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\begin{document}

\title{Waldmann's Disease: Primary Intestinal Lymphangiectasia Diagnosed by
99mTc-labeled Albumin Macroaggregate Scintigraphy - A Case Report in an
Adult Patient}



\author[1]{Alex Castellón}%
\author[1]{Allan Bodan-Campbell}%
\author[2]{Victor  Rosales-Obregón}%
\author[1]{Mohammed Zahran}%
\affil[1]{Manolo Morales Peralta Hospital}%
\affil[2]{Nora Astorga Hospital}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\textbf{''Waldmann's Disease: Primary Intestinal Lymphangiectasia
Diagnosed by 99mTc-labeled Albumin Macroaggregate Scintigraphy - A Case
Report in an Adult Patient.''}

Alex Castell\selectlanguage{ngerman}ón Méndez A\textsuperscript{1}, Allan Bodán Campbell
A\textsuperscript{1}, Mohammed Zahran\textsuperscript{1}, Victor Rosales
Obregón\textsuperscript{2}.

Department of Internal Medicine, Manolo Morales Peralta Hospital,
Managua, Nicaragua.

Department of Nuclear Medicine, Nora Astorga National Radiotherapy
Center, Managua, Nicaragua.

\textbf{Correspondence}

Mohammed Zahran, Manolo Morales Peralta Hospital, Managua, Nicaragua.
Email:\emph{blacke\_star.1991@yahoo.com}/ blackestar.1991@gmail.com

\textbf{INTRODUCTION}

Waldmann's Disease, or Primary Intestinal Lymphangiectasia (PIL), was
first described in 1961\textsuperscript{1}. It is a rare disorder of
unknown etiology that causes protein-losing
enteropathy\textsuperscript{2}. The condition is characterized by the
dilation and leakage of intestinal lymphatic vessels, leading to
hypoalbuminemia, hypogammaglobulinemia, and
lymphopenia\textsuperscript{3}. The symptoms of the disease depend on
the severity and location of the affected lymphatic vessels, ranging
from mild edema in the lower

extremities to generalized edema, ascites, pleural effusion, chronic
diarrhea, among others\textsuperscript{1}. While it typically develops
in early childhood, we present the case of a 55-year-old male.

\textbf{CASE REPORT}

A 55-year-old male with a medical history of intestinal obstruction,
multidrug-resistant pulmonary tuberculosis, and primary antiphospholipid
syndrome with a double risk factor, along with the amputation of the
left upper limb, 10, 9, and 6 years ago, respectively. The patient
reported a 2-year history of chronic diarrhea with a progressive
increase in frequency of liquid stools, associated with approximately
5\% weight loss in the last 6 months, and edema in the lower limbs that
generalized on two occasions.

On physical examination, the patient had a low normal body mass index
(17.4 kg/m2), increased intestinal peristalsis, edema in the lower limbs
with ++ pitting edema, decreased trophism in the examined limbs, and
decreased reflexes.

Laboratory examinations revealed: HGB: 13.5 g/dl, HCT: 39.5\%,
Platelets: 370,000 mm3, WBC: 5910 mm3, Neutrophils: 84.1\% (4970 mm3),
Lymphocytes: 9.8\% (537 mm3), Eosinophils: 0.3\%, PT: 16.7 s, APTT: 37
s, INR: 2, Glucose: 78 mg/dL, Creatinine: 0.54 mg/dL, Serum Albumin:
1.45 g/dL, Total Proteins: 4.12 g/dL, BT: 0.80 mg/dL, BD: 0.34 mg/dL,
BI: 0.45 mg/dL, AST (TGO): 27.63 U/L, ALT (TGP): 30.38 U/L, Urea: 18
mg/dL, LDH: 414.30 U/L, Cholesterol: 160 mg/dL, Triglycerides: 130
mg/dL, LDL: 90 mg/dL, HDL: 30 mg/dL, GGT: 4 U/L, Sodium: 137 mEq/L,
Potassium: 3.1 mEq/L, Corrected Calcium: 8.6 mg/dL, Chloride: 96.7
mEq/L, Vitamin B12: 50 pg/mL (Reference Range: 197-771), Procalcitonin:
0.37 ng/mL, CRP: Negative, Rapid Test: Non-Reactive, General Urine
Examination: Yellow/Turbid, Density: 1015, pH: 6.0, Absent Proteins,
Leukocytes: 1-3 x HPF, Erythrocytes: 0-1 x HPF, Bacteria: Absent,
24-Hour Urine Proteins: 98 mg/24 hours, General Stool Examination: Brown
color, liquid consistency, negative occult blood, no bacteria,
parasites, or yeast, Stool Culture: no growth in 24 hours, Kinyoun
Stain: negative, Xpert Clostridioides difficile in stool: C. difficile
toxigenic negative and 027 presumptive negative, Xpert MTB-RIFG4 in
stool: MTB Negative, RIF Resistance: Not detected. Fecal Calprotectin:
75 ug/g. Serology for celiac disease was performed: ASCA, Anti-TG2 IgA,
Anti-DPG IgA, EMA IgA, all with negative results. p-ANCA: Negative.
Anti-transglutaminase IgA (CLIA): 3.3 U, Complement C3: 0.8 g/L
(Reference Range: 0.9 - 1.8 g/L), Complement C4: 0.2 g/L (Reference
Range: 1 - 4 g/L), profile of antibodies against extractable nuclear
antigens: negative, Anti-dsDNA: 11.6 (Reference Range: \textgreater{}
27), AntiSmith: 12.7 U/mL (Reference Range: \textless{} 15), ANA:
Negative. IgA: 260 mg/dL (Reference Range: 40-230), IgE: 44.7 mg/dL
(Reference Range: 50-100), IgG: 600 mg/dL (Reference Range: 700-1600),
IgM: 13.60 mg/dL (Reference Range: 40-230).

