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\begin{document}

\title{Concurrent monoclonal gammopathy and systemic lupus erythematosus in a
known case of ulcerative colitis: a case report}



\author[1]{mahan shafie}%
\author[1]{Alireza hadizadeh}%
\author[1]{soheil khalaji}%
\author[1]{samaneh parsa}%
\affil[1]{Tehran University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Our patient had previously been diagnosed with Ulcerative colitis. the
clinical manifestations of the patient along with laboratory tests such
as anti-dsDNA and proteinuria were also positive. Therefore, the
clinical manifestation was consistent with SLE. in the following work up
monoclonal gammopathy in serum electrophoresis was also detected.%
\end{abstract}%



\sloppy


\textbf{Title}

Concurrent monoclonal gammopathy and systemic lupus erythematosus in a
known case of ulcerative colitis: a case report

\textbf{Keywords}

\textbf{Ulcerative colitis -- systemic lupus erythematosus -- monoclonal
gammopathy}

\textbf{Background}

Many autoimmune diseases have been reported to be associated with
Ulcerative Colitis (UC). The association between UC and systemic lupus
erythematosus (SLE) has been rarely reported in some case reports,
however, none of them consider a relationship or a link between UC and
SLE. This may be due to SLE colitis may mimic UC and some drugs for UC
treatment, particularly sulphasalazine, may cause drug-induced SLE {[}1
2{]}. In addition, the serum protein electrophoresis of the patients
with SLE usually shows polyclonal gamma globulin rises due to
hyperactivity of B-Lymphocytes and monoclonal gammopathy is a rare
finding in serum electrophoresis in a few cases {[}1 3{]}. In this case
report, we reported a patient with a past medical history of UC and
diagnosed with SLE and revealed monoclonal gammopathy in serum
electrophoresis. To the extent of our knowledge, this is the first case
of a UC that has been diagnosed with SLE and monoclonal gammopathy
simultaneously.

\textbf{Case Presentation}

A 38-year-old woman complaining of bloody diarrhea and general fatigue
was admitted to the emergency department and was then hospitalized. Her
previous medical record included upper gastrointestinal endoscopy and
colonoscopy that revealed crypt destructive colitis and chronic
gastritis. With these findings, she was diagnosed with early UC and was
under treatment with mesalazine (3g daily) and pantoprazole (40mg
daily). In addition, her routine blood tests had revealed pancytopenia
before. This had led the doctor to obtain a bone marrow biopsy which was
inconclusive due to an unsatisfactory sample, and also to request
rheumatologic laboratory tests which were reported negative.

The patient showed symptoms of general fatigue and lethargy along with
fever and night sweats. She also stated that she had involuntarily lost
14 kg in 3 months. Her family members also stated that their younger
sibling also had a history of an unknown rheumatologic disease and was
expired years ago. Her physical examinations showed bilateral pitting
edema in both legs, oral ulcers. she also suffered from bloody diarrhea
and hemoptysis. When she was admitted she was severely ill. Her lower
limb forces were reduced (3/5) and she could barely stand or walk. Her
neck examination showed enlarged lymph nodes on the back of her neck.
However, her vital signs were stable. As the patient's clinical signs
were suggestive for SLE or myositis we ordered prednisolone (1 mg/kg)
before the laboratory results were ready. This significantly improved
limb forces and hemoptysis.

Her laboratory tests were as shown in the table (Table 1, 2). The
significant findings were pancytopenia, mildly elevated liver enzymes, a
high ESR, severely low reticulocyte count, high LDH and B12 levels. Her
urine analysis revealed hematuria and bacteriuria. Her arterial blood
gases were normal. As her hemoglobin levels were deemed too low, she
received 1 unit of packed RBC. We also obtained another bone marrow
biopsy which was not in favor of malignancies. Another notable and
important finding is that her serum protein electrophoresis revealed an
unusual abnormality which was increased gamma globulin levels while
albumin levels were low (Table 3). This presentation was suggestive of
gammopathy.

