The child with severe anemia turned out to be "phagocytosing blood"

*For medical professionals to read and reference this disease is not a common pediatric disease.
When the clinical manifestations are not typical, it is easy to miss the diagnosis
.

The puzzling severe anemia Xiaoming is a 6-year-old boy.
He began to have symptoms of fatigue and paleness in the first half of the month.
The family of the child did not pay attention to it, and no special treatment was given
.

Until the child was obviously fatigued and unwilling to walk, Fang went to the hospital for treatment, and the hemoglobin was checked at 51g/L, and the diagnosis was "severe anemia"
.

Apart from fatigue and pale face, Xiao Ming did not have any other discomfort
.

Detailed medical history, past history, personal history, and family history were all unremarkable
.

Xiao Ming's parents were very puzzled, what caused Xiao Ming to have severe anemia? Where did the disappeared blood go? To find the cause of severe anemia, Xiao Ming was admitted to the hospital for further diagnosis and treatment
.

After admission, blood analysis and bone marrow aspiration were completed.
The results are as follows: Blood routine: normocytic hypochromic anemia, active reticulocyte proliferation
.

Morphology of erythrocytes: Mature erythrocytes vary in size, some of which can be seen with enlarged central light stained area, and occasionally oval erythrocytes, erythrocyte fragments, basophilic stippled erythrocytes, nucleated erythrocytes, and pleochromatic erythrocytes are easily seen
.

 No suspicious immature cells were found in the morphology of white blood cells
.

Bone marrow cytology: Bone marrow image of proliferative anemia, with markedly active erythroid hyperplasia with iron-deficiency-like changes
.

In addition, Xiaoming's liver and kidney function, coagulation function, glucose-6-phosphate dehydrogenase (G-6-PD) enzyme, immunological indicators, Coombs test, routine urine analysis, bilirubin, tuberculin test (PPD) No abnormality was found in the results
.

According to the test results, anemia caused by bone marrow hematopoietic system diseases, infectious diseases, hemolytic diseases, etc.
was quickly ruled out
.

All eyes are focused on: Xiao Ming is suffering from hemorrhagic anemia
.

Due to severe anemia, leukocyte suspension of red blood cells was transfused to correct the anemia
.

However, where did the lost blood go? Is there no need to take a chest X-ray without a cough? Digestive tract loss was considered as the first possible factor.
Could it be that the gastrointestinal tract “devoured” Xiao Ming’s blood? It is imminent to improve the routine examination of stool
.

When asked about the medical history, it turned out that Xiaoming had unresolved stools for several days.
Since the onset of the disease, he had no way of knowing the color and characteristics of his stools.
After a bowel movement, he completed a routine stool examination.
The results showed that occult blood was negative and no red blood cells were seen
.

Combined with the fact that Xiaoming has no symptoms related to the digestive system, the possibility of gastrointestinal bleeding is highly suspected.
However, gastrointestinal endoscopy is also considered whether it needs to be put on the agenda
.

If the blood is not excreted, then it must be "hidden" by some cavity
.

Under the heavy fog, Xiaoming is advised to improve the chest X-ray examination
.

Chest X-ray results reported: diffuse exudative changes in both lungs
.

Xiaoming's chest imaging was very inconsistent with his clinical symptoms.
At this time, it was highly suspected that Xiaoming's blood loss was related to the lungs
.

It turned out that the lungs were "phagocytosing blood".
In order to further understand the condition of Xiaoming's lungs, it was decided to further improve the chest CT examination.
The results reported that the bronchial vascular bundles in both lungs were thickened, and there were scattered ground-glass and strip-like increased density shadows in both lungs.
, the boundary is blurred, the right lung is dense, and the upper lobes of both lungs show white lung-like changes
;
The chest imaging manifestations of diffuse alveolar hemorrhage in both lungs cleared the fog and gradually became brighter.
At this time, it was clinically highly suspected that Xiao Ming's anemia was caused by pulmonary hemorrhage
.

