Disseminated strongyloidiasis in a patient with rheumatoid arthritis: A case report

lNTRODUCTlON

Strongyloidiasis is a disease caused by the human pathogenic parasitic roundworm

(

). Most larvae are excreted in the stool but re-infection or self-infection can occur when the mature larvae burrow into the intestinal wall or the anal tissue.

infections can become chronic and even fatal in immunosuppressed patients[1]. This report describes the clinical features of disseminated strongyloidiasis in an immunosuppressed patient as well as the diagnosis and treatment.

日本骨科協(xié)會(huì)評(píng)估治療分?jǐn)?shù)（Japanese Orthopaedic Association Scores，JOA評(píng)分）[3]：通過(guò)主觀癥狀、臨床體征、日常活動(dòng)能力及膀胱功能評(píng)定腰痛疾患效果，術(shù)前及術(shù)后3個(gè)月進(jìn)行JOA評(píng)分。

CASE PRESENTATlON

Chief complaints

A 68-year-old male with repeated multi-joint pain for 3 years, abdominal pain and abdominal distension for 2 mo and progressive difficulty in swallowing, coughing, hoarseness and dysphonia for 1 wk.

History of present illness

The patient with rheumatoid arthritis was treated successively using a variety of immunosuppressants(methylprednisolone, tocilizumab, adalimumab, rituximab) for the past 3 years. Recently, the patient received treatment in several hospitals for a partial small-bowel obstruction of unknown origin which reoccurred repeatedly after treatment. As the patient’s condition worsened, new symptoms appeared including petechia, progressive difficulty in swallowing, coughing, hoarseness and dysphonia. A neurologist considered peripheral neuropathy because electromyography indicated peripheral nerve axonal damage. High-dose intravenous immunoglobulin therapy (2 g/kg over 5 d) was not effective, so plasmapheresis was recommended. At the same time, a parasite was detected in the stool, however, the species was neither identified nor treated. Due to the progress of bulbar palsy, the patient was referred to our hospital.

History of past illness

Zheng JH designed the study, analyzed the data and wrote the manuscript; Xue LY contributed to study conception and design and revision of the manuscript.

綜上所述，B7-H4和B7-H6蛋白在卵巢良、惡性腫瘤中的表達(dá)存在差異，并與惡性腫瘤患者年齡、組織類型、p53蛋白表達(dá)相關(guān)，提示這兩種蛋白參與卵巢惡性腫瘤的發(fā)病。此外，近年來(lái)已有研究獲得B7家族靶向治療腫瘤的證據(jù)[14-15]，但確切作用機(jī)制尚不清楚，須加大樣本量進(jìn)行深入的體內(nèi)及體外研究。研發(fā)針對(duì)B7-H4和B7-H6的卵巢惡性腫瘤靶向藥物，聯(lián)合經(jīng)典的治療方法，有望為卵巢癌提供新的治療方案，進(jìn)而提高患者的生存率。

Personal and family history

After 1 wk of treatment with albendazole 400 mg tid and other supportive treatments, the sputum smear was still positive. The addition of ivermectin 0.2 mg/kg/d × 2 d every 2 wk was then given. On day 4 of ivermectin treatment, the sputum smear and stool tested negative for intestinal parasites. After 2 wk of comprehensive treatment, the patient's mental state gradually improved and muscle strength of the limbs recovered. After 6 wk of hospitalization, his abdominal pain and all previously mentioned symptoms except for the joint pain had dissipated. The patient was discharged and given a small dose of methylprednisolone + methotrexate + celecoxib to control the rheumatoid arthritis and relieve the joint pain. We used albendazole for 4 wk total and ivermectin for a total of 6 wk[2].

Physical examination

Upon admission, he displayed weight loss, stable vital signs, hoarseness, dysarthria, wet rales audible in both lungs, weak bowel sounds, muscle strength grade 3 in all limbs and diminished tendon reflexes.

