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A case of Griscelli syndrome.

July 25, 2015 By Manish Butte

A case of Griscelli syndrome.

Dermatol Online J. 2014 Nov;20(11)

Authors: Kerketta JA, Lodh M, Mandal K

Abstract
A hallmark of Griscelli syndrome, a rare autosomal recessive disorder, is hair hypopigmentation characterized by a silver-gray sheen and the presence of large clusters of pigment unevenly distributed in the hair shaft. Either a primary neurological impairment or immune abnormalities are associated with this phenotype. We report the case of a 10-year-old child of consanguineous parents. He presented with abdominal pain and fever and was noted to have silvery hair, eyelashes, and eyebrows. Bone marrow studies indicated hemophagocytosis, whilst microscopic examination of the hair showed irregular agglomerations of pigment in hair shafts. The prognosis, treatment, and genetic counseling needs differ considerably among the various forms of Griscelli Syndrome.

PMID: 25419745 [PubMed – indexed for MEDLINE]

Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.

July 25, 2015 By Manish Butte

Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.

Eur J Intern Med. 2014 Nov;25(9):837-42

Authors: Blot M, Boyer P, Samson M, Audia S, Devilliers H, Leguy V, Berthier S, Besancenot JF, Lorcerie B, Lakomy D, Bonnotte B

Abstract
BACKGROUND: Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia.
METHODS: This retrospective observational study included all adult patients with a gammaglobulin level <6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin <5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin <6.4 and ≥5g/L, mild hypogammaglobulinemia).
RESULTS: Among the 4011 serum electrophoreses, 570 samples from 389 patients had gammaglobulin levels below 6.4g/L: 156 (40%) in group 1 and 233 (60%) in group 2. Mean age±SD was 67 (15) years, and sex ratio was 1.04 (M/F) with no difference between the two groups. An etiology was identified in 79% and 58% of patients in groups 1 and 2, respectively (p<0.0001). The main etiologies were similar in both groups and included malignant hemopathy treated with cytostatic agents (n=129, 33%), smoldering or newly-diagnosed hemopathy without treatment (n=49, 13%) and immunosuppressive treatment (n=91, 23%). The incidence of hypogammaglobulinemia-related infections was 22/100/year, with no significant difference between the two groups (p=0.17). Vaccination coverage against pneumococcus was 33%, and higher in group 1 (46% vs. 24%; p<0.0001). When no cause was known at inclusion, an etiology was discovered in 22/130 patients (17%), 11 in each group.
CONCLUSIONS: Though mild hypogammaglobulinemia does not meet the classical criteria for hypogammaglobulinemia (<5g/L), the etiology and infectious risk are similar. It therefore requires investigation and vaccination.

PMID: 25307285 [PubMed – indexed for MEDLINE]

Effects of tDCS-induced motor cortex modulation on pain in HTLV-1: a blind randomized clinical trial.

July 25, 2015 By Manish Butte

Effects of tDCS-induced motor cortex modulation on pain in HTLV-1: a blind randomized clinical trial.

Clin J Pain. 2014 Sep;30(9):809-15

Authors: Souto G, Borges IC, Goes BT, de Mendonça ME, Gonçalves RG, Garcia LB, Sá KN, Coutinho MR, Galvão-Castro B, Fregni F, Baptista AF

Abstract
OBJECTIVE: We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) on chronic pain in human T-lymphotropic virus type I-infected patients.
MATERIALS AND METHODS: This is a sham-controlled randomized clinical trial. Twenty participants were randomized to receive active or sham anodal tDCS over the primary motor cortex (M1), with 2 mA, 25 cm electrodes, for 20 minutes on 5 consecutive days. Pain intensity was measured at baseline and after each day of treatment using a Visual Analog Scale. Associated factors such as pain components description, pressure pain threshold, and Timed Up and Go task were also assessed.
RESULTS: Mild adverse events were reported by 100% of patients in the tDCS group and 90% in the sham group. Comparison of daily Visual Analog Scale pain scores from both groups demonstrated a significant effect for the factor Time (P<0.001), but not for Group (P=0.13) or Time×Group interaction (P=0.06). There were 8 (80%) responders (reduction of 50% or more in pain intensity) in the tDCS group and 3 (30%) in the sham group (P=0.03). Both groups demonstrated improvements for most associated factors evaluated. However, there was no difference in between-groups comparison analyses.
CONCLUSIONS: The analysis of the main outcomes in this study did not demonstrate a significant advantage of anodal tDCS applied to M1 in patients with human T-lymphotropic virus type I and chronic pain in comparison with sham tDCS, although secondary analysis suggests some superiority of active tDCS over sham. The large placebo effect observed in this study may explain the small differences between sham versus active tDCS.

