Coeliac disease as a cause of unusually severe anaemia in a young man with idiopathic pulmonary haemosiderosis

Idiopathic pulmonary haemosiderosis (IPH) is characterized by a triad of recurrent episodes of alveolar haemorrhage, haemoptysis and iron deficiency anaemia. The combination of IPH and coeliac disease (CD) is extremely rare though both diseases may have a common pathogenetic link. As illustrated by our case CD should be specifically looked for in patients with IPH, especially those in whom the severity of anaemia is disproportionate to radiologic findings even in the absence of gastrointestinal symptoms since both diseases may benefit from a gluten-free diet.     

Idiopathic pulmonary haemosiderosis with celiac disease (Lane–Hamilton syndrome) in an adult – a case report

Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder of unknown cause characterised by haemoptysis, diffuse alveolar infiltrates and iron‐deficiency anaemia. IPH predominantly affects children; it is rare in adults, in whom it usually manifests before 30 years. In adults, course is protracted with a better prognosis, in contrast to children. Even rarer is the Lane–Hamilton syndrome, a condition in which IPH is associated with celiac disease. Only 15 cases of Lane–Hamilton syndrome affecting adults are reported in literature. Treatment of IPH is based on anecdotal case reports and case series because of its rare occurrence. High‐dose steroids reportedly reduce morbidity and mortality and delays or stops disease progression; more effectively in adults than children. In Lane–Hamilton syndrome, a gluten‐free diet for the celiac disease in addition to steroids for IPH, is the mainstay of therapy. The optimal treatment duration of steroid therapy is not known but anecdotally a more prolonged course results in improved outcome. We report a case of a young woman who presented with exertional dyspnoea, intermittent haemoptysis, severe anaemia and lung infiltrates but no gastrointestinal complaints. After extensive work‐up, she was diagnosed with Lane–Hamilton syndrome based on a diagnosis of IPH made from lung biopsy and concomitant celiac disease because of positive anti‐gliadin antibody and endomyosial antibody and jejunal biopsy. She was treated with sustained low‐dose steroid therapy for a year and a gluten‐free diet with resolution of her symptoms, anaemia and lung infiltrates. At 4 years of follow‐up, she remains stable, without recurrence.     

Extracorporeal membrane oxygenation to rescue profound pulmonary hemorrhage due to idiopathic pulmonary hemosiderosis in a child

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage (DAH) in pediatric patients. During the acute phase, death due to massive alveolar hemorrhage and subsequent severe respiratory failure with associated multiple organ failure often occurs. We report the case of an 11-year-old girl who developed severe hypoxemic respiratory failure and pulmonary hemorrhage. Extracorporeal membrane oxygenation (ECMO) was instituted on the next day because medical treatment and mechanical ventilation failed to maintain oxygenation. She was successfully decannulated 5 days later without ECMO-related complications. Four months later, she was intubated again and the diagnosis of IPH was made by open lung biopsy. She was treated with systemic steroid therapy and discharged smoothly. We suggest that ECMO provides a chance of recovery and survival for patients with IPH, even if accompanied by severe pulmonary hemorrhage.     

Pathology and pathogenesis of portal venopathy in idiopathic portal hypertension: Hints from systemic sclerosis

Idiopathic portal hypertension (IPH) is a non-cirrhotic presinuosidal portal hypertension of unknown etiology. Stenosis of smaller portal veins with portal fibrosis is a pathologic hallmark of IPH. Association of systemic sclerosis (SSc) with IPH is recognized, and similar pathologic features are reported in small portal tracts and skin of IPH and SSc, respectively. In addition, levels of transforming growth factor-β (TGF-β) and connective tissue growth factor are elevated in serum and in affected skin and portal tracts of these two diseases, suggesting that IPH share fibrogenetic mechanisms with SSc. Endothelial to mesenchymal transition (EndMT) of microvasculatures of skin could be responsible for dermal fibrosis in SSc. In IPH, EndMT of portal vein endothelium via TGF-β/Smad activation may also be involved in small portal venpathy. In IPH, enhanced expression of pSmad2 in venous endothelium of smaller portal veins was associated with reduced CD34 expression. CD34 and S100A4, and CD34 and type I collagen were colocalized to portal vein endothelium in IPH. Such myofibroblastic phenotypes may be responsible for periportal-venous deposition of collagen and compressive portal venous obliteration. These small portal venous lesions may in turn lead to portal venous insufficiency followed by subcapsular atrophy in IPH.     