從圖1可見(jiàn)，1) 在350 nm波長(zhǎng)處生物總堿的吸光度隨小檗堿標(biāo)準(zhǔn)溶液濃度升高而升高，即二者間存在線性關(guān)系，其回歸方程為y=0.022 4x+0.009 7(R2=0.999 4)，即小檗堿溶液濃度為7.712～38.56 μg/mL時(shí)與吸收度有良好的線性關(guān)系。2) 隨著小檗堿含量(C)升高，峰面積(A)呈上升趨勢(shì)，二者間存在線性關(guān)系，其直線回歸方程為A=0.025 2C-0.100 2(R2=0.999 9)。表明，小檗堿含量在48.2～867.6 μg與峰面積有良好的線性關(guān)系。

Laboratory examinations

His biochemistry panel was as follows: K of 3.4 mmol/L, Na of 129 mmol/L, Ca of 1.88 mmol/L, and albumin of 25 g/L. Stool-Rt and sputum smears tested positive for

larvae with active movement (Figure 1).

Strongyloidiasis is a zoonotic intestinal parasitosis caused by

. It is estimated that 30-100 million people are infected worldwide with this parasite[3]. Most infected individuals are asymptomatic or present with intermittent symptoms[4]. Immunosuppressed patients can develop hyperinfection syndrome and disseminated nematode disease which have high mortality rates[5-7]. Strongyloidiasis has been reported following concomitant tocilizumab and methylprednisolone treatment[8]. Some case reports suggest that paralytic ileus may be caused by massive intestinal infestation with

[9].

Imaging examinations

A chest CT showed bilateral infiltrates indicating pneumonia. Echocardiography showed impaired movement of the left ventricular myocardium (EF 42%).

FlNAL DlAGNOSlS

At 3 mo after discharge, a follow-up chest CT and electromyography showed lung and cardiac function had recovered.

TREATMENT

The patient had no specific personal and family history.

OUTCOME AND FOLLOW-UP

The diagnosis of disseminated strongyloidiasis was established.

DlSCUSSlON

（教學(xué)心得：這樣的爭(zhēng)論非常有意思，學(xué)生的直覺(jué)是頂點(diǎn)位置有6個(gè)，這可能是受6個(gè)面的影響。如果在教學(xué)中采用講解的方法，學(xué)生理解會(huì)比較抽象，就算是記住了也很容易遺忘。采用實(shí)驗(yàn)動(dòng)手操作的方法，學(xué)生一看就明白了，從中心出發(fā)，頂點(diǎn)的位置不是6個(gè)，而是8個(gè)，所以在頂點(diǎn)的方塊是8塊。這樣對(duì)空間結(jié)構(gòu)的認(rèn)知和體會(huì)對(duì)將來(lái)進(jìn)一步學(xué)習(xí)立體圖形非常有益。）

結(jié)果提示：在控制了人口統(tǒng)計(jì)學(xué)變量后，社會(huì)隔離對(duì)生存質(zhì)量(β=-0.226，P<0.01)具有顯著的負(fù)向影響，經(jīng)濟(jì)狀況對(duì)生存質(zhì)量(β=0.224，P<0.01)具有顯著的正向影響(見(jiàn)表2)。社會(huì)隔離與經(jīng)濟(jì)狀況的交互項(xiàng)對(duì)生存質(zhì)量具有顯著的負(fù)向影響(β=-0.084，P<0.05)(見(jiàn)表2與圖1)，因此經(jīng)濟(jì)狀況在社會(huì)隔離對(duì)生存質(zhì)量的影響中起調(diào)節(jié)作用。

The Centers for Disease Control and Prevention and World Health Organization recommend ivermectin as the first choice for strongyloidiasis. In endemic areas, a combination of albendazole and ivermectin is recommended[13], and Moxidectin has also been tried as a treatment[14]. Repeated or extended dosing is preferred until worms are no longer detected[15]. Considering that the patient was still taking low-dose methylprednisolone and methotrexate tablets for rheumatoid arthritis, we adopted a multi-dose and long course of treatment. At the 3 mo follow-up, no recurrence of the disease was detected, so the treatment was effective.

CONCLUSlON

This case highlights important considerations for patients receiving immunosuppressive therapy. It is necessary to improve medical workers’ awareness of strongyloidiasis to avoid delays in diagnosis and ensure adequate management of infected patients.

