Brucellosis complicated by piriformis myositis and sacroiliitis: A case report and a review of the literature

Abstract

Brucellosis remains an endemic zoonosis in the Middle East, particularly in Lebanon, owing to the high consumption of raw meat and unpasteurized cheese. In this report, we present the case of a twenty-one-year-old girl who was diagnosed with brucellosis during the investigation of persistent fever and night sweats that was confirmed by an elevated Brucella agglutination titer at 1/160 for Brucella melitensis species, and an indirect Coombs at 1/1280. Unfortunately, owing to non-adherence to the antibiotic regimen prescribed, her condition progressed, resulting in piriformis myositis with sacroiliitis, an unusual complication of brucellosis. Resolution occurred following a treatment regimen comprising intravenous gentamycin 5mg/kg daily for two weeks along with rifampin 300mg TID, and doxycycline 100mg BID for 12 weeks. Furthermore, we conducted a literature review, which revealed the diagnostic and imaging criteria for this uncommon complication to be still unclear, as well as the lack of universally approved guidelines for its treatment. Brucella - myositis should be suspected when patients present with fever and back pain.

Highlights

• •Brucellosis is a zoonotic disease still endemic in the MENA region.
• •Brucellosis can present with a wide array of symptoms , going from fever to endocarditis.
• •Brucella-associated myositis is a very rare occurrence, with only 6 cases reported in the literature.
• •Piriformis myositis has only been reported once in association with brucellosis, to which we add our case.

1. Introduction

Brucellosis, commonly referred to as undulant or Malta fever, is still one of the most common zoonoses worldwide. While the disease has not been reported in many countries in the recent years, it continues to pose a significant burden in various regions, particularly in the Eastern Mediterranean region. Lebanon has experienced its share of the disease, with a total of 1180 cases reported in 2017 and 2018 marking the fifth major brucellosis outbreak worldwide since 2016 [1]. The infection is caused by a gram negative, non-spore-forming coccobacilli bacteria of different species, with Brucella melitensis being the most pathogenic for humans. It is mainly contracted by ingestion of unpasteurized milk or dairy products, or undercooked meat from infected reservoirs [2]. While brucellosis can affect various organ systems within the body, direct muscle involvement is an uncommon presentation of brucella infection. To date, only six case reports in the literature have documented myositis associated with brucellosis, to which we add a unique case of piriformis myositis complicated by sacroiliitis secondary to brucellosis in a healthy young female. We also review the literature on myositis associated brucella infection.

2. Case report

A 21-year-old female patient with no significant past medical, familial, or psychosocial history, presented to the emergency department of the Lebanese Hospital Geitaoui University Medical Center (LHG-UMC) for six weeks-history of fever, associated with night sweats and epigastric pain. On physical examination, the patient was hemodynamically stable and febrile at 38.4˙C. The remainder of her physical exam was unremarkable. Initial laboratory tests revealed a hemoglobin level of 10.2g/dl (reference range 12–16g/dl), a white blood cell count of 3500 cells/mm³ (4800-10800 cells/mm³), and elevated levels of CRP and procalcitonin levels at 45mg/L (reference range <6mg/L) and 0.42 ng/ml respectively. LDH levels were also elevated at 433U/L (91–248U/L). Liver function tests were disturbed; gamma GT 94U/L (7–64U/L), AST 47U/L (10–42U/L). Autoimmune workup and a tuberculosis skin test came back negative. A contrast-enhanced CT scan of the abdomen and pelvis revealed mild 15cm splenomegaly with bilateral infracentimetric nonspecific inguinal lymph nodes, prompting a PET-CT and a lymph node biopsy (Fig. 1A–B). Blood cultures that were drawn upon presentation came back negative on the fifth day of admission, however, the agglutination titer for Brucella was elevated at 1/160 with indirect Coombs at 1/1280. Upon further inquiry, the patient mentioned consuming unpasteurized cheese several months before the onset of her symptoms. Patient was discharged at that time on rifampin 300 mg TD and doxycycline 100 mg BID for 6 weeks.

Fig. 1.