Algorithm for the diagnosis of anaemia without laboratory facilities among small children in a malaria endemic area of rural Tanzania

BACKGROUND: Anaemia among small children in tropical Africa is common and often caused by infection with Plasmodium falciparum. The diagnosis of anaemia is difficult without a laboratory estimation of haemoglobin. The aim of this study was to examine if clinical findings related to malaria and anaemia would help to detect moderate and/or severe anaemia in children in rural Tanzania. METHODS: Children between 6 and 36 months were examined by health workers in an Out Patient Department (OPD) to detect severe anaemia (packed cell volume, PCV< or =20%) and in a cross sectional survey at village level to identify moderate anaemia (PCV 21-25%). History of recent fever and treatments was recorded and a clinical examination was performed. FINDINGS: In the survey, comparison of 65 moderately anaemic children with 373 mild/non anaemic children revealed no differences in history of fever or in the clinical examination. In the OPD comparison of 100 severely anaemic children with 116 non-severely anaemic control children revealed that pallor, respiratory rate, number of fever days last week, deteriorated general condition, heart rate, age, splenomegaly, low body weight and elevated body temperature were all indicators of severe 'anaemia, only pallor, respiratory rate, fever days and palpable spleen however, remained associated with severe anaemia in multiple regression analysis. The combination of any pallor and either respiratory rate >55/min or fever >3 days, could predict severe anaemia with a sensitivity of 96% and a specificity of 71%. This was better than the currently recommended signs of severe pallor or an approximation of the Integrated Management of Childhood Illness (IMCI) criteria's for referral of children. INTERPRETATION: At primary health care level detection of severe anaemia can be improved by information about fever duration and determination of respiratory rate in children with pallor.     

Predominant T helper 1 cells in patients with idiopathic portal hypertension

BACKGROUND: The pathologic mechanism of idiopathic portal hypertension (IPH) is unknown. Because cytokines and the balance of T helper (h) 1 and Th2 CD4+ T cells have been reported to be important for regulating the immune response, in the present study we investigated the role of cytokines and the distribution of cytokine-producing cells in IPH patients. METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, -II, interferon (IFN)-gamma and interleukin (IL)-4 were measured in IPH patients, fatty liver patients, chronic hepatitis patients and control subjects. The percentages of Th0, Th1 and Th2 CD4+ T cells were examined in peripheral and spleen lymphocytes in IPH patients by intracellular staining. RESULTS: Serum levels of TNF-alpha, soluble TNF receptor-I, interferon-gamma and IL-4 of IPH patients were not increased in comparison with control subjects. Only the mean value of soluble TNF receptor-II was significantly higher than that of control subjects and fatty liver patients. The ratios of Th1 and Th2 in both peripheral and spleen lymphocytes of IPH patients were significantly increased compared with the ratios found in peripheral lymphocytes of control subjects. The increase in the ratios was due to a decrease in the percentage of Th2 CD4+ T cells. CONCLUSIONS: These results suggest that the imbalance of Th1 and Th2 CD4+ T cells and TNF may be associated with the pathogenesis of IPH.     

Severe osteomalacia due to undiagnosed cœliac disease: three case reports of Tunisian women

We describe three cases of osteomalacia presenting in Tunisian women, all of whom had previously-undiagnosed cliac disease (CD). Direct enquiry revealed an important weight loss and a history of diarrhoea in two patients, and a 15-year history of anaemia in one patient. Laboratory tests showed severe anaemia in the three cases. Reduced calcium was found in two cases, and corrected calcium was found in one case. Radiological examination showed fissure in two cases. The diagnosis of osteomalacia was made by clinical, biochemical and radiological features. Antigliadin, antireticulin, antiendomysial and anti-tissue transglutaminase antibodies were all positive in the three cases, and a small-bowel biopsy confirmed the diagnosis of CD. Treatment with gluten-free diet (GFD), supplemental calcium and vitamin D was initiated for the three patients, but only one patient complies strictly with the GFD; she showed a marked resolution of her symptoms.     