Our case has two important clinical features. First, the patient had a history of immunosuppression and subsequently developed clinical symptoms (

, intestinal obstruction, pneumonia and petechia).The patient’s heart was also affected. Previous hospitals detected the presence of parasites but focused instead on the neurological manifestations. We confirmed the presence of

larvae in the patient’s stool and sputum[10]. Second, the patient presented with choking and hoarseness at the time of diagnosis. Head, neck, mediastinal MRI, cerebrospinal fluid and other examinations found no evidence of neurological invasion. Therefore, we considered two possibilities: (1) Nutritional deficiencies in vitamin B1, vitamin B12 and folic acid due to long periods of fasting, causing malabsorption and intestinal obstruction which can lead to peripheral neuropathy[11]; and (2)Neurotoxic biological agents (

, TNF inhibitors, anti-IL-6 receptor antibody), which can cause peripheral neuropathy in approximately 42% of cases[12].

脫稿講授，理解通透，嫻熟自如；表達(dá)準(zhǔn)確，分析明晰，論證精要；思路清晰，重點(diǎn)突出，節(jié)奏合理；媒體設(shè)計(jì)得當(dāng)，板書(shū)科學(xué)合理；基礎(chǔ)知識(shí)通俗易懂，適度夠用，針對(duì)性強(qiáng)；專業(yè)知識(shí)深入淺出，啟發(fā)引導(dǎo)，拓展得當(dāng)；技能指導(dǎo)規(guī)范熟練，示范點(diǎn)撥，樂(lè)學(xué)活訓(xùn)；用語(yǔ)規(guī)范，普通話比較標(biāo)準(zhǔn)，快慢適度；表達(dá)流暢，活潑機(jī)智，感染力強(qiáng)；課堂行為，合理靈動(dòng)；教態(tài)端莊，飽滿熱情；互動(dòng)有節(jié)，氛圍融洽；形態(tài)豐富，信息充實(shí)，容量適度。

FOOTNOTES

Diabetic history: Diabetic history for several years, maximum 18 mmol/L. Taking insulin medication,blood sugar is unsatisfactory for control.

Informed consent was obtained from the patient. The participant consented to the submission of the case report to the Journal.

The authors have no conflicts of interest to declare that are relevant to the content of this article.

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/

合理性，就是目標(biāo)定位是否合理，是否符合主體的年齡和身心特征，是否符合主體的能力，是否符合主體的學(xué)段。只有符合這四個(gè)方面的目標(biāo)，才是合理的目標(biāo)。這四個(gè)“符合”會(huì)讓主體看到更多的可能性，幫助主體全力以赴達(dá)成目標(biāo)。

China

Jin-Hao Zheng 0000-0003-0864-5156; Lu-Yu Xue 0000-0001-8773-7088.

Ma YJ

Filipodia

大學(xué)生機(jī)械創(chuàng)新設(shè)計(jì)大賽是教育部舉辦的全國(guó)性科技創(chuàng)新實(shí)踐競(jìng)賽活動(dòng)，是依托全國(guó)普通高等學(xué)校教學(xué)科研這一平臺(tái)。它具有非常強(qiáng)烈的現(xiàn)實(shí)意義和實(shí)際意義，同時(shí)也為促進(jìn)各高校提高工程實(shí)踐和機(jī)械創(chuàng)新設(shè)計(jì)教學(xué)改革和教學(xué)水平，加強(qiáng)學(xué)生理論與實(shí)踐的有機(jī)結(jié)合，養(yǎng)成良好的學(xué)風(fēng)、教風(fēng)，為優(yōu)秀人才脫穎而出創(chuàng)造條件。

Ma YJ

1 Khieu V, Srey S, Sch?r F, Muth S, Marti H, Odermatt P. Strongyloides stercoralis is a cause of abdominal pain, diarrhea and urticaria in rural Cambodia.

2013 ; 6 : 200 [PMID: 23688049 DOI: 10 .1186 /1756 -0500 -6 -200 ]

2 Hofmann D, Smit C, Sayasone S, Pfister M, Keiser J. Optimizing moxidectin dosing for Strongyloides stercoralis infections: Insights from pharmacometric modeling.

