Henoch–Schonlein purpura, also called IgA-vasculitis, is a systemic small vessels vasculitis with immunoglobulin A1-dominant immune deposits. The optimal treatment remains controversial. Because IgA-vasculitis is characterized by leukocyte infiltration of the blood vessel walls along with immunoglobulin A deposition, and because glucocorticosteroids inhibit inflammatory processes, early administration of glucocorticosteroids has been postulated to be effective, but this indication remains controversial. Immunosuppressive agents (azathioprine, cyclophosphamide, cyclosporine, mycophenolate) have been used in combination with glucocorticosteroids without definitive evidence of effectiveness. The efficacy of rituximab in adult IgA-vasculitis has been reported in few cases. We described a monocentric experience on the use of rituximab in adult IgA-vasculitis with biopsy-proven nephritis. The patients achieved a complete remission of nephritis and syndromic manifestations, and no patients experienced adverse reactions. These data have been compared with the limited literature nowadays available.

Letters Acute renal failure in leishmaniasis Sir, Visceral leishmaniasis (VL) has become a frequent complication of AIDS [1]. When Leishmania and HIV interact, a new broad spectrum of leishmaniasis occurs. Leishmanias can spread to unexpected sites other than the reticulo-endothelial system, such as peripheral blood, normal skin, gastrointes-tinal tract and respiratory tract [2]. Acute renal failure (ARF) has rarely been reported [3]. A 28-year-old Nigerian woman, who had been in Italy for 8 months, attended the hospital because of epistaxis, confusion and anuria. Her temperature was 36.3 C, O 2 saturation 98%, blood pressure 120/70 mmHg and cardiac pulse 125/min. Her physical examination was unremarkable, except for abdominal tenderness. pneumoniae IgG and IgM titres, parvovirus IgM and blood cultures were negative. Parvovirus IgG titre was positive 1/256. The patient received nasal packing and blood transfusions, and dialysis was initiated. She died 2 days later, with unremitting epistaxis. Post-mortem examination showed diffuse alveolar haemorrhage, splenomegaly, lomboaortic lymphoadenopathy and haemorrhagic necrosis of naso-pharynx. Light microscopy examination evidenced striking diffusion of Leishmanias in phagocytic cells and extracellular presence in vascular lumina and connective tissues (kidney, liver, nasopharynx, lung, skin, uterus, ovary, lymph nodes, bone marrow, heart and spleen). Renal changes consisted of the following. (i) Glomerular lesions: as segmental collapse of capillary loops, congestion of capillaries filled by Leishmanias (Figure 1), capsular synechiae, focal and segmental areas of glomerular sclerosis, focal thickening of basement membranes , parasite invasion of mesangial axes (cells and matrix) and focal mesangial and epithelial cell hyperplasia with initial crescent formation. Immunohystochemical examination was negative for immunoglobulins and light chains. (ii) Tubulo-interstitial damage: as acute necrotizing tubulitis, tubular necrosis and hyaline casts, focal infiltration of CD68þ and CD3þ cells, and Leishmanias inside of histiocytes in peritubular areas. (iii) Blood vessel changes as focal leukocytoclastic vasculitis of vasa recta and free Leishmanias in the capillary lumina. Acute glomerulonephritis (GN) [4], proliferative GN [5], collapsing focal segmental glomerulosclerosis [6], acute interstitial nephritis [5] and tubular cell necrosis and tubulitis [7] have all been described in patients with Leishmaniasis. ARF [3], nephrotic syndrome [4] and proteinuria [5] have been reported. The renal damage in our patient was mediated through different mechanisms. Tubular necrosis was secondary to ischaemia, due to small vessel obliteration by Leishmanias, and to haemolysis. Necrotizing tubulitis was due to direct invasion by the parasites and by inflammatory reaction. There was a diffuse invasion of renal structures by Leishmanias. Glomerular …

BACKGROUND:In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS.METHODS:GBM distribution of col IV alpha1-, alpha3-, and alpha5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I-III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0-3).RESULTS:Col IV alpha1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IValpha3- and alpha5-chains were observed: positive, negative, and alpha3(IV)-positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete loss of alpha3(IV)- and alpha5(IV)-antigen were significantly more frequent (P<0.05 and P<0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for alpha5(IV)-chain. Intensity of alpha3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving.CONCLUSIONS:Our results suggest that the alpha3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate a more severe renal disease in AS.

s: Wednesday, May 31, 2000: POSTER SESSIONS: POSTER SESSION 17: Therapeutic and Clinical Pharmacology (TH)

