Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis

Control of refractory bleeding in idiopathic pulmonary hemosiderosis (IPH) is challenging. Based on the effect of liposteroid (dexamethasone palmitate) for acute bleeding in two reported cases, the long-term utility was assessed in all nine IPH children (including the first two cases) treated in a tertiary center for 20 years. The median at disease onset was 2.3 years (range, 1.2 to 8.6). All had life-threatening and/or repetitive bleeding on prednisolone (PSL) therapy. Liposteroid was intravenously infused at 0.8 mg/kg/day for three consecutive days at the time of acute bleeding. Single infusion was followed by a longer interval from weekly to monthly accompanied by low-dose PSL (less than 0.3 mg/kg/day). Monthly infusion as maintenance therapy was continued for prophylaxis of bleeding. Treatment outcomes were retrospectively analyzed. During the observation period of a median of 11.0 years (range 2.4–16.9 years), no one died. Five patients were weaned and the other one was being weaned from liposteroid for the cure or long remission (median, 5.5 years). Three others were on liposteroid therapy because of active disease. Neither patient had respiratory symptoms, although three showed subnormal %vital capacity. Serum levels of KL-6 and ferritin were normal in all and all but one patient(s), respectively. Four patients (three on liposteroid therapy) showed low bone mineral density. There were no obese patients. Height SD score did not significantly decrease except for one patient. Conclusion: The liposteroid therapy might improve the survival of IPH patients with reducing the adverse effects of steroids, although prospective control studies are needed.     

Idiopathic pulmonary haemosiderosis: an Oriental experience

OBJECTIVES: Idiopathic pulmonary haemosiderosis (IPH) is a rare but potentially lethal disorder. A retrospective analysis of documented cases of IPH in our hospital was conducted in order to study the clinical spectrum and radiographic features, and to explore therapeutic strategies. METHODS: A retrospective chart review was carried out, collecting medical records of patients with pulmonary haemo-siderosis at Chang Gung Children's Hospital (CGCH), a tertiary children's hospital in northern Taiwan. Secondary causes of pulmonary haemosiderosis were excluded. RESULTS: Five patients were diagnosed as having IPH over a 25-year period. The classical triad of IPH was found at initial presentation in only 2/5 patients. One patient had well-established pulmonary fibrosis, but no pulmonary symptoms. The clinical course of IPH was exceedingly variable, with a mean delay of 9 months before diagnosis was made. Bronchoalveolar lavage (BAL) confirmed IPH in 3/5 patients. Immunological abnormalities were noted in two patients, without progression to immune disorders during follow up. While using corticosteroids alone, 4/5 patients continued to have recurrent bleeding episodes. All five patients required immunosuppressive therapy for maintenance of a symptom-free period, but survived to a mean follow up of 2 years. CONCLUSIONS: Early definitive diagnosis and aggressive immunosuppressive therapy of IPH are imperative in order to avoid pulmonary fibrosis and mortality in IPH. A chest radiograph should be included in a serial work-up of unexplained anaemia in children. An examination using BAL can confirm IPH and high-resolution thoracic computed tomography scans are useful for early detection of pulmonary fibrosis.     

Idiopathic pulmonary hemosiderosis complicated by Down syndrome

We report the case of a 9‐year‐old girl with Down syndrome (DS) diagnosed with idiopathic pulmonary hemosiderosis (IPH). Although acute pneumonia complicated by hemolytic anemia was suspected, IPH was finally diagnosed on bronchoscopy. Treatment with prednisolone achieved good clinical response. An association between IPH and DS was not able to be identified, but immunological issues in DS may contribute to the onset of IPH. Recurrent and intractable respiratory symptoms with marked infiltrative shadows in the bilateral lungs and complicated by severe anemia in patients with DS should suggest IPH.     

Vincristine therapy for severe platelet alloimmunization.

A 19-month-old girl with idiopathic severe aplastic anemia refractory to multi-agent immunosuppressive therapy developed severe platelet alloimmunization following several months of platelet transfusions. She became refractory to human leukocyte antigen (HLA)-matched platelet transfusions and experienced frequent episodes of bleeding. She was treated with intravenous vincristine administered weekly for three doses and showed marked improvement in both clinical and laboratory response to platelet transfusions. When vincristine was held for 3 weeks, she again became refractory to HLA-matched platelet transfusion. Reinstitution of vincristine resulted in cessation of clinical bleeding and improved response to platelet transfusion. The mechanism of response likely involves selective delivery of cytotoxic drug to macrophages. To our knowledge this is the first reported case of alloimmune thrombocytopenia responsive to vincristine.     

