Adenovirus Respiratory Infection among Immunocompetent Patients in a Pediatric Intensive Care Unit During 10-year period: Co-morbidity is common.

BACKGROUND: Adenovirus is responsible for 2-7% of childhood viral respiratory infections, 5-11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection. OBJECTIVES: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU). METHODS: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both. RESULTS: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months-11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died. CONCLUSIONS: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

JC Viruria Is Associated With Reduced Risk of Diabetic Kidney Disease.

PURPOSE: African Americans who shed JC polyomavirus (JCV) in their urine have reduced rates of nondiabetic chronic kidney disease (CKD). We assessed the associations between urinary JCV and urine BK polyomavirus (BKV) with CKD in African Americans with diabetes mellitus. METHODS: African Americans with diabetic kidney disease (DKD) and controls lacking nephropathy from the Family Investigation of Nephropathy and Diabetes Consortium (FIND) and African American-Diabetes Heart Study (AA-DHS) had urine tested for JCV and BKV using quantitative PCR. Of the 335 individuals tested, 148 had DKD and 187 were controls. RESULTS: JCV viruria was detected more often in the controls than in the patients with DKD (FIND: 46.6% vs 32.2%; OR, 0.52; 95% CI, 0.29 to 0.93; P = 0.03; AA-DHS: 30.4% vs 26.2%; OR, 0.63; 95% CI, 0.27 to 1.48; P = 0.29). A joint analysis adjusted for age, sex, and study revealed that JC viruria was inversely associated with DKD (OR, 0.56; 95% CI, 0.35 to 0.91; P = 0.02). Statistically significant relationships between BKV and DKD were not observed. MAIN CONCLUSIONS: The results from the present study extend the inverse association between urine JCV and nondiabetic nephropathy in African Americans to DKD. These results imply that common pathways likely involving the innate immune system mediate coincident chronic kidney injury and restriction of JCV replication. Future studies are needed to explore causative pathways and characterize whether the absence of JC viruria can serve as a biomarker for DKD in the African American population.

Evaluation of the virtues and pitfalls in an HIV screening algorithm based on two fourth generation assays - A step towards an improved national algorithm.

BACKGROUND: Fourth-generation immunoassays used for HIV screening, simultaneously detect anti-HIV antibodies and HIV-1 P24 antigen, but are prone to false-positive results. Usually, they are followed by highly specific third-generation assay, able to differentiate between HIV-1/2 infections. In Israel, screening algorithm is based on consecutive testing by two fourth-generation assays and confirmation by a third-generation test. OBJECTIVES: To evaluate the performance of this algorithm. STUDY DESIGN: Architect HIV1/2 Combo (Combo) reactive results were tested by Vidas HIV Duo Ultra (VD). Confirmation was by INNO-LIA HIV 1/2 or Geenius assays. Five-year results were retrospectively analyzed. HIV true positives (TPs), acute infected (AI), false-positives (FPs) and HIV negatives, were as defined by the algorithm. RESULTS: 501,338 individuals were screened, of which 956 were TPs, 64 AI and 30 F Ps. Specificity was almost 100% and positive predictive value 97%. VD was negative in 94% of confirmed Combo false-reactive individuals. The Combo results in the first tested sample differed substantially between TPs, AI and FPs, enabling the determination of a cutoff value that distinguished 94% of TPs and AI from FPs. CONCLUSIONS: An algorithm is suggested that will use a single sample collection. HIV negative diagnosis will be based on Combo unreactive or Combo reactive/VD negative results. HIV positive diagnosis will be based on Combo reactive/ VD positive results, given a Combo value above a designated cutoff. Below this cutoff samples will be tested by a molecular assay. Since HIV-2 rarely occurs in Israel, the use of a third-generation confirmation assay should be discussed.

Diagnosis of HIV-1 infection: Performance of Xpert Qual and Geenius supplemental assays in fourth generation ELISA-reactive samples.

