A 17-year-old female with Down syndrome and Crohn’s disease: a rare case report from Syria

Abstract

Introduction:

Down syndrome (DS) affects 1 in 787 live births, linked to congenital anomalies and intellectual impairment. Colorectal Crohn’s disease is prevalent in DS patients, presenting with fatigue, abdominal pain, and strictures, often treated with surgery, immunomodulators, and biotherapy for management.

Case presentation:

The patient presented with symptoms of abdominal pain, cramping, and significant bowel sounds, along with weight loss and a decreased appetite. Histopathological examination and upper endoscopy were used to diagnose the condition, and a gluten-free dietary treatment was implemented.

Clinical discussion:

Crohn’s disease can be diagnosed by several methods, including histopathology, and its treatment can involve various approaches, including dietary management. There is a connection with genetic diseases, and it is not necessary for all symptoms and signs of the disease to appear, as they often vary.

Conclusion:

DS with Crohn’s disease is considered a very rare condition, especially in low-income countries and at a young age. It should be taken into account when differentiating diagnoses in autoimmune and intestinal diseases.

Introduction

The most prevalent chromosomal disorder, Down syndrome (DS), affects 1 in 787 live births. This corresponds to around 5000 DS children born in the US each year. In addition to physiological conditions such as congenital heart disease, obstructive sleep apnea, celiac disease, and endocrinopathies, DS is linked to intellectual impairment^[1]. Acute and chronic gastrointestinal disorders are generally somewhat common in people with DS^[2]. All parts of the gastrointestinal system are affected by Crohn’s disease (CD), a chronic inflammatory condition that is more common in affluent nations^[3]. It is linked to particular environmental conditions and is becoming more common in adults and children with verified genetic vulnerability. Frequent signs and symptoms include exhaustion, fever, weight loss, abdominal pain, diarrhea, stomach discomfort, and rectal bleeding. It is more prevalent in the proximal colon and terminal ileum. Stricture is the most typical sign of gastroduodenal CD, resulting in obstructive symptoms. Typical lesions throughout the entire stomach, mucosal abscesses, and sinuses associated with fissures are among its diagnostic criteria. The most popular course of treatment is surgery, which is followed by immunomodulators, biotherapy, and leukocyte isolation therapy. One of the most frequent surgical indications is intestinal obstruction brought on by stricture, which is followed by intestinal obstruction, fistula, and abscess formation^[4]. This is a rare case report of a 17-year-old female patient with DS and CD.

HIGHLIGHTS

• The connection between Down syndrome and Crohn’s disease is rare.

• A biopsy is definitely essential for diagnosing Crohn’s disease.

• A gluten-free diet is a key factor in healing from Crohn’s disease.

Case presentation

A 17-year-old female with DS presented to the department with a 4-month history of daily bilious vomiting, occurring two to three times per day, unrelated to food intake. This was accompanied by watery, bilious diarrhea with mucus, occurring 5–6 times daily, and cramping abdominal pain that lasted for 15 days. Subsequently, the vomiting became coffee-ground in appearance, occurring twice. After being evaluated at an external hospital, the patient was diagnosed with an upper gastrointestinal hemorrhage. The patient later experienced a recurrence of vomiting and diarrhea, up to 10 times daily, along with abdominal distension and firmness. External upper and lower gastrointestinal endoscopy was performed, and a differential diagnosis of CD or intestinal tuberculosis was considered. The patient was treated with antitubercular therapy for 3 months. She was admitted to our department with persistent cramping abdominal pain but no current vomiting or diarrhea. On examination, she exhibited loud bowel sounds, weight loss, and decreased appetite. Her menarche occurred at the age of 11, with regular cycles of 7 days duration every 30 days. However, there has been amenorrhea for the past 4 months, with the last menstrual period 2 weeks prior to admission. The lab results were as follows: Prothrombin time was 12.0 seconds, partial thromboplastin time was 25.0 seconds, INR was 1.0, Activity was 100%, Anti-HCV and HBs-Ag were negative, and all results were within normal limits (Table 1). An upper gastrointestinal endoscopy revealed diffuse acute erosive gastritis, bile stasis with scattered black sediment in the stomach, a markedly contracted gallbladder, and pyloric hypertrophy. Abdominal ultrasound identified multiple enlarged visceral lymph nodes around the aorta, with the largest measuring up to 4 cm, along with significant thickening of the intestinal walls (Fig. 1). A biopsy of the intestine was performed, during which it was observed distortion of the crypts, lymphocyte infiltration, and chronic inflammation of the rectum, limited to the lamina propria (Fig. 2). A gluten-free diet was started, and the patient became more active and her mood improved.

Table 1.

Laboratory findings on admission for a 17-year-old Syrian female with Crohn’s disease and Down syndrome

PT	12.0	F: 11–14	Sec
PTT	25.0	F: 25–35	Sec
INR	1.0	F: 0.8–1.2	Index
Activity	100	F: 70–130	%
Anti HCV	Negative
HBs-Ag	Negative

PT, prothrombin time; PTT, partial thromboplastin time; INR, interactional normalized ratio.

Figure 1.

