Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder.

Summary: Introduction. Most patients with primary and secondary immunodeficiencies need regular Intravenous Immunoglobulin (IVIG) or Subcutaneous Immunoglobulin (SCIG) treatment. This study aimed to evaluate the serum IgG trough levels, frequency of mild and severe infections, frequency and duration of hospitalization, duration of absence of school, and quality of life in patients switching their IVIG therapy to SCIG administration. Materials. Twenty-nine patients with immunodeficiency on regular IVIG treatment and who agreed to receive SCIG treatment were included. Seven patients discontinued treatment after the first SCIG administration. We collected data regarding serum IgG levels, annual numbers of infections, hospital admissions, and adverse events prior to and following SCIG initiation. PedsQL tests such as Scale Total Score (STS), Physical Health Total Score (PHTS), Psychosocial Health Total Score (PsyHTS), emotional functionality, social functionality, school/work problems score were calculated separately for all patients and their parents. Results. In twenty-two cases who were diagnosed as primary immunodeficiency, the most common indication for initiation of SCIG treatment was the long transfusion period of IVIG treatments and the difficulty of access to the hospital. No systemic side effects were noted except local redness, pain, and swelling on the injection site. The median IgG value was 588.9 mg/dl during IVIG treatment and 872 mg/dl one year after SCIG treatment. Annual frequency of infections and absence to school/work decreased significantly in the SCIG group while the annual number of hospitalizations and hospital stay time did not change significantly. There was a significant increase in the "quality of life" scores of the patients and their families. Conclusions. SCIG treatment provides ideal and protective immunoglobulin levels and offers the comfort of treatment in their home environment, thus increasing the patient's satisfaction and quality of life.

A novel TTC37 mutation causing clinical symptoms of trichohepatoenteric syndrome such as pyoderma gangrenosum and immunodeficiency without severe diarrhea

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Disseminated BCG infectious disease and hyperferritinemia in a patient with a novel NEMO mutation

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Do elevated serum IgM levels have to be included in probable diagnosis criteria of patients with ataxia-telangiectasia?

Ataxia-telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder that is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency. Delay in diagnosis or misdiagnosis is probable due to its wide clinical heterogeneity in infancy. Recurrent sinopulmonary infections are often the only presenting symptom and usually patients have decreased immunoglobulins. A total 10% of patients who present with decreased serum immunoglobulin G and A and with normal or elevated immunoglobulin M levels are often misdiagnosed as hyperimmunoglobulin M syndrome. Definitive diagnosis is made if a patient with progressive cerebellar ataxia has a disease causing mutation on the ATM gene. Ataxia-telangiectasia guideline of the European Society for Immunodeficiencies defines the probable diagnosis criteria. We evaluated twenty ataxia-telangiectasia patients (mean age 13.8±4.1 years) retrospectively who were followed-up for a mean of 38.6±27.0 months. Twelve patients had a family history of consanguinity. A total of 80% patients suffered from various infections. Neoplasms occurred in three of them. Patients showed immunological abnormalities as low IgG (45%), low IgA (65%) and elevated IgM (60%) levels. CD3+CD4+ T lymphocyte frequency was low in 45% patients. The mean AFP concentration at the diagnosis was 191.9±140.1 ng/mL and the raised IgM values did not show any statistically significant relationship with high AFP concentrations. Frequency of the elevated IgM concentrations in (60%) patients raises the concerns about thinking this finding has to be accepted as a probable diagnosis criterium.

Spontaneous pneumothorax in children with osteosarcoma: report of three cases and review of the literature.

Spontaneous pneumothorax is a rare manifestation of primary lung cancer or metastasis. It is estimated that < 1% of all cases of spontaneous pneumothorax are tumor-associated and metastatic osteogenic or soft-tissue sarcomas are associated most commonly with pneumothorax especially in the setting of cytotoxic chemotherapy or radiotherapy. In this article, we report three pediatric cases with osteosarcoma that developed spontaneous pneumothorax during chemotherapy with a review of the literature. Two of them had lung metastasis at the time of the detection of pneumothorax and the remaining patient was found to have a bronchopleural fistula. SPx is an emergency situation and early diagnosis and management can improve prognosis and quality of life of the patient however the optimal management has yet to be determined.

