are series describing peripheral arthri- tis, 11"14 spondylitis, 15q8 sacroiliitis, 19 bursitis, I1 sternoclavicular arthritis, ls,2°,11 and other rheu- matological manifestations. 4,2j,22 Brucellosis is considered to be endemic in Israel. Although one epidemic has been reported, 23 there is a paucity of information regarding the clinical and epidemiological manifestations of brucello- sis in Israel. The high incidence locally is found mainly among Bedouin-nomadic tribes who make their living on livestock and consume large amounts of unpasteurized goat milk and goat milk products. The increased awareness of brucellosis and its rheumatic manifestations has prompted us to assess the clinical spectrum of musculoskeletal manifestations in brucellosis in our region.

MATERIALS AND METHODS

We retrospectively reviewed the medical re- cords of 90 hospitalized patients in Soroka Medical Center between 1972-1990, who had been diagnosed as having brucellosis. Patient's identification numbers were collected from the

hospital's archive according to ICD-9 for brucel- losis. Medical records were located, and epide- miological, clinical, and laboratory data were collected. Further laboratory data were col- lected from the hospital's bacteriological and serological laboratories. The diagnosis of brucel- losis was established either by antibody titer greater than 1:160 in the tube agglutination test or Rose Bengal after 2-Mercaptoethanol absorp- tion, or by a positive culture of blood (or any other tissue). 24,25 Patients were diagnosed as having acute (< 2 m), undulant (2 m-12 m) or chronic (> 12 m) clinical course according to the duration of clinical complaints. Patients were divided into two age groups, under and over 16 years, children and adults, respectively. Joint inflammation was documented by the number of peripheral joints with tenderness, effusion, or stress pain (joint pain elicited by gentle stretching). 26-29 The presence of spondy- loarthropathy was based on one or more of the following criteria3°: inflammatory back pain (low back pain made worse by rest and improved with activity associated with night/early morn- ing exacerbations) and stiffness; sacroiliitis on physical examination3°; grade > 2 sacroiliitis or syndesmophytes on radiographs. All drug treat- ment (antibiotic and anti-inflammatory) was recorded as well as the duration of treatment and the time for recovery from brucellosis.

Statistical Analysis

X 2 tests were used to compare proportions. The means of two groups were compared by t tests and the means of three or more groups by analysis of variance.

RESULTS

Ninety medical records of patients with bru- cellosis were analyzed. Table 1 presents the

Table 1: Demographic and Epidemiological Data on 90 Patients with Brucellosis

Age Children 36 (40%) Adults 54 (60%) Gender Males 45 (50%) Females 45 (50%) Race Bedouins 83 (92%) Jews 4 (4%) Exposure to Sheep, Goats Yes 46 (51%) No 32 (36%) Ingestion of Milk Product Yes 55 (61%) No 22 (24%) Brucellosis in Family Yes 59 (66%) No 20 (22%) Arthritis in Family* Yes 25 (42%) No 5 (9%)

Unknown 12 (13%) Unknown 13 (14%) Unknown 11 (12%) Unknown 29 (49%)

NOTE. Total number of patients, 90. Age in years (mean, 25; range 1-72). *Arthritis in a family member suffering from brucellosis (n = 59).

M U S C U L O S K E L E T A L M A N I F E S T A T I O N S 99

e-

o" o LL

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

Fig 1 : Nonrheumato- l l l l logical symptoms and ~ ~ ~ g signs of brucellosis in 90 ~ ~ ~ patients. ~ N

Signs and Symptoms

demographic and epidemiological data relevant to brucellosis in the study population. The man to woman ratio was 1:1 and the adult to child ratio was 3:2. The mean age of patients was 25 years, with a range of i to 72 years. Ninety two percent of the patients were Bedouins, of whom 61_% reported daily ingestion of unpasteurized milk or it's products. A high incidence of brucel- losis (66%) was reported in family members, of whom 42% reported brucellar arthritis. The course of the illness was acute in more than 85;% of the patients, chronic and undulant in less than 10%.

Serological profile and/or culture results were obtained from all patients. It is notable that all patients tested had positive serology, whereas only 54% of blood cultures were positive. Bone marrow and synovial fluid cultures had similar yMds, although fewer patients were tested. Figure 1 shows the distribution of nonrheumato- logical symptoms and signs. Fever was the most common complaint ( > 90%), followed by lymph- adenopathy, splenomegaly, and hepatomegaly. Malaise, anorexia, and sweats were less com- mon (<20%), and other rare manifestations were also documented.

Arthralgia was the most common musculoskel- etal manifestation (61%), followed by myalgia (54%) and arthritis (41%). The hip and knee joints were the most common sites affected (31% each), followed by sacroiliac (17%), shoul- der, and spine involvement (5% each) (Fig 2). Figure 3 shows the musculoskeletal manifesta- tions of brucellosis according to gender and age. Men complained more frequently of myalgia than women (67% versus 42%; P < .01), and adults complained more frequently than chil- dren (67% versus 37%; P < .01). Arthralgia

was reported more often in children (74%) than in adults (52%) (P < .05).

The prevalence of arthralgia was similar in both genders. Arthritis was also more common in children (63% versus 29%; P < .01). There was no difference in the prevalence of arthritis between men and women. Peripheral arthritis was mostly monoarticular or oligoarticular; no cases of symmetrical arthritis were detected. Small joint arthritis was detected mainly in malacarpophalangeal's and proximal interpha- langeal's. Sacroiliitis was usually unilateral. Spondylitis was rarely observed and involved mostly the lumbar spine; one patient had cervi- cal spondylitis. Joint complaints occurred on average 3-4 after disease onset and was mild to moderate in severity. Non steroidal anti-inflam- matory drugs were sufficient to control

31

wrist, elbow, and small joints

hip 31%

spine 5'

should,

ankle 5%

Fig 2:

sacroiliac 17%

Distribution of arthritis in different joints.

