Clinicohistological correlation of etiological spectrum of chronic liver disease diagnosed during noncirrhotic stages in children: Can need of liver biopsy be obviated?

BACKGROUND AND AIM: Limited data exist regarding the etiological spectrum of the subset of chronic liver diseases (CLDs) diagnosed in noncirrhotic states in children. Our primary objective was to study the clinicoetiological profile of CLDs detected in noncirrhotic stages in children younger than 12 years of age. The secondary objective was to find the hepatic histological correlation of provisional diagnosis by different ranks of doctors. METHODS: This was an observational epidemiological study, cross-sectional in design, conducted in a tertiary-care setting over a 2-year period. RESULTS: Thirty-seven cases were enrolled, with a mean ± SD age of 8 ± 4.1 years and a male:female ratio of 1.8:1. Etiologies noted were Wilson disease (n = 8), autoimmune hepatitis (n = 4), secondary hemochromatosis (n = 4), chronic hepatitis B (n = 3), chronic hepatitis C (n = 2), non-alcoholic steatohepatitis (n = 2), progressive familial intrahepatic cholestasis (n = 2), extrahepatic biliary atresia (n = 2), Alagille syndrome (n = 1), galactosemia (n = 1), Gaucher disease (n = 1), Niemann-Pick disease (n = 1), and Budd-Chiari syndrome (n = 1), with an inconclusive diagnosis in five children. Relevant investigations were ordered more frequently by the specialist consultant (SC) and super specialist (SS) combined in comparison with the senior resident (SR) and junior resident (JR) together. (P = 0.0013). Irrelevance of the tests ordered was significantly higher in the junior tier (JR and SR; SR > JR) in contrast to the senior tier of doctors (SC and SS) (P < 0.01). The clinicohistological correlation of an etiological diagnosis significantly differed between the junior and senior ranks of physicians. We noted that an ideal clinical acumen could help to avoid liver biopsy for etiological diagnosis in 78.3% (29/37) of the study population. CONCLUSION: Interpretation of clinical presentation by the senior set of doctors is preferable, which could obviate the need for liver biopsy regarding diagnosis in a proportion of pediatric CLD patients.

Validation of Revised Baveno VI Criteria for Screening of Varices Needing Treatment in Children with Cirrhosis.

BACKGROUND: Baveno VI criteria for screening varices needing treatment (VNT) have not yet been validated in an exclusive pediatric and adolescent set of the population, in whom baseline parameters differ in relation to adults. Therefore, our primary objective was to validate Baveno VI and its expanded form in children below 18 years of age. The secondary aim was to elicit whether any revision of the above criteria with a target of not missing more than 5% VNT could be more accurate for this age group. MATERIALS AND METHODS: The work was carried out in two medical institutes, over a span of 3 years. Consecutively enrolled patients below 18 years of age, with compensated cirrhosis confirmed by liver biopsy, were evaluated for related blood parameters, transient elastography (TE) and esophagogastroduodenoscopy. RESULTS: Out of the 33 recruited patients, five (15.15%) met the criteria for VNT. The sensitivity, specificity, PPV and NPV of Baveno VI and Expanded Baveno VI were observed as 60%, 92.3%, 60% and 92.3%, and 20%, 100%, 100% and 88%, respectively. We found that the Revised Baveno VI criteria with TE <19 kPa and platelet count of >175×109 cells/L, with sensitivity 100%, specificity 79%, PPV 45%, NPV 100% and accuracy of 82%, are more appropriate for this age group. CONCLUSION: We propose that further multicentrer studies with a larger sample size should be conducted before incorporating Revised Baveno VI criteria for high-risk varices in patients below 18 years in future guidelines.

Intracranial Hemorrhage Following Intrathecal Methotrexate Therapy for Acute Lymphoblastic Leukaemia.

BACKGROUND: Acute toxic leukoencephalopathy following intrathecal methotrexate administration is well documented but intracranial haemorrhage is extremely rare. CASE CHARACTERISTICS: A 2-year-6 months old girl with acute lymphoblastic leukemia developed sudden onset neurological deterioration following intrathecal methotrexate. OBSERVATIONS: Computed tomography scan of brain demonstrated intraventricular and subarachnoid hemorrhage. OUTCOME: Child improved gradually on conservative management. Follow-up neuroimaging showed resolution of hemorrhage. MESSAGE: Intracranial haemorrhage is a rare but serious complication of intrathecal methotrexate.

Acute Disseminated Encephalomyelitis in a Child Following Plasmodium vivax Malaria.

Acute Disseminated Encephalomyelitis (ADEM) is a multifocal, monophasic, acute demyelinating disease of the brain and spinal cord, which is commonly preceded by viral infections and occasionally bacterial infections or immunizations. Its occurrence following malarial infection, especially Plasmodium vivax Malaria is very uncommon. We report an 11-year girl who presented with clinical features of encephalopathy and generalized convulsions, 10 days following complete recovery from the Plasmodium vivax Malaria. Diagnosis of ADEM as a complication of Plasmodium vivax Malaria was made based on acute onset of neurological events, characteristic findings on Magnetic Resonance Imaging (MRI) of brain and prompt response to corticosteroid therapy. Follow-up MRI, 6 months after discharge, showed complete resolution of change found on the initial MRI. To the best of our knowledge, only two such cases have been reported in the English literature till date.

