Tuesday, April 2, 2013

Idiopathic Pulmonary Hemosiderosis (IPH)

Idiopathic pulmonary hemosiderosis - (syn.: idiopathic pulmonary progressive induration, purpura immune pulmonary disease, Delen- Gellerstedt disease, etc.) - a disease in which the main symptom is recurrent hemorrhage in lung tissue and the subsequent development of fibrosis and hemosiderin deposition.
              At first the disease was described by Virhow in 1864 under the name "brown lung induration". The basis of the disease is bleeding in lung alveoli, which has usually a diffuse character. Free iron as a result of the collapse of erythrocyte is absorbed by macrophages, which may be found in the sputum of patients (siderophages).
             It is considered that the anomaly of arteriolar-venular anastomoses and pathological structure of the connective tissue of the lungs is hereditary.
                            Pathogenesis.

                  As a result of an inherited defect forced hemocirculation of lung tissue occurs with a significant exit in it red blood cells (per diapedesis) and the progressive sensitization of the organism to them. Iron from haemolysed red cells becomes stable connected with pathologic sulfated mucopolysaccharides and dose not return to the blood, dose not include in the metabolism and synthesis of hemoglobin. Therefore, anemia accompanying IPH is related with iron deficiency. Iron deposition, hemorrhage, inflammation leads to pneumosclerosis, pulmonary hypertension and chronic pulmonary failure. Allergic lesions of the joints, skin, heart, kidneys may develop.

            Morphologically (based on open lung biopsy) there are revealed red blood cells in the cavity of the alveoli, hemosiderin-containing macrophages (siderophages), diffuse interstitial fibrosis, sclerosis of small vessels of the lungs.

                                       Clinic
         The clinical picture of IPH is composed of the respiratory and hematological symptoms. At exacerbation cough appears, in older children accompanied by hemoptysis - the appearance of blood in the sputum. Small children do not expectorate sputum, they swallow it. With abundant pulmonary hemorrhage, they may have vomiting with ingested blood.
           Severity of the clinical picture in the lungs depends on the amount of haemorrhage into the alveoli. Together with cough and fever dyspnea and cyanosis occur. Wheezing in the lungs is listened. Radiographic changes appear in the form of large focus shadows in both lungs. The disease is often diagnosed as pneumonia, which leads to the appointment of inadequate treatment and the worsening of patient's condition.




Laboratory data
1. Complete blood count: signs of anemia, aniso- and poicylocytosis, reticulocytosis, during exacerbation - leukocytosis, leukocyte shift to the left, increasing ESR.
2. Biochemical blood analysis: an increase of the level of indirect bilirubin and decrease of serum iron.
3. General sputum analysis: siderophages are found.
4. Investigation of lung biopsy: at a period of remission hemorrhage is weakly expressed, mainly in the cortical areas of the lung, pleura in these areas is thickened, in the alveoli, intralobulary, around vessels, peribronhially and in connective tissue there are many hemosiderophages, reactive fibrosis. At exacerbation alveolars are filled with fresh red cells, alveolar macrophages containing hemosiderin.
5. Peculiarity of radiological changes in the IPH is the rapid regression of foci shadows.
                                                                                                                
                
Review chest X-ray of patients with idiopathic pulmonary hemosiderosis: small meshy diffuse lung pattern deformation caused by compaction of interstitial lung tissue, multiple foci of diffused small monomorphic shadows.


                  
                  Idiopathic pulmonary hemosiderosis.

                    Hemosiderophages in hemoptysis of a patient with IPH.
                    Materials obtained through bronchoalveolar lavage.

