Flushing patches of skin that resemble hives

Introduction Gastric carcinoids may cause urticaria-like skin flushing plaques due to possible secretion of histamine. Carcinoids, also known as carcinoid tumors, are a group of chromaffin cells that occur in the gastrointestinal tract and other organs. The clinical, histochemical and biochemical characteristics of new organisms may vary depending on where they occur. Such tumors can secrete biological active factors such as serotonin (serotonin), kinins, histamine, etc., causing vasomotor dysfunction, gastrointestinal symptoms, heart and lung lesions, etc., called carcinoid syndrome. ).

Cause

The cause of this disease has not yet been elucidated. Carcinoma is a tumor that produces small molecular peptides or peptide hormones, namely APUD cell tumors, which can act by increasing the cyclic adenine monophosphate by target cells and secrete serotonin with strong physiological activity (5). - serotonin), vasopressin and histamine, and some hormones that secrete other peptides, such as adrenocorticotropic hormone, catecholamines, growth hormone, parathyroid hormone, calcitonin, anti-urea, gonadotropin Hormones, insulin, glucagon, prostaglandins, gastrin, motilin and other substances. The main substances that produce carcinoid syndrome are serotonin and bradykinin, and histamine is also involved in some of the effects.

Serotonin has a direct contraction effect on peripheral blood vessels and pulmonary blood vessels, and also has a strong contraction effect on the bronchus. It has a stimulating effect on the vagus nerve and ganglion cells of the gastrointestinal tract, and the gastrointestinal tract peristalsis is enhanced and the secretion is increased. Bradykinin has a strong vasodilator effect, and some carcinoid tumors, especially gastric carcinoids, can produce a large amount of vasoactive substances such as bradykinin and histamine, which cause skin flushing. Increased serotonin in the circulation can also cause endocardial fibrosis.

Under normal circumstances, only about 2% of the tryptophan ingested in food is used for the synthesis of serotonin (5-HT), and 98% enters the metabolic pathway of niacin and protein synthesis. However, in patients with carcinoid syndrome, 60% of tryptophan can be taken up by tumor cells, resulting in increased 5-HT synthesis and reduced niacin synthesis. 60% of the tumor cells ingested tryptophan catalyzed by 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase, and then converted to 5-HT by dopa decarboxylase, partially stored in the secretion of tumor cells. Inside the granules, the rest goes directly into the blood. Most of the 5-HT free in the blood is degraded into 5-hydroxyindoleacetic acid (5-HIAA) from the urine by monoamine oxidase (MAO) in the liver, lung and brain. The level of 5-HT in the serum of carcinoid patients originating from the midgut system is increased, while the 5-HIAA excretion in the urine is increased. This is a typical carcinoid syndrome. This category accounts for more than 75% of cases of carcinoid syndrome. The carcinoid of the foregut system often lacks dopa decarboxylase and cannot convert 5-HTP to 5-HT. 5-HTP is directly released into the blood, so the 5-HTP level in the patient's serum is elevated, while 5-HT is not Raise. The 5-HTP and 5-HT excretion in the urine of patients increased, while the increase in 5-HIAA was not obvious, which is atypical carcinoid syndrome.

More than 90% of carcinoid tumors occur in the gastrointestinal tract, mainly in the appendix, terminal ileum and rectum, and a few occur in the colon, stomach, duodenum, Mckeel diverticulum, and biliary tract, pancreatic duct, gonad, lung and bronchus. Different races may have differences in the prevalence of carcinoids. In Japan, the incidence of carcinoids in the stomach, duodenum and colon is more than in Europe and the United States, and there are fewer cases of small intestine carcinoids. It is speculated that this may be related to the distribution of chromogranin cells in the organs of Japanese and Europeans. .

Godwin has 2837 cases of carcinoid, and 85.5% is distributed in the gastrointestinal tract. The pathogenesis outside the gastrointestinal tract includes bronchus, lung, head, liver, pancreas, cervix, parotid gland, urethra, and even testicles or ovaries. The distribution of 3,000 cases of gastrointestinal carcinoid in Orloff's comprehensive literature was 47.0% of appendix, 27.5% of ileum, 17.0% of rectum, 2.5% of stomach, 2.0% of colon, 1.5% of jejunum, 1.3% of duodenum, 1.0% of Meckel's diverticulum. , gallbladder 0.2%. Most of them are seen in the appendix, and the appendix, ileum and rectum account for more than 90% of all gastrointestinal carcinoid tumors.