In her following work up a spiral chest computed tomography (CT) scan
without contrast was requested that revealed ground-glass opacities in
the lower lobes of both lungs. This finding was more prominent in the
left lung. This finding was also suggestive of pneumonia. Other
remarkable findings were mosaic attenuation in the parenchyma of both
lungs, air cyst (12~mm~\selectlanguage{ngerman}×12~mm) in left upper lobe, bilateral mild
pleural effusion, cardiomegaly, and mild pericardial effusion.

As the findings were compatible with pneumonia, antibiotic therapy was
initiated and she received 4.5 gr of piperacillin/tazobactam
intravenously 3 times a day and 750 mgr of levofloxacin daily orally.

Due to swelling and edema in her lower limbs, she underwent venous color
doppler sonography and nothing remarkable was observed. the patient also
underwent neck sonography and many reactive lymph nodes were found on
both sides of the neck. the largest ones were (30~mm~×9.5~mm) in zone 2
of the right side and the other (23~mm~× 7~mm) in zone 2 of the left
side. Other sonographic evaluations revealed axillary lymph nodes as big
as (31mm~×15~mm) on the left and (25mm~×17~mm) on the right
respectively.

She also underwent echocardiography to assess cardiac activity and the
prominent finding was a decreased ejection fraction (EF) (45\%). As her
medical condition and the hematochezia had worsened 5mg of prednisolone
3 times a day and also a single unit of IVIG 60mg was ordered.

As the clinical manifestations of the patient were consistent with SLE,
a rheumatologic consultation was requested. Which suggested laboratory
tests that turned out to be positive for anti-dsDNA and also her urine
analysis manifested severe proteinuria. Meanwhile, she had already shown
symptoms of polyserositis, mouth ulcers, and pancytopenia. With all the
aforementioned findings and signs, SLE became a confirmed diagnosis for
the patient. Thus, intensive therapy with rituximab induction therapy
along with 500mg of prednisolone pulse therapy for 3 days was started,
we also used 200 mg of hydroxychloroquine daily simultaneously with a
daily dose of 1.5 gr of mycophenolic acid as a maintenance therapy.

Unfortunately, though, 2 days after the initiation of therapy oxygen
saturation levels suddenly dropped to 70\% and the patient became
dyspneic thus the patient was intubated. Unfortunately, the patient
showed signs of hemoptysis which was suggestive of alveolar hemorrhage.
She was intubated and 2 units of fresh frozen plasma (FFP) were
transfused. An emergent chest X-RAY was obtained that showed diffused
patchy infiltrates that resembled either pneumocystis pneumonia (PCP),
alveolar hemorrhage, or pulmonary thromboembolism (PTE). Portable
echocardiography showed an even more decreased EF (40\%) along with mild
right ventricle enlargement and moderate left ventricle dysfunction.
thereafter a new course of antibiotic therapy started with intravenous
(IV) cotrimoxazole, vancomycin, and cefepime. The patient received
another 500 mg of methylprednisolone pulse therapy and 4 mg of
dexamethasone IV, 3 times a day. However, the patient expired on the
same day due to alveolar hemorrhage arrest.

\textbf{Discussion}

There is no comprehensive consensus about the origin and etiology of UC
however it does fulfill the criteria for an autoimmune disease {[}4
5{]}. some of the characteristics of UC are precisely autoimmune. The
fact that certain human leukocyte antigens (HLAs) are in association
with UC {[}5{]}, certain autoantibodies are found to be involved as
well, and most importantly the response to immunosuppressive therapy has
led to this conclusion {[}4 5{]}. Our patient had previously been
diagnosed and was under treatment for the disease and her medical
history was consistent with our findings as well. However, her early
workup was unsuccessful in diagnosing the underlying cause for
pancytopenia. This phenomenon is thought to be related to the early
stages of SLE in which it had no clinical manifestation {[}4 6{]}.

