\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Good ' s Syndrome Combined with CMV Gastroenteritis: A Case Report and
Literature Review}



\author[1]{Xiaoran Li}%
\author[1]{Yanbin Liu}%
\affil[1]{West China Hospital of Sichuan University}%


\vspace{-1em}



  
  \date{June 11, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Good~'~s Syndrome Combined withCMVGastro} \textbf{enteritis: A
Case Report and Literature Review}

Xiaoran li, Yanbin Liu\textsuperscript{*}

Authors Affiliation: Center of Infectious Diseases, West China Hospital
of Sichuan University, 37\# Guo Xue Xiang, Chengdu 610041,Sichuan ,
China

*Corresponding author:\emph{dr\_liuyanbin@foxmail.com}

\textbf{Key Clinical Message}

GS presents with thymoma, hypogammaglobulinemia, and recurrent
infection. The manifestations of patients diagnosed with GS and CMV
gastroenteritis are rare and non-specific. Early diagnosis and treatment
can improve the prognosis of the rare disease.

\textbf{Key words}

Good's syndrome; chronic diarrhea; \emph{Cytomegalovirus}gastroenteritis

\textbf{Research funding}

Authors state no funding involved.

\textbf{Conflict of interest}

Authors state no conflict of interest.

\textbf{Ethics approval and consent to participate}

The need of ethics approval was waived because the data were obtained
from previous clinical records and the subject provided informed consent
to participate in this study.

\textbf{Consent for publication}

Written informed consent for publication of the clinical details and/or
clinical images was obtained from the patient.

\textbf{Availability of data and materials}

All data are included in this published article. The authors confirm
that the data supporting the findings of this study are available within
the article and its supplementary materials.

\textbf{Introduction}

Good's syndrome(GS), a rare acquired immunodeficiency~ condition, first
described by Dr. Robert Good in 1954, is characterized by thymoma,
hypogammaglobulinemia, and low peripheral B-lymphocyte count. GS tend to
occur in individuals aged 40-60 years, resulting in increased risk of
recurrent infections with kinds of conditionally pathogenic bacteria,
viruses, and fungi{[}1, 2{]}. Almost half of GS patients suffer from
chronic diarrhea due to opportunistic infections, such as
\emph{Salmonella spp.} , \emph{Campylobacter. jejuni} ,
\emph{Clostridium difficile} , and\emph{Cytomegalovirus}(CMV){[}3-5{]}.
CMV, a kind of encapsulated double-stranded DNA \selectlanguage{greek}β-\selectlanguage{english}herpesvirus, is a
common virus that can infect human beings. CMV could cause pneumonia,
retinitis, encephalitis, and enteritis in GS patients{[}4, 6-14{]}.We
will report a female patient with GS and chronic diarrhea due to CMV
infection and make a literature review of related cases to conclude the
characteristics of this condition so as to decrease the misdiagnosis and
delayed diagnosis and improve the clinical diagnosis and prognosis of
this rare disease.

\textbf{Case History}

A 64-year-old female hospitalized in our center complained that she
suffered from intermittent diarrhea for more than 11 years, and her
stool was watery, 5-6 times per day. The patient went to the local
hospital 9 years before admission to our hospital , and her laboratory
examination showed reduced globulin(14.3g/L), hypokalemia(3.07mmol/L),
and hypocalcemia(2.03mmol/L). She underwent colonoscopy, and revealed
scattered congestion and erosion throughout the colon, and chronic
inflammation was found in intestinal mucosa biopsy. Meanwhile, she
received chest computed tomography(CT) examination, which showed that
there was a mass(about 5*4*4cm) in the right mediastinum with rich blood
supply. Subsequently, she was scheduled for mediastinal tumor resection,
and the histopathological report of the tumor was type A thymoma (World
Health Organization classification ). The symptom of diarrhea could be
alleviated with intermittent medication. However, the disease continued
to recur.

The patient had severe diarrhea, abdominal distension, fatigue,
dizziness, weight loss, and numbness of hands and feet two months before
coming to hospital. She then attended the local hospital again.
Laboratory findings are showed in Table 1 .

