Brucellosis with Multisystem Involvement: A Case Report Focusing on Neurological Manifestations and Drug-Induced Dermatitis—Diagnostic and Therapeutic Dilemmas

Abstract

Brucellosis is a widespread zoonotic infection with a broad spectrum of clinical manifestations, often leading to delayed diagnosis and multisystem complications. While typical symptoms include fever, arthralgia, and hepatosplenomegaly, neurological involvement and severe drug reactions are uncommon and pose diagnostic and therapeutic challenges. A 54-year-old male farmer from an endemic area in Inner Mongolia presented with a six-month history of recurrent polyarthralgia, followed by progressive neurological deficits including muscle weakness, sensory impairment, and bilateral adductor pollicis atrophy. Despite confirmed brucellosis serology and standard antibiotic therapy (rifampicin and doxycycline), his symptoms persisted. He later developed generalized drug-induced dermatitis after taking Zhenbao Pill, which resolved only partially upon discontinuation. Lumbar magnetic resonance imaging (MRI) showed multilevel intervertebral disc protrusion, and brain MRI revealed cerebral white matter hyperintensities and small lacunar infarcts. Given the patient’s epidemiological exposure history, progressive clinical symptoms and abnormal imaging findings, suspected neurobrucellosis and possible brucellosis-associated neuropathy were considered clinically, with definitive diagnosis pending further cerebrospinal fluid examination, nerve conduction studies and electromyography. This case highlights the clinical possibility of progressive neurological impairment and potential herbal medicine-related cutaneous adverse reactions in patients with brucellosis. The novelty of this case lies in the co-occurrence of suspected brucellosis-related neurological involvement and drug/herbal-induced dermatitis. This study reminds clinicians to enhance vigilance against atypical and complex manifestations of brucellosis, conduct comprehensive differential diagnosis, and adopt a multidisciplinary collaborative strategy for the standardized management of such intractable cases.

Introduction

Brucellosis, a globally prevalent zoonotic infection, presents a significant threat to public health worldwide, especially in regions with developed animal husbandry. The study estimates approximately 500,000 new cases occur annually, often characterized by delayed diagnosis and diverse complications.^1,2 Transmission typically occurs through the consumption of contaminated unpasteurized dairy products, direct contact with infected animals, or inhalation of bacterial aerosols.³ Clinically, brucellosis manifests with multi-system involvement, including fever, night sweats, arthralgia, and commonly affecting the skeletal, nervous, urinary, reproductive systems, and skin; however, atypical presentations frequently contribute to misdiagnosis.^4,5

Brucellosis, endemic to pastoral regions of China such as Inner Mongolia and Xinjiang, is exhibiting increasing incidence due to the expansion of animal husbandry and increased human mobility. Studies have shown that central nervous system involvement in brucellosis is uncommon, occurring in only 4% of patients.⁵ Patients with neurobrucellosis may present with persistent headache, neck stiffness, consciousness disturbance, epileptic seizures, muscle weakness, paresthesia, and even paralysis.^6,7 In severe cases, neurobrucellosis can lead to serious complications such as meningitis,^6,8 brain abscess,⁶ cerebral infarction,⁹ and may even be life-threatening. Rapidly progressive bilateral radiculoneuropathy with concurrent cutaneous adverse drug reactions has barely been documented in current global literature, highlighting the uniqueness of the present case compared with previously published reports.

This report describes a complex brucellosis case dominated by rapidly progressive suspected radiculoneuropathy and possible drug-induced dermatitis, aiming to enhance clinical vigilance regarding these atypical and complex manifestations.

Case Presentation

In August 2023, a 54-year-old male farmer from Chifeng, Inner Mongolia, an area endemic for brucellosis, presented to our hospital. His occupation involved sheep rearing, representing a significant risk factor for brucellosis exposure. The patient reported a six-month history of recurrent polyarthralgia, followed by mobility impairment and muscle atrophy over the ensuing three months. Notably, he denied exposure to cold or damp environments, plague, radiation, dust, or other sources of infection.

