This disease is not a common pediatric disease, and when the clinical manifestations are atypical, it is easy to miss diagnosis.
Confusing severe anemia
Xiaoming is a 6-year-old boy who began to have symptoms of fatigue in the first half month of treatment, accompanied by pallor, and the children's families did not pay attention to it and did not take special treatment. Until the child's fatigue is obvious and he is unwilling to walk, he goes to the hospital for treatment, checks haemoglobin 51g/L, and is diagnosed with "severe anemia".
Xiaoming did not have any other discomfort except for fatigue and paleness. The medical history is asked in detail, and there is no special history, personal history, or family history. Xiaoming's parents are very confused, what causes Xiaoming to have severe anemia?
Where did the disappearing blood go?
In order to find the cause of severe anemia, Xiaoming was admitted to the hospital for further diagnosis and treatment.
After admission, blood analysis and bone marrow aspiration were completed, and the results were as follows:
Blood routine: positive cell hypochromic anemia, reticulocyte hyperplasia is active.
Erythrocyte morphology: mature RBCs vary in size, some of which can be seen in the enlargement of the central pale stained area, occasionally oval erythrocytes, erythrocyte debris, basophilic occipidophils, nucleated erythrocytes, and polychromatic red blood cells.
No suspicious naïve cells were seen in the form of white blood cells.
Bone marrow cytology: hypertrophic anemia myeloid image, reading red hyperplasia is obviously active with iron deficiency changes.
In addition, Xiaoming's liver and kidney function, coagulation function, glucose-6-phosphate dehydrogenation (G-6-PD) enzyme, immunological indicators, Coombs test, urine routine analysis, bilirubin, tuberculin test (PPD) and other results were not abnormal.
According to the test results, anemia caused by bone marrow hematopoietic system diseases, infectious diseases, and hemolytic diseases was quickly ruled out. All eyes are focused on: Bob is hemorrhagic anemia. Because anemia is severe, leukocyte suspension erythrocytes are infused to correct the anemia.
But where did the vanished blood go?
Is there no need for a chest x-ray without coughing?
Digestive tract loss is a possible factor of primary consideration, is it really the gastrointestinal tract that "devours" Bob's blood? It is imperative to improve routine stool examinations.
Follow up the medical history, the original Xiaoming stool for several days without solution, since the onset of the disease of his stool color, traits, etc. can not be known, after laxative to improve the stool routine examination, the results show: occult blood negative, no red blood cells. Combined with The absence of any digestive-related symptoms, the possibility of gastrointestinal bleeding is highly questionable, but gastrointestinal endoscopy is also considered for the need to be on the agenda.
If the blood is not excreted from the body, then it must be "hidden" by a cavity. Under the fog, it is recommended that Xiaoming improve the chest x-ray examination. Chest x-ray results are reported: diffuse exudative changes in both lungs.
Bob's chest imaging is very inconsistent with his clinical symptoms, and at this time, there is a high degree of clinical suspicion that Bob's blood loss is related to the lungs.
It turned out that the lungs were "bloodphagiarizing"
In order to further understand Xiaoming's lung conditions, it was decided to further improve the chest CT examination, and the results were returned: the bronchial vascular bundle of the double lung was thickened, the double lung was scattered in the distribution of ground glass, the strip density increased, the boundary was blurred, the right lung was dense, and the upper lobe of the double lung showed a white lung-like change; the lower lobe of the right lung saw a cord-like density increased shadow.
Chest imaging of diffuse alveolar hemorrhage in both lungs
At this time, it is highly suspected that Xiaoming's anemia is caused by pulmonary hemorrhage. Xiaoming immediately improved the electronic bronchoscopy and alveolar lavage diagnosis and treatment, electronic bronchoscopy opinion: pulmonary hemorrhage; postoperative alveolar lavage fluid cytology results returned: a large number of hemosiderin-containing cells can be seen. Eventually, Bob was clinically diagnosed with idiopathic pulmonary hemosiderosis (IPH).
Cut and dried
IPH is a relatively rare disease in the clinic, most of the patients are children, the main cause of diffuse pulmonary interstitial disease in Chinese children, when the clinical manifestations are not typical, it is easy to miss or misdiagnose.
▌【Epidemiology】
There are no studies on the exact incidence of IPH, which can occur at any age, but about 80% of cases are in children and usually occur before the age of 10 years.
▌【Susceptibility factors and risk factors】
Genetic and environmental factors: Genetic factors play a role in the occurrence of IPH, or environmental factors may cause some genetically susceptible individuals to develop IPH.
Environmental exposure: second-hand smoke, indoor mold exposure (especially smutella). Environmental exposures may be risk factors for IPH, but no studies have shown a definitive association with IPH.
Down syndrome: Down syndrome may be a predisposing factor for the development of IPH, with children with combined Down syndrome having a higher fatality rate.
▌【Pathogenesis】
The main clinical feature of IPH is repeated bleeding of alveoli, the specific cause of which is not fully understood, and it is mainly related to the following factors.
Abnormal autoimmune mechanism: At present, the mainstream view is that repeated bleeding of IPH alveoli is more likely to be related to immune mechanism, and autoimmune abnormalities may play a certain role in the pathogenesis of IPH, but its specific mechanism has not been clarified. Although immune complexes have been found in the plasma of some patients, no immune complex deposits have been found during immunohistochemical examinations of their lung tissues.
Protein antigen intake: anti-cow's protein antibodies are present in the blood of children with more IPH, suggesting that IPH may be associated with hypersensitivity responses to cow's milk proteins. In addition, more patients with IPH also have Lane-Hamilton syndrome, which relieves lung symptoms when people with IPH are given a gluten-free diet.