Imaging examinations: Abdominal computed tomography (CT) showed no
abnormalities. Upper gastrointestinal endoscopy was unremarkable, and
lower gastrointestinal endoscopy revealed Dispersed white spots with a
'snowflake' appearance at the level of the terminal ileum were observed
(Figure 1). A biopsy was taken, and the report indicates dilation of
vessels with a lymphatic appearance in the lamina propria, associated
with a moderate amount of plasma cells and distortion of the villi:
Intestinal Lymphangiectasia (Figure 2). A nuclear medicine study was
conducted: a scintigram for the detection of intestinal protein loss
revealed an abnormal concentration of the radiotracer in the left flank
in intestinal projection in the late views, confirming intestinal
protein loss (Figure 3).

\textbf{Methodology:}

The case presented involves a patient with a complex condition who was
ultimately diagnosed with intestinal lymphangiectasia, a rare disease
characterized by excessive loss of proteins through the lymphatic
vessels of the small intestine. This disorder can lead to serious
complications due to protein deficiency and the loss of other important
blood components.

The diagnostic approach was meticulous, considering a variety of
possible causes for the patient's symptoms, such as extrapulmonary
tuberculosis, autoimmune diseases like Crohn's disease and systemic
lupus erythematosus, as well as primary immunological disorders. The
observation of characteristic lesions in the small intestine, resembling
''snowflake-like flakes,'' during endoscopic evaluation was crucial in
reaching the diagnosis.

Once the histopathological diagnosis of intestinal lymphangiectasia was
established, it was necessary to confirm the abnormal protein loss at
the intestinal level. Therefore, ''99mTc-labeled Albumin Macroaggregate
Scintigraphy'' was performed, which not only confirmed the losses but
also localized the sites of greatest leakage, mainly in the terminal
ileum, where snowflake-like lesions were found.

Patient management focused on symptomatic treatment, as there is no
specific therapy for this disease. A high-protein diet was implemented,
and human albumin was administered to address protein deficiency.
However, despite these efforts, the patient experienced progressive
deterioration and developed infectious complications that contributed to
a fatal outcome. \textsuperscript{6}

It is crucial to highlight that intestinal lymphangiectasia is a disease
with a variable but potentially severe prognosis that can limit the
patient's life expectancy. Management focuses on relieving symptoms and
preventing complications, but it is not always effective in halting
disease progression. In some cases, such as this one, a fatal outcome is
unfortunately a possibility, especially when severe complications
occur.\textsuperscript{6}

\textbf{CONCLUSION}

This case highlights the atypical presentation of Waldmann's Disease in
adulthood, emphasizing the importance of a multidisciplinary approach
for accurate diagnosis and management. Further research is warranted to
enhance our understanding of this uncommon disorder and its potential
implications for patients with complex medical histories.

\textbf{DISCUSSION}

The rarity of Waldmann's Disease in adulthood and its association with
other significant medical conditions pose diagnostic challenges. The
distinct endoscopic and histological findings, coupled with scintigraphy
results, contribute to a comprehensive understanding of this complex
case. Currently, the sensitivity and negative predictive value of HSA
scintigraphy labeled with 99m Tc make it superior to Alpha 1 antitrypsin
clearance (AATC) in the diagnosis of protein-losing enteropathy (PLE).
In view of the easy application, lack of adverse effects, wide
availability and rapid results, We recommend 99m Tc-labeled HSA
scintigraphy as a method initial diagnostic tool for patients with PLE.
Finally, it is necessary to integrate clinical evaluation, endoscopic,
histological and radiological characteristics, to make an accurate
diagnosis of PLE. case\textsuperscript{4,5}. Differential diagnoses and
management considerations are discussed.

\textbf{AUTHOR CONTRIBUTIONS}

\textbf{Alex Castellón Méndez:} Main Author, Conceptualization; Data
curation; Funding acquisition; Writing -- original draft. \textbf{Allan
Bodán Campbell:} Conceptualization; Investigation; Resources;
Supervision. \textbf{Victor Rosales Obregón:} Conceptualization; Data
curation; Investigation; Project administration; Resources; Writing --
review \& editing. \textbf{Mohammed Zahran:} Conceptualization;
Methodology; Project administration; Resources; Supervision; Writing --
review \& editing.

