Surgery and antibiotics for the treatment of lupus nephritis with cerebral abscesses:A case report

lNTRODUCTlON

Systemic lupus erythematosus(SLE)is an autoimmune disease that is currently managed by long-term glucocorticoid and immunosuppressive treatments.However,such treatments often render patients extremely susceptible to opportunistic infections,which can negatively impact SLE prognosis[1,2].The respiratory system,urinary system and skin are most commonly affected by opportunistic pathogens,and multiple cerebral infections are rarely reported[3,4].We here report an SLE patient with renal involvement and multiple cerebral abscesses who was admitted to our hospital in June 2018.In addition to adjusting glucocorticoid and immunosuppressant therapy,we treated the patient with a combination of surgery and multi-antibiotic therapy to eliminate the abscesses and control the infection.After 2 years of follow-up,the patient's SLE and lupus nephritis(LN)were stable,and the cerebral abscesses resolved.In this case report,we discuss the primary treatment and surgical indications,as well as the postoperative treatment regimen,which may help improve the diagnosis and treatment of similar cases.

CASE PRESENTATlON

Chief complaints

A 46-year-old woman was admitted to our hospital due to repeated fever with headache that lasted 10 d and was exacerbated for 1 d.

History of present illness

The patient developed fever without any obvious cause 10 days before admission,with a body temperature of 39 °C,along with headache and vomiting.The patient initially believed that she had upper respiratory infection,and therefore self-administered anti-cold medication,which did not alleviate the symptoms.

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History of past illness

SLE involving the hematologic system and kidneys was diagnosed 1 year previously,and renalpathology showed class IV LN.The patient underwent hemodialysis several times due to acute kidney injury.Glucocorticoids and immunosuppressants were maintained.The patient’s past medical record is summarized in Tables 1 and 2.

Upon admission,the patient was given dehydration therapy to lower intracranial pressure.Given her history of renal impairment caused by LN,glycerin fructose alternating with furosemide were used as dehydrating agents instead of mannitol and albumin to avoid exacerbation of renal impairment.Mycophenolate mofetil(MMF)was discontinued immediately due to severe infection,but the prednisone dose(20 mg/d)was maintained.The surgical contraindications of anemia and electrolyte imbalance were corrected by red blood cell transfusion and fluid infusion,respectively.The surgery was performed immediately after correcting the preoperative contraindications 3 days post-admission.Large abscesses in the left parietal lobe and right frontal lobe were resectedthe left parietal approach and right frontal approach(Figure 2),respectively.Other small abscesses in the deeper part of the brain were not removed.Local linear incision was made.Through the scalp,bone valve and endocranium,after accurate positioning,brain tissue edema was observed.During brain histostomy,the abscess wall was found intact and tough,and no important cerebrovascular trunk was found around the abscess,and light yellow pus was aspirated from the abscess.The abscess cavity was completely removed,the blood vessels on the abscess wall were cut off,and electrocoagulation hemostasis was performed(Supplementary Figure 1).During the surgery,abscess wall should be removed completely to avoid pus overflow and reduce the damage to the normal vascular and cerebral tissue around the abscess.Finally,the aspirated light yellow pus was sent for bacterial culture and drug susceptibility testing.

Personal and family history

The patient reported significant relief from headache after surgery,and neurological symptoms such as hemiplegia,paresthesia and aphasia were not observed.The patient was given routine postoperative treatments including dehydration therapy(as described previously)and fluid infusion.The bacterial culture obtained on postoperative day 4 indicated.Based on the drug susceptibility test results and taking into consideration the patient’s renal dysfunction,a multi-antibiotic regimen wasselected consisting of sulfamethoxazole-trimethoprim(30 mg/kg,q12h,oral),ceftriaxone(2 g,q12h,i.v.)and amikacin(6 mg/kg,q24h,i.v.)for the first 3 wk post-surgery,and switched to sulfamethoxazoletrimethoprim(30 mg/kg,q12h,oral)and minocycline(0.1 g,bid,oral)based on the patient’s symptoms and vital signs,imaging and laboratory test results,and nephrotoxicity of the antibiotics.The estimated duration of the entire treatment regimen was one year.