Hémosidérose pulmonaire idiopathique et maladie cœliaque chez l’enfant

Idiopathic pulmonary haemosiderosis (IPH) is a rare disease in children, and its association with celiac disease is even rarer. Its immunological origin is now well accepted. We report the case of a fifteen-year-old child admitted for evaluation of recurrent hemoptysis that had been evolving over the previous two years. Physical examination of the patient revealed normal weight and height, but there was cutaneous and mucosal pallor due to anemia (haemoglobin 4 g/dl). The chest x-rays showed alveolo-interstitiel infiltrates in both pulmonary bases. Broncho-alveolar lavage resulted in a GOLDE score of 200. The diagnosis of IPH was made. Positive tissue antitransglutaminase and antiendomysin antibodies suggested an association with celiac disease, although there were no digestive symptoms. Finally, this suspected diagnosis was confirmed by jejunal biopsy. A gluten-free diet was initiated after confirmation of the diagnosis. Evolution of the symptoms under corticosteroid therapy was initially favourable, with an increase of hemoglobin to 10 g/dl, but a relapse of hemoptysis occurred two months after the corticosteroid treatment was stopped, but at the twelve-month follow-up there had been no further hemoptysis, even though the corticosteroid had been stopped.     

A case of adult onset idiopathic pulmonary hemosiderosis markedly improved by steroid therapy]

A case of adult onset idiopathic pulmonary haemosiderosis (IPH) was reported. A 53-year-old man was admitted to our hospital because of repeated bloody sputum on June 2, 2006. Chest radiograph on admission disclosed diffuse infiltrative shadows in both lung fields, and one month later these shadows became more marked. The chest CT on July 5, 2006 showed patchy areas of ground-glass opacity and consolidation, exhibiting a distinctly peripheral distribution. Bronchoscopic findings revealed oozing bleeding from the orifice of B5 in the right lung and B9 in the left lung. We employed video-assisted thoracoscopic surgery for lung biopsy and he as primary IPH was diagnosed clinicopathologically. His symptoms and radiographic findings were markedly improved after steroid therapy, followed by no signs of recurrence. It may be important to establish a definitive diagnosis early, even in IPH, using VATS, for further effective therapy.     

Unusual presentation: pulmonary hemosiderosis with celiac disease and retinitis pigmentosa in a child

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease characterized by anemia, hemoptysis and recurrent alveolar hemorrhage. The combination of IPH and celiac disease (CD) is extremely rare. We report a 9-year-old boy with Lane-Hamilton syndrome, co-occurrence of pulmonary hemosiderosis with CD. This presentation is unique presentation because he has also retinal pigmentation.     

A case of progressive systemic sclerosis complicated by idiopathic portal hypertension with severe anemia]

A 44-year-old woman had been diagnosed with progressive systemic sclerosis (PSS) at the age of 39 years old and mild pancytopenia was noted at that time. At the age of 41 years symptoms of dry mouth appeared. In April 1997, anemia was in progress (Hb 5.8 g/dl) and severe esophageal varices were found by gastrointestinal fiber scope, and massive splenomegaly by abdominal CT. Serological examination was negative for hepatitis virus and for anti-mitochondrial antibody. In addition, Indocyanine Green test was normal and typical findings of liver cirrhosis were not demonstrated by CT scan. Also, the bone marrow result was normal. Therefore hypersplenism with idiopathic portal hypertension (IPH) was suggested and the patient was referred for splenectomy with the aim of improving the pancytopenia. The weight of the spleen was 2100 g and the pressure of the portal vein was measured at 390 mm H2O. The diagnosis of IPH was determined because pathologically there were no findings for liver cirrhosis. After splenectomy, pancytopenia was remarkably improved (Hb 9.6 g/dl). Consequently, this case was diagnosed as IPH complicated with PSS and Sj?gren syndrome.     

Acute Deterioration of Idiopathic Portal Hypertension Requiring Living Donor Liver Transplantation: A Case Report

Case reports of severe idiopathic portal hypertension (IPH) requiring liver transplantation are very rare. We report the case of a 65-year-old woman who was diagnosed as having IPH. At the age of 60 years, her initial symptom was hematemesis, due to ruptured esophageal varices. Computed tomography of the abdomen showed splenomegaly and a small amount of ascites, without liver cirrhosis. She was diagnosed as having IPH and followed-up as an outpatient. Five years later, she developed symptoms of a common cold and rapidly progressive abdominal distension. She was found to have severe liver atrophy, liver dysfunction, and massive ascites. Living donor liver transplantation was then performed, and her postoperative course was uneventful. Histopathological findings of the explanted liver showed collapse and stenosis of the peripheral portal vein. The areas of liver parenchyma were narrow, while the portal tracts and central veins were approximate one another, leading to a diagnosis of IPH. There was no liver cirrhosis. The natural history of refractory IPH could be observed in this case. Patients with end-stage liver failure due to severe IPH can be treated by liver transplantation.     