Transjugular intrahepatic portosystemic shunt in an infant

A 15-month-old girl, who presented with biliary cirrhosis secondary to cystic fibrosis with refractory ascites and recurrent intestinal bleeding, underwent percutaneous transjugular intrahepatic portosystemic shunting. Immediately following the procedure the ascites disappeared and no further bleeding occurred. The stent shunt was patent on Doppler ultrasound until the 22nd day. The patient died on day 22 because of liver failure due to a low-flow syndrome with severe hepatic ischaemia, but with no recurrence of bleeding or ascites. Received: 20 March 1996 Accepted: 30 November 1996     

Severe iron deficiency anemia in a child with idiopathic pulmonary hemosiderosis: a case report

We report a case of idiopathic pulmonary hemosiderosis (IPH) in a three-year-old male patient who presented with severe iron deficiency anemia. The child had been diagnosed with iron deficiency anemia nine months earlier and had received multiple blood transfusions, but the cause of his anemia had not been established. The diagnosis of IPH was made after a biopsy of the left lung showed large numbers of hemosiderin-filled macrophages in the alveoli. He did not respond to standard dose corticosteroid (CS) treatment (2 mg/kg/d). However, high-dose short-term CS treatment was successful in two episodes of acute respiratory hemorrhage in this patient. We conclude that IPH should always be considered when investigating the cause of iron deficiency anemia. A more rapid diagnosis in this case could have prevented unnecessary investigations and blood transfusions. We also suggest that high-dose short-term CS treatment should be kept in mind, especially in patients who do not respond to a standard dose.     

Use of sodium chromate Cr51 in diagnosing childhood idiopathic pulmonary hemosiderosis

The diagnosis of idiopathic pulmonary hemosiderosis (IPH) may be elusive. A 6-year-old boy had microcytic hypochromic anemia and a hemolytic component. Hemosiderin-laden macrophages were not found in the gastric aspirate. He had no pulmonary signs or symptoms. Extensive hematologic and roentgenologic investigations failed to reveal the cause of the anemia. Quantitative serial scintigraphic scanning showed significant (35%) pulmonary sequestration of autologous erythrocytes labeled with sodium chromate Cr51. The half-life of the RBCs was moderately decreased (half-life, 15 days; normal, 25 to 35 days). An open-lung biopsy specimen confirmed the diagnosis of IPH. A diagnosis of IPH should be considered when children have iron deficiency anemia and pulmonary signs or symptoms. Organ sequestration studies may be helpful in equivocal cases.     

Diffuse cavernous hemangioma of the spleen with Kasabach-Merritt syndrome misdiagnosed as idiopathic thrombocytopenia in a child

Background  Most cavernous hemangiomas in the spleen are small lesions that are found incidentally and patients usually present with no symptoms. Imaging is able to detect the lesions that are considered as diagnostic evidence. But some patients with diffuse cavernous hemangioma may present with anemia, thrombocytopenia, coagulopathy and bleeding, which might be misdiagnosed as idiopathic thrombocytopenia with disseminated intravascular coagulation (DIC). Splenectomy is the most effective therapy for diffuse cavernous hemangiomas with symptoms. Methods  The history, imaging results, pathologic findings, diagnosis and treatment of a 34-month-old boy with severe petechiae were reviewed. Results  The boy was diagnosed as having refractory idiopathic thrombocytopenia (ITP) because of low platelet count and bleeding at a local hospital. He had no response to a full-dose of corticosteroid and a high-dose of immunoglobulin (2 g/kg). Huge splenomegaly and DIC were found after 7 months. Diffuse cavernous hemangioma of the spleen was highly suspected, but it was not confirmed by B ultrasound, enhanced CT or MRI. DIC and bleeding were solved by low molecular weight heparin, supplement of fibrinogen and prothrombin complex. A diffuse cavernous hemangioma involving the whole spleen was confirmed pathologically following a successful splenectomy. The boy recovered completely without any complication after the operation. Conclusions  Diffuse cavernous hemangioma of the spleen should be differentiated from ITP associated with splenomegaly. Radiological and overall physical examination should be emphasized for refractory ITP cases.     

