Debkrishna Mallick

Henoch-Schönlein Purpura Triggered by Acute Hepatitis E Virus Infection

Practice Guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to review the new evidence and update the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction, writing on behalf of the 2004 writing committee. Circulation 2008;117:296–329. . Thomas J, Brady WJ. Antiplatelet therapy in acute coronary syndrome: not as confusing as you think. J Emerg Med 2008;35:87–90. . Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomized placebo-controlled trial. Lancet 2005;366:1607–21. . Scirica BM, Sabatine MS, Morrow DA, et al. The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction: ECG CLARITY-TIMI 28 study. J Am Coll Cardiol 2006;48:37–42.

Childhood Plasmodium vivax malaria with severe thrombocytopenia and bleeding manifestations.

Thrombocytopenia of varying magnitude, usually without hemorrhagic manifestations, is commonly observed in Plasmodium falciparum and Plasmodium vivax malaria. However, severe thrombocytopenia associated with bleeding manifestations in malarial infection is distinctly unusual. The pathogenesis of this condition remains speculative till date, although several hypotheses have been put forward. We report a case of 4-year-old boy with P. vivax malaria, who developed severe thrombocytopenia during the course of his infection manifested by bleeding from skin and mucosal surfaces. He improved with antimalarial and intravenous immunoglobulin therapy. Clinicians caring for children should be aware of potential bleeding manifestations that may be the result of apparently innocuous infection like vivax malaria.

Pseudotumor cerebri in childhood hepatitis E virus infection.

We report a 7-year-old boy with acute Hepatitis E virus (HEV) infection who developed pseudotumor cerebri (PC), manifested by symptoms and signs of increased intracranial pressure in the presence of normal cerebrospinal fluid (CSF) examination and cranial magnetic resonance (MR) scan. To our knowledge, this is the first report to describe PC in relation to acute HEV infection in the English literature. A 7-year-old, otherwise healthy boy was initially seen following 7 days of low-grade fever, malaise and dark yellow urine. Mild pallor, icterus and 2.5 cm hepatomegaly were noted on physical examination. The full blood count was normal.The liver function tests showed the following values: total serum bilirubin 6.8 mg/dL (conjugated fraction 3.9), alanine aminotransferase 654 IU/L, aspartate aminotransferase 578 IU/L, prothrombin time 15 seconds (normal: <12 seconds). The serum IgM and IgG anti-HEV antibodies were positive while serological tests were negative for hepatitis A, B, and C viruses, Epstein-Barr virus, Cytomegalovirus, Toxoplasma gondii, Dengue virus,Leptospira,Rubella virus,Parvovirus B19, and HIV. The blood and urine cultures remained sterile. Serum ammonia, lactate and ceruloplasmin values were within the reference range.Abdominal ultrasonography confirmed the hepatomegaly with increased hepatic echogenicity. Forty-eight hours later he complained of generalized headache, double vision, and developed recurrent bouts of vomiting without nausea. There was no impairment in his consciousness.The vitals, including the blood pressure, were normal. His neurological examination revealed impaired abduction in the right eye, suggestive of right 6th cranial nerve palsy. The pupils were bilaterally symmetrical with normal reaction to light and accommodation. The examination of the optic fundi revealed papilledema stage 2 (early papilledema as per Frisen scale). The remainder of the neurological examination was normal. His lumbar puncture showed an increased opening pressure (260 mm of water). The CSF was clear with normal cell count, protein, and glucose content. His cranial MR scan and MR venography were normal. He was managed with supportive therapy for both his conditions. The abducens palsy subsided in 3 days with return of satisfactory vision. The serum bilirubin and liver enzymes returned to normal in 5 weeks. Hepatitis E virus is an enterically transmitted RNA virus endemic in parts of the developing world and associated with poor water sanitation. It manifests itself as a brief icteric illness, similar to hepatitis A, and most often affects young adults. Sporadic reports of neurological manifestations occurring in association with HEV infection are documented that include transverse myelitis, Guillain-Barre syndrome (additionally with left infranuclear facial palsy), and meningoencephalitic seizures. HEV implicated isolated cranial neuropathies consist of a single report each of oculomotor palsy and Bell’s palsy. The temporal course of events and the exclusion of other common etiologies of PC in children, especially infections and drugs, strongly implicate HEV in the causation of the symptoms. In conclusion, acute HEV infection should be included in the list of etiologies responsible for causing PC in children. Supportive management of such children may result in swift and satisfactory outcome.

Childhood hepatitis E infection complicated by acute immune thrombocytopenia.