Gastroscopy and colonoscopy were performed. The results of gastroscopy
showed swelling of the gastric mucosa and gastric body with scattered
erythema. The biopsy results showed that CMV immunohistochemistry was
positive, and \emph{Helicobacter pylori} was negative. Meanwhile,
colonoscopy revealed rough swelling, hyperemia and erosion of the
descending colon mucosa, rough rectal mucosa and obvious congestion and
swelleing of other colons mucosa. Immunohistochemistry of biopsy showed
CMV+, PCK+, CD4+, CD8+, Ki-67+. Therefore the final diagnosis of the
patient was CMV gastroenteritis. She received cefotaxime and
levofloxacin for anti-infection, ganciclovir (250mg Q12h \selectlanguage{ngerman}×14 days)
antiviral treatment, human immunoglobulin (10g×5d), potassium
supplementation, spasmolysis, ,and oral montmorillonite powder and
probiotics. However, she still had recurrent symptoms and then came to
our hospital.

\textbf{Investigations and Treatment}

The serum level of CMV DNA was positive(8.33E+02 copies/mL) in our
hospital, and the autoimmunity screening, including antinuclear
antibodies, rheumatoid factors, anti-ENA autoantibody profiles, and
antineutrophilic cytoplasmic antibodies was negative. According to the
medical history, symptoms, laboratory and endoscopic examination
results, GS combined with CMV gastroenteritis was definitely diagnosed.
Subsequently, she received antiviral therapy with foscarnet sodium
injection(3g q8h ivgtt), intermittent administration of human
immunoglobulin(5g/d), and continuous supplement of potassium, calcium,
and magnesium. Afterwards, the patient felt better than before.
Gastroscopy reexamination showed hyperemia and edema of gastric body
mucosa, erythema of antrum mucosa, and a 0.8cm mucous protrusive lesion
near the pylorus in the anterior wall, with rough and red surface, and
soft biopsy quality. Biopsy suggested mild chronic inflammation of
mucosa with suspicious inclusion body deposition, and further
immunohistochemistry indicated that CMV was negative. Colonoscopy
revealed a 0.3cm polyp in the transverse colon near hepatic curvature
with soft biopsy. Scattered mucosal patches of sigmoid colon were
congested. The rectal mucosa was scattered in sheets with hyperemia and
erosion(Figure 1). Pathological biopsy results showed severe chronic
inflammation of mucosa with activity (+ ++), crypt abscess with erosion,
decreased glands, CMV (+), CD68PGM-1(+).

\textbf{Outcome and Follow-up}

The patient was continuously treated with foscarnet for 3 weeks, human
immunoglobulin replacement, and~electrolyte~supplement, then the serum
level of CMV DNA dropped below 50 copies/L. Finally, she almost
completely relieved her symptoms and discharged, and she then tool oral
ganciclovir for 3 weeks when the symptom of diarrhea completely
recovered and serum level of CMV DNA turned to negative during the
follow-up. And she received intermittent human immunoglobulin
replacement therapy for life.

\textbf{Literature Review}

We searched all cases up to October 2022 using China National Knowledge
Infrastructure database, Wangfang database and China Science and
Technology Journal Database, and PubMed database. Keywords included
Good's syndrome, Good syndrome, thymoma, diarrhea, Cytomegalovirus
infection. According to the literature, 10 patients diagnosed with GS
and CMV gastrointestinal infection meet our inclusion criteria
(Table\emph{2} ).

It is reported that 8 patients had diarrhea without specific endoscopic
manifestation. Although one case showed normal macroscopic appearance of
the colon, the random colonic biopsy revealed CMV inclusion
bodies{[}7{]}. Two cases also manifested as chronic diarrhea due to CMV
enteritis and ulcerative colitis{[}5, 15{]}. All patients received
immunoglobulin replacement therapy. Except for two cases (one case of
CMV infection confirmed by necropsy, and one case did not describe the
regime of antiviral agent), eight cases received ganciclovir as the
initial treatment for CMV, and four cases switched to Foscarnet due to
no response or recurrence of diarrhea, and two cases finally switched to
cidofovir due to no response or intolerance of Foscarnet. Four patients
deteriorated and died due to fulminant bronchopneumonia, sepsis,
recurrent colitis and colonic perforation, and neurological
deterioration with a refractory supraconvulsive state, respectively.