Xiao Ming immediately perfected the electronic bronchoscopy and bronchoalveolar lavage diagnosis and treatment.
The electronic bronchoscopy opinion: pulmonary hemorrhage; the results of the postoperative alveolar lavage fluid cytology test report: a large number of hemosiderin cells can be seen
.

Finally, Xiao Ming was clinically diagnosed as: idiopathic pulmonary hemosiderosis (IPH)
.

It is often said that IPH is a relatively rare disease in clinical practice.
Most of the patients are children.
It is the main cause of diffuse interstitial pulmonary disease in Chinese children.
When the clinical manifestations are not typical, it is easy to be missed or misdiagnosed
.

▌ 【Epidemiology】At present, there is no research on the exact incidence of IPH.
IPH can occur in any age group, but about 80% of the cases are children, and usually appear before the age of 10
.

▌ 【Susceptibility factors and risk factors】 Genetic factors and environmental factors: Genetic factors play a certain role in the occurrence of IPH, or environmental factors may cause some individuals with genetic susceptibility to develop IPH
.

Environmental exposures: Secondhand smoke, indoor mold exposure (especially Staphylococcus niger)
.

Environmental exposure may be a risk factor for IPH, but no relevant studies have shown its exact association with IPH
.

Down's syndrome: Down's syndrome may be a predisposing factor for the development of IPH, and children with IPH with Down's syndrome have a higher mortality rate
.

▌ [Pathogenesis] The main clinical feature of IPH is repeated alveolar hemorrhage.
The specific etiology has not been fully clarified, and it is mainly related to the following factors
.

Abnormal autoimmune mechanism: At present, the mainstream view is that repeated alveolar hemorrhage in IPH is likely to be related to the immune mechanism.
Autoimmune abnormality may play a certain role in the pathogenesis of IPH, but its specific mechanism is not yet clear
.

Although immune complexes were found in the plasma of some patients, immunohistochemical examination of their lung tissue did not reveal immune complex deposits
.

Ingestion of protein antigens: Anti-milk protein antibodies are present in the blood of more children with IPH, suggesting that IPH may be associated with milk protein hypersensitivity
.

In addition, many IPH patients coexist with Lane-Hamilton syndrome, and when IPH patients adopt a gluten-free diet, their pulmonary symptoms can be relieved
.

Iron metabolism: The ability of macrophages in the alveoli to degrade red blood cells and the ability to reprocess hemoglobin iron is relatively weak.
Excessive free iron accumulates in lung tissue and induces the formation of highly toxic hydroxyl radicals, which eventually lead to cell necrosis and necrosis.
Tissue remodeling with pulmonary fibrosis
.

The accumulation of iron in the alveoli stimulates the production of ferritin by macrophages, and the ferritin bound to free iron is processed into a hemosiderin complex, which in turn stimulates the production of more ferritin, resulting in increased serum ferritin levels
.

▌ 【Clinical manifestations】 Typical symptoms of IPH in children include anemia, hemoptysis, and diffuse pulmonary infiltrates, but in children, unexplained mild to severe iron deficiency anemia may be the only early manifestation, and most children lack respiratory symptoms , shortness of breath or difficulty breathing may occur in some severe cases
.

There may be no positive signs in the lungs, and breath sounds may be weakened, or bronchial breath sounds may be heard, and dry or wet rales or stridors may be heard in a few cases
.

Clinically, it can be divided into three phases: acute bleeding phase, chronic recurrent attack phase, quiescent phase or sequelae phase
.

A large number of reticulocytes may appear after a pulmonary hemorrhage, similar to hemolytic anemia; however, specific tests for hemolysis are negative
.

When the child swallows bloody sputum, fecal occult blood may be positive, but there is no evidence of gastrointestinal bleeding
.

▌ 【Laboratory examination】There is no specific serological index for IPH at present
.

Blood loss often results in iron-deficiency microcytic hypochromic anemia with an increased proportion of reticulocytes
.

The typical bone marrow pattern is hyperplastic erythropoiesis and decreased intramedullary iron stores
.