Rare sarcomas at low- or high grade malignancy seem frequently associated with transplants and/or sometimes located at the arteriovenous fistula (AVF). We reported a case of dermatofibrosarcoma protuberans, an uncommon low grade sarcoma of fibrohistiocytic derivation, which originated 3 years after a transplant near the surgical scar of Brescia-Cimino AVF, in 61-year-old Caucasian man. Because of its relentlessly local aggressive capacity and clinically indolent behavior, this tumor may sometimes be dismissed by patients and physicians. We stress the importance of an enhanced dermatological vigilance in patients with grafts and point out the role of immunosuppressive therapy in the pathogenesis of these rare neoplasias. A 61-year-old Caucasian man with end-stage renal failure secondary to reflux-nephropathy underwent a cadaveric kidney transplant in March 1989. He had been treated with hemodialysis for 14 years before the transplant. Immunosuppressive induction protocol consisted of lymphoglobulin during the first week, azathioprine, and steroid. Cyclosporine was initiated at day 6. One episode of acute rejection, methylprednisolone-sensitive, complicated the immediate postoperative course. The patient's following clinical course was uneventful, with baseline serum creatinine of 1.4 mg%. The chronic immunosuppressive regimen was cyclosporine (3.5 mg/kg/day), azathioprine (0.75 mg/kg/day), and prednisone 5 mg/day. In December 1992, at routine follow-up, the patient presented a single reddish exophytic nodular lesion (0.5 cm) over his right arm, near the surgical scar of the Brescia-Cimino AVF. The dermatologist consultant diagnosed benign dermatofibroma. This lesion remained unchanged for the following 3 years. In March 1995, we observed a dimensional increase of the lesion and the appearance of a similar one close to it. A biopsy specimen of the lesion demonstrated ill-limited dermal and hypodermal proliferation of CD34 + fusiform cells with a storiform arrangement. The diagnosis of dermatofibrosarcoma protuberans (DFSP) was made. The patient underwent a wide resection of the lesion (3-cm safety margin and excision of the muscolar layer underneath) with AVF legature, followed by skin grafting. With the patient's consent, the immunosuppressive regimen was modified: azathioprine was stopped, cyclosporine was reduced to 3 mg/Kg/day, and prednisone was unchanged. Until now, no evidence of recurrence has been present, serum creatinine has been unchanged, and proteinuria has been absent. First described by Darier-Ferrand in 1924, DFSP is a rare tumor that constitutes <0.1% of all malignancies and 1.17% of all soft tissue neoplasia (1). It is frequently an intradermic tumor of middle-aged individuals, slightly predominant in men, documented in all races (2). The most common locations are the trunk and proximal extremities. The typical clinical presentation of DFSP is initially an asymptomatic, solitary, indurated plaque (violaceous, red-brown, or flesh colored), sometimes dismissed by patients and physicians for indolent behavior (1). Characteristic of this soft tissue tumor is slow progression of the lesion, with relentless enlargement and development of protuberant nodules within the plaque. Growth is often accelerated when the nodules appear, and sometimes the tumor becomes painful or ulcerates (2). Because of its relentless aggressive capacity, the occult spread of DFSP makes complete removal difficult; thus, high local recurrence rates (20-60%) have been reported (3). Diffuse metastases are rare (1-4%), and survival after distant recurrence is poor. In terms of histological features, DFSP arises in the dermis and involves the subcutaneous tissue. It is composed mainly of dense uniform cells with spindle-shaped nuclei arranged into irregular, interwoven fascicles, resulting in a storiform pattern. "Honeycomb" entrapment of fat is the characteristic histological pattern. Mitoses are rare (4). Immunostaining for CD34 is commonly used to differentiate DFSP from other benign fibrohistiocytic proliferations. This technique seems to be highly specific, but sensitivity has yet to be determined (1). The pseudopod-like extension of the tumoral cells justifies an extensive surgical excision, which is the treatment of choice of DFSP. There is growing evidence that Mohs micrographic surgery reduces the rate of local recurrences, but the authors argued the necessity of longer follow-up (>5 years) in larger series (5) to evaluate the results of this technique. For the rare tendency to distant metastases, prophylactic regional lymphadenectomy was unwarranted. Potential benefits from radiotherapy are suggested, and there is no role for chemotherapy in localized DFSP. The role of the latter in metastatic DFSP remains undefined. Up to 1995, in the Cincinnati Transplant Tumor Registry (6), the rate of occurrence of non-Kaposi sarcomas in organ allograft recipients was 1.7% of all cancers, a considerably higher proportion than in the general population. Soft tissue origin was documented in about half of these sarcomas, and the survival rate is related to the histological pattern and organ localization. DFSP is a rare skin localized low grade sarcoma of fibrohistiocytic derivation, with a relentlessly aggressive capacity for local invasion and a very low incidence of distant metastasis. In our patient, the tumor was near the surgical scar for Brescia-Cimino AVF. Even if the origin of this neoplasia in areas previously subjected to trauma is debated, several striking cases of DFSP arise in surgical scars (7). Rare sarcomas with low- or high-grade malignancy are more frequently reported at the site of the AVF also in transplant recipients (6). We can speculate that immunosupression, the local toxic effect of some immunosuppressant drugs (8), superimposed (in the exposed areas) at ultraviolet irradiation (9) can modify the local apoptotic control and trigger out some oncogenic cells. To our knowledge, this is the second reported case (10) of DFSP in transplant recipients. Because of its characteristic local aggressivity, but also indolent behavior, we stress careful dermatological monitoring of these patients. Franco Picciotto, MD U.O. di Oncologia Dermochirurgica; I.R.C.C.-Ospedale Mauriziano Torino Bruno Basolo, MD1 Carlo Massara, MD Ospedale Giovanni Bosco; Divisione di Nefrologia e Dialisi; Piazza Donatore di Sangue 3; Torino, Italy Virginia Caliendo, MD Divisione di Oncologia Dermochirurgica; A.O.S. Giovanni Battista-Molinette Filippo Aloi, MD Servizio di Istopatologia; Dipartimento di Dermatologia; Università di Torino Silvio Gaia Divisione di Chirurgia Vascolare; A.O.S. Giovanni Battista-Molinette; Torino, Italy Fançois Bayle Service de Nephrologie; Unité de Transplantation; Centre Hopitalier Universitaire; Grenoble, France Francesco Quarello Ospedale Giovanni Bosco; Divisione di Nefrologia e Dialisi; Piazza Donatore di Sangue 3; Torino, Italy