\textbf{Discussion}

The pathogenesis of GS remained still a mystery, which was defined as
the significant reduction or absence of peripheral B cells and impaired
T-cell mediated immunity in adults{[}1, 2{]}. GS patients were
characterized by thymoma and hypogammaglobulinemia. Their initial
symptoms tended to occur due to recurrent infection or secondary to
thymoma itself, and hypogammaglobulinemia was not corrected following
thymectomy{[}21-23{]}.Moreover, GS patients might also suffer from
autoimmune complications, such as pure red cell aplasia, hypothyroidism,
arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren's
syndrome{[}2, 22{]}. In this case, the female patient presented with
chronic diarrhea, hypogammaglobulinemia, absence of B lymphocytes, and
thymoma, and the symptoms were not improved after the tumor removal.
Therefore, the GS was clinically diagnosed based on her history and
blood tests. However, the diagnosis was not confirmed during her initial
manifestation nine years ago, indicating the lacked awareness of GS
among clinicians.

Diarrhea was the patient's initial manifestation. It was reported that
chronic diarrhea was present in almost up to 50\% of GS patients, which
was mainly caused by opportunistic infections, such as \emph{Salmonella
spp.} , \emph{Campylobacter. jejuni} , \emph{Clostridium difficile} ,
and CMV, but in some cases the pathogen was not identified{[}3-5, 24{]}.
A study on GS in China found that 36\% of patients suffered from
diarrhea, and it was postulated that this might be related to
malabsorption. Moreover, it also revealed that CMV was the most common
pathogen among viral infections{[}25{]}. Kelesidis, T. et al
systematically summarized the characteristics of 152 patients with GS,
and discovered that diarrhea was present in 31.8 \% of patients, and
35.7\% of them were caused by infection, while the pathogenesis of most
cases had not been identified. Meanwhile, this study also found that CMV
was the most common opportunistic pathogen reported, and the main cause
of diarrhea in five cases{[}24{]}.~ Except for infections, the
pathogenesis of diarrhea might also be related to immune factors, since
some patients could relieve symptom through thymectomy and human
immunoglobulin replacement treatment or steroids, as well as villous
atrophy of intestines which led to malabsorption{[}5, 26-28{]}. It was
supposed that intestinal malabsorption and inflammation seemed to cause
diarrhea, hypoalbuminemia, and electrolyte~imbalance, resulting in
fatigue, weight loss, and numbness of hands and feet of this patient.

CMV was a common human viral infection, which could cause various system
or organ infections in GS patients{[}4, 6-14{]}. There might be a high
prevalence of undiscovered CMV gastroenteritis in chronic diarrhea of
unknown origin{[}12{]}. CMV could infect the whole alimentary tract,of
which the most common is the colon, and gastric involvement iscommonest
in the upper gastrointestinal tract{[}29, 30{]}. Yeh, P. J. et al
retrospectively investigated 53 cases diagnosed with CMV gastritis in
both immunocompromised and immunocompetent patients and concluded that
gastric ulcer (88.9\%) was the most common endoscopic feature and the
gastric antrum was the most commonly affected location{[}29{]}. You, D.
M. et al reviewed the endoscopic manifestations of gastrointestinal CMV
diseases, including ulcers, fragile, hyperemic, or erythematous mucosa,
edema, and subepithelial hemorrhage{[}30{]}. A recent study also
reported that the commonest endoscopic feature of CMV disease was
ulcers, followed by polypoid lesions and inflammation{[}31{]}. The
endoscopic manifestations of patients diagnosed with GS and CMV
infection with gastrointestinal tract involvement were also
non-specific, mainly charactered by intestinal mocosal ulcers,
inflammation and edema of the intestinal mucosa, which might be easily
confused with inflammatory bowel disease, and even some cases showed
normal manifestations. Therefore, the clinical confirmation depended on
biopsy results and further immunohistochemical method{[}7, 20{]}. In
addition, some patients suffered from both CMV gastroenteritis and
ulcerative colitis, and they responded well to steroids and/or
immunosuppressive treatment, indicating that autoimmune factors might
also play a significant role in the inflammation of
gastrointestinal~mucous membrane{[}5, 15{]}. In the present case, the
patient presented with mucosal inflammation and polypoid lesion under
gastrointestinal endoscopy.