Renal artery stenosis: An unusual etiology of hypertensive encephalopathy in a child with fanconi anemia.

A 9-year-old girl, diagnosed case of Fanconi anemia, presented with generalized convulsion with altered sensorium. She had fever, severe pallor, sinus tachycardia, blood pressure of 180/120 mmHg in both upper and lower limb, pan-systolic murmur of grade 2/6, abdominal bruit and bilateral papilledema. A provisional diagnosis of hypertensive encephalopathy was made and managed with continuous labetalol infusion. Detailed evaluation including magnetic resonance angiography of renal artery detected underlying atrophic and non-functioning right kidney secondary to severe renal artery stenosis on the same side. She was started with multiple antihypertensives, but her blood pressure was maintained poorly. Later on, she underwent rightsided nephrectomy. Following surgery, she was doing well and maintaining normal blood pressure without any antihypertensives. Our child is the second reported case of Fanconi anemia associated with renal artery stenosis presenting with hypertensive encephalopathy.

Association of Joubert syndrome and Hirschsprung disease.

BACKGROUND: Association between Joubert Syndrome and Hirschsprung disease is rare. CASE CHARACTERISTICS: A 9-month-old girl having developmental delay and chronic constipation. OBSERVATION: Molar tooth sign on MRI brain and absence of ganglion cells in rectal biopsy specimen. OUTCOME: Child underwent surgical repair for Hirschsprung disease. MESSAGE: Association of these two rare entities could be explained by ciliopathy.

Acute disseminated encephalomyelitis: an uncommon presentation of hyper IgE syndrome.

The hyper-immunoglobulin E (IgE) syndrome (HIES), also known as Job's syndrome is a rare primary immunodeficiency characterized by the clinical triad of recurrent staphylococcal abscesses of skin, recurrent cyst-forming pneumonia, and an elevated serum IgE level of > 2000 IU/ml. Although, most cases are sporadic, families with autosomal dominant (AD-HIES) and recessive (AR-HIES) traits have been reported. Very few articles were published previously on central nervous system abnormalities with definite neurologic manifestations which may vary from partial facial nerve paralysis to hemiplegia in children but Acute Disseminated Encephalomyelitis (ADEM) in a child with HIES hitherto has not been reported. Here we describe a 5-year-old male child with HIES who presented with neurologic manifestations of ADEM.

Intraosseous pseudotumour in a child with mild hemophilia B: report of a rare case and brief review of literature.

Hemophilic pseudotumor is a rare, but well-known, complication of hemophilia occurring in 1-2 % of individuals with a severe factor VIII or IX deficiency. The hemophilic pseudotumor is defined as an encapsulated hematoma that increases of volume progressively by episodes of recurrent hemorrhage; usually originate in soft tissues or in subperiosteal or intraosseous areas. Very seldom, patient with mild form of hemophilia present with intraosseous pseudotumor. This report describe an 11-year-old boy with mild factor IX deficiency (17 % of normal factor IX activity), who developed a pseudotumor of the femur.

Congenital chylous ascites treated successfully with MCT-Based formula and octreotide.

Medium chain triglyceride (MCT)-based diet, total parenteral nutrition (TPN) and repeated paracentesis are considered as supportive management for congenital chylous ascites (CCA). TPN is considered where therapy with oral MCT is poorly tolerated by the patient especially young infant with unstable hemodynamic. Surgery is recommended when medical therapy fails. Herein, we report a 2½-month-old infant with CCA, treated successfully with octreotide intravenous infusion after the initial failure to response to conventional conservative therapy with MCT-enriched formula and paracentesis.

Tuberous sclerosis presenting with hemorrhagic stroke.

BACKGROUND: Incidence of intracerebral hemorrhage in patients with tuberous sclerosis is rare, and in most of the cases it is associated with either underlying cerebrovascular malformation or hemorrhage into the subependymal giant cell astrocytoma. CASE CHARACTERISTICS: A 2-year-old boy presented with a hemorrhagic stroke, and subsequently diagnosed as a case of tuberous sclerosis. OBSERVATION: Detailed work-up for stroke did not reveal any definite etiology. OUTCOME: Weakness gradually improved. Follow-up neuroimaging showed resolution of hemorrhage. MESSAGE: Clinician must be aware regarding this rare presentation of tuberous sclerosis.

Varadi Papp syndrome, an unusual variant of oral-facial-digital syndrome: Report of a rare case.

Varadi Papp syndrome or oral-facial-digital syndrome type VI (OFDS VI) is a rare autosomal-recessive disorder distinguished from other OFDSs by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. Our patient had a broad forehead, arched eyebrows, left-sided squint, hypertelorism, epicanthic folds, fleshy nodular tongue, midline upper lip cleft, high arched palate, both pre-axial and post-axial polydactyly of limbs, hypotonia and cerebellar hypoplasia with molar tooth sign consistent with the diagnosis of Varadi Papp syndrome.