BACKGROUND: Architect (AR) and Vidas (VD) fourth generation HIV screening immunoassays, which identify early stages of HIV infections, could have false positive results especially at low signal/cutoff (S/C) AR values. Geenius HIV1/2 (GS) is a specific confirmation line immunoassay that is not highly sensitive to early HIV infections. An HIV-1 RNA assay may better detect such infections. OBJECTIVES: To evaluate all AR-VD reactive samples with GS results, and to assess Xpert Qual HIV-1 RNA assay (XQ) as an alternative to GS, in the first low S/C AR-VD-reactive samples from a tested individual. STUDY DESIGN: First AR-VD-reactive-GS-tested results from all individuals with resolved HIV status, collected between March 2015 and March 2017 (n = 749), were retrospectively assessed. Samples with AR-VD-reactive-GS-discordant results and those with low S/C AR-VD-reactive results, were tested by XQ. Receiver operating characteristic (ROC) analysis of GS and XQ sensitivity/specificity was performed. RESULTS: Overall, 94.1% (705/749) of AR-VD-reactive results were true HIV-1 positive. All samples with <3 S/C AR values were false positive. XQ resolved all first samples with AR-VD-reactive-GS-discordant results. The diagnostic accuracy of XQ in low (≤33 S/C) AR-VD-reactive samples was better than that of GS (97.6%, 81/83 versus 73.5%, 61/83, p < 0.01). ROC analysis for low S/C AR samples was optimal for pooled XQ and GS results. CONCLUSIONS: Incorporating XQ in the current screening algorithm for the first AR-VD-reactive-GS-discordant samples may significantly reduce overall turn-around time of HIV-1 diagnosis.

Human enterovirus D68 in clinical and sewage samples in Israel.

BACKGROUND: Since mid-August 2014, North America experienced a wide outbreak of Enterovirus D68 (EV-D68) associated with severe respiratory illness in children. Several other countries also reported cases of EV-D68 in 2014. OBJECTIVES: The aim of this study was to determine whether EV-D68 circulated in Israel in 2014, caused severe respiratory illness in children and was the causative agent of Acute Flaccid Paralysis. STUDY DESIGN: Archived clinical respiratory samples from a cohort of 710 hospitalized pediatric patient's (<10years old) with respiratory illness were screened for clade B specific EV-D68 by real-time PCR. The patients were seen at four medical centers covering the entire country between August and November 2014. We also evaluated 49 patient stool samples from 26 AFP cases during 2014 for presence of EV-D68. In addition, RNA from sewage samples collected throughout Israel during the same study period was also tested for EV-D68. Partial VP1 sequencing was performed on all positive samples. RESULTS: Of the 710 clinical samples evaluated, 7 (1%) were positive for EV-D68. Two patients were from the central part of Israel, while the rest was from the southern part. The majority of the patients did not have any underlying disease. Not only that, but, none of the 26 suspected AFP cases had EV-D68 nucleic acid in their stool samples. EV-D68 RNA was detected in 9 out of 93 sewage samples, mainly from Southern Israel. Sequence analysis of EV-D68 VP1 gene from both sewage and clinical samples indicated that the Israeli EV-D68 RNA belonged to Clade B which was genetically similar to 2014 circulating European and North American EV-D68 virus. CONCLUSIONS: EV-D68 circulated in Israel during the 2014 summer-fall season and caused hospitalization of a small percent of the patients with respiratory illness.

Human Herpes Virus-6 Following Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear. OBJECTIVE: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT. METHODS: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006-June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations. RESULTS: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load. CONCLUSIONS: HHV-6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

[HIV testing: the medical laboratory role in HIV diagnosis and monitoring].

Diagnosis of HIV infection is performed via enzyme immunoassay (EIA), an assay based on screening for antibodies against HIV. Confirmation of diagnosis is performed by Western-Blot, a more specific assay directed at a number of viral proteins for which antibodies exist. Routine follow-up of HIV-infected individuals includes measurement of CD4 cell count to evaluate the immune status, of viral load to assess virus replication, and of changes in the viral genome to characterize resistance to drugs and tropism. In addition, absence of the HLA B*57:01 allele is verified before prescription of abacavir, and drug levels of protease-inhibitors are determined in treatment-failing individuals after ruling out other causes of failure. Rapid diagnosis and regular follow-up improve the quality of life of patients and extend their life expectancy, also helping to control the spread of the epidemic at the national level.

Viral-induced intracranial hypertension mimicking pseudotumor cerebri.