Several reports have demonstated that organ transplant recipients receiving life-long immunosuppression develop a disproportional higher incidence of malignancies when compared with expected cancer rates in age-matched control population. In the long term survival following transplantation, cancers represent a major cause of morbidity and late failure in patients (pts) otherwise living with a well functioning graft. In some reports carcinomas represent 37.6

BACKGROUND:This study investigated whether abnormal circulation of macromolecular IgA and IgA with altered glycosylation or electrical charge plays a role in the recurrence of IgA nephropathy (IgAN) after transplantation.STUDY DESIGN:A total of 92 renal transplant patients were enrolled; 52 IgAN patients and 40 with other non-IgAN. The IgAN group included 10 patients showing IgA mesangial deposits in the grafted kidneys (recurrent group) and 10 who did not (immunohistochemically proven non-recurrent group). In addition another 22 IgAN transplant patients were clinically free of recurrent disease.METHODS:The analyses included macromolecular IgA (IgAIC) detected by the conglutinin assay (K), heavy IgA precipitated in 2.5% polyethylene glycol (PEG), IgA-fibronectin aggregates (IgA/F Aggr), mixed IgA/IgGIC, IgA binding to mesangial matrix components (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine) and IgA with altered glycosylation (Jacalin-binding assay).RESULTS:After transplantation, IgAN patients displayed significantly higher mean levels for each variable measured than non-IgAN (ANOVA, P < 0.05). By stepwise regression analysis, the binding of IgA to fibronectin had the highest coefficient. By comparing data in recurrent and clinically non-recurrent IgAN, we observed that two groups could be distinguished by the results of the two assays for macromolecular IgA (conglutinin IgAIC and IgA-fibronectin aggregates) and IgA with increased affinity for type IV collagen (P < 0.05). When the selected group of immunohistochemically proven non-recurrent IgAN was compared to the recurrent one, a statistically significant difference was found only for the binding of IgA to type IV collagen (P < 0.05). Data from this test were significantly related with proteinuria (P < 0.05) and microscopic haematuria (P < 0.04).CONCLUSIONS:Even though the IgA serology of renal transplant IgAN patients shows peculiar features and recurrent and non-recurrent IgAN differ in many aspects, the prevalence of positive data in the two groups had no predictive value. This suggests that the recurrence of IgAN is modulated by factors affecting the interaction between circulating abnormal IgA and mesangial cells and/or matrix.

The authors review the literature data concerning different aspects of membranous glomerulonephritis (MGN) in the elderly and present a clinical analysis of 32 MGN patients aged more than 65 years followed in their own center.

Two hundred and one patients had biopsies of their native kidneys with ultrasound-guided needle technique. They were evaluated on the second postbiopsy day with colour-coded Doppler sonography. Ten patients out of these 201 were found to have an arteriovenous fistula, which remained asymptomatic for the whole follow-up period (follow-ups ranged from 2 to 31 months). Four of these 10 patients developed a perirenal haematoma as well and five macroscopic haematuria.Our study shows that the systematic use of colour-coded Doppler sonography after renal biopsy facilitates diagnosis of arteriovenous renal fistula.

Computer-assisted medical activity is increasing in several fields, with wide perspectives in nephrology and dialysis accounting for the peculiar characteristics of this population such as number, complexity, follow-up length and economic costs. Since 1980 we have been studying a computerized organization of our Region's departments in order to achieve 3 main results: 1) a registry of all patients undergoing dialysis in the area, with a one- a-year complete clinical update; 2) a computerized medical chart, which could gather all the clinical, technical and managerial aspects of the treatment; 3) a teledialysis program, to follow every session in local and remote stations. The first aim has been reached with useful information for the dialytic policy in the area. The second objective is ongoing with straight evidence of easy, speedy procedures, and accurate data collection. The third goal is on a preliminary phase looking at the safety, reliability and precision of the treatments. Informatic procedures seem to be quite advisable in improving as clinical surveillance of the patients, as technical and managerial aspects of dialysis units.