Physical examination

Physical examination upon admission indicated a body temperature 38.7 °C,a conscious but dispirited state,painful expression,Cushing syndrome,anemic appearance,facial edema,butterfly-shaped erythema visible on both maxillofacial regions,and diffused moist rales audible in both lungs.No abnormalities were identified in the heart and abdomen.Nervous system examination indicated neck stiffness(+),Kernig sign(+),Brudzinski’s sign(+),high muscle tension in the lower limbs,and Babinski sign(+).

Laboratory examinations

Hu QD and Liao LS contributed equally to this study.Hu QD was the patient’s nephrologist,searched the literature,collected data,wrote,and edited the manuscript;Liao LS was the patient’s neurosurgeon;Liao LS and Zhang Y reviewed the literature and contributed to manuscript drafting;Zhang Q and Liu J were responsible for revision of the manuscript for important intellectual content;all authors issued final approval of the version to be submitted.

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Imaging examinations

Chest computed tomography indicated dispersed inflammation and fibrotic lesions in both lungs.Brain enhanced magnetic resonance imaging(MRI)(Figure 1)showed multiple nodular abnormal signals in both frontal lobes,left parietal and temporal lobes,and the left masseteric space(left temporalis and masseter region).

FlNAL DlAGNOSlS

Based on the patient’s medical history and laboratory examinations,she was diagnosed with SLE involving the hematologic system and kidneys(class IV-G LN)complicated with multiple infectious cerebral abscesses.

TREATMENT

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Her personal and family history was unremarkable.

OUTCOME AND FOLLOW-UP

Head MRI one month post-surgery indicated complete resolution of abscesses in the left parietal lobe and right frontal lobe,slight perilesional edema,reduced size of small non-resected abscesses in the left frontal lobe and left caudate nucleus,and significant alleviation of edema around these small lesions.The patient was discharged one month after surgery but continued to receive the prescribed antibiotics(see above),along with prednisone(10 mg/d)maintenance treatment and regular follow-up assessments.Re-examination at 3 mo post-surgery showed further reduction in the size of non-resected lesions in the left frontal and temporal lobes compared to that at 1 mo post-surgery,absorption and dissipation of perilesional edema(Figure 3),and complete disappearance of neurological symptoms.Fortunately,renal function was not affected by the administration of multiple antibiotics(Table 3).Conservative treatment was continued after the patient was updated on her condition.No headaches or other neurological symptoms occurred and LN was stable during the 2-year follow-up period(Table 4 and Figure 4).

DlSCUSSlON

Therefore,in addition to clinical symptoms,imaging and laboratory tests are essential for accurate diagnosis of cerebral involvement in SLE.Cerebrospinal fluid culture and smear are important diagnostic tests,but their positive detection rates are low.Once the abscess is identified by imaging,biochemical,microbiological and pathological testing of pus are useful to determine the subsequent treatment of patients[8].

SLE is an autoimmune disease that affects multiple organs and systems,and is primarily characterized by dysfunctional humoral immunity,reduced CD8T cell cytotoxicity,defective CD4T cell proliferation,and impaired antigen presentation by mononuclear cells[5,6].The current primary treatment for SLE includes high doses of corticosteroids and immunosuppressants.Although these treatments can significantly increase the 5-year and 10-year survival of SLE patients,their prolonged use can exacerbate immunodeficiency and increase the risk of infections,especially intracranial infections,which are one of the major causes of SLE-associated mortality[7].Fever,headache and meningeal irritation are the major symptoms in SLE patients with intracranial infection.However,they can often become atypical after prolonged use of corticosteroids and immunosuppressants,resulting in misdiagnosis and missed diagnosis.Sometimes,these patients are even diagnosed with lupus encephalopathy.