An 8-year 7-month-old girl, born to nonconsanguineous parents, was initially seen for an episode of gum bleed and painless hematuria. She provided a history of new-onset fatigue, low-grade fever, generalized body ache, and anorexia for 2 weeks before admission. The past history was negative for significant illnesses, allergies, or drug intake. She had her last immunization at the age of 5 years (oral polio vaccine). On examination, she was normotensive, alert, icteric, and mildly anemic. Occasional nonpalpable purpuric spots were noted in both the lower extremities. Oral examination revealed an isolated site of bleeding gum over the left upper second incisor. Abdominal examination revealed tender hepatomegaly (liver span 12 cm) and a nontender spleen that was 2 cm palpable. The chest auscultation was normal. The abdominal ultrasound showed an enlarged liver with increased echotexture. Laboratory investigations revealed isolated thrombocytopenia (21,000/mm), mild conjugated hyperbilirubinemia with elevated liver enzymes (aspartate aminotransferase 1080U/L, alanine aminotransferase 878U/L), and normal alkaline phosphatase, serum albumin, g-glutamyl transferase, prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer levels. Urinalysis was significant for plenty of nondysmorphic erythrocytes per highpower field without casts or proteins. She was transfused with platelet concentrates. A bone-marrow aspirate revealed normocellular marrow with normal granulocytic and erythrocytic series and increased number of large, immature megakaryocytes. The serum IgM and IgG anti-Hepatitis E virus (HEV) antibodies were positive using the enzyme-linked immunosorbent assay kits (Genelabs Diagnostics). The optical density ratio for IgM anti-HEV was 3.4 (positive >2) and that for IgG anti-HEV was 3.70 (positive >3). The serologic tests were negative for Hepatitis A, B, and C viruses, Epstein-Barr virus, Cytomegalovirus, Toxoplasma gondii, Dengue virus, Leptospira, Rubella virus, Parvovirus B19, and HIV. The blood and urine cultures remained sterile. The enzyme-linked immunosorbent assay for direct antiplatelet antibodies was positive. Coombs’ test (both direct and indirect), antinuclear antibody, antidouble stranded DNA, antiphospholipid antibodies, anticardiolipin, and cryoglobulins were negative. Intravenous immunoglobulin at 1.0 g/kg/d was administered for 2 days. The platelet count at the end of 1 week was 94,000/mm. There were no further complications during her hospital stay. Clinical evaluation and platelet count at 4 weeks was normal. HEV is a major cause of sporadic and epidemic hepatitis with a worldwide distribution. Mostly asymptomatic, HEV infection is most common in young adults of age 15 to 40 years and commonly presents with a self-limited syndrome of fever, jaundice, anorexia, abdominal pain, and an enlarged tender liver. A variety of hepatotropic viruses are known to cause immune thrombocytopenic purpura, but it is extremely rare in HEV infection. A thorough Medline search revealed only 3 previously reported cases of acute Hepatitis E in adults complicated by autoimmune thrombocytopenia. To our knowledge, this is the first pediatric report on autoimmune thrombocytopenia complicating the course of HEV infection. In view of various corroborating features like isolated thrombocytopenia and otherwise normal peripheral blood smear, normocellular marrow, presence of antiplatelet antibodies, response to intravenous immunoglobulin, and apparent absence of other causes of thrombocytopenia, the present case fits the accepted diagnostic criteria of immune thrombocytopenic purpura. A study from an endemic North Indian region determined the incidence of acute HEV infection at 38.6% of all cases (majority between 11 and 30 y of age) of acute viral hepatitis. Children with acute HEV infection are prone to develop acute liver failure associated with heightened mortality. Given the high incidence of acute HEV infection in endemic areas and the potential for development of acute liver failure, HEV infection should be promptly recognized and treated. In conclusion, although rare, acute HEV infection may be considered one of the etiologies of autoimmune thrombocytopenia in children.

Pharyngeal-Cervical-Brachial Variant of Pediatric Guillain-Barré Syndrome With Antecedent Acute Hepatitis A Virus Infection

Pharyngeal-cervical-brachial weakness is considered a variant of Guillain-Barré syndrome with limited oropharyngeal, neck, and upper limb muscle involvement. The authors report on a 7-year-old boy, who developed pharyngeal-cervical-brachial type of Guillain-Barré syndrome following an antecedent episode of acute hepatitis A virus infection, 2 weeks prior to admission. The presentation was characterized by acute onset dysphagia, loss of head control, and bilateral arm weakness. The diagnosis was confirmed by acute motor axonal changes in the arm and albuminocytologic dissociation of the cerebrospinal fluid. The child was treated with intravenous immunoglobulin, which resulted in gradual improvement over 3 weeks. Documented instances of this form of Guillain-Barré syndrome remain rare in the pediatric age group, with none existing following antecedent hepatitis A virus infection. The authors emphasize that acute hepatitis A virus infection be included in the triggers responsible for Guillain-Barré syndrome in children.