                  In some cases, the X-ray of the chest indicates diffuse small shadows in both lungs, which are the reason of mistake diagnosis of miliary tuberculosis of the lungs.
             Changes in the lungs that maybe detected with X-rays can vary widely: from small to massive infiltration shadows accompanied by atelectasis, emphysema, and reaction from the lymph nodes of the roots of the lungs.
            Immediately after the exacerbation, which lasts 3-5 days, there is marked anemia - microcytic and hypochromic. The level of serum iron falls. In the biochemical analysis of blood there may be elevated levels of bilirubin. Since the regenerative bone marrow function does not suffer, in the peripheral blood reticulocytes appear. In young children in the fecal analysis blood test may be positive (swallowed by coughing phlegm with blood). Often there is hepatosplenomegaly.
           The course of idiopathic pulmonary hemosiderosis is undulating. Periods of crises alternate with periods of remission varying duration. Acute and subacute forms   are relatively distinguishing. At acute form of disease there are a significant worsening, weakness, dyspnea. Older children complain of chest pain, cough with small amount of sputum, relaxed breathing and wet wheezing are listened in lungs. Perhaps may be raising the temperature to febrile scores. There is rapidly increasing cell anemia.
          In the subacute form of IPH pallor of the skin, the symptoms of intoxication gradually develop. Exacerbations of the disease are more severe.

                                        Diagnose.

                 Diagnostic significance has the discovery in sputum or endotracheal aspirate, and in some cases, in gastric lavage sidergophages. Puncture biopsy of the lung is accompanied with serious complications.
          Investigation of respiratory function detects or normal rates of ventilation, if the duration of the disease is little, or restrictive severe violations, reduced lung diffusion capacity, if the disease is prolonged with severe exacerbations.
           If repeated respiratory diseases occur every time with anemia, an unusual radiological pattern in the lungs and ineffectiveness of antiinflammatory therapy are present such a patient should be examined for the presence of IPH.
                    
                                                 Spirometer SPIROVIT SP-1

 Lung Volumes and capacities
 





                                            Lung Volumes and Capacities

          Differential diagnosis should be conducted with tuberculosis and fungal infections of the lungs.
                                            Treatment.
           Treatment of patients with IPH involves the appointment of corticosteroid drugs and symptomatic treatment. During periods of exacerbation oxygen therapy, glucocorticoids, antibiotics, disintoxication, vitamin and treatment of anemia are indicated. If you find high levels of precipients to cow's milk this product is excluded from the diet. Prednisolone is appointed by the dose of 1 -1.5 mg / kg to achieve clinical and laboratory remission. There are reports that after splenectomy resistant prolonged remission may occur.
          Prognosis is serious. Half of the children die in the first five years after onset. Subsequent exacerbations are more difficulty to treat, the average life span of a sick is 2-3 years, rarely – more. Immediate causes of death often are acute massive pulmonary hemorrhage or progressive pulmonary heart failure. Perhaps there is a combination of both reasons. And to predict the probability of acute pulmonary hemorrhage is not possible.
                                      
Primary pulmonary hypertension (PPH)
          Primary pulmonary hypertension is a rise in pressure in the pulmonary artery and right ventricular hypertrophy which are not associated with congenital or acquired pathology of the heart and lungs.
          In 1901 Auerza described patient with marked cyanosis, right ventricular hypertrophy and chronic bronchitis. Family form of primary PH was first described in the report Clarke et al. in 1927. The authors have noted a similar clinic and morphological changes in autopsy material from two sisters, 5 - and 8-years of age and confirmed the presence of primary PH. There are more than 20 titles of the disease. Among them: Idiopathic right ventricular hypertrophy, primary pulmonary artery sclerosis, isolated pulmonary hypertension, a disease Aersa etc.
          Currently there is established the gene BMPR2, localized in the locus of the second chromosome 2q33, which regulates growth and proliferation of endothelial cells. This gene is responsible for the development of a family primary pulmonary hypertension. The disease is inherited in an autosomal-dominant type with incomplete penetrance, which manifests itself in a population with a frequency of 1-2 cases per 1 million people. Family nature of PPH is approximately in 6% of patients, the remaining cases are sporadic. Family form of PPH is not clinically different from sporadic, but after the first symptoms is usually diagnosed earlier. In sporadic cases diagnose of PPH is usually established in the advanced stages of disease.   

