儿童自身免疫性肝炎诊断及治疗

自身免疫性肝炎((autoimmune hepatitis,AIH)是一种呈进行性进展、以汇管区周围炎症为主的自身免疫性肝脏疾病.AIH发病率低,尤其对于儿童患者,缺乏特异的症状和体征,在临床上容易误诊或漏诊.目前用于诊断AIH的评分系统主要有国际自身免疫性肝炎小组的IAIHG评分系统,简化评分系统亦可用于诊断儿童AIH.目前AIH在治疗上也取得一定的进展,但主要是对成年人AIH的治疗.糖皮质激素及多种免疫抑制剂可用于治疗儿童AIH,但仍需根据AIH患儿病情选择合适的治疗方案.     

ERYTHEMA ANNULARE CENTRIFUGUM COINCIDENT WITH EPSTEIN-BARR VIRUS INFECTION IN AN INFANT

ABSTRACT. Hammar, H. (Department of Dermatology, Karolinska Sjukhuset, Stockholm, Sweden). Erythema annulare centrifugum coincident with Epstein-Barr virus infection in an infant. Acta Paediatr Scand 63: 788, 1974.—Persistent annular erythemas include various more or less distinctly defined clinical entities mostly found in adults but are sometimes seen in infants. Erythema annulare centrifugum is distinguished as one group among these dermatoses. The pathogenesis of the annular erythemas is not clearly understood. A two-week-old girl who developed recurrent erythema annulare centrifugum during her first 6 months of life is described. Significant changes in the titres of anti-Epstein-Barr virus antibodies were coincident with the clinical course. The general health of the girl was not affected and there were no signs of infectious mononucleosis either in the girl or in her mother. The eruption left an apparently normal skin except for one lesion with atrophy and telangiectases one year after its first appearance. The coincistence of the significant rise and fall of anti-Epstein-Barr antibody titres with the clinical appearance of erythema annulare centrifugum strongly suggests a pathogenetic effect of the virus on the skin eruption.     

Muscle weakness in a girl with autoimmune hepatitis and Graves' disease

Autoimmune hepatitis (AIH) is a chronic hepatic autoimmune disease of unknown etiology associated with inflammatory changes and autoantibodies. The combination of AIH, Grave’s disease, and myasthenia gravis (MG) is rare, with only one other case reported. We report a pediatric patient with AIH type 2 and Grave’s disease who developed MG whilst on a treatment with corticosteroids. A 13-year-old girl, diagnosed with thyrotoxicosis, was identified as having AIH type 2. During the course of her therapy, she developed muscle weakness. Investigations revealed increased anti-acetylcholine receptor (AChR) antibodies and her electromyopgraphy (EMG) was characteristic for MG. Her course is described here. This case highlights the importance of investigating muscle weakness in severely ill hospitalized patients. Support: none.     

Erythema annulare centrifugum as the presenting sign of Pseudomonas aeruginosa sepsis in a newborn

We report a case of erythema annulare centrifugum (EAC) with neonatal onset. The patient presented on the fourth day of life with erythematous papules that enlarged centrifugally to form annular or policyclic plaques on anterior surface of trunk and legs without signs of systemic toxicity. Subsequently, she developed sepsis and disseminated intravascular coagulation and died on the sixth day of life. Blood culture grew Pseudomonas aeruginosa. The coexistence of P. aeruginosa sepsis with the clinical appearance of erythema annulare centrifugum strongly suggests a pathogenetic effect of the microorganism on the skin eruption. To the best of our knowledge, this is the first report of EAC with P. aeruginosa sepsis in a newborn.     

Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association

We report a 7-year-old girl with 22q13 deletion syndrome, 46,XX,Ish del(22)(q13.3)(ARSA-; D22S1726), who developed a fulminant autoimmune hepatitis requiring orthotopic liver transplantation. Recently, it has been suggested that the Shank3 gene product, whose deficiency is responsible for the features observed in this syndrome, could play a role in immunological response. Despite an increased incidence of respiratory infections, autoimmune diseases have thus far not been reported in patients with this syndrome. This is the first case of fulminant autoimmune hepatitis associated with the 22q13 deletion syndrome. The possible relationships between immune system dysfunctions peculiar of this syndrome and autoimmune hepatitis are discussed.     