PMID: 24300224 [PubMed – indexed for MEDLINE]

Small Bowel Bacterial Overgrowth in Children: A Comprehensive Review.

July 22, 2015 By Manish Butte

Small Bowel Bacterial Overgrowth in Children: A Comprehensive Review.

J Pediatr Gastroenterol Nutr. 2015 Jul 20;

Authors: Sieczkowska A, Landowski P, Kamińska B, Lifschitz C

Abstract
OBJECTIVES: To perform a comprehensive review of the pathogenesis, available diagnostic procedures, prevalence, clinical manifestations and consequences of small bowel bacterial overgrowth (SBBO) as well as treatment options in the pediatric population.
METHODS: A literature search including MEDLINE, PubMed and Web of Science databases was performed.
RESULTS: SBBO is found in a varierty of childhood conditions in which the normal homeostatic mechanisms restricting bacterial colonization in the small bowel are disturbed by congenital or acquired anatomical abnormalities, diminished gastric acid secretion, congenital alteration of intestinal motility or acquired small bowel diseases, or other chronic disorders including primary or acquired immunodeficiency. Data show that SBBO may be an under-recognized cause of pediatric morbidity. Although several diagnostic tests for SBBO determination are available, each has its drawbacks and limitations. Indeed, there is still no “gold standard’ for SBBO diagnosis in the pediatric population. Due to lack of established guidelines and very few published interventional studies that assess the effectiveness of SBBO therapy, treatment of children with SBBO remains empiric and comprises antibiotic or probiotic therapy.
CONCLUSIONS: Further research is needed to determine the clinical impact of SBBO and to establish diagnostic and therapeutic guidelines applicable to children.

PMID: 26196206 [PubMed – as supplied by publisher]

Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease.

July 21, 2015 By Manish Butte

Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease.

Gastroenterology. 2015 Jul 16;

Authors: Kelsen JR, Dawany N, Moran CJ, Petersen BS, Sarmady M, Sasson A, Pauly-Hubbard H, Martinez A, Maurer K, Soong J, Rappaport E, Franke A, Keller A, Winter HS, Mamula P, Piccoli D, Artis D, Sonnenberg GF, Daly M, Sullivan KE, Baldassano RN, Devoto M

Abstract
BACKGROUND & AIMS: Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed ≤5 y of age, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development.
METHODS: Patients with VEO-IBD and parents (when available) were recruited from the Children’s Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (ages 3 weeks to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by post-processing and variant calling. Following functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency <0.1%, and scaled combined annotation dependent depletion scores ≤10. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n=45) or adult-onset Crohn’s disease (n=20) and healthy individuals (controls, n=145) were obtained from the University of Kiel, Germany and used as control groups.
RESULTS: Four-hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling > 1 Mbp of coding sequence, were selected from the whole exome data. Our analysis revealed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19.
CONCLUSIONS: In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the identification of previously unidentified IBD-associated variants.

PMID: 26193622 [PubMed – as supplied by publisher]

Lung disease in primary antibody deficiency.

July 21, 2015 By Manish Butte

Lung disease in primary antibody deficiency.

Lancet Respir Med. 2015 Jul 15;

Authors: Verma N, Grimbacher B, Hurst JR

Abstract
This Review summarises current knowledge on the pulmonary manifestations of primary antibody deficiency (PAD) syndromes in adults. We describe the major PAD syndromes, with a particular focus on common variable immunodeficiency (CVID). Respiratory infection is a common presenting feature of PAD syndromes. Respiratory complications are frequent and responsible for much of the morbidity and mortality associated with these syndromes. Respiratory complications include acute infections, the sequelae of infection (eg, bronchiectasis), non-infectious immune-mediated manifestations (notably the development of granulomatous-lymphocytic interstitial lung disease in CVID), and an increased risk of lymphoma. Although minor abnormalities are detectable in the lungs of most patients with CVID by CT scanning, not all patients develop lung complications. Mechanisms associated with the maintenance of lung health versus lung disease, and the development of bronchiectasis versus immune-mediated complications, are now being dissected. We review the investigation, treatment, and management strategies for PAD syndromes, and include key research questions relating to both infectious and non-infectious complications of PAD in the lung.

