Langerhans cell histiocytosis

　　The etiology of Langerhans cell histiocytosis is not yet clear, and it may be related to environmental factors, genetic factors, dietary factors, and emotional and nutritional factors during pregnancy, but the specific correlation is still unclear in current research. Although the genetic characteristics are not yet clear, there is a certain degree of familial aggregation, and the incidence rate in siblings is much higher than that in ordinary children. Some also believe that the disease has the nature of a tumor.

　　What diseases can Langerhans cell histiocytosis cause, a brief description is as follows.

　　Severe skin damage often becomes a secondary infection focus. Local swelling occurs when soft tissue is involved, most commonly seen in the head and neck, often coexisting with adjacent bone damage. Soft tissue invasion of the external auditory canal can lead to purulent discharge from the external auditory canal, often coexisting with otitis media and otitis externa.

　　2, Severe cases may have ascites and edema due to liver cirrhosis, even liver failure. In cases with明显 enlarged spleen, it can cause leukopenia due to hypersplenism.

　　3, 9.1% of patients with combined cranial bone destruction and exophthalmos, similar to the results reported abroad. Patients with diabetes insipidus may have developmental disorders related to pituitary growth hormone deficiency. In the late stage, other CNS damage signs may occur, with cerebellar lesions being the second most common site of LCH in the CNS, which can cause ataxia and other manifestations. Some patients may find cerebellar lesions many years after the disappearance of LCH. Fever may occur during the course of the disease, and it is more common in young children. In addition to the fever caused by LCH itself, infection is an important cause of fever.