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A previous study demonstrated that sufficient dosage and duration of antibiotic treatment combined with surgery can effectively treat a Nocardia-induced cerebral abscess[11].However,the treatment has not yet been standardized based on patients’ physical conditions,surgical approach,and selection and timing of postoperative antibiotics.We believe that the satisfactory outcome of our patient was the result of two factors:the development of a personalized surgical procedure,and immediate identification of the pathogen and its antibiotic susceptibility following surgery.Resection of the two largest cerebral abscesses rapidly resolved the primary symptom(severe headache)of the patient at diagnosis,and prevented further complications that might have been caused by an increase in intracranial pressure.Our patient developed multiple non-uniform cerebral abscesses,most of which were located in important functional regions of the brain.However,preoperative head MRI revealed that the patient’s intracranial pressure was mainly caused by the two large abscesses and perilesional edema in the left parietal lobe and right frontal lobe.Given that the patient was in poor physical condition before surgery(multi-organ damage due to SLE),we selectively resected the two lesions in the left parietal lobe and right frontal lobe,and applied conservative treatment for the smaller lesions in the deeper parts of the brain.A phase II resection strategy was also planned,to be performed when necessary.In addition,we developed a rational anti-microbial regimen taking into account the patient’s renal function.Testing of pus samples aspirated from the cerebral abscesses and maxillofacial region confirmedinfection.As a review of the literature indicated that sulfonamides are currently the first-line treatment for Nocardia[12,13],we selected a combination of sulfamethoxazole-trimethoprim,ceftriaxone and amikacin to ensure treatment efficacy.After 3 wk of intravenous administration,the patient no longer experienced fever,and routine blood testing during follow-up indicated resolution of the infection.To reduce nephrotoxicity of the drugs and prevent further renal impairment,we switched to continuous oral sulfamethoxazole-trimethoprim plus minocycline for one year[14,15].The antibiotic regimen described above showed good results and avoided secondary surgery.In addition,stopping immunosuppressants was also the right decision.

CONCLUSlON

In summary,we can draw three conclusions from this case.First,SLE patients often have secondary infections due to corticosteroid and immunosuppressive treatments,and due to more emphasis on the lungs,the brain and other organs are often not screened.Second,timely discontinuation of MMF during infection was conducive to improving the patient's own immunity to fight the infection.This also indirectly relieved SLE due to reduction of the systemic inflammatory response,rather than suddenly aggravated by withdrawal of MMF.This also reflects the need for a holistic immune balance in the body.Third,timely identification of the pathogen and source of infection,treatment adjustment,by means of surgery,and development of a personalized antibiotic regimen can result in a satisfactory treatment outcome for rare diseases.

Nocardia is a genus of obligate aerobic actinomycetes that are widely found in soil,and most species are non-pathogenic parasites that are found in rotting organic matter.The latter are not part of the normal human microflora and generally do not cause endogenous infections.However,they can cause exogenous conditional infections in patients with late stage progressive disease or immune disorders,especially those with Cushing syndrome,diabetes or under long-term usage of corticosteroids,immunosuppressants and broad-spectrum antibiotics[9].A similar case was reported previously.After treatment with methylprednisone and cyclophosphamide,a 24-year-old woman with LN developed severe pleural pneumonia and occipital abscess,both caused by.Although she was treated with multiple antibiotics,she ultimately died[10].Our patient was diagnosed with SLE and LNone year before presenting at our hospital,and had been receiving corticosteroids and immunosuppressants,and had undergone hemodialysis due to acute kidney injury.Therefore,she was highly likely to be immuno-deficient and was considered Nocardia-susceptible.In addition,the patient had facial pigmentation along both sides of the jaw and previous skin damage,together with an infectious lesion in her left masseteric space.Puncture aspiration indicated Nocardia infection.We believe that the left jaw was the source of infection,from where the bacterium entered the circulation and eventually reached the brain,forming multiple cerebral abscesses.

FOOTNOTES

Routine blood tests showed a white blood cell count of 12.34x10/L,neutrophil % of 83.6%,hemoglobin of 92 g/L,hematocrit of 28.5%,platelets of 123 × 10/L,high sensitivity C reactive protein of 18.85 mg/L,procalcitonin of 0.296 ng/mL,erythrocyte sedimentation rate of 60 mm/h,creatinine of 233 μmol/L,albumin of 22.5 g/L,and a CD4/CD8 ratio of 0.31.A urine test for 24 h urine protein was 5769.4 mg to 9443.5 mg/24 h.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist(2016),and the manuscript was prepared and revised according to the CARE Checklist(2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See:https://creativecommons.org/Licenses/by-nc/4.0/

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Qiong-Dan Hu 0000-0003-3712-056X;Li-Shang Liao 0000-0003-4811-9556;Yong Zhang 0000-0003-2627-2314;Qiong Zhang 0000-0003-4419-8533;Jian Liu 0000-0002-6818-2061.

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