IgG-anti-IgA antibodies: an autoimmune finding in patients with psoriasis vulgaris.

AIM: Psoriasis is thought to be an autoimmune disease caused by inappropriate activation of the cellular immune system. In this study, we aimed to search out IgG-anti-IgA antibody levels, serum immunoglobulins and antinuclear antibodies (ANA). METHODS: The study enrolled 38 psoriasis vulgaris patients and 40 healthy controls. RESULTS: Mean IgG-anti-IgA levels were significantly higher in psoriasis patients. The frequency of positive ANA testing was 21.1%; however, there was no correlation between IgG-anti-IgA antibody levels and ANA positivity. Only one patient had low IgA levels without high IgG-anti-IgA concentrations. CONCLUSION: The data about high IgG-anti-IgA antibody levels are noteworthy for a new evidence of autoimmune mechanism.

Hyper-immunoglobulin M syndrome type 3 with normal CD40 cell surface expression.

Mutations of the CD40 gene have been found in patients with autosomal recessive hyper-immunoglobulin M (HIGM) syndrome type 3. Five patients from four unrelated families with CD40 mutation have been reported so far. Clinical manifestations include recurrent sinopulmonary infections, Pneumocystis carinii pneumonia and Cryptosporidium parvum infection. Affected patients typically have very low levels of IgG and IgA and normal or high levels of IgM. Flow cytometry analysis of these five patients demonstrated that peripheral blood B lymphocytes lacked expression of surface CD40. Herein, we present two siblings from second-degree consanguineous Turkish parents with homozygous CD40 deletion of four nucleotides including the stop codon resulting presumably to a longer protein. Clinical and immunological profile of these patients is similar to the already reported HIGM3 patients except normal CD40 expression on B lymphocytes. This observation emphasizes the requirement of CD40 mutation analysis for definite diagnosis of HIGM3 despite normal flow cytometric expression of CD40, particularly if the immunological and clinical profile is suggestive for HIGM3.

Correlation between c-erbB2 expression, lymphovascular invasion and other biological and clinical prognostic factors and preoperative tumor markers in patients with early-stage and locally advanced breast cancer.

PURPOSE: To evaluate the correlation between c-erbB2 expression, lymphovascular invasion and other biological and clinical prognostic variables and preoperative CA 15-3 and CEA levels in patients with early-stage and locally advanced breast cancer. METHODS: Preoperative serum concentrations of CA 15- 3 and CEA were measured in 123 patients undergoing surgical treatment for stage I-III breast cancer and the association between these markers and clinical and biological variables were evaluated. RESULTS: With cut-off values of 45 U/ml (CA 15-3) and 2.5 ng/ml (CEA), the sensitivity for CA 15-3 and CEA was 10% and 24% and their mean values were 23 U/ml and 2.32 ng/ml, respectively. A significant correlation between preoperative levels of CA 15-3 and CEA was noticed (p=0.023). Preoperative CA 15-3 levels were significantly higher in patients with tumors > 5 cm (p<0.0001), with positive axillary lymph nodes (p=0.04), with increasing nodal burden (p= 0.025) and in patients with stage III disease (p=0.003). Tumor size >5 cm (p=0.002), increasing axillary nodal burden (p=0.02) and stage III disease (p<0.0001) were also significantly correlated with CEA values above the cut-off level. There were no correlations between CA 15-3 and CEA levels and other variables including c-erbB2 expression, age, grade, hormone receptor status, and lymphovascular invasion. CONCLUSION: Preoperative CA 15-3 and CEA levels are significantly correlated with tumor size, axillary nodal status and stage in patients with non-metastatic breast carcinoma. No correlation between preoperative values of CA15-3/CEA and c-erbB2 status, lymphovascular invasion and other prognostic factors was detected.