In acute pulmonary hemorrhage, ground-glass and cloud-like shadows can be seen on chest X-ray; ground-glass shadows can be seen on chest CT, which are obvious in the middle and lower lung fields, and may be accompanied by air bronchus signs and hemosiderin deposition in the pulmonary interstitium.
The resulting thickening of the interlobular septa
.

Honeycomb cysts can be seen in patients with a chronic course
.

The sensitivity of sputum examination is low, some children have no sputum, and induced sputum excretion has the potential risk of exacerbating bleeding, so this examination is not currently recommended routinely
.

Most patients need to complete fiberoptic bronchoscopy, and the differential count of alveolar lavage fluid cells is mainly hemosiderin-containing alveolar macrophages
.

▌ [Diagnosis] IPH is an exclusive disease, and diffuse alveolar hemorrhage is a prerequisite for the diagnosis of IPH
.

In addition, the following typical clinical features are often required: (1) hemoptysis, hematemesis or old blood in gastric juice; (2) microcytic hypochromic anemia; (3) diffuse flocculent or ground-glass opacity on chest X-ray or chest CT
.

The detection rate and sensitivity of gastric juice and sputum are low.
At present, a large number of lung hemosiderin cells are found in bronchoalveolar lavage fluid to establish the diagnosis of alveolar hemorrhage
.

After establishing alveolar hemorrhage, other related diseases such as autoimmune diseases, hematological diseases, tuberculosis, bronchiectasis, etc.
still need to be excluded
.

Clinically, if you encounter the following conditions, you need to think of this disease: ①Recurrent unexplained iron-deficiency anemia in the child, with or without respiratory symptoms such as cough, hemoptysis, etc.
; ②The chest X-ray shows cloudy shadows or diffusion Punctate shadows should be highly suspected when pneumonia cannot be fully explained
.

PS: Careful readers may have discovered that Xiao Ming’s anemia is normocytic hypochromic anemia.
When acute blood loss and iron deficiency coexist, the author believes that the diagnosis of IPH does not need to be restricted to microcytic hypochromic anemia
.

▌ [Treatment] (1) Glucocorticoids are the main treatment for acute alveolar hemorrhage, which can significantly improve the symptoms of children, and are still the first choice for the treatment of IPH
.

Studies have shown that systemic corticosteroids can reduce the morbidity and mortality of acute alveolar hemorrhage
.

For acute exacerbation of alveolar hemorrhage without respiratory failure, foreign experts recommend [1]: the initial dose of prednisone is 0.
5-0.
75 mg/(kg·d) (maximum dose is 60 mg/d), and induction therapy is continued until pulmonary hemorrhage.
It usually takes about 1-2 months to be controlled, and then the dose of prednisone is gradually reduced by 5 mg every 2 weeks, and finally maintained at 10-15 mg/d
.

For children with severe alveolar hemorrhage leading to respiratory failure, foreign experts recommend [1]: high-dose glucocorticoid combined with another immunosuppressive therapy
.

Intravenous methylprednisolone (20mg/kg·d) pulse therapy can be used
.

After the patient's condition is stable, oral corticosteroids can be changed, prednisone 0.
5-1mg/(kg·d), and the dose can be gradually reduced to the maintenance dose
.

(2) Combined use of immunosuppressive therapy can be considered for those with poor hormone therapy, hormone dependence or continuous decline in lung function, but the side effects such as bone marrow suppression and co-infection, liver and kidney function damage and adverse effects must be closely observed during long-term application.
retinal effects,
etc.

(3) Most patients with acute alveolar hemorrhage caused by IPH receive empiric antibiotic therapy initially until infection is clearly excluded
.

(4) In addition to the acute attack period, traditional Chinese medicines for promoting blood circulation and removing blood stasis and improving immune function can be tried
.

References: [1] UpToDate Clinical Consultant [2] Hu Yamei, Jiang Zaifang, Shen Kunling, etc.
Zhu Futang Practical Pediatrics (8th Edition) [M].
Beijing: People's Health Publishing House, 2015: 1316-1320.
[3] Gui Yonghao, Xue Xindong, Du Lizhong.
Pediatrics (3rd Edition) [M].
Beijing: People's Health Publishing House, 2020: 235-238.