Abdominal ultrasound revealed the presence of multiple enlarged visceral lymph nodes surrounding the aorta, the largest of which measured approximately 4 cm. Additionally, there was notable thickening of the intestinal walls.

Figure 2.

A biopsy of the intestine was conducted, revealing distortion of the crypts, infiltration of lymphocytes, and chronic inflammation of the rectum, restricted to the lamina propria.

Discussion

CD was initially described in 1932 by Dr. Burrill B. Crohn and associates. Alongside ulcerative colitis, which is a subtype of chronic idiopathic inflammatory bowel disease (IBD).

The incidence of CD ranges from 3 to 20 cases per 100 000 people. CD is more prevalent in developed nations, especially in Western Europe and North America, although it is becoming more common in Asia and South America. CD is more prevalent among people of Ashkenazi Jewish heritage than in non-Jews, and it may be somewhat more prevalent in women. Although several genetic and environmental variables have been demonstrated to raise the risk of CD and cause the abnormal gut immune response that is a hallmark of the disease, the precise pathogenesis of the condition is unclear. Changes in the gut microbiota, intestinal mucosal disturbances, and genetics seem to be risk factors for the development of CD^[5]. CD is a recurrent, chronic illness that is mostly brought on by granulomatous transmural inflammation. Macroscopic signs of the disease include ulceration, skip lesions, or cobblestone-like lesions in the gastrointestinal tract. It usually has an intermittent and recurring pattern, marked by notable illness during flare-ups. Affected individuals may have incapacitating symptoms^[6]. Although the symptoms that manifest vary greatly, they may somewhat correspond with the location and phenotype of the illness. Certain patients might have symptoms for years prior to receiving a CD diagnosis. Abdominal discomfort and diarrhea are common signs of inflammatory diseases, but they can also develop more systemic symptoms, including weariness, low-grade fevers, and weight loss. Bowel obstructions, most frequently minor bowel blockages, are prevalent in people with stricturing disease. Lack of flatus and bowel movements, hyperactive bowel noises, and nausea and vomiting are symptoms of bowel obstructions^[5]. Between 20% and 85% of CD patients experience nutritional deficits, with protein-energy malnutrition being the most prevalent^[7]. Any portion of the gastrointestinal system, from the mouth to the anus, can be impacted by CD; however, the small intestine, particularly the terminal ileum, is typically more severely affected. Extraintestinal symptoms such as cholelithiasis, nephrolithiasis, arthralgia, eye irritation, skin or mouth sores, and other hepatobiliary illnesses can also be signs of CD. In all age groups, it equally affects men and women, with vulnerability rising in the second and third decades of life and, in certain situations, a hereditary tendency^[6]. CD is diagnosed clinically, and because the presenting symptoms might be subtle and vague, it can be challenging. Red flag signs that indicate the following symptoms warrant additional assessment: iron deficiency, bloody diarrhea, weight loss, and overnight awakenings. Similar to this, a substantial family history of IBD, inexplicable increases in the amount of C-reactive protein and the pace at which erythrocytes sediment, other acute-phase reactants (such as ferritin and platelets), or inadequate vitamin B12 might provoke more research for potential CD. Anemia, leukocytosis, hypoalbuminemia, and increases in erythrocyte sedimentation rate and C-reactive protein are useful laboratory findings in CD. Anti-Saccharomyces cerevisiae antibodies, which are frequently positive in CD, and antineutrophil cytoplasmic antibodies, which are negative for CD, are the serologic indicators of clinical significance. Although these tests are suggestive of CD, they should not be considered as diagnostic tests because healthy individuals may have good results. These antibodies are mostly useful for differential diagnosis in individuals who exhibit traits of CD and other illnesses^[8]. In our case, the antibody results were negative (Table 1). CD is diagnosed based on radiologic and endoscopic findings as well as symptoms. Pathology may serve as a confirmatory test. Endoscopic results in patients of colonic or ileal CD are typically characterized by patches of normal-looking mucosa adjacent to skip lesions with variable degrees of inflammation (such as erythema, friability, erosions, and ulcers). Luminal strictures and, less frequently, fistulae may be observed during endoscopy. In pathology, a noncaseating granuloma is the typical discovery of CD. These are uncommon, though, occurring in fewer than 25% of cases, and they are neither specific nor indicative of CD. Variable levels of lymphocyte, plasma cell, and granulocyte infiltration, basal lymphoplasmacytosis, crypt atrophy, crypt abscesses, crypt branching, and deformation of the crypt architecture with shortening and disorder of the crypts are more frequent pathologic findings. The presence of Paneth cell metaplasia further supports the pathologic finding of chronicity^[5]. In our patient’s case, the histopathological examination revealed distortion of the crypts, lymphocyte infiltration, and chronic inflammation of the rectum, limited to the lamina propria (Fig. 2). CD can be diagnosed using imaging as well. Magnetic resonance enterography and computed tomography enterography both make it possible to see the mucosa, intestinal wall, and extraluminal problems^[5]. A definitive diagnosis of CD may still be elusive despite the widespread use of diagnostic techniques like colonoscopy, CT scans, barium x-rays, and ultrasound. Although there is no single “gold standard” sign for this illness^[8]. The intensity, location, and subtype of CD (inflammatory, stricturing, or penetrating) all affect how the illness is treated. Less than 30 years of age at diagnosis, substantial anatomic involvement, perianal disease, deep ulcers, previous surgery, and stricturing and/or penetrating disease are risk factors for severe disease activity^[5]. Medical management aims to keep the condition in remission without requiring surgery; however, once strictures and/or fistula complications develop, surgery might be necessary. Sadly, many people will need several procedures over the course of their lifetime because surgery is not a cure for CD. A variety of medications are used to treat CD. Despite being tested in several studies, mesalamine has not been proven to successfully induce or sustain CD remission. Mesalamine’s safety profile is probably connected to its perceived advantages. Although there is little evidence to support their usage, antibiotics are also utilized in CD. Antibiotics are mostly used to treat CD’s suppurative or perianal problems. For many years, immunosuppressants such as MTX, AZA, and mercaptopurine (MP) have been used to treat CD. Due to their delayed onset of effect, these medications are usually used to sustain remission. More recent research, however, casts doubt on the general effectiveness of AZA/MP as monotherapy and its application in early CD. According to more recent findings, these medications may be used in conjunction with anti-tumor necrosis factor (anti-TNF) medications to both raise the concentrations of anti-TNF medications and reduce their immunogenicity. Anti-TNF medications have been the cornerstone of CD treatment. Many CD patients can age by taking a conservative approach that includes sulfasalazine, iron, folic acid, antioxidants, multivitamins, a healthy diet, and enough sleep. The ultimate objectives of medical treatment are to improve the patient’s quality of life, avoid complications and surgery, and induce and sustain a clinical remission free of steroids^[8]. In our patient’s case, the symptoms and signs were early, and the patient was placed on a gluten-free diet, which led to an improvement in her health condition, resulting in greater stability.