Iron metabolism: the ability of macrophages in the alveoli to degrade red blood cells and the reprocessing ability of hemoglobin iron is relatively weak, and excessive free iron accumulates in lung tissue, inducing the formation of highly toxic hydroxyl radicals, which eventually leads to cell necrosis and tissue remodeling with pulmonary fibrosis. Iron accumulation in the alveoli stimulates macrophages to produce ferritin, which binds to free iron is processed into a hemosiderin complex, which in turn stimulates the production of more ferritin, resulting in elevated levels of ferritin in the serum.
▌【Clinical Manifestations】
Typical symptoms of IPH in children include anaemia, haemoptysis, and diffuse pulmonary infiltrates, but unexplained mild to severe iron deficiency anaemia may be the only early manifestation of it, with most children lacking respiratory symptoms and some severe cases experiencing tachypnea or dyspnea. There may be no positive signs in the lungs, or a weakened breath sound, or bronchial breath sounds, and a few dry, wet, or stridors may be heard. Clinically, it can be divided into three stages: acute bleeding, chronic recurrent, quiescent or sequelae.
Pulmonary hemorrhage may be followed by a large number of reticulocytes, similar to hemolytic anemia; however, specific tests for haemolysis are negative. When the child swallows bloody sputum, fecal occult blood may be positive, but there is no basis for gastrointestinal bleeding.
▌【Laboratory test】
There is currently no specific serological indicator of IPH. Blood loss often leads to iron deficiency small cell hypochromic anemia, and the proportion of reticulocytes is increased. Typical bone marrow images are hypertrophic erythropoiesis and decreased intramedullary iron stores.
In acute pulmonary hemorrhage, ground glass and cloud flocculent shadows may be seen on chest x-ray, and ground glass-like shadows may be seen on chest CT, which are evident in the middle and lower lung fields, with bronchial inflator signs and thickening of lobular septs due to hemosiderin deposition in the interstitium of the lungs. Honeycomb cysts may be seen in patients with chronic course.
Sputum tests are less sensitive, some children are sputum-free, and there is a potential risk of exacerbating bleeding by inducing sputum discharge, and routine testing is not recommended at this time.
Most patients require perfect fiber bronchoscopy, and the alveolar lavage fluid cell classification count is dominated by hemosiderin-containing alveolar macrophages.
▌【Diagnosis】
IPH is an exclusive disease, and diffuse alveolar bleeding is a prerequisite for diagnosing IPH. In addition, it is often necessary to have the following typical clinical features: hemoptysis, hematemesis, or old blood in gastric juice; small cell hypochromic anemia; and diffuse flakes or ground glass shadows on chest x-ray or chest CT.
The positive rate and sensitivity of gastric juice and sputum are low, and a large number of pulmonary hemosiderin cells are found in bronchoalveolar lavage fluid to establish the diagnosis of alveolar hemorrhage. After alveolar hemorrhage is established, other related diseases such as autoimmune diseases, hematologic diseases, tuberculosis, bronchiectasis and other related diseases need to be excluded.
Clinically, if the following conditions are encountered, it is necessary to associate this disease: the child's recurrent unexplained iron deficiency anemia, with or without respiratory symptoms such as cough, hemoptysis, etc.; chest x-ray to see cloud flocculent or diffuse punctate shadow, pneumonia can not be fully explained when the disease should be highly suspected.
PS: Careful readers estimate that it has been found that Bob's anemia is positive cell hypochromic anemia, and when acute blood loss coexists with iron deficiency, the author believes that the diagnosis of IPH does not need to be stuck in small cell hypochromic anemia.
▌【Treatment】
(1) Glucocorticoids are the main treatment methods for the treatment of acute alveolar bleeding, which can significantly improve the symptoms of children, and are still the preferred drug for the treatment of IPH. Studies have shown that systemic glucocorticoids reduce the incidence of complications and mortality due to acute alveolar bleeding.
For acute onset of alveolar hemorrhage without respiratory failure, foreign experts recommend [1]: the initial dose of prednisone is 0.5-0.75 mg/(kg·d) (the maximum dose is 60 mg/d), continuous induction therapy until pulmonary hemorrhage is controlled, usually takes about 1-2 months, and then gradually reduce the dose of prednisone, reduce 5 mg every 2 weeks, and finally maintain treatment at 10-15 mg/day.
For children with respiratory failure caused by severe alveolar hemorrhage, foreign experts recommend [1]: high-dose glucocorticoids combined with another immunosuppressant therapy. Intravenous methylprednisolone (20 mg/kg·d) impact therapy can be used. Patients can be changed to oral glucocorticoids, prednisone 0.5-1 mg/kg/day, after stabilization, and tapered to a maintenance dose.
(2) Patients with poor effect of hormone therapy, hormone dependence or continuous decline in lung function may be considered for combined immunosuppressant therapy, but their side effects must be closely observed for long-term application, such as bone marrow suppression and co-infection, liver and kidney function damage and retina effects.
(3) Patients with acute alveolar hemorrhage caused by IPH are mostly initially treated with empiric antibiotics until the infection is clearly ruled out.
(4) In addition to the acute onset period, traditional Chinese medicines that activate blood stasis and improve immune function can be tried.
bibliography:
[1] Clinical Advisor to UpToDate
Hu Yamei, Jiang Zaifang, Shen Kunling, etc. Zhu Futang Practical Pediatrics (8th Edition)[M].Beijing:People's Medical Publishing House,2015:1316-1320.
[3] Gui Yonghao, Xue Xindong, Du Lizhong. Pediatrics (3rd Edition)[M].Beijing:People's Medical Publishing House,2020:235-238.]
Source: Pediatrics Channel of the Medical Professions
Author: Sycamore
Editor-in-charge: Zheng Huaju
Proofreader: Zang Hengjia
Plate making: Xue Jiao