Discussion and conclusions
Both of our two patients less than 2 years old. Upper GIT endoscopy revealed scattered superficial erosions, haemorrhagic ulcerations or villous atrophy from the duodenum to the beginning of the jejunum. Colonoscopy revealed that the entire colonic mucosa was oedematous with multiple erythaematous lesions, and ulcers were also occasionally observed in the rectal mucosa. The time from symptom onset to diagnosis was approximately five months. The symptoms in both patients improved significantly after receiving chemotherapy according to the SCMC-LCH-2018 Group 1 and CCHG-LCH-2019 protocols.
GIT involvement in LCH is rare. Due to its rarity and lack of clinical report, 4 patients were reportedly misdiagnosed with cow protein allergy, neonatal enterocolitis or inflammatory bowel disease [
2‐
5]. The reported incidence of LCH ranges from 2.6 to 8.9 cases per million children younger than 15 years per year [
6]. In the other 6 reports in the literature in which GIT symptoms were the initial manifestation, all 7 patients were younger than 2 years [
2,
4,
5,
7‐
9]. It seems that GIT-LCH was common in children aged < 2 years at the time of diagnosis.
The clinical symptoms of LCH-GIT include nausea, vomiting, abdominal pain, diarrhoea, haematochezia, constipation, intestinal obstruction, intussusception, and intestinal perforation [
10,
11]. GIT symptoms lack specificity and are difficult to identify, and it is difficult to diagnose LCH without lesions in other systems (i.e., the lung or bones) at initial presentation. The main gastrointestinal symptoms in our two patients were refractory diarrhoea and protein-losing enteropathy. Among the above 7 patients, the initial GIT symptoms were diarrhoea in 5 patients, abdominal distension in 1 patient, and vomiting in 1 patient, while hypoalbuminaemia was reported in 6 patients [
2,
4,
5,
7‐
9].
GIT endoscopy is important for identifying the cause of chronic diarrhoea. As GIT symptoms in LCH patients are rare, few cases of endoscopic manifestations have been reported. Combining the endoscopic findings of our two patients with those of other case reports, patchy erythema of the colorectal mucosa and narrowness and erosion of the distal duodenum might be suggestive manifestations of GIT involvement in LCH on endoscopic examination [
5,
7,
8]. However, it is still difficult to directly distinguish LCH from other diseases, such as inflammatory bowel disease, by endoscopic manifestations.
Pathologic examination is the gold standard for definitive diagnosis of LCH. Typical LCH lesions show large cells, pale cytoplasm, and reniform nuclei on haematoxylin and eosin staining. LCH lesions are granulomatous lesions consisting of pathologic “Langerhans cells” (LCs), lymphocytes (primarily T cells), eosinophils, and macrophages [
12]. LCH lesion LCs express CD1a, S100 and langerin surface markers according to immunohistochemical examination, and alternative BRAF mutations have also been described [
1,
12]. As the diagnosis of LCH is based on histology, experienced clinicians should guide pathologists in identifying the manifestations of LCH and perform corresponding immunohistochemical staining tests.
Rashage and bone presentation were the main abnormalities in addition to GIT symptoms in our patients. The rash was easy to ignore initially due to a lack of clinical experience. Rash was found in 5 cases with GIT-LCH; all of these cases involved the trunk and presented with scattered red papules, but only two of them showed rash [
2,
4,
5,
7‐
9]. If this typical lesion can be recognized, it may be possible to perform a skin biopsy for early definitive diagnosis.
Bone involvement is also characteristic of LCH and can present as either single or multiple osteolytic lesions, including those of the skull, mandible, spine, or long bones [
10]. In our case, bone-related X-rays, CT and MRI were negative, but PET-CT showed osteolytic lesions in the bones or involvement in the liver and bone marrow. Therefore, PEC-CT is sensitive and necessary when considering the diagnosis of LCH. It is beneficial to locate the other organs involved in LCH to divide patients into single- or multiple-system groups precisely for further treatment.
Due to its rarity and the lack of known cases, the initial presentation of LCH-GIT is easy to misdiagnose. When refractory diarrhoea is accompanied by recurrent hypoalbuminaemia, especially when accompanied by abdominal rash, LCH should be considered. Endoscopic and pathologic examinations are essential for definitive diagnoses, while PET-CT is necessary to determine the involvement of other organs. All examination methods are conducive to treatment.
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