Determination of cut-off titers and agreement between immunofluorescence and immunoblotting methods for detecting antinuclear antibodies in children.

Detection of antinuclear antibodies (ANA) is a diagnostic adjunct in patients with suspected autoimmune connective tissue diseases, and various detection methods are in use. The aim of this study was to analyze the agreement between the ANA immunoflourescence (IF) and immunoblotting (IB) methods and determine cut-off for children subjects in a laboratory setting. We evaluated 729 serum samples that were analyzed by both ANA IF and IB. The results were evaluated by chi(2) test and, for agreement, kappa index was used. Frequencies determined for both 1:40-1:100 cut-off titers of ANA IF in relation to IB testing supported the idea that 1:100 starting dilution should be recommended in children subjects for ANA IF method and antigen specific immunoblot testing was needed, especially for some of the ANA IF negative samples. Agreement between the two methods, especially with homogenous, granular, and nucleolar ANA IF patterns, was statistically significant.

A novel Y331X nonsense mutation in TNFRSF1A gene in two unrelated Turkish families with periodic fever syndrome.

The autoinflammatory disorders differ in severity, as well as age of onset, duration, and manifestations, but they all share some common features: recurring fever peaks, inflammation of serosal membranes, musculoskeletal involvement, varying types of skin rash, amyloidosis as a sequel of the disease. TRAPS is very rare in Turkish population and we present two unrelated Turkish children with similar clinical phenotypes and laboratory findings related with autoinflammatory disorders and with novel p. Y331X mutation in TNFRSF1A gene. Both of the patients were male and they had recurrent fever without abdominal pain and arthralgia. Full cDNA and exon-intron binding regions of TNFRSF1A, MEFV, MVK, CIAS1 genes were analysed by direct DNA sequencing methods in order to differentiate TRAPS, FMF, HIDS, CINCA/MWS/FCAS respectively. We screened ten exons of TNFRSF1A gene, and detected a heterozygous c.1080C>G nucleotide substitution in exon 10 in both of the unrelated patients, resulting p.Y360X nonsense (protein truncated) mutation. According to classical TNFRSF1A gene nomenclature and the agreement of 30th amino acid as the first one, it is accepted as p.Y331X. It was interesting to determine same mutations in fathers of two patients. In one of the cases, E148Q heterozygous mutation, which is one of the disease-causing mutations of MEFV gene, was detected. No nucleotide substitution was identified in exon and exon-intron splicing regions encoding 396 amino acid of MVK gene in both of the patients. In CIAS1 gene, two different nucleotide substitutions resulting synonymous amino acid mutation were detected in exon 3: c.[732G>A] and c.[786A>G] nucleotide substitutions and compatible p.A242A (according to c.DNA p.A244A) and p.R260R (according to c.DNA p.R262R) synonymous amino acid mutations. These nucleotide substitutions were also detected in parents and were reported to be normal variations in Turkish population. In conclusion, in Turkish patients, with dominantly inherited recurrent fever, TRAPS is a diagnosis worthy of attention and novel mutations have to be reported with phenotype associations.

Leiomyoma of the seminal vesicle mimicking tumoral extension of prostatic carcinoma.

Leiomyoma of the seminal vesicle is an extremely rare tumour. The diagnosis of this entity is important when it co-exists with prostatic carcinoma, since it can simulate tumour extension from prostate or bladder cancer on MR imaging and lead to overstaging. In this report, we describe a 74-year-old man with a leiomyoma of the seminal vesicle that mimics tumour extension from co-existent prostatic cancer on T2-weighted MR imaging. To our knowledge, this is the first description of imaging findings of concurrent leiomyoma of the seminal vesicle and prostatic carcinoma.

Renal involvement as a rare complication of Dorfman-Chanarin syndrome: a case report.