特发性肺含铁血黄素沉着症研究进展

特发性肺含铁血黄素沉着症（idiopathic pulmonary hemosiderosis，IPH）是一种罕见的，以肺泡毛细血管反复出血，肺间质含铁血黄素沉着为显著特点的疾病。其病因及发病机制尚未完全明了，过敏反应、霉菌感染等可能诱发IPH，免疫因素在IPH发病中起着至关重要的作用，最新的研究已经发现细胞因子和自身免疫性血管炎在IPH发病中有一定作用。其临床表现多样，无明显特异性，主要表现为反复发作的咯血、气促和贫血。痰涂片或肺泡灌洗液经铁染色为重要的诊断方法，高分辨CT对于痰液检查正常的患者具有一定的诊断意义，免疫抑制治疗为主要治疗方法，肺移植的可行性存在争议。我们较为详细地总结了近年来有关于本病的病因、发病机制、临床特点、诊断治疗及预后的研究进展。     

Idiopathic pulmonary hemosiderosis: clinical profile and follow up of 26 children

OBJECTIVES: To describe the clinical details and follow up of children with idiopathic pulmonary hemosiderosis. DESIGN: Retrospective case series. SETTING: Pediatric chest clinic of a tertiary care hospital. SUBJECTS: Children diagnosed as suffering from idiopathic pulmonary hemosiderosis (IPH). METHODS: Charts of patients diagnosed as IPH were reviewed for clinical features and treatment regimen. Diagnosis was based on presence of iron deficiency anemia, chest radiography and demonstration of hemosiderin laden macrophages in bronchoalveolar lavage (BAL), gastric aspirate, or sputum. Treatment consisted of oral prednisolone, hydroxychloroquine (HCQ) and inhaled corticosteroids (ICS). RESULTS: The common clinical features in 26 children with IPH (mean age 75 months) included: cough, breathlessness, fever, hemoptysis and wheezing in 26 (100%), 22 (85%), 19 (73%),15 (58%) and 14 (54%) children, respectively. Clubbing, hepatomegaly and splenomegaly was seen in 16 (62%), 15 (58%) and 10 (38%) children, respectively. Hemosiderin laden macrophages were documented in BAL and gastric aspirate in 92% and 30% patients, respectively. Symptoms did not recur in 17 patients who received prednisolone and HCQ initially. 5 patients had recurrence of symptoms and required short courses of oral prednisolone, 4 patients required frequent courses of prednisolone and were started on azathioprine. Older age, longer duration of illness, history of hemoptysis and jaundice were associated with poor response. CONCLUSION: Treatment with prednisolone and hydroxychloroquine followed by inhaled corticosteroids may improve survival in children with IPH.     

小儿贫血与特发性肺含铁血黄素沉着症

目的探讨特发性肺含铁血黄素沉着症的诊断和鉴别诊断。方法对我院1989～2004年收治的50例特发性肺含铁血黄素沉着症患者资料进行回顾性分析。结果本病多以贫血,咯血,咳嗽为特点,而本病的贫血极易误诊为营养性缺铁性贫血。结论为正确诊断本病常规拍胸部X线片及早发现肺间质性损害同时进行痰液或胃液检查寻找含铁血黄素巨噬细胞(即心衰细胞)3～6次是必要的。     

Is there a role for magnetic resonance imaging in the evaluation of non-traumatic intraparenchymal haemorrhage in children?

Background In contrast to adults, intraparenchymal haemorrhage (IPH) is at least as common as ischaemic stroke in children. There is often uncertainty about the most appropriate modality for imaging in the acute stage.Objective To examine the diagnostic value of MRI and MR angiography (MRA) in the detection of underlying pathology in children with non-traumatic IPH.Materials and methods A retrospective review was conducted of children with IPH from January 1997 to March 2003. After exclusion of patients with traumatic IPH or previously diagnosed vascular malformation, aneurysm, or brain tumour, 50 children were identified. Case notes and imaging studies were reviewed.Results An underlying lesion was demonstrated with MR in two-thirds of children (25/38) with IPH. A vascular lesion was the commonest cause, followed by tumour. Three children had false-negative MR scans.Conclusion MR is a valuable non-invasive imaging modality for detection of both vascular and non-vascular causes of paediatric IPH. The high rate of the latter in childhood makes incorporation of MR into paediatric IPH imaging protocols especially important. Clinical guidelines regarding the optimum sequence of investigations in non-traumatic IPH would be helpful to standardize practice and enable critical appraisal.     