BACKGROUND: Pseudotumor cerebri or idiopathic intracranial hypertension is characterized by normal spinal fluid composition and increased intracranial pressure in the absence of a space-occupying lesion. METHODS: This study describes a subgroup of 10 patients with the same typical presenting symptoms (headache, vomiting, and papilledema) but without nuchal rigidity, meningeal signs, or change in mental status. Patients had normal neuroimaging studies and intracranial hypertension but also pleocytosis in the cerebrospinal fluid, suggesting central nervous system infection. From the results it can be hypothesized that those children represent a unique subgroup of viral-induced intracranial hypertension when comparing their risk factors, clinical course, treatment, and outcome with 58 patients who had idiopathic intracranial hypertension. RESULTS: All patients with viral-induced intracranial hypertension presented with papilledema but none had reduced visual acuity or abnormal visual fields, compared with 20.7% of patients who had idiopathic intracranial hypertension. They also responded better to treatment with acetazolamide, needed a shorter duration of treatment (7.7 ± 2.6 months vs 12.2 ± 6.3 months, P = 0.03), and had no recurrences. CONCLUSIONS: The results suggest that children who fulfill the typical presenting signs and symptoms and all diagnostic criteria for pseudotumor cerebri other than the normal cerebrospinal fluid component may represent a unique subgroup of viral-induced intracranial hypertension and should be managed accordingly. The overall prognosis is excellent.

Detection, control, and management of a respiratory syncytial virus outbreak in a pediatric hematology-oncology department.

BACKGROUND: Immunocompromised patients are at increased risk for severe respiratory syncytial virus (RSV) infection. Palivizumab is approved for prevention of RSV in specific populations but not for treatment. Few studies demonstrated the safety and successful treatment with intravenous (IV) palivizumab. We describe our experience with IV palivizumab treatment for RSV in a pediatric hematology-oncology department during an outbreak. METHODS: During a short period of renovations, oncology patients were placed in a general pediatric ward. After a case of severe fatal RSV pneumonia in a 2-year-old male patient with acute myeloid leukemia, all patients were actively screened twice weekly regardless of symptoms. Respiratory samples were tested for RSV using rapid immunochromatography detection, immunofluorescence, or reverse transcriptase polymerase chain reaction. A single dose of palivizumab (15 mg/kg) was given to children below 3 years of age who tested positive for RSV. RESULTS: Over a 6-week period, 12 patients tested positive for RSV. Seven patients were treated with palivizumab. Five patients had respiratory symptoms, and 2 were asymptomatic. No adverse events were attributed to IV palivizumab treatment. Early-treated patients had no complications attributed to RSV. CONCLUSIONS: Containment of RSV outbreak in high-risk children is difficult. Screening with reverse transcriptase polymerase chain reaction and the early use of IV palivizumab is safe and may prevent complications of RSV infection among these patients.

New rising infection: human herpesvirus 6 is frequent in myeloma patients undergoing autologous stem cell transplantation after induction therapy with bortezomib.

Herpesvirus 6 (HHV-6) infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT) after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD) (n = 41; 66%) or thalidomide-dexamethasone (TD) (n = 21, 34%) induction, together with melphalan 200 mg/m(2) autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF) in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%), accounting for 35% of those screened; its incidence was 19.5% (n = 8) in the VD group versus 9.5% (n = 2) in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

Reactivation of varicella presenting as pseudotumor cerebri: three cases and a review of the literature.

The possible association of pseudotumor cerebri and varicella infection was previously mentioned in a few case reports. In those cases, the history and clinical features of active varicella were obvious, and signs were directly related to the varicella infection. We describe three immunocompetent children with pseudotumor cerebri as the only manifestation of Varicella zoster virus reactivation, with a review of the literature. We suggest considering Varicella zoster virus in children with pseudotumor cerebri, even in the absence of a history of recent varicella infection.

Absence of APOL1 risk variants protects against HIV-associated nephropathy in the Ethiopian population.