A wide variety of disorders are also thought to have an autoimmune basis
such as celiac disease, ankylosing spondylitis, primary sclerosing
cholangitis, etc. one of such disorders that is rarely concurrent with
UC is SLE {[}7{]}. In a case-control study conducted by Shor et al. UC
was more prevalent in patients diagnosed with SLE {[}8{]}. However, in
multivariate regression models, SLE was not in association with UC.
There is a certain problem that also makes establishing the relation
between the two even more difficult and that is the fact that certain
medications, 5-aminosalicylic acid (5-ASA) compounds, in particular, can
cause drug-induced lupus {[}2{]}. And sometimes it's hard to distinguish
between these two. Even though lupus can be both idiopathic and
drug-induced, there are certain differences between the two. While
anti-dsDNA antibodies and more importantly hypocomplementemia are common
findings among idiopathic cases and they are rarely associated with
drug-induced type {[}2{]}. Even though our patient had been on 5-ASA
medication for a considerable amount of time we believe that her SLE
diagnosis was true and accurate as she fulfilled the EULAR/ACR criteria.

In a study conducted by Snook Ja, the association between autoimmune
diseases and inflammatory bowel disease had been studied and it turns
out that 6.6 \% of the patients with UC had another autoimmune disease
{[}4 9{]}. However, the gastrointestinal manifestations of both UC and
SLE are similar and common in both, and might be difficult to
distinguish between the two; particularly in lupus colitis which is
caused by inflammation, vasculitis, and necrosis in vessels of the
intestine. Kurlander and Kisner described the involvement in patients
with concurrent SLE and UC to be mostly in 2 forms {[}10{]}; 1) a
predominating vasculitis with bleeding and perforation usually
associated with a clinical picture suggestive of SLE; or 2) non-specific
ulcerative or granulomatous colitis.

Although many cases have been suggestive for the association between UC
and SLE, the link between the two needs more study and more
investigation as to its too rare.

Another disease manifestation of our patient which was interesting was
monoclonal gammopathy. This phenomenon is rarely associated with SLE
however several mechanisms have been proposed to be involved; polyclonal
B-cell activation both peripheral and in the bone marrow, abnormal
B-cell clones, And immunosuppressive agents prescribed for SLE patients
that disposes them to malignancies especially multiple myeloma, are some
of these mechanisms {[}1 3{]}. In a study conducted by YM Ali, et al at
the University of Toronto they concluded that the prevalence of
monoclonal gammopathy in SLE patients (5.4\%) is higher than the general
population (1--2\%) {[}3{]}. In this study, it's also suggested that
this disorder is not associated with any malignancies. Our patient had a
very high ESR level this inflammatory factor had prompted us to obtain a
serum protein electrophoresis. As the pathogenicity of gammopathy in
such patients has not been discovered we suggest that all patients go
through malignancy workup.

\textbf{Conclusion}

The association between UC and SLE seems to be a rare phenomenon and it
is not fully clear yet whether it is due to a common physiopathology or
not. on the other hand, we expected the serum protein analysis of our
patient to be in favor of polyclonal hypergammaglobulinemia as she was
diagnosed with SLE, however, the results showed monoclonal gammopathy.
Epidemiological links between SLE and monoclonal gammopathy and to a
lesser extent ulcerative colitis has been suggested by previous studies,
but the unusual phenomenon we observed was the concurrency of all three
in a single case.

Table 1. Patient's lab data on addmission\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
5.6\strut
\end{minipage} & \begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
ANA\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
p-ANCA\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
c-ANCA\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
RF\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Anti Ro\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Anti La\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\textgreater{}300\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Anti-dsDNA\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
5.6\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Lupus Anticoagulant\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
GBM-Ab\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Anti-centromere Ab\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Anti-SCL70 Ab\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Wright\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Coombs Wright\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2ME\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
PPD\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Volume=1600 Protein=496 Cr=400 Ca=3\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
24h Urine\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

ANA, anti-nuclear antibody; p-ANCA, perinuclear anti-neutrophil
cytoplasmic antibodies; c-ANCA, cytoplasmic anti-neutrophil cytoplasmic
antibodies; RF, rheumatoid factor; Anti-dsDNA, \emph{anti} -\emph{double
stranded DNA; GBM-Ab,} anti--glomerular basement membrane;
anti-centromere Ab, \emph{anti} -\emph{centromere antibodies;}
Anti-SCL70 Ab, anti-topoisomerase I; 2ME, 2-Mercaptoethanol; PPD,
purified protein derivative; Cr, Creatinine; Ca, Calcium

