Effect of Interferon-α Therapy in a Patient with Common Variable Immunodeficiency and Chronic Epstein-Barr Virus Infection

We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was delected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-α (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-α is a valid alternative in therapy of immunodeficient EB virus-infected patients.     

Pediatric Hodgkin Lymphoma in a South Indian Regional Cancer Center: Its Immunomorphology,Tumor-Associated Macrophages,and Association with Epstein–Barr Virus

Pediatric Hodgkin lymphoma (HL) comprises approximately a fifth of all patients with HL in India. Seventy-four cases of pediatric classical Hodgkin Lymphoma (cHL) from a regional cancer center in southern India were analyzed on a tissue microarray (TMA) for the stage of B-cell differentiation of the Hodgkin/Reed Sternberg (HRS) cell by immunohistochemistry (IHC) using CD10, bcl6, MUM1/IRF4, and CD 138. Fifty-two of seventy-four (70.3%) cases were of late germinal center/early post-germinal center phenotype (CD10?/bcl6?/MUM1+/CD138?). Epstein–Barr virus (EBV) association using Epstein-Barr virus encoded RNA (EBER) RISH and EBV-LMP1 immunohistochemistry (IHC) revealed an EBV association of 93%. Tumor-associated macrophages (TAM) in the microenvironment were also assessed on the TMA by CD68 IHC, and most cases (59.7%) showed >25% TAMs, with no case showing ≤5%. These findings indicate that pediatric cHL in India is a tumor, predominantly, of late germinal center/early post-germinal center B cells, is almost invariably EBV associated, and with a high number of TAMs in the microenvironment. This latter finding suggests that criteria other than TAM scores need to be developed for risk stratification of pediatric EBV-associated HL especially in developing countries.     

Cell-Free Epstein–Barr Viral Loads in Childhood Hodgkin Lymphoma: A Study from South India

Cell-free Epstein–Barr viral (EBV) DNA is detectable in plasma of patients with EBV-related lymphomas. The aim of this study was to evaluate the utility of plasma EBV DNA as a biomarker of EBV association in childhood Hodgkin lymphoma (HL). Furthermore, an attempt was made to evaluate the effectiveness of viral quantitation for assessing response to chemotherapy. Thirteen cases of childhood HL were included in this study. All 13 cases were EBV associated as reflected by expression of EBV LMP1 in the tumor specimen. Eighty-five percent had detectable EBV DNA levels; viral loads ranging from 2.9 to156.2 × 10³ copies/ml (mean 29 × 10³ copies/ml); while in 2 patients and 30 controls tested, viral DNA was undetectable. In four patients, follow-up samples were available after three cycles of chemotherapy; all had EBV DNAemia prior to chemotherapy but undetectable EBV DNA posttherapy. This corroborated with complete response in these four patients. Plasma EBV viral load quantification maybe a useful tool for detecting EBV association with lymphomas and in monitoring response to treatment in childhood HL in centers with limited resources, more so in India where majority of childhood HL is likely to be EBV associated. This is the first Indian study estimating plasma EBV viral loads in HL.     

Lipschütz ulcer in a 17-month-old girl: a rare manifestation of Epstein–Barr primoinfection

Lipschütz ulcer is an uncommon entity that is clinically characterised by a flu-like syndrome accompanied by an acute painful necrotic vulvar ulcer. It typically occurs in young women with no sexual contact history, and it is very rare among children. The aetiology is unknown, although recently several reports have related Epstein–Barr virus primary infection with this entity. We report a 17-month-old girl with fever and an acute genital ulcer. All the complementary tests for the most frequent causes of vulvar ulcers yielded negative results, whereas viral serology and polymerase chain reaction technique confirmed the presence of an acute Epstein–Barr virus infection. When main causes of genital ulcer have been excluded, and there is no history of sexual contact, Lipschütz ulcer should be included in the differential diagnosis. Detection of Epstein–Barr virus genome by polymerase chain reaction can lead to an earlier diagnosis.     