Nasal hemophilic pseudotumor: favorable response to radiotherapy.

Hemophilic pseudotumors are rare but dangerous complications of Hemophilia. We hereby report a 3-year-old boy with Hemophilia B, presenting with nasal pseudotumor, showing favorable response to radiotherapy after unsuccessful treatment with factor IX replacement therapy. The diagnosis and treatment of this rare condition is also reviewed.

Etiology, clinical spectrum and outcome of metabolic liver diseases in children.

OBJECTIVE: To determine the etiology, clinical spectrum and outcome of metabolic liver diseases (MLD) in children admitted in a tertiary care hospital of Eastern India. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Paediatric Liver Clinic and Paediatrics Inpatient Department of Nilratan Sircar Medical College and Hospital, Kolkata, Eastern India, from April 2009 to March 2011. METHODOLOGY: All children aged 0 - 12 years having characteristic clinical features along with diagnostic hallmark of any MLDs were included in this study and data were collected on a pre-designed proforma. After appropriate management and discharge, all patients were followed-up for next 6 months. RESULTS: Fifty one children with mean age 4.34 ± 3.78 years (range 2 days - 12 years), male: female ratio 1.55:1, were studied. The etiologies were Wilson's disease (33.33%, n = 17); glycogen storage disorder (23.53%, n = 12); galactosemia (19.61%, n = 10); non-alcoholic fatty liver disease (11.76%, n = 6); Gaucher disease (5.88%, n = 3); mucopolysaccharidoses (3.92%, n = 2) and familial hyperlipoproteinemia type-I (1.96%, n = 1). Jaundice (n = 24) and hepatomegaly (n = 47), was the commonest symptom and sign respectively. Of the 17 non-responders, most were Wilson's disease (n = 7) cases. There was statistical difference in outcome with respect to INR > 1.3 at diagnosis (p = 0.026). CONCLUSION: High index of suspicion, early detection and screening, simple dietary modification and cost effective drugs along with good compliance are sufficient to treat and even prevent evolution of most causes of the MLDs.

Massive pericardial effusion as the only manifestation of primary hypothyroidism.

Small pericardial effusion (PE) is not an infrequent manifestation in primary hypothyroidism. But massive PE with or without cardiac tamponade is rare and often associated with severe form of the disease. Here we report an eight-year-old boy who was admitted with massive PE that required repeated pericardiocentesis. Detailed examinations failed to identify the etiology initially. Five months later, child was readmitted with massive PE with impending cardiac tamponade. Primary hypothyroidism was diagnosed based on the clinical and laboratory finding and was thought to be the underlying etiology of previously encountered undiagnosed massive PE. Beside pericardiocentesis, child was treated with thyroid hormone replacement. Condition gradually improved without further recurrence of PE till date. Therefore, irrespective of the presence of clinical signs, primary hypothyroidism should be suspected in every patient presenting with massive PE to prevent recurrence as well as its serious complications like cardiac tamponade.

Dengue fever with unusual thalamic involvement.

Dengue is the most important mosquito-borne viral disease in the world and is caused by four distinct viruses (type 1 to 4) that are closely related antigenically. Infection by dengue virus may be asymptomatic or may lead to undifferentiated fever, dengue fever or dengue haemorrhagic fever. Recent observations indicate that the clinical profile of dengue is changing and the neurological complications are being reported more frequently. The neurological features includeheadache, seizures, neck stiffness, depressed sensorium, behavioural disorders, delirium, paralysis and cranial nerve palsies. Such neurological symptoms in dengue fever wereattributed to cerebral oedema, haemorrhage, haemoconcentration due to increasing vascular permeability, coagulopathy and release of toxic substances. Cerebral oedema, encephalitis-like changes (oedema and scattered focal lesions), intracranial haemorrhages as well as selective involvement of bilateral hippocampus in dengue infection have been reported previously on selective neuro-imaging but thalamic involvement is rare. We here report a case of a typical presentation of encephalopathy with left sided complete hemiplegia due to thalamic involvement in dengue infection.

Cerebral infarction following intracranial hemorrhage in pediatric Moyamoya disease - A case report and brief review of literature.

Moyamoya disease is a clinical entity characterized by progressive cerebrovascular occlusion with spontaneous development of a collateral vascular network called Moyamoya vessels. This disease mainly manifests as cerebral ischemia. Intracranial bleeding is another major presentation of patients with Moyamoya disease. We report here a 12-year-old male child who presented with severe headache, vomiting and meningismus. Initial neuroimaging study with noncontrast computed tomography scan revealed fresh intraventricular hemorrhage in right-sided lateral ventricle. Magnetic resonance imaging with angiography of brain was done 5 days later when the child developed right-sided hemiparesis, and the diagnosis of Moyamoya disease was confirmed along with lacunar infarction of right posterior peri and paraventricular area and in the left paraventricular area and centrum semiovale. Simultaneous presence of cerebral infarction along with intraventricular hemorrhage in adult with bleeding-type Moyamoya disease is reported in literature, but it is a rare entity in a child.