Thrombocytopenia is one of the most common hematological abnormalities found in neonates. The causes, treatment modalities, and outcomes of neonatal thrombocytopenia have to be evaluated for providing better care and follow-up. In this study, our aim was to assess the prevalence, causes, treatment modalities, and outcomes of thrombocytopenia in neonates. A retrospective analysis was conducted on the medical records of all neonates hospitalized at our hospital between January 2007 and December 2011 and those with thrombocytopenia were included in the study. Of the 3,515 neonates, 134 (3.8%) had thrombocytopenia. Ninety-seven of them (72%) were preterm. In the patients admitted to neonatal intensive care unit, the prevalence of thrombocytopenia was found as 12%, whereas it was found as 1.2% in neonatal service. The highest prevalence was detected in the year 2008 by 5.3%, and the lowest prevalence was detected in the year 2011 by 2.4%. Sepsis was the most common etiologic factor between years 2007 and 2009. Intrauterine growth restriction, metabolic disorders, drugs, and asphyxia were more common causes in the recent years. Severe thrombocytopenia was found in 26% of neonates and 11 % of thrombocytopenic neonates had major hemorrhage. Intracranial hemorrhage ratio was 5.9% and all of these patients were preterm. Thrombocytopenia improved in 92.5% of patients and persisted in 3% of patients. Death occurred in 4.5% of neonates. This study shows that the causes of neonatal thrombocytopenia may show variations with respect to time and the prevalence, complications, and risks of thrombocytopenia may be lowered by eliminating preventable factors.

IntroductionInterleukin-1 receptor antagonist deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. The underlying genetic abnormality involves a recessive mutation in IL1RN, which encodes interleukin-1 receptor antagonist. In this case report, we describe a case of a 12-year-old Turkish girl who initially was presented at 1 year of age, older than previously reported children with interleukin-1 receptor antagonist deficiency, and with a novel mutation, p.R26X, in ILR1N.Case presentationOur patient developed pustular cutaneous lesions at 1 year of age. At the age of 12 years, she was hospitalized for arthralgia of her knees, elbows, and ankles and arthritis of the left knee, with simultaneous pustular cutaneous lesions. She was admitted to the intensive care unit because of septicemia and respiratory insufficiency during follow-up. A skin biopsy of hyperpigmented lesions demonstrated neutrophil infiltration in the epidermis and subepidermal pustular dermatosis. Interleukin-1 receptor antagonist deficiency was suspected, and genetic analysis revealed a homozygous mutation (p.R26X) in IL1RN, which led to a diagnosis of interleukin-1 receptor antagonist deficiency. Treatment with canakinumab (recombinant human anti-human interleukin-1β monoclonal antibody) 150mg subcutaneously once every 6 weeks was initiated. Our patient did not experience further cutaneous lesions or arthritis. Her post-treatment inflammatory markers were normal; she gained weight; and she was able to walk independently.ConclusionsIn this case report, we describe a patient with interleukin-1 receptor antagonist deficiency who responded excellently to canakinumab treatment. We believe more awareness is warranted for interleukin-1 receptor antagonist deficiency in children. It is possible that the mutation in our patient was a founder mutation that may lead to diagnosis of additional cases in Turkey.

Chronic Mucocutaneous Candidiasis (CMC) is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF) (c.1154 C>T, p.Thr385Met) in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT) was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

Defective adaptive immune responses are well studied in common variable immunodeficiency (CVID) patients; however, more focus is needed on innate immune system defects to explain CVID’s clinical and laboratory heterogeneity. This is the first study comparing migratory function of granulocytes, oxidative burst activity of phagocytic cells, surface integrin expressions on neutrophils and lymphocytes, natural killer (NK) cell numbers and cytotoxic activity, natural killer T cells, lymphocyte subsets such as CD8+CD28+, CD4+CTLA-4+ cells in CVID patients (n: 20) and healthy controls (n: 26). The relationship between laboratory findings and some clinical was also investigated. CD3+CD8+ T cytotoxic cells were found to be elevated in CVID patients, but CD3+CD8+CD28+ or CD3+CD8+CD28− cells did not show any significant difference. CD4+CTLA-4+ cell percentages were significantly lower in CVID patients compared to healthy controls. Severe CVID patients had decreased percentages of NK cells with increased NK cell cytotoxicity suggesting possibly increased activation. Furthermore, CD3−CD16+CD56+CD28+ cells of CVID patients were elevated while percentage of CD28− NK cells was decreased. Neutrophil migration percentages were lower but and oxidative burst activity was not affected. CD11a expressions on these cells were depressed in contrast to increased expression of CD18. Innate immunity defects may affect the extent of recurrence and severity of infections in CVID. Our observations highlight some of these associations and indicate the need for further similar studies for improving better innate system evaluation batteries for these patients. Further phenotypic correlations of these analyses will help clinicians reach a more definitive target for the molecular genetic diagnostic of pediatric CVID patients.

Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the IL10RB gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.