Manish Butte

[Disseminated infection by Bacillus Calmette-Guérin in an immunodeficient infant: case report].

Rev Peru Med Exp Salud Publica. 2019 Jan-Mar;36(1):134-137

Authors: Apagüeño-Ruiz C, Peceros-Escalante J, Pomar-Morante R, Véliz-Lazo B, Ballona-Chambergo R

Abstract
The Bacillus Calmette-Guerin (BCG) vaccine given to newborns in countries with a high incidence of tuberculosis may cause local reactions up to disseminated infection in immunocompromised patients. We report the case of a six-monthold male infant with a history of having received the BCG vaccine at birth, and presenting repeated infectious, soft violet nodules in the trunk and extremities with the presence of acid-alcohol-resistant bacilli (BAAR) in histopathology and skin culture; the molecular study reported the presence of Mycobacterium bovis BCG. In the tomography, interstitial opacities were observed in the lungs and in the gastric lavage BAAR was identified. The genetic study of the patient and the mother revealed the presence of a mutation in the IL2RG gene confirming the diagnosis of severe combined immunodeficiency. Received treatment with human immunoglobulin and anti-tuberculosis scheme with isoniazid, rifampicin, and ethambutol. We present the case because of the implication in the life prognosis of these patients and because of the need for an accurate and timely diagnosis.

PMID: 31116327 [PubMed – indexed for MEDLINE]

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The influence of hospital-based intravenous immunoglobulin and home-based self-administrated subcutaneous immunoglobulin therapy in young children with Primary Immunodeficiency Diseases on their parents/caregivers satisfaction.

Pediatr Int. 2019 Dec 27;:

Authors: Lechanska-Helman J, Sobocinska A, Jerzynska J, Stelmach I

Abstract
OBJECTIVES: Immunoglobulin replacement (IgR) has been standard therapy for patients with primary immunodeficiency diseases (PIDD). Intravenous Ig (IVIg) is delivered at the hospital, whereas subcutaneous Ig (SCIg) is used at home-based treatment. The aim of the study was to determine advantages and disadvantages of IVIg and SCIg in Polish children 1-5 years, with PIDD and the satisfaction of their parents/caregivers regarding immunoglobulin-replacement.
METHODS: The research involved parents of 23 children with PIDD, aged 1 – 5 years. All children were given IVIg therapy and after at least 6 months they were switched towards home SCIg therapy for at least 6 months. Questionnaire assessing advantages and disadvantages of preferred types of treatment and the quality of life of PIDD patients’ families’ lives was used.
RESULTS: The research showed that IVIg therapy was better accepted by parents than SCIg therapy (p=0,034) for the following reasons: possibility of taking treatment once per month (60%) and fear of performing injections to the children (60%), better control of the disease at the regular visits in the hospital (53,33%). Parents noticed however that IVIg has a significant impact on absence at school or work (70%). Parents who prefer for their children SCIg, are guided mainly by the smaller number of side effects (40%), and the fact that infusions do not interfere with parent’s work, child’s school (40%).
CONCLUSION: The results showed that IVIg therapy was better accepted by parents than SCIg therapy Parents of children with SCIg do not have an impression of being time-bounded, but this group of parents is less satisfied with their life, and feel anxiety about their children disease, which is related to administering the medicine by themselves.

PMID: 31880367 [PubMed – as supplied by publisher]

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Development of multiple gallstones in a child with lipopolysaccharide-responsive beige-like anchor protein mutation.

Cent Eur J Immunol. 2019;44(3):332-335

Authors: Kutluǧ Ş, Boztuǧ K, Yıldıran A

Abstract
A defect in the lipopolysaccharide-responsive beige-like anchor protein (LRBA) gene is a newly defined rare cause of primary immunodeficiency diseases, which manifests as immune dysregulation and humoral immune deficiency. LRBA deficiency is a combined immunodeficiency. A boy with LRBA deficiency is described in this report. He had been diagnosed with Evans syndrome in a haematology clinic. He was referred to an immunology and allergy clinic for frequent respiratory tract infections. He also had hepatosplenomegaly but no lymphadenopathy. Immunological evaluation revealed hypogammaglobulinaemia, increased double-negative T cells, decreased memory B cells and switched B cells, and an inverted CD4/CD8 ratio. LRBA deficiency was considered due to common variable immunodeficiency-autoimmune lymphoproliferative overlap syndrome. A homozygote mutation (c.1964C>T) in LRBA was found through exome sequencing. Gastrointestinal investigation was performed due to unexplained abdominal pain. It revealed atrophic gastritis, partial villous atrophy, and multiple gallstones. There was no chronic diarrhoea or failure to thrive. The abdominal pain disappeared after a cholecystectomy. Multiple gallstones have not been reported in other LRBA-deficient patients who also had autoimmune haemolytic anaemia. Multiple gallstones that require cholecystectomy can develop in LRBA-deficient patients during adolescence.

PMID: 31871423 [PubMed]

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Complex profile of multiple hepatobiliary and gastrointestinal complications after hematopoietic stem cell transplantation in a child with Nijmegen breakage syndrome.