Typical gastrointestinal carcinoid, tumor is often a small yellow or gray submucosal nodular mass, single or multiple, mucosal surface more complete, its shape is different, nodular, polypoid or ring . A small number of tumors can form ulcers on the surface, which looks like adenocarcinoma and often invades the muscular and serosal layers. Some patients may have multi-source carcinoid tumors. The ileal carcinoid is often multiple, the tumor is small, the diameter is 3.5cm or less, and it is about 1.5cm. A group of 78 cases in China, the rectal carcinoid sites are in the rectum below 10cm, the tumor size is about 0.2 ~ 2.5cm, more than 1.0cm, more like a polyp, but no pedicle. The cut surface is gray or grayish yellow, hard and has a clear boundary. Carcinoid cells are square, columnar, polygonal or circular under the microscope. The nucleus is uniform, with few mitotic phases, and eosinophilic granules in the cytoplasm. According to the observation of electron microscopy, the cytoplasmic granule morphology and histochemistry of various parts of the gastrointestinal tract are different. Small intestinal cancer cells contain large and polymorphic particles, which are positive for silver staining. The particles of gastric cancer cells are round, and when silver staining reaction, it is necessary to add an exogenous reducing agent to be positive, so it is argyrophilic. The rectal cancer cells are large, round, uniform, and the staining reactions of both silver and silver are negative, so they are non-reactive.

The histological structure of carcinoid tumors is characterized by a variety of arrangement of tumor cells, and Soga et al. are classified into 5 types according to the arrangement.

Type A: The cancer-like cells are aggregated into nodular solid nests. The cells are roughly circular, irregularly arranged, and infiltrated around the cord. Carcinoid, which is more common in the midgut system of origin, is the most typical type.

Type B: The tumor cells are in a small structure, arranged in a layer, such as a shell, and the nucleus is arranged in a peripheral part, such as a grid or a strip, which is more common in carcinoid originating from the foregut system.

Type C: The square cells are arranged in a glandular shape, but there is no cavity, or a rose pattern.

Type D: The shape of the tumor cells is irregular and irregularly arranged into a large myeloid structure. Types C and D are more common in carcinoid originating from the hindgut system.

Type E: Various types of the above four types.

The atypical hyperplasia and mitotic phase of carcinoid are not obvious, and it is generally difficult to judge the degree of malignancy from the cell morphology. Can refer to:

The size of type 1 cancer, combined with 843 surgical data, the maximum diameter of 1cm or less, 90% to 100% showed a benign course. Between 1 and 2 cm, 30% to 50% have metastasis. For those with a diameter > 2 cm, 80% to 100% have a transfer.

2 degree of infiltration, according to statistics have invaded the carcinoid muscle of the gastrointestinal tract, 90% of metastases.

3 The growth site and appendix carcinoids are almost all benign. Even if they have infiltrated into the serosa, metastasis is still rare. The metastasis rate of small intestine carcinoid is 30%, and the colon is 38%. The duodenum and stomach are malignant. Carcinoid is rarer than the small intestine.

Carcinoid metastasis pathways can directly infiltrate and grow, penetrate the serosa into the surrounding tissue, and lymphatic metastasis or hematogenous metastasis can occur. There is no report of local lymph node metastasis and direct hematogenous metastasis. Hematogenous metastasis is most common in the liver, and can also be transferred to bone, lung and brain. Other rare metastatic sites are reported: ovary, epididymis, skin, bone marrow, retroperitoneum, eyelids, adrenal glands, spleen, pancreas, kidney, thyroid gland. , bladder, prostate, cervix. There are also reports of metastasis into the breast, the clinical signs of which are very similar to the primary breast cancer.

Carcinoid cells originate from the enterochromaffin cells (also known as kulchitsky cells) in the APUD cell system. These cells are derived from embryonic neural crests and are widely distributed in the digestive tract. They have chromophore-pro-silver particles and can produce a variety of peptide amines. Hormone. In recent years, with the advancement of immunohistochemistry techniques, various hormones have been confirmed on tissue sections. Carcinoid syndrome is due to the formation of metabolites of serotonin and various vasoactive substances through the liver. The blood enters the lungs and heart, causing the pulmonary arteries and subendocardial fibrous tissue to proliferate. About half of the cases are accompanied by right heart valve lesions, including pulmonary valves. And tricuspid valve thickening, shortening, stiffness, adhesion. Endocardial and chordae tend to cause fiber thickening, causing pulmonary stenosis and tricuspid atresia. The left subendocardial elastic fiber has focal changes such as focal or diffuse fibrosis, especially in the bronchial carcinogenesis. The left heart, pulmonary artery, tricuspid valve, and aortic valve fibrosis are more common.