The patient’s initial symptoms began in February 2023 with unprovoked pain in his left ankle, which progressively extended to his knees, elbows, and lumbar region. Laboratory tests revealed negative ASO and RF results, ruling out streptococcal infection and rheumatoid arthritis. After multiple hospital visits, serological tests (Agglutination test antibody titer: 1:100, ++) confirmed brucellosis in May 2023, but a 10-day hospitalization failed to relieve symptoms. Following discharge, the patient received oral rifampicin 600 mg once daily, doxycycline 100 mg twice daily, and the Mongolian herbal remedy Zhenbao Pill. Despite this treatment regimen, his arthralgia persisted, and new symptoms, including paresthesia and pain in both hands, emerged. The patient was readmitted due to worsening neurological symptoms: upper limbs and left lower limb, muscle weakness, grip impairment, and progressive atrophy of the bilateral adductor pollicis atrophy. The onset of thumb flexor muscle atrophy had begun two years prior but accelerated six months after the brucellosis diagnosis. Lumbar magnetic resonance imaging (MRI) revealed multi-level disc protrusion, while cranial MRI demonstrated white matter hyperintensities and small infarcts (Figure 1). Integrating epidemiological history, positive serology and imaging manifestations, we suspected brucellosis-associated polyradiculoneuropathy. However, the patient simultaneously suffered from cervical and lumbar degenerative disease, osteophytosis, renal and ureteral calculi, and hypokalemia—all conditions capable of causing limb numbness, weakness and muscle atrophy, which cannot be fully excluded as independent causes of neurological deficits.

Figure 1.

The MRI image of the patient’s head shows high signal in the white matter of the brain. The red circles in the figure indicate vascular-origin white matter hyperintensities.

Despite correction of hypokalemia during a 21-day hospitalization, which included a 5-day hormonotherapy, the patient exhibited no significant improvement in arthralgia, neurological symptoms, or muscle atrophy. Following discharge, while continuing rifampicin and doxycycline, the patient developed a generalized erythematous maculopapular rash with severe pruritus after administration of Zhenbao Pill. This prompted immediate discontinuation of the Zhenbao Pill due to suspected allergic reaction, although the rash persisted for 5 days thereafter. Subsequent treatment with Chinese herbal decoctions at a local clinic provided partial relief of joint pain; however, numbness in the bilateral upper limbs and left lower limb remained unresolved.

Upon admission in August 2023, physical examination revealed sensory numbness, muscle weakness, and grip impairment in both upper limbs, accompanied by progressive bilateral adductor pollicis atrophy. While the atrophy had a mild onset two years prior, it exhibited rapid progression following the diagnosis of brucellosis. Concurrent left lower limb and lumbar paresthesia, coupled with gait instability, were consistent with polyradiculoneuropathy. Dermatological assessment identified bilateral edematous erythematous patches on the arm extensors and abdomen (Figure 2), clinically diagnosed as drug-induced dermatitis, considering the patient’s exposure to rifampicin, doxycycline, oxytetracycline, and Zhenbao Pill over the preceding five months. The patient was subsequently managed with oral loratadine and topical hydrocortisone butyrate cream under close monitoring. From the initial diagnosis to the most recent follow-up, the total duration of antibiotic therapy was approximately 6 months. However, the patient self-reported intermittent non-adherence to the medication due to allergic reactions, including skin rash, which may have adversely affected treatment outcomes. After the rash subsided, we recommended a combined anti-infective regimen consisting of rifampicin, doxycycline, and ciprofloxacin, with a minimum planned course of 6 weeks. Enhanced adherence counseling and regular follow-up visits were also arranged.

Figure 2.

The patient has symptoms of skin allergy. (A): abdomen; (B): arm.

Discussion

Brucellosis, a widespread zoonotic infection, presents a complex pathogenic profile characterized by multi-system and diverse non-specific clinical manifestations.^10,11 While classic symptoms such as undulant fever, profuse sweating, arthralgia, and hepatosplenomegaly are frequently observed, neurological complications as the pre-dominant or initial presentation remain relatively uncommon, accounting for less than 4% of cases.⁵ Central nervous system complications may include cerebrovascular inflammation, cerebral or epidural swelling, stroke, and cerebellar ataxia, while peripheral nervous system involvement can present as neuropathy, radiculopathy, Guillain‑Barré syndrome, or poliomyelitis‑like syndromes.¹² Of note, peripheral nervous system symptoms are reported in only 7% of neurobrucellosis cases.¹³ Our patient exhibited a distinctive feature—rapidly progressive polyradiculoneuropathy accompanied by significant sensory and motor dysfunction—necessitating careful differentiation from potentially confounding lumbar or cervical degenerative lesions. Imaging findings in neurobrucellosis can be classified into four categories: normal, inflammatory (manifesting as granulomas and enhancement of the meninges, perivascular spaces, or lumbar nerve roots), white matter changes, and vascular changes.¹⁴ We suspected neurobrucellosis based on the patient’s clinical symptoms, epidemiological investigation, laboratory findings, and Brucella agglutination test titers.