　　The onset of this disease is not uniform, and the symptoms are diverse. LCH, skin, solitary or multiple bone damage, with or without diabetes insipidus, is considered localized; liver, spleen, lung, hematopoietic system, and other organ damage, or with bone and skin lesions, is considered extensive. In this patient, multiple systems and multiple organs are involved, indicating an extensive LCH.
　　Mild cases are solitary painless bone lesions, while severe cases are widespread organ infiltration accompanied by fever and weight loss.
　　1, Skin rash Skin lesions are often the primary symptom of the disease. The rash is of various types in acute patients, mainly distributed on the trunk and hairline of the scalp, behind the ears. Initially, it presents as maculopapular rash, which quickly develops into exudation (similar to eczema or seborrheic dermatitis), which may be accompanied by bleeding, followed by scab formation, desquamation, and finally leaving hyperpigmented spots. These spots are difficult to fade over time. Rash in different stages can coexist or some may fade while others appear. There is often fever during the rash, and chronic cases may have rashes scattered throughout the body. Initially, they are faint maculopapular rashes or warty nodules, which become concave and flat when they fade. Some are dark brown, very similar to scabbed chickenpox. Finally, the local skin becomes thin and slightly concave, with a slight sheen or some desquamation. Rashes can appear simultaneously with other organ damage or exist as the only affected manifestation, and are common in male infants under 1 year of age.
　　2, Osteolytic lesions are almost seen in all LCH patients, with solitary bone lesions being more common than multiple bone lesions, mainly manifested as osteolytic damage. The most common site is cranial bones, followed by lower limb bones, ribs, pelvis, and spine. Mandibular lesions are also quite common. On X-ray films, they often show irregular bone resorption, with cranial bone destruction ranging from eroded-like changes to large defects or perforation-like changes, irregular in shape, presenting as circular or elliptical defects with jagged edges. The borders of primary or progressive lesions are indistinct, and there is often increased intracranial pressure, suture separation, or communicating hydrocephalus. Headaches may occur, but during the recovery period, the bone quality becomes gradually clear at the edges, showing a hardening band. The bone density is uneven, and the bone defects gradually decrease, finally completely repaired without leaving any trace. Other changes in flat bones include visible swelling and thickening of the ribs, thinning or cystic changes in bone quality, followed by bone resorption, atrophy, and thinning. Vertebral body destruction may become flat vertebral bodies, but the intervertebral spaces do not narrow, and angular deformities are rare. Vertebral arch destruction is prone to cause compression of the spinal nerves, and a few cases have para vertebral soft tissue swelling. Mandibular lesions can manifest as alveolar and mandibular body types.
　　3. Lymph Nodes The lymph node lesions of LCH can manifest in three forms: ① Simple lymph node lesions, known as primary lymph node eosinophilic granuloma; ② Accompanying lesions of localized or focal LCH, often involving osteolytic damage or skin lesions; ③ As part of systemic disseminated LCH, often involving solitary lymph nodes in the neck or inguinal region. Most patients have no fever, and a few have pain only at the enlarged lymph node site. Simple lymph node involvement usually has a good prognosis.
　　4. Ear and Mastoid LCH The external auditory inflammation is often the result of lymphocytic histiocytic proliferation and infiltration of soft tissue or bone tissue in the auditory canal. It is sometimes difficult to distinguish from diffuse bacterial ear infections. The main symptoms include otorrhea, swelling behind the ear, and conductive hearing loss. CT examination can show lesions of both bone and soft tissue. Mastoid lesions can include mastoiditis, chronic otitis media, cholesteatoma formation, and hearing loss.
　　5. Bone marrow Under normal circumstances, there is generally no LC in the bone marrow, and even in LCH that invades multiple sites, it is difficult to see LC in the bone marrow. However, once LC invades the bone marrow, patients may present with anemia, decreased white blood cells, and decreased platelets. The degree of bone marrow dysfunction is not proportional to the amount of LC infiltration in the bone marrow, and the presence of LC in the bone marrow alone is not sufficient to serve as a diagnostic criterion for LCH.
　　6. Thymus The thymus is one of the organs frequently involved by LCH.
　　7. The pulmonary lesions of LCH can be part of systemic involvement or exist independently, known as primary pulmonary LCH. Pulmonary lesions can occur at any age, but they are more common in infants during childhood. Symptoms include varying degrees of dyspnea, hypoxia, and changes in pulmonary compliance. Severe cases may present with pneumothorax, subcutaneous emphysema, and are prone to respiratory failure and death. Pulmonary function tests often show restrictive damage.
　　8. The systemic LCH often invades the liver, and the affected areas of the liver are mostly in the triangular region of the liver. The extent of involvement can range from mild biliary stasis to severe tissue infiltration at the hepatic hilum, leading to liver cell injury and biliary involvement, manifested as abnormal liver function, jaundice, hypoalbuminemia, ascites, and prolonged prothrombin time. Further progression can lead to sclerosing cholangitis, liver fibrosis, and liver failure.
　　9. Diffuse LCH of the spleen often has splenic enlargement, accompanied by a decrease in one or more series of blood cells in peripheral blood, the cause may be the expansion of the spleen, causing the blockade of platelets and granulocytes, not an increase in destruction, the blood cells blocked by the spleen can still reach a dynamic balance with peripheral blood cells, so bleeding symptoms are not common.
　　10. Gastrointestinal lesions are common in systemic diffuse LCH, symptoms are often related to the affected site, the most commonly affected are the small intestine and ileum, with symptoms such as vomiting, diarrhea, and malabsorption, which can cause growth stunting in children over a long period of time.
　　11. Central nervous system LCH central nervous system involvement is not uncommon in LCH, the most common affected area is the thalamus-pituitary posterior lobe, diffuse LCH can have parenchymal brain lesions, most patients' neurological symptoms appear several years after other sites of LCH, common symptoms include ataxia, dysarthria, nystagmus, hyperreflexia, alternating movement disorder, dysphagia, blurred vision, etc. Diabetes insipidus caused by thalamic and/or pituitary granulomas can occur before, simultaneously, or after brain symptoms, or can be the only manifestation of CNS.
　　12. Letterer-Siwe disease is the most severe type of Langerhans cell histiocytosis, accounting for about 1% of typical cases are infants under the age of 2, with scaly seborrheic eczema-like rashes, sometimes presenting purpuric rashes, involving the scalp, ear shell, abdomen, and neck and facial folds. Skin damage can become a gateway for microbial invasion, leading to sepsis. Common symptoms include ear discharge, lymphadenopathy, and enlargement of the liver and spleen. Severe cases may present with liver dysfunction accompanied by hypoalbuminemia and reduced synthesis of coagulation factors, anorexia, irritability, weight loss, and obvious respiratory symptoms (such as cough, rapid breathing, pneumothorax). Severe anemia, sometimes with neutropenia, and thrombocytopenia are often a sign of impending death. Due to these symptoms, young patients are often misdiagnosed or missed.

　　Langerhans cell histiocytosis is caused by the ability of tobacco smoke to induce the release of frog skin peptide-like peptides from airway neuroepithelial cells, which further activate alveolar macrophages to release cytokines such as tumor necrosis factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), or other mediators, which may enhance the recruitment and activation of Langerhans cells. At the same time, frog skin peptide-like peptides can also stimulate the proliferation of fibroblasts, promoting the formation of pulmonary fibrosis. Therefore, not smoking or quitting smoking can effectively prevent the occurrence of Langerhans cell histiocytosis.