PMID: 26188881 [PubMed – as supplied by publisher]

Five years of self-administered hyaluronidase facilitated subcutaneous immunoglobulin (fSCIg) home therapy in a patient with primary immunodeficiency.

July 19, 2015 By Manish Butte

Five years of self-administered hyaluronidase facilitated subcutaneous immunoglobulin (fSCIg) home therapy in a patient with primary immunodeficiency.

J Clin Pathol. 2015 Jul 17;

Authors: Carne E, Ponsford M, El-Shanawany T, Williams P, Pickersgill T, Jolles S

PMID: 26188056 [PubMed – as supplied by publisher]

Single-center experience of unrelated and haploidentical stem cell transplantation with TCR-alpha/beta and CD19 depletion in children with primary immunodeficiency syndromes.

July 19, 2015 By Manish Butte

Single-center experience of unrelated and haploidentical stem cell transplantation with TCR-alpha/beta and CD19 depletion in children with primary immunodeficiency syndromes.

Biol Blood Marrow Transplant. 2015 Jul 14;

Authors: Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, Laberko A, Livshits A, Novichkova G, Maschan A

Abstract
The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of posttransplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as #NCT02327351). Thirty-seven PID patients, with a median age of 2.6 years (range, 0.2-17 years), were transplanted from MUD (n=27) or haploidentical MMRD (n=10) after TCRαβ+/CD19+ graft depletion. The median numbers of CD34+ and TCRαβ+ cells in the graft were 11.7 × 10(6)/kg and 10.6 x10(3)/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUD and MMRD; 7 of those patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (non-engraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with one alkylating agent in the conditioning regimen. All these patients were successfully re-transplanted with different rescue protocols. The preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/ul, primarily bearing the CD45RA+ naïve phenotype, on day +120. Based on our preliminary data, there was no significant difference between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main posttransplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαβ+-depleted HSCT.

PMID: 26187864 [PubMed – as supplied by publisher]

Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study.

July 18, 2015 By Manish Butte

Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study.

Biomed Res Int. 2015;2015:183523

Authors: Santangelo ML, Criscitiello C, Renda A, Federico S, Curigliano G, Dodaro C, Scotti A, Tammaro V, Calogero A, Riccio E, Pisani A, Carlomagno N

Abstract
Immunodeficiency is associated with higher cancer incidence. However, it is unknown whether there is a link between immunodeficiency and development of multiple primary malignancies. In the present study we analyse this link focusing on kidney-transplanted patients, as they are at higher risk of developing cancer due to the chronic assumption of immunosuppressants. We followed up 1200 patients who underwent kidney transplantation between 1980 and 2012. A total of 77/1200 kidney-transplanted patients developed cancer and 24 of them developed multiple cancers. Most multiple cancers were synchronous with a nonsignificant association between cancer and rejection episodes. In the general cancer population, one-ninth of patients are at higher risk of developing a second tumor over a lifetime; hence it would be reasonable to conclude that, from a merely theoretical and statistical viewpoint, long-term transplanted patients potentially have a higher risk of developing MPMs. However, data did not confirm this assumption, probably because these patients die before a second primary malignancy appears. Despite many observations on the increased incidence of different tumor types in immunodeficient patients and despite immunosuppression certainly being a predisposing factor for the multicancer syndrome, data so far are not robust enough to justify a correlation between immunodeficiency and multiple primary malignancies in transplanted patients.

PMID: 26185750 [PubMed – as supplied by publisher]

Clinical and genotypic spectrum of chronic granulomatous disease in 71 Latin American patients: First report from the LASID registry.

July 18, 2015 By Manish Butte

Clinical and genotypic spectrum of chronic granulomatous disease in 71 Latin American patients: First report from the LASID registry.

Pediatr Blood Cancer. 2015 Jul 15;

Authors: de Oliveira-Junior EB, Zurro NB, Prando C, Cabral-Marques O, Pereira PV, Schimke LF, Klaver S, Buzolin M, Blancas-Galicia L, Santos-Argumedo L, Pietropaolo-Cienfuegos DR, Espinosa-Rosales F, King A, Sorensen R, Porras O, Roxo-Junior P, Forte WC, Orellana JC, Lozano A, Galicchio M, Regairaz L, Grumach AS, Costa-Carvalho BT, Bustamante J, Bezrodnik L, Oleastro M, Danielian S, Condino-Neto A

Abstract
AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database.
RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene.
CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

PMID: 26185101 [PubMed – as supplied by publisher]