When comparing our patient’s presentation with prior literature, we note that most published neurobrucellosis cases with peripheral nerve involvement typically present with symmetric distal sensorimotor polyneuropathy or mononeuritis multiplex, and often show significant clinical improvement within 1–2 months of appropriate antibiotic therapy. In contrast, our patient exhibited a rapidly progressive, predominantly muscle weakness, sensory impairment, and bilateral adductor pollicis atrophy, and showed minimal response to 6 months of treatment, which is unusual and suggests either delayed diagnosis, inadequate drug penetration, or an alternative or overlapping pathology. Furthermore, the coexistence of severe drug-induced dermatitis, which required discontinuation of the offending agent and prolonged symptomatic management, is rarely documented in neurobrucellosis case series, adding another layer of complexity to our case.

Several potential pathogenic mechanisms, including direct bacterial invasion of the nervous system and indirect immune-mediated damage via cross-reactive antibodies and inflammatory cytokine responses, have been hypothesized for neurobrucellosis in previous studies. Notably, cranial MRI findings, including white matter hyperintensities and small infarcts, suggest brucellosis may directly invade the nervous system through pathogen dissemination or indirectly in-duce damage via immune-mediated mechanisms, such as cross-reactive antibodies or inflammatory cytokine storms. Nevertheless, no cerebrospinal fluid analysis, electrophysiological examination, or targeted laboratory evidence was obtained in this case to verify the above mechanisms. Accordingly, the neurological damage observed in this patient can only be regarded as a tentative correlation with brucellosis, rather than a definitive causal relationship.

Therapeutic challenges included suboptimal response to standard antibiotic and adverse drug reactions. Specifically, despite treatment with rifampicin and doxycycline, the patient experienced persistent arthralgia and neurological symptoms. These enduring symptoms may be attributable to several factors, including reduced pathogen drug sensitivity, inadequate drug penetration across the blood-brain barrier or into nerve roots, an insufficient duration of treatment, or the slow resolution of multi-systemic damage, particularly affecting the nervous system. Furthermore, the patient developed delayed drug-induced dermatitis (generalized edematous erythema with pruritus) after taking Zhenbao Pill, and the reaction persisted post-discontinuation. This may stem from herb-drug interactions between Zhenbao Pill’s components and the patient’s concurrent antibiotics. Though subsequent Chinese herbal decoctions partially relieved pain (hinting Chinese herb’s potential in complex brucellosis), rigorous safety protocols and component checks are needed, with more evidence-based research to clarify Chinese herb’s efficacy and safety here.

This case report has several limitations that need to be fully acknowledged. First, cerebrospinal fluid analysis, nerve conduction studies and electromyography were not performed, lacking direct objective evidence to diagnose neurobrucellosis. Second, only Brucella serum agglutination test results were recorded, without supplementary blood culture or molecular pathogen detection data to strengthen microbiological diagnosis. Third, multiple underlying diseases including cervical/lumbar degeneration, cerebral small infarcts and hypokalemia could independently induce neurological symptoms, which cannot be fully excluded. Fourth, detailed quantitative neurological examination data, such as standardized muscle strength grading, deep tendon reflex scoring, and comprehensive sensory mapping, were not available in the original medical records.

Conclusion

In summary, this case underscores the complexity of brucellosis-induced multi-system involvement, where neurological manifestations and adverse drug reactions can confound both diagnosis and treatment. In the absence of cerebrospinal fluid analysis, electrophysiological studies, and complete microbiological confirmation, the neurological involvement in this patient can only be regarded as a potential association with brucellosis rather than a proven causal relationship. Clinicians should maintain high vigilance for atypical brucellosis phenotypes, implement comprehensive differential diagnosis to rule out spinal degenerative and cerebrovascular diseases, and cautiously evaluate the causal relationship between clinical manifestations and Brucella infection when auxiliary examinations are incomplete. A multidisciplinary approach is crucial to ensure individualized patient care and optimize clinical outcomes in such complex cases.

Abbreviations

MRI, Magnetic Resonance Imaging.

Ethics

The case was approved for publication by the ethics committee of Inner Mongolia People’s Hospital.

Patient Consent

The authors declare to have the written informed consent of the patient for publication of this case report.

Disclosure

The author(s) report no conflicts of interest in this work.