Cent Eur J Immunol. 2019;44(3):327-331

Authors: Gałązka P, Czyżewski K, Szaflarska-Popławska A, Dębski R, Krenska A, Styczyński J

Abstract
Patients with Nijmegen breakage syndrome (NBS) can develop life-threatening immunodeficiency, which should be treated with hematopoietic stem cell transplantation (HSCT). We report the case of a 14-year-old girl with NBS who due to an increasing number of severe complications was referred for HSCT from a matched unrelated donor. After reduced-intensity conditioning and transplantation of peripheral blood hematopoietic cells, during the early post-transplant period (days 0-30), the girl suffered from severe mucositis, fever episodes, mild acute renal injury and facial vasculitis. All these complications were managed successfully. During the intermediate post-transplant period (days 30-100) a number of hepatic and gastrointestinal complications occurred, including cholecystitis, cholelithiasis with choledocholithiasis, pancreatitis as well as acute bleeding from the lower gastrointestinal tract caused by rectal and recto-sigmoid junction ulcers. All the obstacles were obviously attributable both to the primary congenital disease, its complications, and transplantation itself. We overcame these complications and treated the patient with the best possible and safe methods. The multidisciplinary approach based on combined surgical, endoscopic and conservative management of multiple post-transplant complications was successful for the patient.

PMID: 31871422 [PubMed]

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Vaccine-derived rotavirus strains in infants in England.

Arch Dis Child. 2019 Dec 23;:

Authors: Gower CM, Dunning J, Nawaz S, Allen D, Ramsay ME, Ladhani S

Abstract
OBJECTIVE: To describe infants with acute gastroenteritis symptoms in primary and secondary care who have the Rotarix vaccine-derived G1P[8] rotavirus strain identified in their stools.
DESIGN: This is a prospective national surveillance conducted by Public Health England (PHE). Rotavirus-positive samples from vaccine-eligible children are routinely submitted to PHE for confirmation, and general practitioners are requested to complete a surveillance questionnaire for all cases. The modified Vesikari Score was used to assess severity of gastroenteritis.
SETTING: England, July 2013-September 2016.
RESULTS: 2637 rotavirus strains were genotyped and 215 (8%) identified as the Rotarix vaccine-derived G1P[8] strain. There were no Rotarix vaccine-derived G1P[8] strains detected in unimmunised infants. Rotarix vaccine-derived G1P[8] strains clustered around the time of rotavirus vaccination and were responsible for 82% (107 of 130) of rotavirus-positive samples in 2-month-old infants and 68% (36 of 53) in 3-month-old infants. However, 13 samples were obtained more than 7 weeks after the last vaccination date; 10 of these specimens were from six children who were subsequently diagnosed with severe combined immunodeficiency (SCID). Diarrhoea was the single most common presenting symptom (83.0%) in infants with Rotarix vaccine-derived G1P[8] strains, who were less likely to present with fever, vomiting, dehydration or severe gastroenteritis than infants with wild-type rotavirus infection.
CONCLUSIONS: Rotavirus identified in stools of infants around the time of their routine immunisations is most likely the Rotarix vaccine-derived G1P[8] strain. Infants with undiagnosed SCID at the time of rotavirus immunisation may experience prolonged gastroenteritis symptoms. Most infants with vaccine strains in their stools more than 7 weeks after immunisation had SCID.

PMID: 31871043 [PubMed – as supplied by publisher]

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A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation.

Clin Immunol. 2019 Dec 20;:108328

Authors: Chear CT, Nallusamy R, Canna SW, Chan KC, Baharin MF, Hishamshah M, Ghani H, Ripen AM, Mohamad SB

Abstract
Autoinflammatory disorders are characterized by dysregulated innate immune response, resulting in recurrent uncontrolled systemic inflammation and fever. Gain-of-function mutations in NLRC4 have been described to cause a range of autoinflammatory disorders. We report a twelve-year-old Malay girl with recurrent fever, skin erythema, and inflammatory arthritis. Whole exome sequencing and subsequent bidirectional Sanger sequencing identified a heterozygous missense mutation in NLRC4 (NM_001199138: c.1970A > T). This variant was predicted to be damaging in silico, was absent in public and local databases and occurred in a highly conserved residue in the leucine-rich repeat (LRR) domain. Cytokine analysis showed extremely high serum IL-18 and IL-18/CXCL9 ratio, consistent with other NLRC4-MAS patients. In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations.

PMID: 31870725 [PubMed – as supplied by publisher]

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The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma.

Front Pharmacol. 2019;10:1387

Authors: Marone G, Granata F, Pucino V, Pecoraro A, Heffler E, Loffredo S, Scadding GW, Varricchi G

Abstract
Approximately 5-10% of asthmatic patients worldwide suffer from severe asthma. Experimental and clinical studies have demonstrated that IL-13 is an important cytokine in chronic airways inflammation. IL-13 is involved in Th2 inflammation and has been identified as a possible therapeutic target in the treatment of asthma. Two different human monoclonal antibodies (mAbs) anti-IL-13 (tralokinumab and lebrikizumab) block binding and signaling of IL-13 to its receptors, IL-13Rα1 and IL-13Rα2. Several randomized, double-blind, placebo-controlled multicenter studies have evaluated the safety and efficacy of tralokinumab and lebrikizumab in the treatment of adult patients with severe asthma, but all have failed to meet their primary endpoints. No serious adverse events related to the treatment with these anti-IL-13 mAbs have been reported in these studies. These negative clinical results contrast with positive findings from blocking IL-13 signaling in experimental models of asthma, raising doubts about the transferrable value of some models. Interestingly, dupilumab, a mAb which blocks both IL-4 and IL-13 signaling reduces exacerbation rates and improves lung function in severe asthmatics. These results suggest that IL-4 and IL-13 share some, but not all functional activities in airway inflammation. Tralokinumab might show efficacy in a highly selected cohort of asthmatics characterized by overexpression of IL-13.

PMID: 31866859 [PubMed]

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