Pathomorphology.
            Pathomorphologic changes in primary pulmonary hypertension are clear. There is right ventricular hypertrophy, expansion of large branches of pulmonary artery with layer fibroelastosis of the intima, the presence of atriovenose anastomoses, thrombosis and fibrinous necrotizing arteritis of small branches of the pulmonary artery.

                                         
Clinic.
                       In the initial stages the objective symptoms are mild, cardialgia in children is atypical. There is a poor tolerance to physical activity through the development of shortness of breath, sometimes accompanied by attacks of breathlessness. The appearance of syncope point at severe phase of the disease, they often appear at an exercise, RV heart failure increases.
           There are three stages of development of pulmonary hypertension in children. At I stage increased pulmonary pressure is the only hemodynamic abnormality, patients do not have distinct symptoms, there may be shortness of breath during physical activity, which often does not wary the doctors and patients for the presence of the disease and is usually associated with poor training of the body.
           When a decrease in cardiac output (II stage) occurs, there are detailed clinical symptoms in the form of hypoxemia, dyspnea and syncope. Pressure in the pulmonary artery remains stable at a high level.
           With the advent of right heart failure III stage of disease occurs: in this case, despite the consistently high values of pulmonary pressure, cardiac output falls sharply, there are venous congestion and peripheral edema.
            There is variability in the duration of different stages of the disease, an average from 6 months to 6 years or more from the stage of minimal hemodynamic changes to the lethal disease. The reason of death is the developing prolonged functional overload the right heart, destructive and sclerotic changes in lung tissue and myocardium.
      PPH affects mainly young patients, and the disease is usually fatal, although in the literature there are described isolated cases of spontaneous remission.
           It is assumed that the therapeutic activities of the patients of childhood will be more effective, as the remodeling of the pulmonary vessels in children can be prevented and even reversed. The development of new directions in treatment can increase survival and improve quality of life of patients.  

                     
                               The child 13 yrs old with PPH.
                       Weight - 33,5 kg (norm - 44,1 ± 8,68 kg), height - 144 cm (average 155,7 ± 6,57 cm). There are mixed apnea, tachypnea to 38 per minute. Skin is pale, cyanosis of the lips, acrocyanosis.

 
Deformation of the terminal phalanges as "drumsticks" and "watch glasses", enlargement of the abdomen (ascites) in patient with PPH.

ECG of patient with PPH. Sinus tachycardia (cardiac rate 140 per minute).
Rightgram. Atrioventricular blockade Іst. (PQ–0,20"). Expressed hypertrophy of right
ventricular. Dilatation of the both auricles.

           
                             A                                                                         B
                                                                                                 
                                   
           C                                                                 D

A. Hypertrophy of media and adventitia of small pulmonary arteries.
B. Concentric intimal fibrosis of pulmonary arteries with a diameter of 180 microns, there is also hypertrophy of the middle and the outer shell of the vessel.
C. Obliteration of the lumen of the pulmonary artery.
D. Plexiform defect. Note the absence of elastic membrane in the wall plexiform structure.
Increasing x 100. Coloured by Verhoeff's - Van Gieson.

 
Muscularization of arterioles: a - hematoxylin and eosin. ґ400 b - immunohistochemical coloration on actin of smooth muscle (SMA). ґ200.

Necrotizing arteritis. Coloured                   Rechanaled thrombus of branch of
by hematoxylin and                                     pulmonary artery. Coloured                                          
eosin  ґ100..                                                  by hematoxylin and eosin  ґ40.                                                                    
  


EchoCG. A-wave is escaped.  
               Treatment is symptomatic: antihypertensives, anticoagulants, antiplatelet agents. Effects are minor.
               Prognosis is poor. Life expectancy is from several months to 10 years from onset of the first symptoms.

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