Research

Chronic granulomatous disease: why an inflammatory disease?

Braz J Med Biol Res. 2014 Aug 29;0:0

Authors: Roxo-Junior P, Simão HM

Abstract
Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. Patients can present with severe, recurrent infections and noninfectious conditions. Among the latter, inflammatory manifestations are predominant, especially granulomas and colitis. In this article, we systematically review the possible mechanisms of hyperinflammation in this rare primary immunodeficiency condition and their correlations with clinical aspects.

PMID: 25184375 [PubMed – as supplied by publisher]

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Primary ciliary dyskinesia diagnosed by electron microscopy in one case of Kartagener syndrome.

Rom J Morphol Embryol. 2014;55(2 Suppl):697-701

Authors: Rugină AL, Dimitriu AG, Nistor N, Mihăilă D

Abstract
Primary ciliary dyskinesia (PCD) is associated with abnormalities in the structure of a function of motile cilia, causing impairment of muco-ciliary clearence, with bacterial overinfection of the upper and lower respiratory tract (chronic oto-sino-pulmonary disease), heterotaxia (situs abnormalities), with÷without congenital heart disease, abnormal sperm motility with male infertility, higher frequency of ectopic pregnancy and female subfertility. The presence of recurrent respiratory tract infections in the pediatric age requires differentiation between primary immunodeficiency, diseases with abnormal mucus (e.g., cystic fibrosis) and abnormal ciliary diseases. This case was hospitalized for recurrent respiratory tract infections and total situs inversus at the age of five years, which has enabled the diagnosis of Kartagener syndrome. The PCD confirmation was performed by electron microscopy examination of nasal mucosa cells through which were confirmed dynein arms abnormalities. The diagnosis and early treatment of childhood PCD allows a positive development and a good prognosis, thus improving the quality of life.

PMID: 25178347 [PubMed – as supplied by publisher]

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Reduced-intensity conditioning for hematopoietic cell transplantation of chronic granulomatous disease.

Pediatr Blood Cancer. 2014 Aug 30;

Authors: Oshrine B, Morsheimer M, Heimall J, Bunin N

Abstract
Hematopoietic cell transplantation (HCT) is the only available curative therapy for chronic granulomatous disease (CGD), but its use is limited by transplant-related mortality (TRM) in patients who often come to transplant with existing infections or organ dysfunction. Reduction in the intensity of the preparative regimen mitigates these risks, but increases the potential for mixed donor-recipient chimerism (MC) that may progress to graft loss. Recently a busulfan-based reduced-intensity conditioning (RIC) regimen has been described with excellent survival and little MC. We report our experience with a similar RIC regimen at our institution, demonstrating problems with donor chimerism and graft loss. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

PMID: 25175046 [PubMed – as supplied by publisher]

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[Adverse effects with ambulatory intravenous immunoglobulin administration in adult patients with common variable immunodeficiency.]

Rev Alerg Mex. 2014 Jul-Sep;61(3):131-40

Authors: Rodríguez-Mireles KA, Galguera-Sauceda A, Gaspar-López A, López-Rocha EG, Campos-Romero F, Del Rivero-Hernández L, Amaya-Mejía A, Galindo-Pacheco L, O’Farril-Romanillos P, Segura-Méndez NH

