[Asthenia in adolescents]. / L'adolescente astenico.

Fatigue is defined as a subjective sensation of tiredness or weariness that occurs at rest. The perception of fatigue among 12-15 years-old Italian adolescents in a school survey was about 70%. Generally the symptoms are reported after a viral illness or an infection. In adolescents with persistent or severe fatigue a selected screening evaluation to look for an underlying organic disorder is warranted. A practical diagnostic approach is given and a brief description of chronic fatigue syndrome is reported according to CDC revised diagnostic criteria published in 1997.

Treatment with deferiprone (L1) in a thalassemic patient with bone lesions due to desferrioxamine.

A male thalassemia major patient who developed bone and cartilage abnormalities with a standard dose of desferrioxamine (DFX) given subcutaneously from the age of 4 years was treated with the oral iron chelator deferiprone (L1). During L1 treatment an improvement of genu valgum, evidence of healing and filling in of bone at the periphery of knee metaphysis and improvement in growth velocity were observed. However, the sitting height had decreased further, confirming the irreversibility of platyspondylosis, so affecting the near final standing height (156.8 cm) which was below the mid-parental height (168 cm). Prospective studies are warranted to determine the effect of different iron chelators on the bone metabolism of patients with thalassemia.

[Long-term follow-up and bone imaging in acquired osteochondrodysplasia in a female patient with thalassemia and desferrioxamine hypersensitivity]. / Follow-up auxologico e imaging scheletrico nell'osteocondrodisplasia acquisita in una paziente talassemica con ipersensibilità alla desferrioxamina.

We report a female thalassaemia major patient who developed short stature and osteochondrodystrophic lesions during therapy with desferrioxamine (DFX). Healing was noted after the dose of DFX was decreased for 3 years. Unfortunately the spinal cartilage abnormalities did not change suggesting an irreversibility of the ossification process.

Immune responses to administration of a vaccine against Haemophilus influenzae type B in splenectomized and non-splenectomized patients.

OBJECTIVES: we investigated the cause of hypo-responsiveness to vaccines in splenectomized subjects. METHODS: we evaluated the immune responses to a Haemophilus influenzae type b vaccine and the sizes of lymphocyte subpopulations in 25 splenectomized and 45 non-splenectomized thalassaemic patients, in 12 individuals who had been splenectomized after trauma and in 20 controls. RESULTS: the immune response in the controls was significantly higher (P < 0.001) than in splenectomized patients after trauma and in both, the response was higher (P < 0.001) than in thalassaemic patients. In asplenic subjects after trauma, percentages of CD3 and CD4 cells were lower (P < 0.001) than in patients in the other groups; the controls had higher percentages of CD8 cells (P < 0.001) than patients in the other groups. The natural logarithm of the mean percentage of (CD19 showed a quadratic trend from thalassaemic patients through asplenic subjects to controls (P < 0.001). Levels of CD16+ natural killer (NK) cells were higher (P < 0.001) only in asplenic subjects after trauma. CONCLUSIONS: the significant decrease in the immune response of the splenectomized thalassaemic patients vs. non-splenectomized thalassaemic patients may, in part, be due to their basic immunological condition. Thus, the best strategy for protecting these subjects is to vaccinate them before the splenectomy.

Thromboembolic events in beta thalassemia major: an Italian multicenter study.

Thromboembolic (TE) events have been frequently reported in beta-thalassemic patients in association with known risk factors such as diabetes, complex cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and postsplenectomy thrombocytosis. In a recent survey involving 9 Italian thalassemic centers, we identified 32 patients with TE episodes in a total of 735 subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia, corresponding to 3.95 and 9.61%, respectively. There was a great variation in localization: the main one (16/32) was CNS, with a clinical picture of headache, seizures and hemiparesis. Other localizations were the pulmonary (3 patients), mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were observed in 2 others during pregnancy. Since our patients with TE events present a statistically significantly higher incidence of associated dysfunction (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those without TE events (50 vs. 13.8%), we suggest close monitoring of those patients who are at higher risk of developing TE events because of the presence of one or more of these predisposing factors.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia.

No experience has been reported to date in treating chronic hepatitis C virus (HCV) infection with interferon (IFN) therapy after BMT, mainly due to concerns related to the impact of an immunomodulatory drug in patients who are immunologic and haematologic chimeras. However, chronic inflammatory activity related to HCV infection results in a chronic fibrogenous mechanism potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, patients transplanted for beta-thalassemia could be at greater risk because of concomitant iron overload and pre-existing fibrous liver damage. Eleven patients with serological, biochemical, histological and molecular biological evidence of HCV infection were included in the study and treated for 6-12 months with recombinant IFN 24-65 months following BMT. The serum alanine aminotransferase (ALT) was persistently elevated (range 85-1242 U/l; mean 416) for at least 1 year prior to IFN treatment. Ten patients completed the protocol; five were considered as responders to treatment. In these five patients the liver histology showed an overall reduction of inflammation and necrosis: histological inflammatory activity improved from chronic active hepatitis (CAH) to chronic persistent hepatitis (three patients) or minimal residual inflammatory activity (two patients). The Knodell total activity score varied from 5.4 (range 3-9) to 1.4 (range 1-2; P = 0.05). All responding patients revealed negativization of serum HCV-RNA, that has been persistent in four (follow-up 1-3 years). ALT level fell to 15-80 U/l (mean 52; P = 0.0027). No major complications occurred during the therapy and no influence on marrow engraftment parameters were noted. We conclude that IFN therapy does not adversely interfere with engraftment and that it is a feasible therapy for treatment of chronic hepatitis C virus after BMT.