Table 2. Patient's lab data during hospitalization\selectlanguage{english}
\begin{longtable}[]{@{}llllllllllll@{}}
\toprule
day 11 & day 10 & day 9 & day 8 & day 7 & day 6 & day 5 & day 4 & day 3
& day 2 & day 1 &\tabularnewline
\midrule
\endhead
4500 & 4000 & 3100 & 1900 & 2400 & 1700 & 1500 & 1700 & 1400 & 1500 &
2100 & WBC (count)\tabularnewline
10.1 & 9.9 & 8.9 & 9.2 & 10.2 & 8.5 & 9.6 & 7.2 & 7.9 & 8.2 & 7.9 & Hb
(\%)\tabularnewline
139000 & 132000 & 123000 & 107000 & 85000 & 93000 & 97000 & 84000 &
103000 & 127000 & 100000 & Plt (count)\tabularnewline
31 & 30 & 20 & 27 & 27 & 26 & 17 & 16 & 16 & 27 & 37 & Urea
(mg/dl)\tabularnewline
0.9 & 0.9 & 0.9 & 0.9 & 0.9 & 0.9 & 0.9 & 1 & 1.1 & 1.2 & 1.3 & Cr
(mg/dl)\tabularnewline
\bottomrule
\end{longtable}

WBC, white blood cell; Hb, Hemoglobin; Plt, Platelet; Cr, Serum
Creatinine\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Frigue 1. Axial thoracic CT scan cut of lower thoracic region set at
pulmonary window; this cut depicts pleural effusion, ground glass
opacity and collapse consolidation\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2. Axial thoracic CT scan cut of lower thoracic region set at
thoracic window; in this cut pericardial effusion is also noticeable.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Figure 3. Capillary serum protein electrophoresis

\textbf{Abbreviations}

Ulcerative Colitis (UC)

Systemic Lupus Erythematosus (SLE)

Computed Tomography (CT)

Eection Fraction (EF)

Fresh Frozen Plasma (FFP)

Pneumocystis Pneumonia (PCP)

Human Leukocyte Antigens (HLAs)

5-Aminosalicylic Acid (5-ASA)

European League Against Rheumatism/American College of Rheumatology
(EULAR/ACR)

Anti\emph{-} double stranded DNA (Anti-dsDNA)

Erythrocyte Sedimentation Rate (ESR)

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

This study was approved by the research and ethics committee of Tehran
University of Medical Sciences. The patient's family have given their
informed consent to publish this case.

\textbf{Consent for publication}

Written informed consent was obtained from the patient's next of kin for
publication of this case report and any accompanying images. A copy of
the written consent is available for review by the Editor-in-Chief of
this journal.

\textbf{Availability of data and materials}

Data sharing is not applicable to this article as no datasets were
generated or analyzed during the current study.

\textbf{Competing interests}

The authors have no conflict of interest to declare.

\textbf{Funding}

None

\textbf{Authors' contribution}

MS contributed in developing the research idea and composing and
revising the manuscript. AH contributed in composing and revising the
manuscript. SK contributed in composing and revising the manuscript. SP
contributed in developing the research idea and revising the manuscript.

\textbf{Acknowledgments}

None

\textbf{References}

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6. Alarc\selectlanguage{ngerman}ón-Segovia D, Herskovic T, Dearing WH, Bartholomew LG, Cain JC,
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7. Stevens H, Ostlere L, Rustin M. Systemic lupus erythematosus in
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8. Shor DB-A, Dahan S, Comaneshter D, Cohen AD, Amital H. Does
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Autoimmunity reviews 2016;\textbf{15} (11):1034-37

9. Snook J, De Silva H, Jewell D. The association of autoimmune
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10. KURLANDER DJ, KIRSNER JB. The association of chronic'' nonspecific''
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\textbf{Hosted file}

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