An 8-year-old boy with autoimmune hepatitis and Candida onychosis as the first symptoms of autoimmune polyglandular syndrome (APS1): identification of a new homozygous mutation in the autoimmune regulator gene (aire)

An 8-year-old boy presented in 1995 with a 2-year history of hypertransaminasemia and hypergammaglobulinemia. Afterwards the patient displayed onychosis with a positive culture test for Candida albicans (CA). Because of the persistence of hypertransaminasemia, a percutaneous liver biopsy was performed showing ‘low grade chronic active autoimmune hepatitis’ (AIH), positive for liver-kidney microsomal autoantibodies and antibodies to the hepatic autoantigen cytochrome P450-1A2. Immunosuppressive treatment was initiated. In 2003 he developed Addison’s disease resulting in the diagnosis of autoimmune polyendocrinopathy candidiasis-ectodermal dysplasia (APECED) syndrome, also known as autoimmune polyendocrine syndrome type 1 (APS1). Anti-17OH hydroxylase antibodies tested negative, anti-21-OH hydroxylase autoantibodies were positive. Among the other relevant organ- and non organ- specific autoantibodies, aromatic L-amino acid decarboxylase (ADDC) autoantibodies and anti-tryptophan hydroxylase autoantibodies were positive. The patient also presented polyuria and polydypsia with diabetes insipidus. Because of the presence of two diagnostic criteria of APS1, mutations in the autoimmune regulator gene (AIRE) were performed, which revealed the presence of a novel mutation (c1314- 1326 del 13/insGT) in exon 11. In conclusion, the diagnosis of APECED should be suspected in any child with minimal hypertransaminasemia, anti-microsomal autoantibodies and Candida albicans onychosis.     

Detection of autoimmune regulator gene mutations in children with type 2 autoimmune hepatitis and extrahepatic immune-mediated diseases

Autoimmune regulator gene mutations were identified in 3 children with type 2 autoimmune hepatitis and extrahepatic immune diseases, including 1 child with immune hepatitis recurrence after liver transplantation. These findings suggest that autoimmune regulator gene variants might predispose children to systemic autoimmune disease, a recurrence of immune disease, or both.     

Autoimmune hepatitis

Autoimmune hepatitis is one of the causes of chronic progressive liver disease in childhood. Here we report 14 cases with clinical findings, therapeutic management and prognosis, in order to define the course of the disease. Diagnosis of autoimmune hepatitis was done with the presence of at least one of these autoantibodies; antinuclear antibody, smooth muscle antibody, liver-kidney microsomal type 1 antibody, and perinuclear antineutrophilic cytoplasmic antibody. Patients were seen every 3 to 6 months. After doing a complete physical examination, biochemical parameters and autoantibodies determined at each visit. Mean age at diagnosis was 10.9±2.6 years (range, 7–15.5 years) and female to male ratio was 1∶3. Thirteen patients had jaundice and all had high levels of ALT, AST and gammaglobulin. Hepatomegaly was found in 71.4% and splenomegaly in 64.3% of the patients. All patients were classified as type 1 autoimmune hepatitis. Liver biopsies revealed severe active hepatitis with mononuclear cell infiltration in portal areas, piecemeal necrosis. Drug therapy consisted of prednisone (2 mg/kg/day) per oral at the beginning, and addition of azathioprine (1.5 mg/kg/day) per oral at the 3rd-6th month with slow tapering of prednisone in 12 children. Both drugs were started together to two patients. Follow-up period was 30.7±15.6 months (range, 12–72 months). Sustained normalization of ALT could not be obtained with tapering doses of prednisone alone. Decrease in ALT levels did not correlate with disappearance of serum autoantibodies. None of the patients showed decompensation of liver disease. Azathioprine administration is necessary to decrease prednisone dose and to maintain a sustained normal transaminase values.     

