A high incidence of α1‐antitrypsin (AAT) deficiency has been reported in patients with C‐ANCA systemic vasculitis in association with antibodies against proteinase‐3 (PR3). To clarify the role of AAT ...deficiency in the acute vasculitic process as well as in progression of the disease, we studied 84 patients with either C‐ANCA or P‐ANCA vasculitis with special reference to: (a) the AAT gene, (b) the phenotypic (Pi) variants and (c) the serum levels during both acute illness and remission. The PiZ gene was found in six patients (8% vs. 1.5% controls) irrespective of the type of autoantibodies (C‐ANCA vs. P‐ANCA). All PiZ patients displayed the ability to raise their AAT serum levels up to the normal range during acute illness. In contrast, 24 patients with the PiM phenotype presented low AAT serum levels during acute illness. In all these patients, the AAT levels returned to normal values during the remission. Low AAT levels were associated with low levels of C‐reactive protein (PCR) (P < 0.001), with a less severe renal involvement or a minor risk of death, and, in one tested patient, with a novel point mutation (TCGA → TCAA) at the enhancer–promoter region of the AAT gene. Low AAT serum levels did not correlate with either type/titre of autoantibody or distribution/severity of the vasculitis process. In the case–control study, high AAT levels emerged as a major determinant of progression towards end‐stage renal failure odds ratio 3 (95% CI 1.1–8.4). These results indicate: (a) a high incidence of the PiZ gene of AAT in systemic vasculitis irrespective of the type of autoantibodies; (b) a novel form of AAT deficiency associated with the normal PiM phenotype becoming manifest only during acute illness; (c) dysregulation of the acute‐phase response affecting selectively AAT or both AAT and PCR; (d) correlation between low plasma levels of AAT and less severe renal involvement or risk of death.
We report on five patients from three families with neurogenic arthrogryposis, cholestasis and tubular renal dysfunction. Despite a similar clinical picture the liver histology showed a broad ...pathological spectrum, ranging from pigment storage to parenchymal giant cell transformation and ductopenia. The findings are compared with those of other cases from the literature in search of a correct nosology of the syndrome characterized by arthrogryposis, renal and liver disease. CONCLUSION. We propose to consider the picture of arthrogryposis, renal tubular dysfunction and cholestasis as a single syndrome.
A 22-year-old female presented, in December 199B, with asthenia, itching and hypereosinophilia. In January 1997, due to the same clinical picture, the patient had inappropriately been diagnosed ...elsewhere to have an “idiopathic eosinophilic syndrome” and complete remission was obtained after short-term steroid treatment. Upon admission, physical examination was negative and blood tests revealed absolute eosinophilia (42%, i.e., 3800 of 9600 white blood cells), aspartate aminotransferase 4 × upper limits of normal, alanine aminotransferase 5 × upper limits of normal and alkaline phosphatase 2 × upper limits of normal. Both liver biopsy and endoscopic retrograde cholangiopancreatography findings were totally consistent with primary sclerosing cholangitis, while all known causes of hypereosinophilia and alteration in liver function tests were carefully excluded. The clinical course was characterized by complete clinical and biochemical normalization in absence of any treatment and further follow-up was completely negative.
To assess incidence, risk factors, histology, and outcome of severe hepatotoxicity (SH) during antiretroviral treatment (ART).
Seven hundred fifty-five HIV-seropositive patients consecutively ...prescribed new ART were selected. Liver function tests were assessed at baseline, after 1 month, and every 4 months thereafter. Liver biopsy was recommended in case of SH (i.e., increase in liver enzymes >/=10 times the upper limit of normal or 5 times baseline if markedly abnormal).
Twenty-six cases of SH were observed with an incidence of 4.2% person-years. Liver failure (LF) was rarely seen (1.1 per 100 person-years). Liver damage was invariably observed in patients with chronic viral hepatitis. Liver histology showed exacerbation of viral hepatitis in all 16 patients for whom a liver biopsy was available at the time of SH. A direct correlation was found between alanine aminotransferase increase and increase in CD4 T-cell count in patients with SH (r = 0.53, p <.001). Death occurred during follow-up in 7 of 26 (27%) patients, all of whom showed LF and baseline CD4+ count less than 200 cells/mm(3) (7/7 patients = 100% vs. 8/19 patients without LF; p <.01). Relapse of SH was observed after ART was recommenced in 7 of 17 (41%) patients. Five of these 7 patients did not show further SH relapse after treatment with interferon.
This study provides estimates of SH and LF in a large population-based setting where hepatitis C virus coinfection is highly prevalent and provides indications that liver damage may be caused by immune reconstitution and related exacerbation of viral hepatitis. A strict follow-up for hepatotoxicity is mandatory when ART is initiated in patients with <200 CD4+ T cells/mm(3). Antihepatitis pre- or comedication could be an effective preventive or curative measure.
Adenomyomatosis of the gallbladder (ADMG) is defined as an acquired disease characterized by localized or diffuse hyperplastic extensions of the mucosa into, and often beyond, the thickened ...gallbladder muscular layer (Rokitansky-Aschoff's sinuses). In recent years, attention has been drawn to its malignant potential. The occurrence of ADMG has never been reported in children. The authors report the case of a 5-year-old boy with symptomatic ADMG, who was successfully treated by laparoscopic cholecystectomy.
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