Abstract
BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, affecting 1:25,000-75,000 people. It is characterized by the absence or decrease antibody production. Treatment for CVID consists on human immunoglobulin administration, and the intravenous route is the most common route for administration, at 400-800 mg/kg of weight every 3-4 weeks. Adverse effects associated with intravenous immunoglobulin (IVIg) use occur in 25% of all infusions, with severe adverse reactions presenting in less than 1% of all patients. Acute renal failure can occur as a severe adverse reaction, which presents 1-10 days after starting IVIg treatment. In our center we implemented an ambulatory scheme for IVIg administration, which allows its administration in an average of 3 hours, without severe adverse effects.
OBJECTIVES: To describe adverse effects and to evaluate the frequency of renal failure secondary to ambulatory IVIg administration in patients with common variable immunodeficiency.
MATERIAL AND METHOD: A descriptive and prospective study was done including adult patients con definitive diagnosis of common variable immunodeficiency, receiving IVIg at replacement dose every 3 weeks. All patients were evaluated with clinical exploration, somatometry, serum creatinine, albumin and urea determination, 24 hours creatinine clearance, glomerular filtration rate with CKD-EPI, and immediate renal function associated with accumulated IVIg. Results were analyzed with descriptive statistics.
RESULTS: We determined adverse effects in 25 patients with common variable immunodeficiency (15 women and 10 men, average age 36.7 years), during a 10 months period (January-September 2013). During this period 284 IVIg infusions were administered using our scheme, frequency of adverse effects were 12.9%, with 5.2% of early adverse effects and 7.7% late adverse effects, all being mild to moderate, in some cases required analgesic and/or antihistamine administration, without having to stop the IVIg infusion. In the renal function study 19 patients were included (12 women and 7 men, average age 36 years, average weigh 58.74 kg and average height 1.60 m), evaluated from January 2009 to October 2013. Average serum creatinine was 0.76 ± 0.18 mg/dL, average serum urea was 28.6 ± 7.6 mg/dL, none patient presenting acute renal failure. Glomerular filtration rate was determined with CKD-EPI formula, and the average was 116 ± 34 mL/min/1.73 m2, finding chronic renal failure in 4 patients. Average 24 hours creatinine clearance was 98.64 ± 22 mL/min/1.73 m2, with chronic renal failure data in 6 patients.
CONCLUSIONS: There were no severe adverse effects with this ambulatory IVIg scheme (anaphylaxis, acute renal failure). We did not find data of acute renal failure secondary to IVIg administration in this population, but we did find data of chronic renal failure secondary to IVIg administration through 24 hours creatinine clearance in 6 patients. No relation was found between accumulated IVIg dose in the last 5 years and decreased glomerular filtration rate. Another benefit worth of mentioning with this scheme is the reduction in costs for the health institution and to the patient.

PMID: 25177848 [PubMed – as supplied by publisher]

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[Wiskott-Aldrich syndrome. A report of a new mutation.]

Rev Alerg Mex. 2014 Jul-Sep;61(3):219-23

Authors: Guillén-Rocha N, López-Rocha E, Danielian S, Segura-Méndez N, López-González L, Lugo-Reyes SO

Abstract
Wiskott-Aldrich syndrome was first reported clinically in 1937, and in 1954 the classic triad was identified: eccema, recurrent infections and thrombocytopenia with an X-linked transmission. Its incidence is estimated at 1 to 10 in one million live births per year. Wiskott Aldrich syndrome is caused by mutations in a gene in the short arm of chromosome X that encodes the Wiskott-Aldrich syndrome protein (WASp), which identification and sequencing was first performed in 1994, and since then about 300 mutations have been reported. This paper describes the case of a boy with Wiskott-Aldrich syndrome, with clinical and genetic diagnosis, with a considerable diagnostic delay attributable to an atypical presentation misdiagnosed as immune thrombocytopenia.

PMID: 25177856 [PubMed – as supplied by publisher]

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Medical History, Lifestyle, Family History, and Occupational Risk Factors for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project.

J Natl Cancer Inst Monogr. 2014 Aug;2014(48):41-51

Authors: Slager SL, Benavente Y, Blair A, Vermeulen R, Cerhan JR, Costantini AS, Monnereau A, Nieters A, Clavel J, Call TG, Maynadié M, Lan Q, Clarke CA, Lightfoot T, Norman AD, Sampson JN, Casabonne D, Cocco P, de Sanjosé S