A- PET-CT showing abdormal FDG avid retroperitoneal and mesenteric lymph nodes. B- Pathology of the biopsied lymph node showing sinusoids populated by atypical medium sized cells with high nucleocytoplasmic ratio and irregular nuclei. Multiple mitosis is noted. C- Axial short tau inversion recovery (STIR) image, MRI with intravenous gadolinium contrast injection of the right hip. High intensity signal over the right piriformis muscle, consistent with edema. D- Axial STIR image, MRI with intravenous gadolinium contrast injection of the pelvis: High signal intensity at the right Sacro-iliac joint, consistent with edema. E− Oblique coronal STIR image, MRI with intravenous gadolinium contrast injection over the right sacroiliac joint: High signal intensity at the right Sacro-iliac joint, consistent with edema

F- Coronal T2 weighted image with fat saturation: Follow up MRI without contrast injection (1 year after antibiotic treatment initiation) shows complete resolution of the right sacroiliac joint pathology; no soft tissue collections; no left sacroiliac joint abnormalities.

Six weeks after the initiation of treatment for brucellosis, the patient complained of four-day onset of severe right hip pain radiating to the gluteal region and extending down to the calf. Pain worsened upon walking and extending the leg and was refractory to analgesics. The patient denied any numbness or tingling sensation. Initial laboratory investigation revealed prolonged erythrocyte sedimentation rate (ESR) of 59mm/1^sth. Liver and kidney function tests, LDH, and creatine kinase levels were within normal limits. Lumbar MRI (Fig. 1C) revealed edema involving the right piriformis muscle. Pelvic MRI with gadolinium (Fig. 1D–E) revealed right sacroiliitis with inflammatory infiltrate extending around the lumbosacral plexus. Upon reviewing the patient's medical history, it was discovered that she had taken rifampin and doxycycline for two weeks instead of the prescribed six week duration. The patient was considered as having piriformis myositis and sacroiliitis associated with a relapse brucellosis, further supported by the isolation of Brucella melitensis species from blood culture retrieved upon presentation when she was found to have fever (38.7 ˙C). The patient received intravenous gentamycin 5mg/kg daily for two weeks along with rifampin 300mg TID, and doxycycline 100mg BID for 12 weeks. Patient reported clinical improvement starting the sixth day of treatment with a complete resolution of her symptoms and normal physical examination by the end of the treatment course. Treatment protocol was well tolerated by the patient and a metabolic panel; including complete blood count, liver and renal function tests performed monthly during treatment and one month after finishing antibiotherapy were within reference range. A follow up MRI of the pelvis that was conducted 6 months following the completion of antibiotic regimen (Fig. 1F) demonstrated a complete resolution of the previously identified abnormalities as well as a negative Wright serology. At one-year follow-up, the patient remained asymptomatic.

3. Discussion

Brucella infection is endemic in most Middle Eastern countries, with Syria and Iraq reporting the world's highest incidence rates [3]. Brucellosis has a wide clinical spectrum, ranging from asymptomatic to chronic debilitating infection [2]. The non-specific manifestations of brucella infection and the clinical presentation that can mimic numerous disease processes and lead to errors in diagnosis and delay in treatment initiation. In contrast, direct muscle association with brucella infection is quite rare. A review of 81 participants from the country of Georgia, which is known to be endemic for brucellosis, didn't report any patient with myositis [4]. A larger study from the Balkan Peninsula involving 418 patients diagnosed with brucellosis, also failed to document any cases of myositis associated with brucella infection [5]. A Turkish study involving 1028 brucellosis cases, reported myalgia among 36.1% of the patients but none of them had evidence of myositis [6]. A systematic review and meta-analysis study including 68 publications related to clinical features of human brucellosis with 12,842 patients from China, reported myalgia in 66% of all the studies but didn't report any case of myositis [7]. A literature review of myositis associated with brucella infection using the keyword “Brucellosis” “Brucella infection” and “myositis”, revealed only six case reports (Table 1).

Table 1.

Table 1: Case reports showing brucellosis infection associated with myositis in patients of both genders, of different ages, from different countries.