T-cell large granular lymphocytic leukaemia: successful response to 2-deoxycoformycin

We report a 25-year-old woman with T-cell large granular lymphocytic leukaemia presenting with severe neutropenia, anaemia and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+, TCRgamma delta+, CD4-, CD5+, CD7+, CD8+, CD57+ large granular lymphocytes. Clonality was demonstrated with T-gamma polymerase chain reaction analysis which revealed clonal rearrangement of the TCRgamma chain gene. Cyclosporine, granulocyte colony-stimulating factor, methothrexate and a combination of cyclophosphamide, vincristine and prednisolone failed to correct the neutropenia and the anaemia. Finally, treatment with 2-deoxycoformycin resulted in both clinical and haemotological complete responses, despite molecular evidence of the persistence of the abnormal T-cell clone.     

Protected carotid artery stenting in patients with severe stenosis

Intraplaque hemorrhage (IPH) and ulcers are the major findings of unstable plaques. In addition, initial symptoms are associated with postprocedural complications after carotid artery stenting (CAS). The aim of this study was to determine the safety of CAS using an embolic protection device in symptomatic patients with severe carotid artery stenosis and unstable plaques such as IPH and ulcers.This retrospective study included 140 consecutive patients with severe carotid stenosis. These patients underwent preprocedural carotid vessel wall imaging to evaluate the plaque status. We analyzed the incidence of initial clinical symptoms, such as headache, nausea, and vomiting, after CAS. The primary outcomes analyzed were the incidence of stroke, myocardial infarction, and death within 30 days of CAS.Sixty-seven patients (47.9%) had IPH, and 53 (38.9%) had ulcers on carotid wall imaging/angiography. Sixty-three patients (45.0%) had acute neurological symptoms with positive diffusion-weighted image findings. Intraluminal thrombi on initial angiography and flow arrest during CAS were significantly higher in patients with IPH and symptomatic patients. Symptoms were significantly higher in patients with IPH than in those without (63.5% vs 35.1%, P < .001). There were no significant differences in clinical symptoms after stenting or in primary outcomes, regardless of IPH, ulcer, or initial symptoms.IPH and plaque ulceration are risk factors in symptomatic carotid stenosis. However, IPH and plaque ulceration were not a significant risk factors for cerebral embolism during protected carotid artery stent placement in patients with carotid stenosis. Protected CAS might be feasible and safe despite the presence of unstable plaques.     

Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group.

OBJECTIVES: To describe changes in haemoglobin over time and to determine the joint prognostic value of the current haemoglobin, CD4 lymphocyte count and viral load among patients from across Europe. PATIENTS: The analysis included 6725 patients from EuroSIDA, an observational, prospective cohort of patients with HIV from across Europe. METHODS: Normal haemoglobin was defined as haemoglobin greater than 14 g/dl for men and 12 g/dl for women; mild anaemia was 8-14 g/dl for men and 8-12 g/dl for women; severe anaemia was defined as less than 8 g/dl for both males and females. Linear regression techniques were used to estimate the annual change in haemoglobin; standard survival techniques were used to describe disease progression and risk of death. RESULTS: At recruitment to the study, 40.4% had normal levels of haemoglobin, 58.2% had mild anaemia and 1.4% had severe anaemia. At 12 months after recruitment, the proportion of patients estimated to have died was 3.1% [95% confidence interval (CI) 2.3-3.9] for patients without anaemia, 15.9% for patients with mild anaemia (95% CI 14.5-17.2) and 40.8% for patients with severe anaemia (95% CI 27.9-53.6; P < 0.0001). In a multivariate, time-updated Cox proportional hazards model, adjusted for demographic factors, AIDS status and each antiretroviral treatment as time-dependent covariates, a 1 g/dl decrease in the latest haemoglobin level increased the hazard of death by 57% [relative hazard (RH) 1.57; 95% CI 1.41-1.75; P < 0.0001], a 50% drop in the most recent CD4 lymphocyte count increased the hazard by 51% (RH 1.51; 95% CI 1.35-1.70; P < 0.0001) and a log increase in the latest viral load increased the hazard by 37% (RH 1.37; 95% CI 1.15-1.63; P = 0.0005). CONCLUSIONS: Severe anaemia occurred infrequently among these patients but was associated with a much faster rate of disease progression. Among patients with similar CD4 lymphocyte counts and viral load, the latest value of haemoglobin was a strong independent prognostic marker for death.     