Abstract
BACKGROUND: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are two subtypes of non-Hodgkin lymphoma. A number of studies have evaluated associations between risk factors and CLL/SLL risk. However, these associations remain inconsistent or lacked confirmation. This may be due, in part, to the inadequate sample size of CLL/SLL cases.
METHODS: We performed a pooled analysis of 2440 CLL/SLL cases and 15186 controls from 13 case-control studies from Europe, North America, and Australia. We evaluated associations of medical history, family history, lifestyle, and occupational risk factors with CLL/SLL risk. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: We confirmed prior inverse associations with any atopic condition and recreational sun exposure. We also confirmed prior elevated associations with usual adult height, hepatitis C virus seropositivity, living or working on a farm, and family history of any hematological malignancy. Novel associations were identified with hairdresser occupation (OR = 1.77, 95% CI = 1.05 to 2.98) and blood transfusion history (OR = 0.79, 95% CI = 0.66 to 0.94). We also found smoking to have modest protective effect (OR = 0.9, 95% CI = 0.81 to 0.99). All exposures showed evidence of independent effects.
CONCLUSIONS: We have identified or confirmed several independent risk factors for CLL/SLL supporting a role for genetics (through family history), immune function (through allergy and sun), infection (through hepatitis C virus), and height, and other pathways of immune response. Given that CLL/SLL has more than 30 susceptibility loci identified to date, studies evaluating the interaction among genetic and nongenetic factors are warranted.

PMID: 25174025 [PubMed – as supplied by publisher]

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Related Articles

IgA deficiency in primary antiphospholipid syndrome.

Joint Bone Spine. 2014 Jan;81(1):97-8

Authors: Bonin CC, Rodrigues CE, de Carvalho JF

PMID: 23809213 [PubMed – indexed for MEDLINE]

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Interpret and manage (not only autoimmune) cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment.

Blood. 2014 Aug 27;

Authors: Seidel MG

Abstract
Autoimmunity and immune dysregulation may lead to cytopenia and represent key features of many primary immunodeficiencies (PID). Especially when cytopenia is the initial symptom of PID, the order and depth of diagnostic steps have to be performed in accordance with both an immunologic and a hematologic approach and contain not only the exclusion of systemic lupus erythematosus, common variable immunodeficiency, autoimmune lymphoproliferative syndromes, but also hemophagocytic disorders, lymphoproliferative diseases, and novel differential diagnoses such as MonoMac syndrome (GATA2 deficiency), CD27 deficiency, LRBA (lipopolysaccharide-responsive beige-like anchor) deficiency, activated PI3KD syndrome (APDS), XMEN disease (MAGT1 deficiency) and others. Immunosuppressive treatment often needs to be initiated urgently, impeding relevant further immunologic laboratory analyses aimed to define the underlying PID. Awareness of potentially involved disease spectra ranging from hematologic to rheumatologic and immunologic disorders is crucial to identify a certain proportion of PID pheno- and genotypes among rather descriptive diagnoses such as autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, severe aplastic anemia / refractory cytopenia and others. A synopsis of pathomechanisms, novel differential diagnoses, and advances in treatment options of cytopenias in PID is provided to facilitate the essential multidisciplinary management and to bridge approaches.

PMID: 25163701 [PubMed – as supplied by publisher]

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The Value of Family History in Diagnosing Primary Immunodeficiency Disorders.

Case Rep Pediatr. 2014;2014:516256

Authors: Hendaus MA, Alhammadi A, Adeli MM, Al-Yafei F

Abstract
Eliciting proper family medical history is critical in decreasing morbidity and mortality in patients with primary immunodeficiency disorders (PIDs). Communities with a common practice of consanguinity have a high rate of PIDs. We are presenting 2 cases where digging deeply into the family medical history resulted in the diagnosis of Omenn syndrome, a possibly fatal entity if not managed in a reasonable period.

PMID: 25161792 [PubMed – as supplied by publisher]

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Malakoplakia and Primary Immunodeficiency.

J Pediatr. 2014 Aug 22;

Authors: Archer SR, Abramowsky CR, Kobrynski L, Simoneaux S, Vogler LB, Ricketts RR, Parker C, Elawahbdeh N, Shehata BM

Abstract
Malakoplakia, a rare granulomatous disease caused by impaired macrophage response, has been reported only rarely in children. We report 3 unique cases, with lesions occurring in unusual locations in children with primary immune deficiencies.

PMID: 25155967 [PubMed – as supplied by publisher]

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