[Prevalence of hepatitis A antibodies in polytransfused thalassemic patients]. / Prevalenza degli anticorpi antiepatite A nei pazienti talassemici politrasfusi.

Chronic liver disease in polytransfused thalassemic patients is an important cause of morbidity and mortality. The genesis is multiform: haemosiderosis and virus infections, resulting from repeated transfusions, may play an important role. Since HAV infection could make greatly worse the prognosis, in order to evaluate the opportunity of the HAV vaccination in polytransfused thalassemic patients, we studied the prevalence of HAV infection by detection of anti HAV antibodies (IgG) (enzyme immunoassay competitive technique) in 75 thalassemic patients (36 males, 39 females, aged 21.1 +/- 9.6, mean +/- SD). Fourty-two patients (56%) were HCV positive with persistent increase of transaminases. Eight patients were HAV antibodies positive (10.6%); the prevalence was 2.7% in patients aged 1 to 19 years, 11.4% in patients aged 20-39 years and 100% over 40 years of age. No differences were observed between sexes. Five out of fourty-two patients HCV positive were HAV antibodies positive (11.9%). In conclusion, in order to reduce further the incidence of liver infections in polytransfused thalassemic patients, we recommend an active immunization for HAV.

[Celiac disease associated with major thalassemia. A case report]. / Malattia celiaca in una paziente affetta da talassemia maior. Descrizione di un caso.

The spectrum of clinical manifestations of coeliac disease, the most common chronic intestinal disorder in children, has widened considerably over the past years and new associations with other diseases, both immunological and non-immunological, have been described. AGA and EMA have proved to be an efficient screening method both in populations with gastrointestinal pathologies and in groups of pauci- or even asymptomatic subjects. The clinical picture of beta-thalassemia has gradually altered over the years owing to improved treatment. However, growth is still affected in a considerable proportion of thalassemic patients. A number of hormonal and other causes, combined in varying ways, contribute to determining this clinical condition. The authors report a case of coeliac disease in an adolescent with thalassemia major characterised by anorexia, arrest of weight gain and low stature. The identification of a new association between coeliac disease and thalassemia major highlights the need to search for this pathology in all thalassemic patients who present scarce growth in stature and weight.

[Horizontal transmission of hepatitis C virus to family members of infected polytransfused pediatric patients]. / Transmissione orizzontale del virus dell'epatite C tra i familiari di pazienti pediatrici politrasfusi infetti.

The aim of this study is to evaluate the prevalence of the HCV antibodies in the relatives of polytransfused patients with different haemoglobinopathies. Our results have shown that 4.7% of relatives are aHCV positive. This incidence is much higher than that one reported in scientific publications with regard to non-haemoglobinopathis aHCV positive patients. Therefore a careful prevention and surveillance is needed in order to avoid the risk of infection in these subjects.

Immune status and immune response to diphtheria-tetanus and polio vaccines in allogeneic bone marrow-transplanted thalassemic patients.

We evaluated the immune status against diphtheria (D), tetanus (T) and polio viruses (PV) and the immune response to re-administration of the respective vaccines in a series of 23 transplanted homozygous beta-thalassemic patients, aged 5-17 years (mean age 12.1 +/- 3.1 years). They had been given compulsory DT toxoids and types 1, 2 and 3 PV vaccine in infancy and had been successfully submitted to allogeneic BMT 2-6 years previously. Prior to revaccination, a high percentage of subjects (from 48% for type 2 PV to 83% for D) had antibody levels below the protective levels and low geometric mean titers (GMTs). After revaccination (three doses of DT toxoids and of inactivated PV vaccine) the percentage of subjects with protective levels of antibodies rose to 86-100% and the GMTs increased markedly. We conclude that: (1) the protection afforded by compulsory DT and PV vaccines administered in infancy is almost entirely lost in beta-thalassemic patients for several years after BMT, (2) revaccination is necessary in these subjects, and (3) at least three doses of DT and PV vaccines must be administered to recover adequate protection.

Familial Jarcho-Levin syndrome.

Jarcho-Levin syndrome is a variety of autosomal recessive spondylocostal dysostosis characterized by severe deformity of the thoracic cage, leading to respiratory failure and early death. There are often associated dysmorphic features. The disease is more frequent in Puerto Ricans and rare in Europe. A Sicilian family with four affected individuals in two interrelated sibships is reported.