Ganciclovir was considered as the first-line therapy for CMV disease.
The recommended dose for ganciclovir was 5 mg/kg intravenously twice
daily (the dose shouled be adjusted according to the glomerular
filtration rate, and the infusion time should last for over one
hour).The course of treatment was at least 2-3weeks, or even 3-6 weeks.
However, in immunocompromised individuals, the potential adverse effects
of ganciclovir were common, including headaches, elevated transaminases,
fever, rash, and myelosuppression. On this basis, Foscarnet, 90 mg/kg
twice daily, could be considered as the initial therapy or in patients
with ganciclovir nonresponse or intolerance. In addition, combined
therapy might be effective after failure of monotherapy{[}30{]}. Pierce,
B. et al showed that Foscarnet was effective in the treatment of most
ganciclovir-resistant CMV documented in the literature, and the
incidence of nephrotoxicity in patients with solid organ transplantation
was lower{[}32{]}. Wang, C. H. suggested in his report that the
treatment of disseminated CMV infection in GS could be similar to that
of solid organ transplant recipients due to severe immunosuppression
condition{[}33{]}. The patient, Tavakol, M. reported, diagnosed with
unilateral CMV retinitis with GS switched to oral valganciclovir
maintenance after 6 months of intravenous ganciclovir treatment, and
subsequent follow-up examination of the involved retina showed partial
response{[}3{]}.

There was insufficient evidence or consensus on standard treatment
strategies for CMV gastroenteritis with GS, and reference to other
systems for the prevention and treatment of CMV infection might be
reasonable. According to the literature review, ganciclovir could be
used as the first line of initial treatment for GS and CMV
gastroenteritis, and Foscarnet or combined with both could be used for
ganciclovir resistance or symptom recurrence, and cidofovir could be
used for those who were not responsive or intolerant to Foscarnet, which
was currently the accepted treatment option. Although our patient was
not tested for resistance, there was no significant clinical improvement
after 2 weeks of ganciclovir and human immunoglobulin replacement
therapy. Considering that ganciclovir might be resistant or the course
of treatment might be inadequate, foscarnet sodium was adjusted for
antiviral treatment with a dose according to the drug instruction. After
3 weeks of foscarnet treatment, serum CMV DNA level decreased and the
symptom of diarrhea improved almost completely.

Despite active treatment, four patients still deteriorated and died, and
the main cause of death was refractory severe infection and
complications according to the literature review. Therefore, it was
significant for GS patients to prevent the infection. Because the
immunodeficiency persisted after thymectomy, patients with GS should
receive regular lifelong human immunoglobulin replacement therapy(IGRT),
every three months or once a month, so as to maintain IgG levels of
above 500 mg/dL in case of low IgG, and furthermore, if a patient had
recurrent infection regardless of IgG levels, IGRT could reduce the
incidence of further severe infections{[}4, 23, 33{]}. Wang, C. H.
reported that the GS patient who was recurrently admitted to the
hospital for pneumonia was administered with human immunoglobulin to
maintain serum IgG levels of at least 500 mg/dL, while monitoring for
signs of infection, and further infections had been prevented in the
1-year follow-up{[}33{]}. Most reports had come to similar conclusions.
Therefore, it was necessary for our patient to undertake periodic human
immunoglobulin replacement treatment and monitor immunity status in
order to prevent and timely identify opportunistic infection.

\textbf{Conclusion}

It is of paramount importance for clinicians to consider the possibility
of GS when adult-onset patients present with thymoma,
hypogammaglobulinemia, and recurrent infection. Chronic diarrhea was
present in almost up to 50\% of GS patients. Additionally, CMV infection
is a common opportunistic pathogen and the main cause of diarrhea. The
endoscopic manifestations of patients diagnosed with GS and CMV
gastroenteritis are also non-specific, mainly characterized by ulcers,
inflammation and edema of intestinal mucosa. Therefore, clinical
confirmation depends on biopsy results and further immunohistochemical
methods. The recognized regime suggests that ganciclovir can be used as
the initial therapy, and can be switched to Foscarnet, or combined with
both for ganciclovir resistance or symptom recurrence. Finally, it is
necessary for GS patients to undertake periodic human immunoglobulin
replacement therapy and monitor their immune status,so as to prevent and
timely identify opportunistic infection.