Mechanisms of autoimmune hepatitis

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease with a female preponderance, responsive to immunosuppressive treatment. Two types of AIH are described: type 1 AIH is characterized by positivity for smooth muscle and/or antinuclear antibody, while type 2 AIH is positive for liver kidney microsomal type 1 antibody. The putative mechanisms leading to the development of this condition include genetic predisposition to autoimmunity through possession of specific human leukocyte antigen alleles, immune reactions to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed toward structurally similar self-components, and an impairment in immune regulation. AIH has been described to arise de novo after liver transplantation. The mechanisms leading to post-transplant autoimmunity remain to be defined.     

Seronegative autoimmune hepatitis in childhood

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children, although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis. Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated. The absence of autoantibody positivity, hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease. In general, seronegative autoimmune hepatitis often presents with acute hepatitis, and its treatment and prognosis similar to seropositive autoimmune hepatitis. The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood, and those of which current knowledge is vague.     

Decreased health-related quality of life in children and adolescents with autoimmune hepatitis

Objective

The objective of this study was to evaluate the health-related quality of life in children and adolescents with autoimmune hepatitis.

Abdominal tuberculosis with autoimmune hemolytic anemia

An eight-year-old male child presented with progressive distension of abdomen, fever, pallor and jaundice with a history of tubercular contact. Investigations were suggestive of abdominal tuberculosis with autoimmune hemolytic anemia. The child responded well to a course of oral steroids with antitubercular treatment. A literature search did not reveal any previous case report of an association between tuberculosis and autoimmune hemolytic anemia.     

Giant cell hepatitis with autoimmune hemolytic anemia in a Korean infant

Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AHA) is a very rare disease characterized by early onset and severe clinical manifestations, including immune hemolytic anemia and hepatitis with cholestasis. The prognosis is poor despite aggressive immunosuppressive therapy. We report here the first case of GCH with AHA in East Asia. A 2‐month‐old boy was admitted with jaundice. Blood test indicated abnormal liver function and low hemoglobin. Direct Coombs test and several autoantibodies associated with liver disease were positive, and liver biopsy was consistent with GCH. He was treated with prednisolone and ursodeoxycholic acid, and at the time of writing was in clinical and biochemical remission after prednisolone was stopped.     

Orthotopic liver transplantation for acute liver failure secondary to autoimmune hepatitis in a child with autoimmune polyglandular syndrome type 1

Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal-recessive condition characterized by hypoparathyroidism, autoimmune Addison's disease, and chronic mucocutaneous candidiasis. Autoimmune hepatitis develops in 10-20% of affected patients and has a variable course ranging from asymptomatic chronic liver disease to lethal fulminant hepatic failure. Liver transplantation has been documented previously in only two patients. We report a 14-yr-old boy with APS-1 who developed acute liver failure secondary to associated autoimmune hepatitis. He did not respond to corticosteroid therapy and was successfully treated with an orthotopic liver transplant.     

Subcutaneous (deep) granuloma annulare in children: a possible mimicker of epithelioid sarcoma

Subcutaneous granuloma annulare (SGA) is a self-limited inflammatory lesion consisting of dermal or subcutaneous nodules usually affecting children. Lower extremity involvement is the most common anatomic site. Because of the subcutaneous location, the morphological diagnosis of SGA can be challenging, and differential diagnoses are both benign and malignant processes including epithelioid sarcoma. Our article examines the clinical, histopathological, and immunohistochemical aspects of SGA in comparison to ES. We present 3 cases of SGA in children, who were initially diagnosed with ES and discuss the differential diagnoses features between SGA and ES. Because SGA can simulate ES, the awareness of this possibility is important to avoid overtreatment, like amputation, of the benign condition (SGA).     

Asymptomatic autoimmune chronic active hepatitis in a male adolescent

We report a 12-year-old boy presenting with smooth muscle antibody-positive auto-immune chronic active hepatitis. Suspicion of the diagnosis arose after a routine blood test which revealed abnormal liver function tests. In spite of the presence of cirrhosis and patchy necrosis on liver biopsy, our patient never showed any clinical feature of impaired liver function. This observation demonstrates that auto-immune hepatitis may exist for a long time before clinical symptoms appear and probably explains why some cases of auto-immune hepatitis finally present as fulminant liver failure.