Idiopathic pulmonary haemosiderosis

Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder characterized by recurrent bouts of haemoptysis, iron deficiency anaemia, and pulmonary infiltrates on chest radiograph. We present such a case and believe that it is the first report from the Middle East.     

Familial idiopathic pulmonary hemosiderosis.

Two brothers, aged 3 and 6 years, respectively, had their pulmonary conditions diagnosed as idiopathic pulmonary hemosiderosis (IPH). Both boys had severe iron-deficiency anemia, chronic cough, hemoptysis, and exertional dyspnea, and one had recurrent epistaxis. The results of light microscopic lung histopathologic studies in both patients showed numerous hemosiderinladen macrophages and chronic interstitial pneumonitis. No specific patterns of immunofluorescence of the alveolar capillary basement membranes were found. The results of electron microscopic examinations showed intact alveolar and capillary basement membranes and no evidence of electron-dense deposits. The lack of clinical or biochemical evidence for renal disease as well as the absence of serum antinuclear and antibasement membrane antibodies excluded associated autoimmune disorders. Evaluation for milk-protein allergy was negative and neither child demonstrated a clinical response to a milk-free diet. Sequential pulmonary function studies performed over four years showed episodes of acute obstructive airway disease that correlated with pulmonary hemorrhage and mild persistent restrictive lung disease. The results of this family study suggested that some cases of IPH may have a genetic basis.     

Intracranial haemorrhage in the preterm sheep fetus

The germinal layer in the brain of the sheep fetus at 58--85 days of gestation was found to resemble that of the human infant at 28--30 wk of gestation. Experiments were done on 65 exteriorized fetuses to explore the effect of various combinations of asphyxia and raised intravascular pressures in causing bleeding into the germinal layer, ventricles and other parts of the brain. Asphyxia by itself did not produce an increase in the incidence of intracranial hemorrhages when compared with control fetuses. The combination of asphyxia with intermittent increases in arterial or venous pressure, or both, did cause haemorrhages. Large increases in arterial pressure without asphyxia also caused intracranial haemorrhages, whereas increases in venous pressure without asphyxia did not. The types of haemorrhage observed closely resembled those seen in the preterm human infant, although massive intraventricular haemorrhages (IVHs) were rare. We conclude that: (1) the sheep fetus can be used for investigating factors associated with intracranial haemorrhage in the preterm brain; (2) the most effective method of producing haemorrhages into the germinal layer was by a combination of asphyxia with intermittent increases in cerebral intravascular pressure. Similar mechanisms may be at work in the newborn human infant, and could lead to IVH.     

High-dose dexamethasone therapy for a 14-month-old boy with refractory idiopathic thrombocytopenic purpura

A 14-month-old boy with refractory idiopathic thrombocytopenic purpura (ITP), who was successfully treated with pulsed high-dose oral dexamethasone therapy is reported. The platelet count increased after six scheduled courses of treatment (10 mg/day × 4 days, six courses). Twenty-four months later, the platelet count remained over 10.0 × 10⁴/μL. No obvious side effects were observed during or after the therapy. This treatment could be taken into consideration not only for adults but also for young children with refractory ITP. It is effective, safe, easy to administer, patient comfort is taken into consideration, and hospitalization duration and costs are minimized.     

SYNOVECTOMY AS A PROPHYLACTIC MEASURE IN RECURRENT HAEMOPHILIC HAEMARTHROSIS Follow-up of 23 Cases

ABSTRACT. Because of frequently recurring haemarthrosis which could not be controlled by conservative management 19 haemophiliacs were subjected to synovectomy on a total of 23 joints—17 knees, S elbows, and 1 hip. The patients were followed for an average of 23 months. Primary postoperative complications occurred, in the form of recurrent bleeding, in 8 joints. Rehabilitation was often difficult and long-lasting, and the range of joint motion was essentially restricted in 4 cases. After a follow-up period exceeding 6 months the findings in the remaining, mobile 19 synovectomized joints were: 12 had been relieved of haemorrhage, 5 had rare and two frequent haemorrhages. The reduction in the number of haemorrhages was significant (p<0.01). In the light of the complicated postoperative course it is concluded that synovectomy should be used only on strict indications, viz. only in otherwise intractable cases of progressing haemophilic arthropathy.     