　　The laboratory examination of Langerhans cell histiocytosis includes:
　　1. Immunohistochemical staining
　　Immunohistochemical staining with ATPase, S-100 protein, α-D-mannosidase, peanut lectin receptor, and elastin can show positive reactions, these indicators are highly sensitive but not specific.
　　2. Only when Langerhans cells with Langerhans granules or CD1 antigen expression on the cell surface are detected by electron microscopy can the diagnosis be confirmed.
　　3. The diagnosis of Langerhans cell histiocytosis can be made based on the histopathological characteristics of the biopsy specimen. Langerhans cells are often predominant in the pathological slides and vary with the duration of the disease. In early lesions, the proliferating Langerhans cells are well differentiated. In late lesions, Langerhans cells are fewer, and in some cases, they are absent. Necrosis with a very small number of Langerhans cells may occasionally be seen. Polymorphic histiocytes are common and coexist with other inflammatory cells (such as granulocytes, eosinophils, macrophages, and rare lymphocytes and plasma cells).
　　If there are new skin rashes, a rash pressure film should be made, and if a skin biopsy of the rash site can be performed, it is more reliable. For lymphadenopathy, lymph node biopsy can be performed, for bone destruction, a tumor excision can be done, and the excised material can be sent for pathological examination, or a fine needle aspiration can be performed at the site of bone destruction, and the aspirate can be smeared and sent for examination.
　　5. X-ray examination
　　Pulmonary X-ray examination usually shows reticular or网点状 shadows of pulmonary vessels, blurred grain edges, and not arranged according to the bronchial branches. Small cystic emphysema is common, and in severe cases, it presents as honeycomb lung. It can be accompanied by interstitial emphysema, mediastinal emphysema, subcutaneous emphysema, or pneumothorax. Many patients can have pneumonia, which is more likely to cause cystic changes at this time. After the pneumonia subsides, the cystic changes can disappear, but the reticular changes become more obvious, and chronic patients may develop pulmonary fibrosis.
　　6. Blood count
　　Systemic disseminated LCH often has moderate to severe anemia, reticulocytes and leukocytes can slightly increase, platelets decrease, and a few cases may have leukopenia.
　　7. Bone marrow examination
　　Most LCH patients have normal bone marrow proliferation, while a few may show hyperplasia or decrease. A few LCH cases can invade the bone marrow, manifesting anemia and decreased platelets, so this examination is only performed when peripheral blood abnormalities are found.
　　8. Liver and kidney function
　　In some cases, liver function abnormalities are present and indicate poor prognosis. This includes increased SGOT, SGPT, alkaline phosphatase, and bilirubin, decreased plasma protein, prolonged prothrombin time, decreased fibrinogen content, and reduced partial thromboplastin generation tests. Renal function includes urine osmolality, and those with diabetes insipidus should have urine specific gravity measured and undergo water restriction tests.
　　9. Pulmonary function tests and blood gas analysis
　　Severe pulmonary lesions can lead to varying degrees of pulmonary dysfunction, which often indicates poor prognosis. If significant hypoxemia occurs, it suggests lung dysfunction.
　　10. Erythrocyte sedimentation rate
　　In some cases, an accelerated erythrocyte sedimentation rate can be seen.

　　What foods are good for Langerhans histiocytosis patients to eat:

　　1. Eat more foods rich in high-quality protein.

　　2. Eat more foods rich in vitamins.

　　3. Eat more foods rich in trace elements.

　　Treatment plans for Langerhans cell histiocytosis:
　　One, surgical and radiotherapy treatment plans
　　After a comprehensive evaluation, only patients with solitary bone involvement and patients with multiple sites of involvement in certain cases can use local therapy. The skin surface of the patient's skin injury, which is easily accessible and non-dangerous, can be surgically scraped, but excessive orthopedic and plastic surgery should be avoided during the operation. High-voltage equipment is used for local radiotherapy, which is suitable for skeletal deformities, pathological fractures, vertebral compression, spinal cord injury, or patients with severe pain or systemic lymphadenopathy.
　　1. Chemotherapy
　　(1) Plan A: Low-risk children over 2 years old with a single systemic disease or bone damage in one or more locations.
　　Plan: Local treatment is given without systemic treatment. If the treatment is ineffective or the erythrocyte sedimentation rate continues to rise, it may indicate the presence of a serious systemic disease.
　　(2) Plan B: Low-risk children over 2 years old with multiple systemic diseases but without invasion of the hematological system, liver, lung, or spleen can be given chemotherapy, which often has sustained efficacy. However, most patients are under 2 years old, and the hematological, liver, lung, or spleen organ systems are involved, especially children with functional disorders. Despite chemotherapy, they still die.
　　2. Antibiotic Treatment
　　Suitable for: Severe patients
　　Plan: Hospitalization and administration of the maximum dose of antibiotics, maintaining airway patency, providing high-energy nutritional support, blood products, skin care, performing debridement, and even possibly removing severely damaged gingival tissue to limit oral lesions. Scalp seborrheic dermatitis can be treated with selenium-containing shampoos (twice a week), and if the shampoo is ineffective, a small amount of topical corticosteroid medication can be used locally to control small lesions in the short term. Most patients with diabetes insipidus or other symptoms of pituitary hypofunction require hormone replacement therapy. At the same time, physical therapy and necessary medical care should be provided. Strict hygiene measures should be implemented to effectively reduce otitis media, skin, and gingival damage.
　　3. Prognosis
　　In patients with systemic Langerhans cell histiocytosis, chronic disabilities that may be caused by the disease and treatment, such as cosmetic or functional orthopedic, skin damage and neurotoxicity, as well as mood swings, should be monitored.
　　For patients with extremely poor prognosis, HLA typing should be performed during diagnosis, and consideration should be given to bone marrow transplantation, cyclosporine, or experimental immunosuppression or other immunomodulatory therapy.