Jarcho–Levin Syndrome Associated with a Complex Congenital Heart Anomaly

Jarcho-Levin syndrome is characterized by "crab-like" rib cage deformity and multiple vertebral anomalies that cause respiratory failure. Reports of complex congenital heart defects with this syndrome are rare. We describe a female infant with this syndrome and a complex congenital heart defect and review the literature. Congenital heart defects are occasionally complicated by Jarcho-Levin syndrome. Heart defects involving heterotaxic morphology should be included as one of the important clinical features of this syndrome.     

Persistent Interstitial Pulmonary Emphysema–like Cyst Associated with Metastatic Synovial Sarcoma

Interstitial pulmonary emphysema is characterized by the presence of gas dissecting the interstitial tissues of the lung. Clinically, it may be acute or persistent, and the latter can be further categorized as localized or diffuse. Usually, it appears in preterm neonates with a history of assisted ventilation or respiratory distress. Although far from frequent, the localized variety of persistent interstitial pulmonary emphysema (PIPE) can develop spontaneously in full-term babies or infants without any obvious underlying pulmonary disease. Histologically, PIPE is characterized by the presence of uni- and multinucleated histiocytes lining the inner surface of the cysts. In this report, we describe a 15-year-old male with synovial sarcoma (SS) of the right ankle diagnosed 4 years previously who developed pulmonary metastasis, one of which presented cystic changes with features of PIPE. Received April 2, 1999; accepted July 23, 1999.     

Tetralogy of Fallot with Pulmonic Atresia with Cyclic Occlusion of an Associated Aortic Sinus of Valsalva–Pulmonary Artery Window

A first case of an unusual aortopulmonary window with tetralogy of Fallot associated with pulmonary atresia is presented. The aortopulmonary window was at the aortic sinus of Valsalva. The left aortic leaflet prevented pulmonary hypertension by occluding the window in systole.     

Congenital Pulmonary–Systemic Collateral Vein without Obstructed Left Atrial Egress Is Associated with Conotruncal Anomalies

We present a case of congenital pulmonary systemic collateral vein associated with truncus arteriosus. Pulmonary systemic collateral vein with nonobstructed left atrial egress is different from those with obstructed left atrial egress in that it is functionally redundant. Including this case, 8 patients among 33 reported cases with pulmonary systemic collateral veins have had nonobstructed left atrial egress. Association with conotruncal anomalies in 4 of these 8 patients, as well as the reported finding that neural crest cells are distributed not only in the conotruncus but also in the cardinal vein, indicates that neural crest cells play roles in remodeling of the systemic venous system.     

Long term clinical and electrophysiological assessment of Croatian children with corticospinal tract involvement in Guillain–Barré syndrome (GBS)

Guillain–Barré syndrome (GBS) is characterized by areflexia. Hyperreflexia is reported in acute motor axonal neuropathy (AMAN). We present 16 children with GBS at the age of 14 months to 13 years. All children studied fulfilled accepted diagnostic criteria for GBS. Hyperreflexia or positive Babinski sign were obtained in all children studied during follow up. Brain and spinal cord MR scans did not reveal any significant structural and morphological abnormalities of central nervous system. The children were examined clinically and electromyoneurographically 2–5 times successively during 1–8.5 years of follow-up. According to established electrodiagnostic criteria demyelinating form of GBS was most common (68%) compared to axonal (18,7%) or mixed form (12,5%). No children had antecendent Campylobacter jejuni infection. Antiganglioside antibodies were detected in 18,7% of patients associated with demyelinating or mixed (axonal/demyelinating) form. Time to nadir and recovery period of walking ability is prolonged more often in demyelinating GBS. Clinical improvement occur earlier compared to improvement of abnormal electrophysiological parameters.Outcome was excellent in 11 in the period 1 month–8.5 years. Hyperreflexia usually appeared in recovery period suggesting involvement of upper motor neurons or spinal interneurons occurring in Croatian children with both demyelinating and axonal form of GBS usually associated with milder course of disease.