\textbf{References}

{[}1{]}Shi Y and Wang C. When the good syndrome goes bad: A systematic
literature review. Front Immunol. 2021;12:679556.

{[}2{]}Kabir A, Alizadehfar R and Tsoukas CM. Good's syndrome: Time to
move on from reviewing the past. Front Immunol. 2021;12:815710.

{[}3{]}Tavakol M, Mahdaviani SA, Ghaemi MR, Vaezi M, Dorudinia A,
Jamaati H, et al. Good's syndrome-association of the late onset combined
immunodeficiency with thymoma: Review of literature and case report.
Iran J Allergy Asthma Immunol. 2018;17:85-93.

{[}4{]}Kwok CT and Yeung YC. Good's syndrome presenting with cmv
pneumonitis and oesophageal candidiasis: A case report. Respirol Case
Rep. 2022;10:e0888.

{[}5{]}Liu K and Cowlishaw JL. Beware of the patient with thymectomy:
Good's syndrome in a patient presenting with diarrhea. ACG Case Rep J.
2013;1:33-5.

{[}6{]}Makinson A, Corne P, Pellé C, Ben Hadj Salem M, Pouessel D,
Landreau L, et al. Good syndrome and cytomegalovirus pneumonia. Rev Med
Interne. 2003;24:330-1.

{[}7{]}Ho JK, Wong MM, Tai TK and Tse DM. A rare combination of
recurrent pneumonia, diarrhoea, and visual loss in a patient after
thymectomy: Good syndrome. Hong Kong Med J. 2010;16:493-6.

{[}8{]}Lee SW, Lee YW and Bae JH. Cytomegalovirus retinitis as the first
manifestation of good syndrome. Ocul Immunol Inflamm. 2018;26:122-4.

{[}9{]}Downes KM, Tarasewicz D, Weisberg LJ and Cunningham ET, Jr. Good
syndrome and other causes of cytomegalovirus retinitis in hiv-negative
patients-case report and comprehensive review of the literature. J
Ophthalmic Inflamm Infect. 2016;6:3.

{[}10{]}Mateo-Montoya A, Stanescu D, Wolff B, Sahel JA and Bonnel S.
Cytomegalovirus retinitis associated with good's syndrome. Eur J
Ophthalmol. 2010;20:479-80.

{[}11{]}Isobe S, Sano A, Otsuka H, Azuma Y, Koezuka S, Makino T, et al.
Good syndrome with cytomegalovirus hepatitis: Successful resection of
thymoma: A case report. J Cardiothorac Surg. 2020;15:141.

{[}12{]}Koriyama N, Fukumoto O, Fukudome M, Aso K, Hagiwara T, Arimura
K, et al. Successful treatment of good syndrome with cytomegalovirus
duodenoenteritis using a combination of ganciclovir and immunoglobulin
with high anti-cytomegalovirus antibody titer. Am J Med Sci.
2004;327:49-54.

{[}13{]}Striano P, Tortora F, Evoli A, Palmieri G, Elefante A, Zara F,
et al. Periodic myoclonus due to cytomegalovirus encephalitis in a
patient with good syndrome. Arch Neurol. 2007;64:277-9.

{[}14{]}Cucchiara BL, Forman MS, McGarvey ML, Kasner SE and King D.
Fatal subacute cytomegalovirus encephalitis associated with
hypogammaglobulinemia and thymoma. Mayo Clin Proc. 2003;78:223-7.

{[}15{]}Kahraman A, Miller M, Maldonado-Lopez E, Baba HA, Treichel U and
Gerken G. A 55-year-old woman with thymoma and hypogammaglobulinemia
(good syndrome), ulcerative colitis, and cytomegalovirus infection. Med
Klin (Munich). 2009;104:150-4.

{[}16{]}Gupta S, Saverymuttu SH, Gibbs JS, Evans DJ and Hodgson HJ.
Watery diarrhea in a patient with myasthenia gravis, thymoma, and
immunodeficiency. Am J Gastroenterol. 1985;80:877-81.

{[}17{]}Crawford WW, Yusin JS and Klaustermeyer WB. Nonsurgical
regression of thymoma following corticosteroid/azathioprine therapy. Ann
Allergy Asthma Immunol. 1999;83:13-6.