2022 ; 15 : 700 -708 [PMID: 34889057 DOI:10 .1111 /cts.13189 ]

3 Sch?r F, Trostdorf U, Giardina F, Khieu V, Muth S, Marti H, Vounatsou P, Odermatt P. Strongyloides stercoralis: Global Distribution and Risk Factors.

2013 ; 7 : e2288 [PMID: 23875033 DOI: 10 .1371 /journal.pntd.0002288 ]

4 Olsen A, van Lieshout L, Marti H, Polderman T, Polman K, Steinmann P, Stothard R, Thybo S, Verweij JJ, Magnussen P.Strongyloidiasis--the most neglected of the neglected tropical diseases?

2009 ; 103 : 967 -972[PMID: 19328508 DOI: 10 .1016 /j.trstmh.2009 .02 .013 ]

5 Marcos LA, Terashima A, Canales M, Gotuzzo E. Update on strongyloidiasis in the immunocompromised host.

2011 ; 13 : 35 -46 [PMID: 21308453 DOI: 10 .1007 /s11908 -010 -0150 -z]

6 Comelli A, Mangioni D, Scaramella L, Maraschini A, Gaudino C, Folli C, Ceriotti F, Triulzi F, Canetta C, Gori A, Bandera A. Strongyloides stercoralis central nervous system dissemination in a migrant misdiagnosed with eosinophilic granulomatosis with polyangiitis.

2022 ; 29 [PMID: 34718667 DOI: 10 .1093 /jtm/taab177 ]

7 Mah J, Lieu A, Holmes E, Vaughan S. A case of disseminated strongyloidiasis after multiple courses of immunosuppression.

2022 ; 194 : E89 -E92 [PMID: 35074835 DOI: 10 .1503 /cmaj.211056 ]

8 Lier AJ, Tuan JJ, Davis MW, Paulson N, McManus D, Campbell S, Peaper DR, Topal JE. Case Report: Disseminated Strongyloidiasis in a Patient with COVID-19 . Am J Trop Med Hyg 2020 ; 103 : 1590 -1592 [PMID: 32830642 DOI:10 .4269 /ajtmh.20 -0699 ]

9 Yoshida H, Endo H, Tanaka S, Ishikawa A, Kondo H, Nakamura T. Recurrent paralytic ileus associated with strongyloidiasis in a patient with systemic lupus erythematosus.

2006 ; 16 : 44 -47 [PMID: 16622724 DOI:10 .1007 /s10165 -005 -0447 -1 ]

10 Buonfrate D, Fittipaldo A, Vlieghe E, Bottieau E. Clinical and laboratory features of Strongyloides stercoralis infection at diagnosis and after treatment: a systematic review and meta-analysis.

2021 ; 27 : 1621 -1628 [PMID:34325063 DOI: 10 .1016 /j.cmi.2021 .07 .016 ]

11 Morís G. Inflammatory bowel disease: an increased risk factor for neurologic complications. World J Gastroenterol 2014 ;20 : 1228 -1237 [PMID: 24574797 DOI: 10 .3748 /wjg.v20 .i5 .1228 ]

12 Spagnoli C, Pisani F, Di Mario F, Leandro G, Gaiani F, De' Angelis GL, Fusco C. Peripheral neuropathy and gastroenterologic disorders: an overview on an underrecognized association.

2018 ; 89 : 22 -32 [PMID:30561392 DOI: 10 .23750 /abm.v89 i9 -S.7956 ]

13 Henriquez-Camacho C, Gotuzzo E, Echevarria J, White AC Jr, Terashima A, Samalvides F, Pérez-Molina JA, Plana MN.Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection.

2016 ;CD007745 [PMID: 26778150 DOI: 10 .1002 /14651858 .CD007745 .pub3 ]

14 Bisoffi Z, Buonfrate D. Moxidectin: an ally to ivermectin for treating Strongyloides stercoralis? Lancet Infect Dis 2021 ; 21 :1060 -1061 [PMID: 33798488 DOI: 10 .1016 /S1473 -3099 (20 )30718 -0 ]

15 Mejia R, Nutman TB. Screening, prevention, and treatment for hyperinfection syndrome and disseminated infections caused by Strongyloides stercoralis.

2012 ; 25 : 458 -463 [PMID: 22691685 DOI:10 .1097 /QCO.0 b013 e3283551 dbd]