Dorfman-Chanarin syndrome is a rare, autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma due to an acylglycerol recycling defect. It is characterized by accumulation of neutral lipids in different tissues. Liver, muscle, ear, eye, and central nervous system are generally involved, so we presented a patient with severe ichthyosis, lipid vacuoles in neutrophils, and multiorgan involvement including a very rare complication, renal involvement. A 7-month-old girl was presented with frequent respiratory infection, congenital ichthyotic erithroderma and suspicion for immune deficiency. On her physical examination hepatomegaly, developmental delay, palmar and plantar hyperkeratosis and increased deep tendon reflexes with clonus and high tonus were found. Laboratory investigations revealed elevation at transaminases levels, hypoalbuminemia, hypergammaglobulinemia, presence of autoantibodies and eosinophilia. Vacuolization in leukocytes confirmed Dorfman-Chanarin syndrome, whereas no mutation at RAG1-2 and ARTEMIS genes ruled-out immune deficient status of the patient. At the age of eight months the patient died from severe renal failure. Her necropsies demonstrated microvesicular lipid accumulation not only at the liver but also at the renal species. The variability of involvement of different systems in Dorfman-Chanarin syndrome is well described, however the renal findings has not been reported previously at the literature.

The efficiency of different chemoradiotherapy regimens in patients with paediatric nasopharynx cancer: review of 46 cases.

The purpose of this study was to evaluate the role of combined modality treatment in patients with paediatric nasopharynx cancer (NPC). Forty-six patients with paediatric NPC were retrospectively analysed. Forty-four of 46 patients received combined modality treatment. Five-year overall survival and progression-free survivals were 70% and 72% for the whole group, and only three of 46 patients had loco-regional relapse. Complete remission was obtained in 18 of 45 patients (40%), and the overall survival (94% vs. 62% and 19%, p = 0.0009) and disease-free survivals (93% vs. 70% and 16%, p = 0.0002) were significantly better in complete responders when compared with the patients who had partial response or stable disease. The 5-year overall survival and disease-free survivals of the patients who received neoadjuvant chemotherapy (CT) and radiotherapy (RT) followed by CT were superior to the other groups (77% and 80%, respectively). The number of total CT cycles (p = 0.0001), nodal stage (p = 0.05) and treatment response (p = 0.0009) were significant prognostic factors for overall survival. The treatment type (p = 0.02), the number of total CT cycles (p = 0.0006), nodal stage (p = 0.05) and treatment response (p = 0.0002) were found as significant prognostic factors for disease-free survival. The survival of patients receiving six or more CT cycles was also significantly better than that of patients receiving less than six cycles (p = 0.0001). In patients with locally advanced paediatric NPC, CT should be added to RT to improve outcome. However, a standard protocol is yet to be identified, and further studies evaluating the addition of interferon or immunotherapy to CT and RT shall be performed.

The role of postoperative radiotherapy in node negative breast cancer patients with pT3-T4 disease.

AIMS: To evaluate the role of postmastectomy radiotherapy (PMRT) in patients with pT3-T4N0M0 breast cancer. METHODS: 156 patients with T3-T4N0M0 breast cancer were retrospectively analyzed. RESULTS: Locoregional recurrences were seen in 17 of 156 patients with a median time for development of 27 months (5.7-248.7 months). Two of 9 patients who were not treated with post-operative radiation therapy had locoregional recurrence as compared with 16 of 147 patients receiving radiotherapy. In multivariate analysis, presence of locoregional recurrence was the only significant prognostic factor for overall survival (18% vs. 86%, p<0.001, RR=9.05). The patients with a median number of dissected lymph nodes >or=10 had a significantly better locoregional disease free survival rate as compared with patients with dissected lymph nodes <10 (90% vs. 78%, p=0.04). Chest wall recurrences were clearly higher in patients without chest wall RT since 5 of 49 patients without RT had recurrences in the chest wall region while only 4 of 107 who received chest wall RT had recurrence. However receiving RT to peripherical lymphatic regions had no additional effect on reducing recurrences in these regions (5% vs. 4%). CONCLUSIONS: Due to the lack of phase III randomized trials directly addressing the role of postmastectomy radiotherapy in these stages, our series suggest that postmastectomy radiotherapy to the ipsilateral chest wall is recommended for patients with PT3N0 and T4N0 breast cancer. The need for irradiating axillary or supraclavicular region shall be neglected in patients who undergo sufficient axillary sampling.