{[}18{]}McCune CA, Hughes S and Unsworth DJ. Thymoma, autoimmunity and
fatal immunodeficiency. Qjm. 2000;93:559-60.

{[}19{]}Tarr PE, Sneller MC, Mechanic LJ, Economides A, Eger CM, Strober
W, et al. Infections in patients with immunodeficiency with thymoma
(good syndrome). Report of 5 cases and review of the literature.
Medicine (Baltimore). 2001;80:123-33.

{[}20{]}Rey M, Rico D, López Panqueva RDP and Vásquez Roldán M.
Apoptotic colopathy as a manifestation of good's syndrome. Rev Esp
Enferm Dig. 2022;114:115-6.

{[}21{]}Malphettes M, Gérard L, Galicier L, Boutboul D, Asli B, Szalat
R, et al. Good syndrome: An adult-onset immunodeficiency remarkable for
its high incidence of invasive infections and autoimmune complications.
Clin Infect Dis. 2015;61:e13-9.

{[}22{]}Zaman M, Huissoon A, Buckland M, Patel S, Alachkar H, Edgar JD,
et al. Clinical and laboratory features of seventy-eight uk patients
with good's syndrome (thymoma and hypogammaglobulinaemia). Clin Exp
Immunol. 2019;195:132-8.

{[}23{]}Turaes AS, Alharbi WK, Alqurashi RK, Touman A and Bulkhi A.
Persistent fever and cough in a patient with good's syndrome: A case
report. Cureus. 2022;14:e24996.

{[}24{]}Kelesidis T and Yang O. Good's syndrome remains a mystery after
55 years: A systematic review of the scientific evidence. Clin Immunol.
2010;135:347-63.

{[}25{]}Dong JP, Gao W, Teng GG, Tian Y and Wang HH. Characteristics of
good's syndrome in china: A systematic review. Chin Med J (Engl).
2017;130:1604-9.

{[}26{]}Yue PC, Zhang JY, Wu TN and Lei XY. {[}good syndrome with
diarrhea: A report of two cases{]}. Zhonghua Nei Ke Za Zhi.
2022;61:1161-4.

{[}27{]}Qu J, Lü X, Gao Q and Zhang Y. Good syndrome, a rare cause of
refractory chronic diarrhea and recurrent pneumonia in a chinese patient
after thymectomy. Clin Vaccine Immunol. 2013;20:1097-8.

{[}28{]}Verne GN, Amann ST, Cosgrove C and Cerda JJ. Chronic diarrhea
associated with thymoma and hypogammaglobulinemia (good's syndrome).
South Med J. 1997;90:444-6.

{[}29{]}Yeh PJ, Chiu CT, Lai MW, Wu RC, Kuo CJ, Hsu JT, et al.
Cytomegalovirus gastritis: Clinicopathological profile. Dig Liver Dis.
2021;53:722-8.

{[}30{]}You DM and Johnson MD. Cytomegalovirus infection and the
gastrointestinal tract. Curr Gastroenterol Rep. 2012;14:334-42.

{[}31{]}Yeh PJ, Wu RC, Chiu CT, Lai MW, Chen CM, Pan YB, et al.
Cytomegalovirus diseases of the gastrointestinal tract. Viruses.
2022;14:352.

{[}32{]}Pierce B, Richardson CL, Lacloche L, Allen A and Ison MG. Safety
and efficacy of foscarnet for the management of ganciclovir-resistant or
refractory cytomegalovirus infections: A single-center study. Transpl
Infect Dis. 2018;20:e12852.

{[}33{]}Wang CH, Chan ED, Perng CL, Chian CF, Chen CW, Perng WC, et al.
Intravenous immunoglobulin replacement therapy to prevent pulmonary
infection in a patient with good's syndrome. J Microbiol Immunol Infect.
2015;48:229-32.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1. The endoscopic features of the patient}

\textbf{Footnote:} : a 0.8cm mucous protrusive lesion near the pylorus;
: a 0.3cm polyp in the transverse colon; : congested and scattered
mucosal patches of sigmoid colon; : scattered rectal mucosa with
hyperemia and erosion