Idiopathic pulmonary haemosiderosis

Twenty seven years old woman was admitted to our hospital with dyspnea, severe hemoptysis and iron deficiency anemia. The chest X-ray showed bilateral interstitial markings with homogenous infiltration at right costodiafragmatic sinus. The patient was investigated for all alveolar hemorrhagic syndromes. The diagnosis of idiopathic pulmonary haemosiderosis (IPH) was made by open lung biopsy. IPH usually presents in infancy or within the first decade of life and is unknown aetiology. It is most common between ages 1-17 and exceedingly rare in adults. Clinical presentation of IPH varies from an insidious onset with anemia, cough, dyspnea to a fulminant onset with recurrent acute hemoptysis. Histological confirmation with open lung biopsy is often necessary for definite diagnosis.     

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. METHODS: Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. FINDINGS: By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. INTERPRETATION: In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.     

Idiopathic portal hypertension with splenic infarct. An unreported complication

We present a case of Idiopathic Portal Hypertension (IPH) with Splenic infarct in a 23-year-old female. She was referred to the hospital because of enlargement of liver and spleen. A computed axial tomography revealed Splenic infarct. The spleen was surgically removed. At laparotomy the liver was found to be enlarged and a liver biopsy performed. The biopsy showed characteristic changes of IPH. After the splenic resection all hematologic manifestations disappeared, suggesting that they were due to hypersplenism. The IPH is very uncommon in western countries. We don't know of any case previously reported in Argentina and our patient is the first case of IPH with Splenic infarct.     

特发性门脉高压肝移植术后随访第3年再发1例报告及文献复习

目的 复习1例特发性门脉高压(IPH)患者接受肝移植(LT)后第3年出现病情“再发”,并进行了相关文献复习,以提高对该病的认识。方法 报道1例我们诊治的IPH患者的病例资料,并检索MEDLINE、EMBASE、万方等数据库经LT治疗的IPH患者的研究报道,分析其治疗和转归。结果 本文报道的病例为57岁女性,因消化道出血、腹水行LT术,组织病理学检查诊断为IPH;术后随访第3年病情复发,行经皮肝穿刺活检术,病理学检查提示结节性再生性增生(NRH)、轻度汇管区炎症及纤维化,提示IPH再发;文献检索到81例LT治疗的IPH患者,其中42例在LT前诊断为肝硬化;LT后最长随访时间为248个月,8例死亡,其中5例分别在首次LT后3.5月～14年进行肝活检,组织病理学检查提示NRH,3例分别于LT后第7月、第3年和第14年出现具有门脉高压表现的NRH。结论 具有严重的门脉高压或肝功能衰竭的IPH患者需要LT治疗。少数患者在LT后可能出现IPH“再发”。     

Pathomorphologic study on the extrahepatic portal vein in idiopathic portal hypertension

Patients with idiopathic portal hypertension (IPH) are known to have sclerotic changes of the intrahepatic portal vein radicles. In order to elucidate the pathological changes in the extrahepatic portal venous system in IPH, studies were carried out on the portal trunk in 12 patients with IPH, 59 patients with liver cirrhosis including some with associated hepatocellular carcinoma, and 12 normal matched control subjects. Histological examinations including histomorphometry were performed on the transverse sections of the portal trunk taken at autopsy. Most of the patients with IPH showed severe phlebosclerosis which was more pronounced than seen in liver cirrhosis. Thrombosis was also frequently observed in IPH. In IPH, the portal trunk was characterized by fibrous thickening of the intima and media with a prominent increase of elastic fibers. The mean area and thickness of the intima and media were significantly greater than in patients with liver cirrhosis. Sclerosis extensively involving both the extrahepatic and intrahepatic ramifications of the portal vein appeared to be characteristic of IPH.