Is early postradiation dysplasia almost associated with poor prognosis? A case report and review of the literature.

Following radiotherapy for cervical carcinoma, abnormal cytologic changes have been reported in a number of publications. These reactions occur at varying periods of time following irradiation and do not necessarily reflect the presence of invasive cancer. On the basis of cytologic and histopathologic features, these reactions were determined as postradiation dysplasia (PRD). PRD has been reported to occur in 18.7-26% of patients treated by radiotherapy for cervical cancer. In the literature, it was reported that patients diagnosed with PRD less than 3 years after the initial diagnosis of cervical cancer had a mean survival rate of 33.8% as compared with a 100% 5-year survival rate in patients with a delayed (>3 years) onset of period. We present a case of stage IIIB cervical squamous cell carcinoma with PRD detected 6 months after radiotherapy. The patient is still tumor free 8 years after radiotherapy. In the light of this patient, we review the literature and discuss the relationship of PRD with survival in the cervical carcinomas.

Treatment results and prognostic factors in oral tongue cancer: analysis of 80 patients.

Treatment results and prognostic factors for 80 patients with oral tongue cancer admitted to Istanbul University Oncology Institute between 1987 and 2000 were retrospectively analysed. The patients were treated by surgery and postoperative or curative radiotherapy. Median age was 55 (22-93) out of which 41 patients (51%) were male and 39 (49%) were female. One patient (1%) had stage I disease, 28 patients (36%) stage II, 18 patients (23%) stage III and 32 patients (40%) stage IVA disease. Nineteen patients (24%) were medically inoperable or refused surgical treatment, so were treated with curative radiotherapy to a total dose of 70Gy (group A). The remaining 61 patients (76%) were treated with surgery and postoperative external beam radiotherapy (group B). The median follow-up time was 44 months. The 5-year overall and loco-regional disease-free survival rates were 42% and 46%, respectively. The 5-year overall survival rates were 16% in group A and 49% in group B (P=0.0002). The 5-year disease-specific survival rate was 23% in group A while in group B it was 49%; the difference was statistically significant (P=0.02). Combined treatment improves overall and disease-free survival in patients with stage II, III and IVA oral tongue cancer. In patients who are not candidates for surgery, the effect of radiotherapy may be increased with the use of brachytherapy.

Fc gamma RIIa, IIIa and IIIb polymorphisms in Turkish children susceptible to recurrent infectious diseases.

The efficacy of IgG-induced Fc gamma receptor (FcgammaR) function displays interindividual heterogeneity due to genetic polymorphisms of three FcgammaR subclasses: FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb. FcgammaR polymorphisms may contribute to disease susceptibility or may alter disease course. The aim of this study is to examine FcgammaR gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well known humoral immunodeficiencies. For the patients in the study group (n=52), recurrent infection was defined as the presence of at least six infection episodes a year. Seventy-one healthy children with a maximum of two infections in a year were enrolled as the control group. Subjects in both groups had no abnormalities in serum immunoglobulins, IgG subsets and specific antibody levels. For FcgammaRIIa: H131H, H131R, R131R genotypes and 131R, 131H alleles; for FcgammaRIIIa: F158F, F158V, V158V genotypes and 158F, 158V alleles; and for FcgammaRIIIb: -NA1/NA1, NA1/NA2, NA2/NA2 genotypes and NA1, NA2 alleles were determined by using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Compared with the control group, the FcgammaRIIa-R131R genotype and 131R allele were found to be significantly elevated in the study group, and FcgammaRIIa-H131H genotype and 131H allele in the study group were significantly lower than in the control group. Genotypes and alleles related with FcgammaRIIIa and FcgammaRIIIb gene polymorphisms did not show any significant difference between the study and control groups. FcgammaRIIa gene polymorphism (R131R) may increase the risk and susceptibility for recurrent infectious diseases in children.