Childhood Hepatitis A Virus Infection Complicated by Bell's Palsy

The full blood count was normal. The liver function tests (LFT) showed the following values: total serum bilirubin 4.6 mg/dL (conjugated fraction 3.0), alanine aminotransferase (ALT) 436 IU/L, aspartate aminotransferase (AST) 348 IU/L, prothrombin time (PT) 15 seconds (normal, <12 seconds). Because of the clinical presentation and the deranged LFT, hepatitis screen was undertaken. IgM and IgG antibodies to HAV were detected in the serum of the patient. The serologies for other hepatotrophic viruses (hepatitis B virus [HBV], hepatitis C virus, hepatitis E virus, Epstein-Barr virus, herpes simplex virus, and cytomegalovirus) were negative. Blood and urine cultures remained sterile. Serum ammonia, lactate, and ceruloplasmin values were within the reference range. Abdominal ultrasonography revealed an increase in echogenicity of the liver parenchyma. Cranial computed tomography scans of both the mastoids and fundoscopy were noncontributory. The patient was managed with supportive therapy for both her conditions. Corticosteroids were not used to treat the facial palsy because of the concomitant HAV infection. There was gradual improvement in her condition, with serum bilirubin and liver enzymes returning to normal in 12 days and facial weakness recovering in 1 month.

Recurrent Limb Weakness in a 17-Year-Old Boy:

Wilson disease is a relatively rare inherited disorder of copper accumulation and toxicity, caused by a defect in an enzyme that is part of the pathway of biliary excretion of excess copper. A 17-year-old boy presented with numerous episodes of hypokalemic weakness of the lower limbs of undetermined etiology since 12 years of age. Clinically, lower-motor neuron type of weakness of the limbs with preserved reflexes and paucity of sensory abnormalities were prominent. The investigations revealed distal renal tubular acidosis, hepatitis, and bilateral Kayser—Fleischer ring. The diagnosis of Wilson disease was confirmed by the demonstration of low serum ceruloplasmin, high serum copper, and high urinary copper excretion per se and after penicillamine challenge. He responded satisfactorily to penicillamine and zinc. Careful search of an underlying etiology in children presenting with hypokalemic weakness of the limbs in the face of metabolic acidosis and unexplained hepatitis may reveal Wilson disease.

Hepatitis E virus infection in a 7-year-old boy with glucose 6-phosphate dehydrogenase deficiency.

REFERENCES 1. Magrath IT. Malignant non Hodgkin’s lymphomas. In: Pizzo P, Poplack D, eds. Principles and Practice of Pediatric Oncology. Philadelphia: J B Lippincott; 1989: 415–417. 2. Pietsch JB, Shankar S, Ford C, et al. Obstructive jaundice secondary to lymphoma in childhood. J Pediatr Surg. 2001;36: 1792–1795. 3. Chung ME, Travis MD, Conran RM. Pancreatic tumors in children: radiologicpathologic correlation. Radiographics. 2006;26:1211–1239. 4. Malbora B, Avci Z, Alioglu B, et al. A case with mature B-cell acute lymphoblastic leukemia and pancreatic involvement at the time of diagnosis. J Pediatr Hematol Oncol. 2008;30:87–89. 5. Turkish A, Levy J, Kato M, et al. Pancreatitis and probable paraneoplastic cholestasis as presenting manifestations of pancreatic lymphoma in a child. J Pediatr Gastroenterol Nutr. 2004;39:552–556. 6. Fernández-Plaza S, Sevilla J, Dı́az MA, et al. Dyspnea as the first manifestation of primary pancreatic lymphoma. Pediatr Blood Cancer. 2008;50:434. 7. Kurosawa H, Matsunaga T, Shimaoka H, et al. Burkitt lymphoma associated with large gastric folds, pancreatic involvement, and biliary tract obstruction. J Pediatr Hematol Oncol. 2002;24:310–312. 8. Meier C, Kapellen T, Trobs RB, et al. Temporary diabetes mellitus secondary to a primary pancreatic Burkitt lymphoma. Pediatr Blood Cancer. 2006;47:94–96. 9. Eisenhuber E, Schoefl R, Wiesbauer P, et al. Primary pancreatic lymphoma presenting as acute pancreatitis in a child. Med Pediatr Oncol. 2001;37:53–54.

Cayler cardiofacial syndrome with situs inversus totalis

Cayler cardiofacial syndrome is characterised by congenital unilateral hypoplasia of the depressor anguli oris muscle (DAOM) in association with congenital cardiac defects. Hypoplasia of this muscle causes inability to move one corner of the mouth downward and outward while crying or grimacing, giving rise to an ‘asymmetric crying face’ appearance. A variety of congenital cardiac defects have been described. Occasionally, other organ system anomalies may be additionally present. We present an instance of right-sided hypoplasia of the DAOM in a male newborn, which additionally had dextrocardia as a component of situs inversus totalis. To our knowledge, situs inversus totalis has not been previously documented as a part of this syndrome. Additionally, we reiterate that paediatricians need to be aware that this minor facial anomaly may be associated with severe internal organ system anomalies, with cardiac being most common.

Childhood Plasmodium falciparum malaria complicated by acute pancreatitis

Summary Falciparum malaria is occasionally associated with multiple organ system complications. However, acute pancreatitis rarely occurs as a part of the spectrum. A 13-year-old boy presented with falciparum malaria complicated predominantly by acute pancreatitis. He recovered satisfactorily with supportive measures. To our knowledge, there are less than 10 such documented instances in the literature and they are mostly adults. Acute abdomen in Plasmodium falciparum infection may reveal pancreatitis which should be detected at the earliest.