Arterial elastorrhexis in beta-thalassaemia intermedia, sickle cell thalassaemia and hereditary spherocytosis.

Arterial and stromal elastorrhexis, an elastic tissue disorder, was recently described in beta-thalassaemia major. Histopathological material from 10 patients with thalassaemia intermedia, 14 with sickle cell thalassaemia and 18 with hereditary spherocytosis was examined in order to investigate the specificity of the arteriopathy. Histological re-examination was made in a total of 42 spleens with parasplenic lymph nodes in 14 cases, 26 surgical liver biopsies and 16 gallbladders with associated regional lymph nodes. Arteriopathy, qualitatively similar to that seen in beta-thalassaemia major, was found in up to 90% of extrasplenic muscular arteries. Elastorrhexis lesions were also found in intrasplenic arteries and in stromal elastic tissue of spleens and parasplenic lymph nodes, in the absence of tissue iron overload. The arteriopathy appears in the first decade of life even in spleens of normal weight, and seems unrelated to the severity of permanent anaemia. It is suggested that patients suffering from hereditary chronic haemolytic diseases are subject to an elastic tissue disorder which is similar to hereditary pseudoxanthoma elasticum, the earliest and most frequent manifestation of which is arterial elastorrhexis of muscular extrasplenic arteries.

Arterial elastorrhexis: manifestation of a generalized elastic tissue disorder in beta-thalassaemia major.

Pseudoxanthoma elasticum-like lesions of the eye and skin are frequently observed in beta-thalassaemia, and there has been speculation about associated vascular lesions. This led to our study of histopathological material from thalassaemic patients. Histological re-examination was made of a series of 45 spleens and 45 surgical liver biopsies from 45 patients with beta-thalassaemia major, aged 6-25 yr and treated over the 20-yr period 1975-95. Correlations between clinical, laboratory and histological findings were demonstrated by statistical analysis. Arteriopathy characterized by fragmentation and multiple defects of the internal elastic lamina ('arterial elastorrhexis'), with deposits of iron and calcium salts, was found in the hilar arteries of the spleen with a frequency of 96%. Similar lesions were observed in the parenchymal arteries and the stromal elastic tissue ('stromal elastorrhexis') of the spleen, liver and lymph nodes. Arterial and elastic tissue alterations appear in the first decade of life and become generalized over the course of the disease, independent of the time of onset of transfusion and iron chelation therapy. Arterial elastorrhexis is the earliest and most frequent manifestation of a systemic elastic tissue disorder in beta-thalassaemia major. It appears to be an acquired pseudoxanthoma elasticum-like syndrome, related primarily to tissue hypoxia and disturbance of elastin metabolism.

Myofibroblasts and the progression of crescentic glomerulonephritis.

BACKGROUND: The cellular and humoral factors involved in the pathogenesis of glomerulosclerosis and renal fibrosis following a crescentic glomerulonephritis have not been fully elucidated. Myofibroblasts and transforming growth factor-beta (TGF-beta) have been implicated in the development of experimental and clinical renal fibrosis. We have attempted to identify these mediators in crescentic glomerulonephritis and determine their role in the progression of the disease. PATIENTS AND METHODS: We studied retrospectively 21 patients with crescentic and necrotizing glomerulonephritis (CNG) with emphasis on the renal expression (detected by immunohistochemistry) of myofibroblasts (alpha-smooth muscle actin+ cells), TGF-beta and collagen (III and IV) as well as their relationship with the clinical outcome of these patients. In situ hybridization histochemistry was applied to determine the site of synthesis of TGF-beta1 and collagen III. All the patients were treated by immunosuppression and followed up for a median period of 14 months. RESULTS: Myofibroblasts and TGF-beta were detected in the crescents as well as in the periglomerular and tubulointerstitial areas in CNG biopsies. TGF-beta1 was also detected within renal tubular cells. The percentage of glomeruli with fibrotic and fibrocellular crescents was positively correlated with the severity of Bowman's capsule disruption (r = 0.631, P < 0.01) and with the intensity of myofibroblast expression in the interstitium (r = 0.504, P < 0.05). Strong interstitial immunostain for myofibroblasts and TGF-beta was also noted in association with interstitial fibrosis. In situ hybridization revealed the site of synthesis of TGF-beta1 to be the renal tubular cells of patients with CNG. By contrast, the site of synthesis of collagen III appeared to be confined to interstitial cells surrounding vessels, tubules and the glomeruli in a distribution identical to that of myofibroblasts. There was a significant positive correlation between the number of interstitial alpha-SMA+ cells and both interstitial TGF-beta (r = 0.591, P < 0.01) and interstitial collagen IV (r = 0.588, P < 0.01). In addition, the number of interstitial alpha-SMA+ cells and the extent of immunostain for collagen IV were positively correlated with the final serum creatinine (r = 0.517, P < 0.05 and r = 0.612, P < 0.01 respectively) and partially predicted functional outcome (R2 = 26.7% and 37.5% respectively) as well as the response to treatment. An association was observed between periglomerular myofibroblasts and the generation of fibrotic and fibrocellular crescents. CONCLUSION: These observations suggest a causal link between myofibroblasts and fibrotic crescent formation. We also believe that interstitial myofibroblasts are actively involved in the pathogenesis of interstitial fibrosis in CNG.

Oligohydramnios syndrome and XYY karyotype.

A case of oligohydramnios syndrome was found to have an XYY karyotype and an inherited 9qh inversion. It is suggested that normal and extra Y chromosomes are a predisposing factor in the aetiology of severe congenital renal anomalies.