Table 1 . Laboratory results of the patient.\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Items & Results & Reference ranges\tabularnewline
\midrule
\endhead
White Blood Cell Count(WBC, \selectlanguage{ngerman}×10\textsuperscript{9}/L) & \textbf{14.57} &
3.5-9.5\tabularnewline
Neutrophil(NEU\#,\selectlanguage{ngerman}×10\textsuperscript{9}/L) & \textbf{10.23} &
1.8-6.3\tabularnewline
Lymphocyte (LYMPH\#,\selectlanguage{ngerman}×10\textsuperscript{9}/L) & \textbf{3.36} &
1.1-3.2\tabularnewline
Monocyte(MON\#,\selectlanguage{ngerman}×10\textsuperscript{9}/L) & \textbf{0.95} &
0.1-0.6\tabularnewline
Eosinophil(EOS\#,\selectlanguage{ngerman}×10\textsuperscript{9}/L) & \textbf{0} &
0.02-0.52\tabularnewline
Hemoglobin(HB,g/L) & \textbf{96} & 115-150\tabularnewline
Platelet (PLT,\selectlanguage{ngerman}×10\textsuperscript{9}/L) & 300 & 125-350\tabularnewline
C-Reactive Protein (CRP, mg/L) & \textbf{42.35} &
\textless{}10\tabularnewline
Albumin (ALB, g/L) & \textbf{31.4} & 35-55\tabularnewline
Globulin(GLB, g/L) & \textbf{12.2} & 20-35\tabularnewline
Potassium (K, mmol/L) & \textbf{2.19} & 3.5-5.3\tabularnewline
Sodium (Na, mmol/L) & 144 & 135-148\tabularnewline
Chlorine (CL, mmol/L) & 104.6 & 96-108\tabularnewline
Calcium (Ca, mmol/L) & \textbf{1.32} & 2.21-2.81\tabularnewline
Magnesium (Mg, mmol/L) & \textbf{0.15} & 0.66-1.07\tabularnewline
Immunoglobulin G(IgG, g/L) & \textbf{1.49} & 6.9-16.2\tabularnewline
Immunoglobulin M(IgA, g/L) & \textbf{0.06} & 0.3-3.7\tabularnewline
Immunoglobulin A(IgM, g/L) & \textbf{0.02} & 0.6-2.6\tabularnewline
T lymphocytes(CD3, \%) & \textbf{91.91} & 50-84\tabularnewline
T-helper lymphocytes(CD4, \%) & 32.35 & 27-51\tabularnewline
T-suppressor lymphocytes(CD8, \%) & \textbf{52.63} &
15-44\tabularnewline
B lymphocytes(CD3-/CD19+, \%) & \textbf{0} & 5-18\tabularnewline
CD4/CD8 ratio & \textbf{0.61} & 0.71-2.78\tabularnewline
NK lymphocytes(CD16+CD56, \%) & 7.25 & 7-40\tabularnewline
serum \emph{Cytomegalovirus} deoxyribonucleic acid(CMV DNA) & Negative &
Negative\tabularnewline
\bottomrule
\end{longtable}