Background patterns and sleep-wake cycles on amplitude-integrated electroencephalography in preterms younger than 30 weeks gestational age with peri-/intraventricular haemorrhage

AIM: The objective of this prospective study was to evaluate the influence of peri-/intraventricular haemorrhage (PIVH) grades I-IV on amplitude-integrated electroencephalographic (aEEG) activity in preterm infants<30 weeks gestational age (GA). METHODS: The aEEG tracings of the first 2 weeks of life of 56 preterm infants younger than 30 weeks GA (2 groups: group A=23-26 weeks GA, group B=27-29 weeks GA) born during a 4-year period with PIVH grades I-IV were assessed for the relative duration of four background aEEG activity patterns (continuous pattern, discontinuous high-voltage pattern, discontinuous low-voltage pattern and nearly isoelectric pattern), the presence of seizure activity and the appearance of sleep-wake cycles and compared to the tracings of 75 neurologically healthy preterms without PIVH. RESULTS: Analysis of aEEG background activity showed a decrease of continuous activity whereas discontinuous activity increased in both groups with larger haemorrhages (grades III and IV) and when compared to controls. Suspected seizure activity was more common with increasing degree of bleeding in group A (50% with PIVH I or II, 75% with PIVH III or IV) and when compared to controls and was the same with increasing degree of bleeding in group B (47% with PIVH I or II, 45% with PIVH III or IV). Sleep-wake cycles were less common with larger haemorrhages in both groups (group A: 41% with PIVH I or II, 25% with PIVH III or IV; group B: 52% with PIVH I or II, 9% with PIVH III or IV) and when compared to controls. CONCLUSIONS: The aEEG characteristics of severe PIVH consist in a combination of a more discontinuous background pattern, a lack of sleep-wake cycles and a higher likelihood of seizure activity when compared to age-matched controls.     

Duration and morbidity of chronic immune thrombocytopenic purpura in children: five-year follow-up of a Nordic cohort

Aim: To describe the clinical course, morbidity and platelet recovery in an unselected Nordic cohort of children with chronic Immune Thrombocytopenic Purpura (ITP). Methods: Prospective 5‐year follow‐up of 96 children with ITP lasting more than 6 months, with reporting of hospital admissions, severity of bleeding episodes and stabilization of platelet counts above 20, 50 and 150 × 10⁹/L. Results: The estimated 5‐year recovery rate was 52%; exclusion of 12 splenectomized children did not change the estimate. Events eliciting admission to hospital occurred in 39 (41%). Major haemorrhages occurred in eight children (8%), including a nonfatal intracranial haemorrhage in one child (1%). The overall admission rate was 0.4/year of thrombocytopenia, decreasing during follow‐up as thrombocytopenia converted to milder degrees. Early recovery within 2 years of diagnosis occurred in 35%, was associated with low morbidity and was more likely in young children with abrupt onset of symptoms. Conclusion: In a Nordic cohort of children with chronic ITP, one half had recovered 5 years after diagnosis, more than half never required hospitalization and <10% experienced serious bleeding episodes, always with a platelet count <20 × 10⁹/L. Aggressive management can be restricted to the minority of children with continuing severe thrombocytopenia and frequent, clinically significant bleeding events.     

Association of Celiac Disease With Idiopathic Pulmonary Hemosiderosis; Lane Hamilton Syndrome

Introduction:

Idiopathic Pulmonary Hemosiderosis (IPH) is a rare cause of alveolar hemorrhage, which is seen primarily in childhood. Celiac disease is defined as a chronic, immune-mediated enteropathy of the small intestine, caused by exposure to dietary gluten in genetically pre-disposed individuals. Association of IPH and celiac disease is known as Lane Hamilton syndrome. There are limited number of case reports of this syndrome in literature.

Case Presentation:

Although there were no growth and developmental delay and gastrointestinal symptoms like chronic diarrhea, chronic constipation, vomiting, abdominal bloating and pain in the two patients with IPH, they were diagnosed with Lane Hamilton Syndrome. After initiation of gluten-free diet, their IPH symptoms disappeared and hemoglobin levels were observed to return to normal.

Conclusions:

Even if there were no gastrointestinal symptoms in a patient with IPH, celiac disease should be investigated. These patients may benefit from gluten free diet and IPH symptoms may disappear.