Reference	Gender	Age (years)	Country of exposure	Epidemiol-ogical antecedent for brucellosis	Blood cultures	Brucella serology titer	Tests to confirm diagnosis of myositis	Antibiotics regimen and duration
Suleiman et al. [8]	M	16	Saudi Arabia	Ingestion of unpasteuri-zed camel milk	Negative	1:5210	Biopsy of the left deltoid muscle EMG	G/1w S/1w C -D/3 m
Faris et al. [9]	F	22	Jordan	Ingestion of unpasteuri-zed milk	Positive	1:640	Pelvic MRI	G/1w R-D/3 m
Aygul et al. [10]	M	25	Turkey	Contact with infected animal	Positive	1:640	EMG	S/4 w R-D/3 m
Pantelis et al. [11]	M	19	Greece	NR	Positive	>1:1280	Pelvic MRI	D-R- C/6 m
Dafni et al. [12]	F	58	Greece	NR	Positive	NR	Pelvic MRI	D-C –Ra/6w
Kushal et al. [13]	M	35	India	Contact with infected animal and ingestion of unpasteuri-zed milk.	Negative	1:640	EMG	D-R/6w

M: male, F: female, NR: not reported, EMG: electromyography, MRI: magnetic resonance imaging, IV: intravenous, IM: intramuscular, G: gentamicin, S: streptomycin, C: ciprofloxacin, D: doxycycline, R: rifampicin, w: week, m: month.

^aRifampicin was replaced by trimethoprim–sulfamethoxazole because of rifampicin-related hemolysis.

This is only the second case of piriformis myositis secondary to Brucella infection [11], and the first documented case in Lebanon. Due to the proximity of the piriformis muscle to the sciatic nerve, piriformis myositis can present as sacroiliitis or sciatica, making the diagnosis of brucella associated myositis even more challenging. MRI has a high sensitivity for the diagnosis of spondylitis [14] but its sensitivity for brucella myositis requires further investigations to help differentiate brucella spondylitis from other infectious spondylitis [15], and diagnostic standards for piriformis brucellosis are still lacking. Treatment of human brucellosis has been well described, with an optimal regimen consisting of a dual or triple antimicrobial regimen over an extended period. While treatment protocols have been described for multiple organ involvement in brucellosis, treatment for Brucella associated myositis is still uncertain and data is still limited to case reports and observational studies [16]. In fact, no unified therapeutic protocol was adopted in the six reported cases of myositis associated with brucellosis, with treatment duration ranging from six weeks [12,13] to up to six months [11]. All reported cases achieved remission at follow-up visits. Further studies are needed to optimize the antibiotherapy for this specific involvement and high index of suspicion for brucellosis myositis should be made when a patient from an endemic area presents with muscular pain and/or weakness with undulant fever. This case report presents several limitations. Firstly, blood culture returned negative results at initial presentation, and the diagnosis relied on serological tests and the presence of risk factors, that is the history of consuming unpasteurized dairy products. However, Brucella species were isolated from blood during the patient's second admission when she was diagnosed with piriformis myositis secondary to her non-compliance to initial treatment. The absence of unified therapeutic protocols for myositis associated Brucella infection stands out as a significant limitation. The varying treatment duration ranging from six weeks to six months in the six reported cases suggests a lack of consensus on the optimal antibiotherapy. Despite all patients reporting complete recovery during follow-up, none of the case reports detailed side effects secondary to the treatment protocols. Our patient was treated for three-month duration and remained asymptomatic during a one-year follow-up. However, due to the singular nature of the case, generalizing the data to draw robust conclusions is challenging. Additionally, although the patient remained symptom-free for one year, the uncertainty surrounding potential long-term complications introduces another limitation.

4. Conclusion

In conclusion, this case highlights the rarity of myositis associated with Brucella infection. The scarcity of reported cases, coupled with the absence of documentation in large studies, underscores the unique nature of this manifestation within the spectrum of brucellosis. Furthermore, our case brings attention to the potential complications associated with brucellosis, especially in cases of inadequate adherence to the treatment regimen. This underscores the crucial role of thorough patient education to ensure compliance with the prescribed antibiotic regimen, thereby preventing relapses and associated complications. The presenting case emphasizes the need for further research to optimize antibiotherapy specifically for Brucella-associated myositis. Finally, clinicians should maintain a high index of suspicion in patients presenting with muscular pain and/or weakness concomitant with undulant fever. Early recognition and intervention are essential in managing Brucella-associated myositis, considering its unique and challenging clinical presentation.

Data availability statement

All relevant data are within the paper. Further data are available upon request.

Ethical statement

Written and signed consent was obtained from the patient to publish her clinical history.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Nicolas Sandakly: Writing – review & editing, Writing – original draft, Visualization, Methodology, Investigation, Data curation, Conceptualization. Georgio El Koubayati: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision. Abir Ayoub: Writing – review & editing, Writing – original draft, Visualization, Data curation, Conceptualization. Fady Haddad: Writing – review & editing, Writing – original draft, Validation, Supervision.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.