BACKGROUND: Susceptibility to end-stage kidney disease (ESKD) among HIV-infected Americans of African ancestral heritage has been attributed to APOL1 genetic variation. We determined the frequency of the APOL1 G1 and G2 risk variants together with the prevalence of HIV-associated nephropathy (HIVAN) among individuals of Ethiopian ancestry to determine whether the kidney disease genetic risk is PanAfrican or restricted to West Africa, and can explain the previously reported low risk of HIVAN among Ethiopians. METHODS: We studied a cohort of 338 HIV-infected individuals of Ethiopian ancestry treated in one Israeli and one Ethiopian center. We sought clinical evidence for HIVAN (serum creatinine >1.4 mg/dl or proteinuria >30 mg/dl in a spot urine sample). Genetic analyses included the genotyping of the APOL1 G1 and G2 variants, and a panel of 33 genomic ancestry-informative markers. Statistical analysis compared clinical and genetic indices for HIV-infected individuals of Ethiopian ancestry and overall Ethiopians to those reported for HIV-infected African-Americans, overall African-Americans, West Africans and non-Africans. FINDINGS: Three (0.8%) of 338 HIV-infected patients of Ethiopian ancestry showed clinical criteria compatible with renal impairment. Two of these 3 patients also have severe poorly controlled diabetes mellitus. The third nondiabetic patient underwent renal biopsy which ruled out HIVAN. This absence of clinically apparent HIVAN was significantly different from that reported for African-Americans. The APOL1 G1 and G2 risk variants were found, respectively, in 0 and 2 (heterozygote state) of the 338 HIV-infected individuals. Global ancestry and the frequencies of the APOL1 G1 and G2 variants are not statistically different from their frequencies in the general Ethiopian population, but are significantly and dramatically lower than those observed among HIV-infected African-Americans, African-Americans and West Africans. INTERPRETATION: The coinciding absence of HIVAN and the APOL1 risk variants among HIV-infected individuals of Ethiopian ancestry support a Western rather than Pan-African ancestry risk for ESKD, and can readily explain the lack of HIVAN among individuals of Ethiopian ancestry.

Sole pathogen in acute bronchiolitis: is there a role for other organisms apart from respiratory syncytial virus?

BACKGROUND: Acute bronchiolitis (AB) is a common disease of young children with peak incidence during the winter season. Respiratory syncytial virus (RSV) is a major causative organism, yet recent relatively small sized studies have suggested an increased role of other organisms as sole or codetected organisms. The aim of this study was to assess the prevalence of sole- and mixed-organisms infections in hospitalized children with AB, using combined antigen-based and polymerase chain reaction assays (PCR). METHODS: Sputum or nasal wash specimens obtained from 490 previously healthy children < or =2 years of age hospitalized with AB between December 1, 2005 and March 31, 2006 were tested: (1) For RSV, by rapid antigen detection test; (2) For RSV, influenza A, B, Parainfluenza 1 to 3, and adenovirus antigens by direct fluorescent assay; (3) For influenza A and B, RSV, Parainfluenza 1 to 3 viruses RNA by reverse transcription (RT) PCR assay; (4) For human metapneumovirus and rhinovirus RNA by RT real-time PCR assay; (5) For adenovirus, and Bordetella pertussis DNA by conventional PCR assays; (6) For human bocavirus DNA by real-tine PCR assays. RESULTS: At least 1 organism was detected in 465 (91%) children. In 283 (61%), 117 (25%), and 23 (5%) children, 1, 2, and 3/4 organisms were detected, respectively. The most commonly detected organism was RSV, detected in 76%, and as a sole organism in 49%. Rhinovirus, human metapneumovirus, influenza virus A, bocavirus, Bordetella pertussis, and adenovirus were detected as a sole organism in 7%, 2.1%, 1%, 0.6%, 0.6%, and 0.2% of the children, respectively. CONCLUSIONS: Respiratory organisms were detected in the majority of the children, of whom about one third suffered from mixed organism infection. RSV was the most prevalent sole detected organism. The relevance of all other organisms may be much less than previously suggested.

Incidence and clinical manifestations of adenoviral infection among children undergoing allogeneic stem cell transplantation.

BACKGROUND: Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT in Israel is not known. OBJECTIVE: To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection. METHODS: Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records. RESULTS: Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03). CONCLUSIONS: In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT.

Relationship between human herpesvirus 8 loads and disease stage in classic Kaposi sarcoma patients.

Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma (KS)-associated herpesvirus, is causally implicated in all forms of KS, including the classic form. Our objective was to investigate the relationship between HHV-8 load in peripheral blood mononuclear cells (PBMCs) and the stage of the disease in classic KS (CKS) patients. HHV-8 loads were measured in 41 PBMC samples from CKS patients with different Krigel-based classification stages using a quantitative real-time polymerase chain reaction assay. Low HHV-8 DNA loads reaching a maximum of 75.5 copies/10(5) cells were detected in 73.2% of the patients. HHV-8 loads in patients with stages I and II were similarly distributed. An increased detection rate of HHV-8 DNA, although not statistically significant, was evident in patients diagnosed with CKS stages III and IV. We conclude that the measurements of HHV-8 load in PBMCs provide a limited correlation with the clinical stage of KS.

