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Case Report Widespread Nocardiosis in a Patient with Refractory ANCA-Associated Vasculitides: Relapse Or Mimics? a Case Report and Literature Review

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Case Report Widespread Nocardiosis in a Patient with Refractory ANCA-Associated Vasculitides: Relapse Or Mimics? a Case Report and Literature Review Int J Clin Exp Med 2019;12(6):7878-7886 www.ijcem.com /ISSN:1940-5901/IJCEM0089770 Case Report Widespread nocardiosis in a patient with refractory ANCA-associated vasculitides: relapse or mimics? A case report and literature review Wo Yao1, Jing Xue2 Departments of 1Allergy, 2Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China Received December 13, 2018; Accepted April 9, 2019; Epub June 15, 2019; Published June 30, 2019 Abstract: Immunocompromised patients are at high risk of Nocardia, however infection in these patients can also mimic relapsed or refractory autoimmune disease and that make diagnosis difficult. Herein is described a 60-year- old male diagnosed with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) who presented with fever, short of breath, cough, headache, and a subcutaneous mass in his right forearm after 3 months therapy with full-dose oral corticosteroid and intravenous cyclophosphamide. Given that the currently available laboratory tests and associated imaging features are nonspecific, it was quite difficult to differentiate between a recurrence of the patient’s AVV and infection as a complication. The patient was finally diagnosed with systemic nocardiosis base on a subcutaneous abscess puncture fluid culture after 3 weeks of hospitalization. Trimethoprim-sulfamethoxazole (TMP-SMX) was administered while the steroid was tapered, after which the patient’s systemic manifestations grad- ually resolved. A literature review identified 24 cases of nocardiosis as a complication of systemic vasculitis was performed. Male patients with systemic vasculitis (especially AAV or Behcet’s disease) aged ≥ 60 years who were treated with corticosteroid in conjunction with or without immunosuppressant therapy were at high risk of Nocardia infection. Although cases can simultaneously have multiple systems involved and elevated inflammation indexes, it might be helpful to take a detailed disease history and check for evidence of abscesses. Moreover, clinical suspi- cion combined with repeated tissue biopsy and bacteria culture should be encouraged because making the correct diagnosis as soon as possible will lead to better prognosis. Keywords: Nocardia, nocardiosis, systemic vasculitis, anti-neutrophil cytoplasmic antibody-associated vasculitis, corticosteroid, immunosuppressant, inflammation, infection, diagnosis, trimethoprim-sulfamethoxazole Introduction a variety of pathogens, including Nocardia. De- spite the similar clinical manifestations of both The genus Nocardia is a ubiquitous group of Nocardia infection and the active condition of environmental bacteria that usually induce an systemic vasculitis, the management of these opportunistic infection in immunocompromised two diseases is very different. Determining the hosts [1]. Recent reports have shown an different features of these conditions such that increase in the incidence of infections due to the correct diagnosis can be made is very Nocardia spp., probably due to a higher degree important for improving the prognoses of both. of clinical suspicion and the use of more aggres- Here, a case of systemic nocardiosis with anti- sive treatments for other conditions (e.g., corti- neutrophil cytoplasmic antibody (ANCA)-as- costeroid, chemotherapeutic agents and immu- sociated vasculitis (AAV) is described with a nosuppression for organ transplantations) [2, presentation that mimicked the active stage of 3], as well as the appearance of acquired AAV. A review of all similar cases reported in immunodeficiency syndrome [4]. Patients with English is also included. systemic vasculitis are always treated with Case report high-dose corticosteroid and immunosuppres- sants. During this period, some systemic vascu- A 60-year-old Chinese male was admitted to litis patients could be exposed to infections by our hospital in July 2011 because of swelling Nocardiosis with ANCA-associated vasculitides Figure 1. HRCT of the patient’s chest on week after admission. Multiple lesions of cavitation lesions (B, arrows) and small nodules (A, arrows) are visible in both lungs. and pain with both shins, headache, numbness Hp. His serum creatinine level and liver function in his toes, and a fever lasting for 2 weeks. were still normal. Blood bacterial and fungal Three months previously, he had been diag- cultures from both hands (performed 3 times nosed with AAV based on muscle pain, fever, each) were all negative, and pANCA showed peripheral neuritis, interstial lung disease, pro- 1:40 positive with myeloperoxidase (MPO) (220 teinuria with markedly elevated perineuclear- IU/ul). A biopsy of the rashes on his lower ex- type anti-neutrophil cytoplasmic antibodies tremities revealed nonspecific inflammatory (pANCA 1:40, IIF), and increased myeloperoxi- changes. Antibiotic therapy, including moxiflox- dase levels of 200 IU/mL (normal level: < 30 IU/ acin, azithromycin and ceftriaxone, were admin- ml as assessed by