Individuals with DS often exhibit immunological dysregulation, which may affect their susceptibility to inflammatory diseases, including CD. This altered immune response can lead to atypical clinical presentations, such as a higher prevalence of gastrointestinal manifestations that may obscure or complicate the diagnosis. Symptoms commonly associated with CD, such as abdominal pain and diarrhea, may be misattributed to the underlying gastrointestinal motility disorders frequently observed in DS patients^[5–7].

Diagnostic challenges may arise due to the overlapping gastrointestinal symptoms and the potential presence of congenital anomalies, such as duodenal atresia or other structural abnormalities, that are more prevalent in individuals with DS. Enhanced imaging techniques and a high index of suspicion for CD are crucial for accurate diagnosis in this population^[7,8].

Treatment strategies for CD in individuals with DS must consider potential pharmacological interactions and the unique metabolic profiles associated with trisomy 21. Additionally, the presence of comorbid conditions, such as cardiac defects or thyroid disorders, may necessitate a multidisciplinary approach to management, which includes tailored dietary recommendations and close monitoring of medication side effects^[5,7,8].

The progression of CD in individuals with DS may differ from the general population, potentially resulting in a more aggressive disease course or altered response to therapy. Longitudinal studies are warranted to elucidate the relationship between DS and the course of CD, ultimately informing clinical practice and optimizing patient outcomes in this unique cohort^[5–8].

Conclusions

DS associated with CD is regarded as a very rare condition, particularly in Syria. It’s intriguing to learn that CD, which primarily affects adults, can appear at any age. Many other gastrointestinal diseases that require medical attention can mirror the symptoms of CD. It should be remembered, therefore, as one of the reasons for severe abdominal pain, particularly in patients with a lengthy history of intestinal diseases and genetic illnesses for which there are widely disparate treatment options. Differentiating CD from other inflammatory illnesses of the digestive tract is crucial to establishing a suitable treatment to prevent potentially fatal short- and long-term consequences. Additionally, there is growing evidence that patients with CD have a higher risk of developing adenocarcinoma, which makes a histopathologically verified diagnosis imperative. The intersection of DS and CD presents unique clinical challenges that have significant implications for practice. Clinicians managing CD in patients with DS should remain vigilant for atypical presentations due to the immunological and anatomical considerations inherent in this population.

Ethical approval

Not applicable.

Consent

Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images and videos. A copy of the written consent is available for review by the editor of this journal.

Sources of funding

Not applicable.

Author contributions

M.K.A.H. wrote a part of the manuscript. M.A.K. wrote a part of the manuscript. S.K.I. wrote a part of the manuscript. Abdulrahman Ahmad Othman wrote a part of the manuscript. R.A. wrote a part of the manuscript. H.F.H. wrote a part of the manuscript. B.A.M.AL. wrote a part of the manuscript. A.H.A. wrote a part of the manuscript. B.M.B. wrote a part of the manuscript. E.I.I. wrote a part of the manuscript. B.S. wrote a part of the manuscript. M.S. wrote a part of the manuscript. All authors approved the final manuscript.

Conflicts of interest disclosure

No conflict of interest.

Research registration unique identifying number (UIN)

Not applicable because our article is a case report.

Guarantor

Bilal Sleiay.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

Not applicable.

Methods

The work has been reported in line with the SCARE criteria^[9].