Sexually transmitted diseases among patients with human immunodeficiency virus in northern Israel.

BACKGROUND: The co-morbidity of human immunodeficiency virus and other sexually transmitted diseases in Israel has not been established. OBJECTIVES: To compare the prevalence of STDs among HIV-positive patients to HIV-negative patients visiting an STD clinic in northern Israel. METHODS: Between December 2000 and December 2001, 176 HIV-positive individuals (53% males) were screened and compared to 200 HIV-seronegative individuals (76% males). Demographics, symptomatology and risk factors were obtained via questionnaire. First-void urine samples were tested for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Serum was tested for type-specific herpes simplex virus-2, hepatitis B and syphilis. RESULTS: Relative to the seronegative STD patients, HIV-positive patients exhibited significantly greater risk-reducing sexual behaviors such as consistent condom use [29/86 (33.7%) vs. 16/187 (8.6%), P < 0.001], and abstinence in the previous 6 months [43/125 (34%) vs. 7/185 (3.8%), P < 0.001]. Nevertheless, STD prevalence was higher among HIV-positive than HIV-negative patients (79.5% vs 37.5%, P < 0.001). HSV-2, syphilis and HBV were more common among HIV-positive than HIV-negative patients [120/175 (68.8%)] vs. 18/200 (9%), P < 0.001)], [43/161 (26.7%) vs. 0%, P < 0.001)], [13/171 (7.6%) vs. 3/200 (1.5%), P < 0.01)], respectively. In contrast, Chlamydia and gonorrhea were more common in HIV-negative patients than HIV-positive patients [3/176 (1.7%) vs.13/200 (6.5%), P < 0.05] vs. [0% vs.5/200 (2.5%), P < 0.05], respectively. CONCLUSION: Despite the low risk sexual behavior of Israeli HIV patients, they had a high prevalence of chronic STDs (e.g., HSV-2, HBV and syphilis). The lower prevalence of Chlamydia and gonorrhea among HIV-immunosuppressed patients may be attributed to routine antibiotic prophylaxis against opportunistic infections. Nevertheless, as advocated by international health organizations, it appears prudent to recommend the routine screening of these asymptomatic HIV-positive patients for STD pathogens.

[Insemination from HIV-positive males].

INTRODUCTION: Discordant couples, in which the man is HIV positive and the woman is HIV negative, face limited options when they wish to produce healthy children whilst practicing safe sex. In order to conceive they must abandon unprotected sex, which carries high risk of HIV infection to the woman. OBJECTIVE: To develop a method for removing the HIV from semen and then perform intra uterine insemination, following verification of the HIV-negative spermatozoa fraction by PCR. METHODS: Motile spermatozoa were isolated from semen samples by the gradient and "swim-up" techniques. HIV-RNA was tested before and after the procedure in both the semen and the purified spermatozoa fraction. Insemination was performed on ovulation day only when the absence of any viral particles was verified by PCR. RESULTS: Four couples underwent a total of 8 cycles of intra uterine insemination (IUI). Presently, two healthy babies were born. The two mothers and newborn were found to be HIV negative following the delivery. CONCLUSION: We report a safe procedure which enables biological parenthood for HIV-1 discordant couples without the risk of infecting the female partner. Our clinical data corroborate with the collaborative European data on this subject.

Bullous herpes zoster in a child with leukemia: case report and review of the literature.

Blistering disorders in childhood are usually difficult to diagnose and pose complicated management dilemmas. The incidence of herpes zoster in children with malignancy and immunodeficiency is greatly increased compared to normal children of comparable age. Although herpes zoster is known to occur in children with malignancy, the bullous form of herpes zoster is rare; to the authors' knowledge, there was no previous report of this phenomenon in children in general and in children with cancer in particular. The authors describe a 3.5-year-old girl who was diagnosed with acute lymphoblastic leukemia; 7 months after presentation, during chemotherapy treatment, she developed the bullous form of herpes zoster on her right hand. The authors describe the method of diagnosis and provide a review of the literature concerning this rare phenomenon. Recognizing this entity and differentiating it from other bullomatous conditions enable the application of appropriate treatment, without unnecessary delay.