\textbf{FUNDING INFORMATION:}

The authors of this article declare that no funding was obtained for the
writing and preparation of this manuscript.

\textbf{CONFLICT OF INTEREST STATEMENT:}

The authors declare that they have no conflicts of interest with any
organization regarding the article submitted for publication.

\textbf{DATA AVAILABILITY STATEMENT:}

We commit to ensuring the availability and confidentiality of the
information related to the presented clinical case. Our priority is to
safeguard patient privacy and adhere to the highest ethical standards in
handling medical information. All clinical documentation will be
protected and used solely for educational and academic discussion
purposes.

\textbf{ETHICS STATEMENT:}

This involves the description of a clinical case. It is not a clinical
trial, and no experimentation has been conducted on animals or humans.
The authors of this manuscript have adhered to the protocols of our
workplace (Manolo Morales Peralta Hospital) for the publication of
clinical cases, and patient anonymity has been preserved.

\textbf{CONSENT}

Written informed consent was obtained from the patient and their family
to publish this report in accordance with the journal's patient consent
policy.

\textbf{ORCID:}

Alex Castellón:\emph{https://orcid.org/0009-0008-2409-6613}

Allan Bodán: \emph{https://orcid.org/0009-0009-8581-4727}

Zahran
Mohammed\textsuperscript{:}\emph{https://orcid.org/0009-0003-9526-6812}

Victor Rosales:

\emph{https://orcid.org/0000-0002-1748-1651}

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Huber R, Semmler G, Mayr A, Offner F, Datz C. Primary intestinal
  lymphangiectasia in an adult patient: A case report and review of
  literature. \emph{World J Gastroenterol} 2020; 26(48):
  7707-7718.\emph{https://doi.org/10.3748/wjg.v26.i48.7707}
\item
  Ahmet Ozen, M.D., and Michael J. Lenardo, M.D. Protein-Losing
  Enteropathy. N Engl J Med 2023;
  389:733-748.\emph{https://doi.org/10.1056/NEJMra2301594}
\item
  Levitt, D. G., \& Levitt, M. D. (2017). Protein losing enteropathy:
  comprehensive review of the mechanistic association with clinical and
  subclinical disease states. Clinical and experimental
  gastroenterology, 10,
  147--168.\emph{https://doi.org/10.2147/CEG.S136803}.
\item
  T.N. Chau, M.Y. Mok, E.Y.T. Chan, W.H. Luk, K.B. Lai, F.T.W. Li,
  V.K.S. Leung, R. Wong; Evaluation of Performance of Measurement of
  Faecal \selectlanguage{greek}α\selectlanguage{english}1-Antitrypsin Clearance and Technetium-99m Human Serum Albumin
  Scintigraphy in Protein-Losing Enteropathy. Digestion
  2011;84:199--206. \emph{https://doi.org/10.1159/000327914} .
\item
  Khalesi M, Nakhaei AA, Seyed AJ, Treglia G, Zakavi SR, Sadeghi R,
  Kianifar HR. Diagnostic accuracy of nuclear medicine imaging in
  protein losing enteropathy : systematic review and meta-analysis of
  the literature. Acta Gastroenterol Belg. 2013 Dec;76(4):413-22.
\item
  Cl\selectlanguage{ngerman}áudio Martins, Alice Gagnaire, Florian Rostain and Come Lepage.
  Waldmann's disease: a rare cause of protein losing enteropathy in an
  adult patient. 2017 2017; 109(5):385-388
\end{enumerate}\selectlanguage{english}
\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

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\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

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Principio del formulario

Final del formulario

Figure 1. A and B) Mucosa of the second portion of the duodenum with
scattered white spots resembling ''snowflakes'' at the level of the
terminal ileum. Endoscopy Department, Manolo Morales Peralta Hospital,
Managua, Nicaragua.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure 2. A) H\&E 10x. Distorted intestinal villi. B) H\&E 40x. Dilation
of lymphatic vessels. Pathology Department, Manolo Morales Peralta
Hospital - Q 5635-22. Managua, Nicaragua.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image6/image6}

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\includegraphics[width=0.70\columnwidth]{figures/image7/image7}

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\includegraphics[width=0.70\columnwidth]{figures/image8/image8}

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\end{figure}

Figure 3. Scintigram with 99mTc-labeled albumin macroaggregate. A) Hour
1, early phase, physiological uptake in the liver and spleen. B) Hour 2.
C) Hour 3. D) Hour 4, late phase, abnormal concentration of the
radiotracer in the left flank in intestinal projection. Nuclear Medicine
Department, National Center of Radiotherapy - Managua, Nicaragua.

\textbf{Hosted file}

\verb`280124 figure Waldmann Disease Corrections.docx`  available at \url{https://authorea.com/users/761280/articles/737368-waldmann-s-disease-primary-intestinal-lymphangiectasia-diagnosed-by-99mtc-labeled-albumin-macroaggregate-scintigraphy-a-case-report-in-an-adult-patient}

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