Table \emph{2} . Profiles of patients with GS and CMV infection
gastrointestinal tract involved\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Case number\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Publish year\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Gender/age\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
gastrointestinal presentation\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Endoscopic features\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Biopsy results\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Treatment\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Outcome(cause of death)\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1985{[}16{]}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male/69\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
watery diarrhea\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
/\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
widespread cytomegalovirus infection with duodenal and ileal ulceration,
subtotal villous atrophy, marked nonspecific inflammation of the small
intestine at necropsy\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Infusions of gamma-globulin\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Died(fulminant bronchopneumonia)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1999{[}17{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Male/59\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
weakness, fever, and diarrhea\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
/\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
CMV enterocolitis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Antiviral therapy and replacement intravenous immunoglobulin (IVIG)
therapy\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Improved\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
2000{[}18{]}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Male/47\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
severe anorexia, dysphagia, and vomiting\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
severe pan-gastritis with a normal oesophagus and duodenum\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
granulation tissue, but no gastric epithelium, specific immunostaining
for CMV was strongly positive.\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Intravenous immunoglobulin(0.4g/kg/month); Repeated courses of anti-CMV
therapy in the form of ganciclovir, then Forscarnet, combination therapy
with both, and Cidofovir.\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
Died(sepsis)\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2001{[}19{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Male/54\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
diarrhea, fever, and weight loss\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
multiple mucosal ulcers\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
acute and chronic inflammation, with giant cells, intranuclear, and
cytoplasmic inclusions; acute necrotizing inflammation and CMV inclusion
bodies\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Ganciclovir (2.4 mg/kg every 8 hours for 14 days),~following a second
course of ganciclovir, combined with high-dose IVIG (500 mg/kg every
other day); Foscarnet (43 mg/kg every 8 hours) was then given for 21
days, then Foscarnet was continued at 75 mg/kg every 24 hours\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Died( recurrent colitis and colonic perforation)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
2001{[}19{]}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male/59\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
epigastric pain and melena\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
severe ulcerative gastritis\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
acute ulcerative gastritis with extensive CMV-like intracellular
inclusions bodies and strongly positive CMV-immunofluorescent
staining\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
~Ganciclovir (5 mg/kg every 12 hours)~for 14 days, then Foscarnet (60
mg/kg every 8 hours) was added to the ganciclovir for 24 days. Two doses
of IVIG and 1 infusion of CMV-immune globulin were given. Ganciclovir
was stopped after 12 weeks, after follow-up endoscopy showed improved
gastritis with no inclusions and negative CMV immuno-stain.\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Improved\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2004{[}12{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Female/64\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
watery diarrhea, abdominal distention\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
gastritis, a duodenal polyp, and mucosal edema in duodenum\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
intracellular inclusion bodies in the epithelial cytosol that were
strongly positive to mouse anti-CMV antibody\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ganciclovir and CMV-immune globulin\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Improved\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
2009{[}15{]}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Female/55\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
dysphagia, watery diarrhea, a weight loss o, abdominal pain\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
several ulcers in the descendens duodeni; edematous swelling of the
mucosa with contact vulnerability, multiple ulcers in the rectum and
sigmoid colon as part of ulcerative colitis.\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
duodenitis; positive immunohistochemical reactivity against CMV protein
of the endothelium and fibroblasts\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Steroid (1 mg/kg body weight) and immunosuppression with azathioprine
(1.5 mg/kg body weight) and mesalazine and topical therapy in the form
of clysters; a 3-week therapy with ganciclovir; then subsequent therapy
with Foscarnet had to be discontinued due to gastrointestinal side
effects and was replaced with cidofovir and CMV-specific
immunoglobulins; azathioprine switched to mycophenolate mofetil\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Improved\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2010{[}7{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Male/68\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Watery diarrhea, reduced appetite\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Normal\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
CMV inclusion bodies.\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
intravenous ganciclovir 5 mg/kg 12 hourly for 2 weeks, followed by
lifelong oral maintenance with valganciclovir 900 mg daily for CMV
retinitis; Monthly immunoglobulin infusion.\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Improved\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2013{[}5{]}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Female/80\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
watery, non-bloody diarrhea\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
left-sided colitis suggestive of ulcerative colitis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
diffuse active chronic inflammation and atypical cells with inclusion
bodies that stained positive for CMV\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Prednisone; intravenous ganciclovir 5 mg/kg every 12 hours for 2 weeks
for disseminated CMV infection; intravenous immunoglobulin (IVIG)
followed by monthly maintenance infusions.\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Improved\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
2022{[}20{]}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Undescribed /44\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
fever, weight loss of 30 kg and chronic diarrhea\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
ulcers in the sigmoid colon\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
acute colitis with cryptic apoptosis without evidence of chronicity,
compatible with CMV colitis\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
ganciclovir and nitazoxanide; gamma-globulin\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Died(neurological deterioration with a refractory supraconvulsive
state)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Note:} GS: Good's syndrome; CMV: Cytomegalovirus.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/figure1/figure1}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/775955/articles/884290-good-s-syndrome-combined-with-cmv-gastroenteritis-a-case-report-and-literature-review}

\textbf{Hosted file}

\verb`Table2.docx`  available at \url{https://authorea.com/users/775955/articles/884290-good-s-syndrome-combined-with-cmv-gastroenteritis-a-case-report-and-literature-review}

\selectlanguage{english}
\FloatBarrier
\end{document}