80% 70%

O~ 60% 50%

~D 40%

o 30%

20%

10%

0%

100%

90% 80% 70% 60% 50%

U 40%

30% 20% 10% O%

p<0.05

MYALGIA ARTHRALGIA ARTHRITIS

I CHILDREN [ ] ADULTS [ ] MALE [ ] FEMALE

Fig 3: Distribution of myalgia, arthralgia, and arthritis by age and gen- der.

pain in all cases. Joint symptoms resolved 3 to 4 days after specific antibiotic therapy was started.

Synovial fluid was obtained from 25% of the patients with brucellosis and arthritis, and 65% of samples yielded positive cultures. Synovial fluid was studied in 23 patients with peripheral arthritis. All fluids were exudates and white blood cell counts ranged between 180 and 10,250 cells/mm 3. Positive radiological findings were shown in 6 patients with sacroiliitis, three with spondylitis and 10 with peripheral arthritis. Total peripheral white cell count was higher in patients with arthritis (7000 cells/ram 3 range 4000-10,000) than with those without arthritis (5000 cells/ram 3 range 3000-8000; P < .005).

Similar results were found in the platelet counts of these patients (P < .05). No pathological findings were observed in other laboratory tests.

Resolution of symptoms was achieved in all patients after antibiotic treatment with tetracy- cline (500 mg orally four times daily) for 3 to 6 weeks plus streptomycin (1 g intramuscularly daily) for the first 2 weeks. In patients in whom this regimen could not be used (3 pregnant women), trimethoprim-sulphamethoxasole (480/ 2400 mg per day) was given for 4 weeks.

DISCUSSION

Brucellosis in the Middle East is caused almost exclusively by B melitensis, and this series

100 ZAKS ET AL

m :=

~iiiiii!iill

iiiiiiiiiiii iiiiiiiiiiii ;iiiiiiiiii

Mani fe s ta t ion

[ I PRESENT STUDY [] KUWAIT [ ] SAUDI ARABIA NN PERU (13) (22) (4)

Fig 4: Extraarticular manifestations in patients with brucellosis in different studies.

MUSCULOSKELETAL MANIFESTATIONS 101

80%

70%

60%

50%

40% .%

30%

20%

10%

0% A R T H R A L G I A MYALGIA

Manifestation

• PRESENT STUD3(

[ ] KUWAIT (13)

[] SAUDI ARABIA (22)

[] PERU (4)

ARTHRITIS

Fig 5: Musculoskeletal manifestations of brucel- losis in different studies,

is no exception. The fact that the Soroka Medi- cal Center serves as the only referral center for a population of 90,000 seminomadic Bedouins enabled us to study the epidemiological and the clinical features of the disease. The lifestyle of this population leads to exposure to this patho-

gen, as reported by other groups from this region.7,15,22,3~

The inclusion criterion used in the present study, a titer of _>1:160, has been used by others 6 and yields more cases than the "gold standard" of growing the pathogen from a body fluid. 4'11 In this endemic region, a titer of > 160 correlates well with positive blood cultures. Positive blood culture was obtained in 54% in this series. This high figure is probably due to a high degree of suspicion and adequate labora- tory technique. The occurrence of the chronic form of the disease is due to low awareness of the disease and decreased availability of medi- cal care in this population.

The frequency of clinical manifestations in the present series was compared with other reports (Fig 4). Fever seems to be the universal presentation, but other constitutional signs such as weakness, chills, or anorexia were less fre- quent in the present series. Localized signs, such as lymphadenopathy and hepatospleno- megaly, were more common in comparison with other series.

More than 50% of our patients suffered from musculoskeletal manifestations. When com- pared with other studies (Fig 5), this is in the same order of magnitude: Lulu 7 reports 31%, ShehabP 1 found 77%, and Khateeb ~3 has 48%. When specific entities are compared with large series, 4,7,1~,13,31 our patients had more peripheral arthritis and sacroiliitis. Arthralgia and myalgia are subjective complaints and vary in different

80% 70%

;~ 60%

50%

40%

¢~ 30% [~ 20%

10%

0%

I PRESENT STUDY

[ ] SAUDI ARABIA (22)

[] v~Ru (4) IN V~RU (21) [ ] KLrvVAIT (13)

peripheral sacroiliitis spondylitis mixed arthritis

Location

Fig 6: Inflammatory joint disease in brucellosis in different studies.

102 ZAKS ET AL

cultures, making it difficult to compare data from different continents.

The high frequency of arthralgia found in the present group was more common in children, similar to findings in Kuwait. 7 Myalgia was more common in male patients and in children, a finding that was not previously described. Arthri- tis was twice as common in children than in adults. In other reports, 4,7J3 the sacroiliac joint was affected most often (Fig 6).

In this group, the hip and the knee were the most commonly involved joints, whereas sacro-

iliitis was found only in 17% of patients. Most of the affected joints were peripheral, and spondy- litis was especially uncommon (5%). This distri- bution is found in acute or undulant cases, 4 as were our patients. Peripheral 4 and large joints I1 are more commonly involved in children, but we found no relation between age and location of joint involvement. The role of geographical, genetic, ethnic, or other factors in the clinical presentation of Brucellosis remains to be eluci- dated.

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