an examination

Related inspection

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1. 24-hour urine 5-hydroxyindole acetic acid greater than 30mg. In the cancerous cells of the stomach, the dehydroxylase is absent and the concentration of serotonin in the blood is not high, and the concentration of serotonin is increased. The 5-hydroxyindole acetic acid excretion in the 24-hour urine fluctuated greatly and was affected by food. If you eat potatoes, bananas, and pineapples, the amount of 5-hydroxyindole acetic acid in the urine will increase. Therefore, it is necessary to repeat the urine test several times to make the diagnosis more reliable.

2. In patients who are highly suspected of carcinoid, and the amount of 5-hydroxyindoleacetic acid excreted in the urine does not increase, it can be used as an excitation test. The test method is to first intravenously inject 5% glucose 500ml, blood pressure and pulse once every half minute, but after blood pressure and pulse stabilization, intravenous injection of 1g of adrenaline, if there is no reaction, add 1g every 15 minutes until A reaction appeared. However, the maximum dose should not exceed 15 g each time, and the test was not performed when 15 g remained unreacted. This test should be particularly careful as the challenge test can cause severe hypotension and bronchospasm.

3. The carcinoid of the gastrointestinal tract can be examined by X-ray. B-mode ultrasonography and CT have diagnostic value for patients with liver metastases. Bronchocarcinoma can be found in the sputum for bronchoscopy, chest tomography and other examinations. When carcinoid occurs in the pelvic cavity, the tumor can be found by gynecological examination, B-mode ultrasound, CT and other methods.

Differential diagnosis

It should be differentiated from the following symptoms:

1. Burning pain behind the sternum

Chest pain is a very common symptom in the clinic. Pain is often accompanied by the back of the sternum. The pain often occurs during or after swallowing, often accompanied by difficulty swallowing. Post-sternal pain is often seen in the clinic. It refers to the pain between the neck and the lower edge of the thorax (the middle or the lateral side of the chest). The nature of the pain can be various. It is one of the common symptoms, usually caused by chest diseases (including chest wall disease). Caused by).

2. Post-sternal pain

Post-sternal pain is often seen in the clinic. It refers to the pain between the neck and the lower edge of the thorax (the middle or the lateral side of the chest). The nature of the pain can be various. It is one of the common symptoms, usually caused by chest diseases (including chest wall disease). Caused by). After some people have post-sternal pain, they often suspect coronary heart disease and blindly treat them with coronary heart disease. In fact, there are many causes of post-sternal pain. Cardiovascular, pulmonary, mediastinal, esophageal, etc. may be sick. Once the sternal pain occurs, you should go to the hospital as soon as possible, and confirm the diagnosis with clinical symptoms.

3. The lower end of the sternum is tender

The tenderness of the lower sternum is one of the important signs of leukemia. In addition, it can also be seen in malignant lymphoma and myeloproliferative diseases, but the latter two are relatively rare.

Leukemia, also known as blood cancer, is one of the most important signs when people suffer from leukemia, especially acute leukemia. According to clinical observations, the most obvious site of sternal tenderness in most patients is in the lower part of the sternum, which is equivalent to the sternum of the fourth and fifth intercostal spaces. Medical scientists believe that the cause of bone pain is mainly caused by the proliferation of leukemia cells in the bone marrow, the increase of the volume pressure of the bone marrow cavity, and the infiltration of the periosteum by the leukemia cells to stimulate the sensory nerve. From an anatomical point of view, the sternum plate is very thin, the skin covering this part is also very thin, and the periosteal sensory nerve is also rich, so it is sensitive to the touch pressure, and tends to produce obvious tenderness.

4. The intercostal space may have tenderness

Pain in the intercostal space is a clinical manifestation of intercostal neuralgia. Physical examination of patients with intercostal neuralgia found that there was significant tenderness in the paraspinal and intercostal space of the thoracic spine; typical patients with intercostal intercostal neuralgia had a positive neck test; the distribution of affected nerves often showed neurological impairment such as hyperesthesia or hypoesthesia. .

5. sternal tenderness

In most patients, the most obvious part of sternal tenderness is in the lower part of the sternum, which is equivalent to the sternum of the fourth and fifth intercostal spaces.

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