ELISA). At that time, methyl- istrated for 1 week with no response. prednisolone (mPSL) with an initial dose of 80 mg daily was then administered for 10 days, Because of the multiple cavitation lesions and followed by 60 mg of oral prednisone daily small nodules in both lungs detected by high- along with intravenous cyclophosphamide (0.6 resolution computed tomography (HRCT) of the g per month for 2 months). The majority of his chest (Figure 1A and 1B), a lung puncture was AVV symptoms were improved quickly, and the also performed, and the corresponding histo- prednisone treatment was gradually tapered to logic examination showed something resem- 35 mg daily for 1 week. bling Aspergillus hypha in the necrotic tissue. A lumbar puncture was also performed, which Two weeks before the patient’s admission, he revealed a normal cerebrospinal fluid (CSF) had suffered from a relapse of fever, headache, pressure (120 mmH2O) with a white blood cell short of breath, and he had many rashes along count of 28×106 cells/L (neutrophilic granulo- the neck area and shins as well as erythema on cyte: 20%, lymphocyte: 80%). Another puncture his right forearm. Upon admission, his body of the subcutaneous mass in the patient’s right temperature was 37.9°C with a pulse rate of 99 forearm was performed, and the resulting bpm and blood pressure of 121/70 mmHg. smear showed only some inflammatory cells Inspiratory and expiratory crackles were heard that were mostly neutrophils, without any in both sides of lower lungs. The patient was microorganisms detected. The administered slightly positive for signs of meningeal irritation antibiotic was changed to caspofungin, but the but was negative for bilateral Babinski’s signs. patient did not respond to this drug either. Laboratory tests revealed increased white blood cell count (12,400/μL), increased eryth- Because of the patient’s severe headache and rocyte sedimentation rate (ESR) (37 mm/h), altered state of consciousness without any and increased level of C-reactive protein (CRP) positive finding via brain MRI, a repeated lum- (148.3 mg/L), compared with normal levels. bar puncture was performed, and it revealed Urine analysis results showed a slight protein- that the white blood cells count had fur- uria with 620 mg/24 h and hematuria with 30/ ther increased to 290×106 cells/L (neutrophils: 7879 Int J Clin Exp Med 2019;12(6):7878-7886 Nocardiosis with ANCA-associated vasculitides Literature review A systematic literature search was performed in PubMed using the subject terms “nocar- diosis” and “vasculitis” to iden- tify relevant articles from De- cember 1949 through No- vember 2018. The publication language was restricted to English. Review articles, arti- cles with important informa- tion missing, and articles for which the full text was not found were excluded. In total, 52 articles were identi- fied by the search criteria, of which eight non-English arti- Figure 2. Histopathological findings of pus culture revealed filamentous cles, 21 articles that did not branching rods, which was Nocardia brasiliensis (acid-fast stain, oil micros- describe cases of nocardiosis copy ×100) (arrow). in patients with systemic vas- culitis, and one article lacking 90%, lymphocytes: 10%). Thus, AAV with infec- the full text were excluded from this review. tious disease including intracranial infection Twenty-two articles [5-26] with comprehensive was considered to be the most likely diagnosis, clinical and laboratory data from 24 patients and the patient was given 60 mg of methylpred- were analyzed in detail, including the age of nisonelone intravenously. Finally, a repeated onset, gender, primary disease, symptoms, lab- puncture of the subcutaneous mass in his right oratory tests results, MRI, or CT images, treat- forearm was performed, and the culture of the ment, and prognosis (Table 1). puncture fluid was positive for Nocardia brasil- Statistical analysis iensis (Figure 2). Trimethoprim-sulfamethoxa- zole (TMP-SMX) (1280 mg + 6400 mg/d) was Date were analysis with Microsoft Excel 2010. then added to the patient’s drug regimen, and The age range of disease onset was from 19 to voriconazole was switched to ceftriaxone. His 83 years old, and the median age was 58.3 ± symptoms of fever, headache, subcutaneous 19.2 years old. There were 13 patients whose mass in the right forearm, and cough were onset age was ≥ 60 (54.2%). The ratio of males gradually alleviated 1 week later. A third lumbar to females was 19:5. Of the total 24 cases, 9 puncture was performed, which revealed a had been diagnosed with AAV (37.5%) and 6 white blood cell count with 20×106 cells/L (neu- had been diagnosed with Behcet’s disease trophils: 10%, lymphocytes: 90%). (25%). Glucocorticoids were used in all patients, and immunosuppressants were administrated After a sufficient dose of TMP-SMX therapy for to 15 of them (62.5%). The disease activity of 21 days, a low dose maintenance treatment vasculitis was stable in majority cases at the (160 mg + 800 mg/d) was used for one year to time when they were diagnosed with Nocardia infection. The most commonly involved organs prevent the recurrence of nocardiosis due to included lung (66.7%), brain (45.8%), skin the patient’s long-term therapy with glucocorti- (33.3%) and eyes (12.5%).
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