In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is one of the predominant antibody deficiency disorders, some evidence of which indicates that chromosome instability is present in these patients. An increased risk of cancer in patients with CVID has been documented. This study was undertaken to highlight radiation sensitivity in CVID patients and to clarify the genetic basis of this defect in these cases. Stimulated lymphocytes of the studied subjects were exposed to low-dose gamma-rays in the G2 phase or the G0 phase of the cell cycle and chromosomal aberrations were scored. Lymphocytes of healthy individuals, ataxia telangiectasia (AT) cases and a group of acute lymphoblastic leukemia (ALL) patients were investigated in the same way as controls. By two methods of analysis (one-way ANOVA and unpaired t-test), the CVID cases were significantly more radiosensitive than healthy controls based on the results of the G2 and the G0 assays. First-degree relatives of CVID patients were radiosensitive by the micronucleus assay which showed a significant difference as compared with normal controls (p = 0.001). In conclusion, this study may support that chromosomal radiosensitivity in CVID patients is a marker of genetic predisposition to the disease. The results might be a clue to describe the increased risk of cancer in CVID patients.

Spectrum of bone marrow failures of myeloid series: new report of neutropenic patients from a referral pediatric center in Iran.

Neutropenia is a reduction of the absolute neutrophil count (ANC), which could be seen in different conditions, while its association with a number of primary immunodeficiency diseases has been reported. This study was performed in all neutropenic patients who were admitted in a referral pediatric hospital during a 6-year period (2006-2011). One hundred and forty patients with ANC of below 1500/mm(3) were investigated in this study. The most common causes of neutropenia were severe congenital neutropenia (41%), aplastic anemia (19%), cyclic neutropenia (11%), hyperimmunoglobulin M syndrome (9%), and fanconi anemia (7%). The patients experienced their first manifestation at a median age of 1 year, while the median diagnostic age was 21 months. Parental consanguinity was present in about half of the cases. The most common clinical manifestations of the patients were sinusitis (62 cases), periodontitis (51 cases), acute diarrhea (39 cases), pneumonia (38 cases), abscess (36 cases), skin rashes (35 cases), and otitis media (31 cases). Twenty two patients (16%) died during the study period. Considering the differential diagnosis of neutropenia, making the diagnosis and appropriate treatments are the keys in management of patients with neutropenia to avoid further complications.

Diffuse cutaneous mastocytosis: report of a severe case with fatal outcome.

Diffuse cutaneous mastocytosis (DCM) is a rare variant of mastocytosis. We describe a case of DCM with a very severe presentation at birth and fatal outcome.

Severe valvular toxicity and pericarditis early after radiation therapy in a patient treated for Hodgkin's lymphoma.

Hodgkin's disease can be cured in most cases by radiotherapy. However, it can increase the risk of cardiotoxicity. Here, we report a patient with Hodgkin's disease and superior vena cava syndrome who was treated with chemotherapy in combination with radiotherapy. Four months after the initiation of this therapy, she developed progressive dyspnea. Pleural and pericardial effusion, severe mitral regurgitation, moderate aortic insufficiency, and mild tricuspid regurgitation were detected in echocardiography, which suggested heart failure. The patient was then treated with intrapericardial drainage and received dopamine and diuretics for congestive heart failure; she responded well to this treatment and was discharged in good condition. After high-dose mediastinal radiation, cardiologic screening is recommended in order to identify patients with radiation-induced heart disease and to assess their need for treatment and follow-up.

Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia.

Severe congenital neutropenia (SCN) and CD40 ligand deficiency (CD40LD) are two primary immunodeficiency diseases caused by different underlying genetic defects. In this report, we present a case who clinically presented as a SCN patient, but subsequent mutation analysis of this patient was compatible with CD40LD. The patient is a 3-year-old boy, who was referred to our center because of pneumonia, oral and anal ulcers, and periodontitis. As severe consistent neutropenia and maturation arrest in the myeloid series were observed in the bone marrow, a diagnosis of SCN was made. However, no mutations were found in the ELA2 and HAX1 genes. As functional T cell defects were observed, we suspected CD40LD. DNA sequencing showed a 17-base pair deletion in the CD40L gene. Although the patient did not have a decreased serum level of IgA, and his serum IgM level was within the normal range, the diagnosis of CD40LD was confirmed, suggesting that CD40LD should be suspected in any male patient with recurrent infections and neutropenia.

Hodgkin lymphoma in two siblings with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by decreased serum immunoglobulin levels, and increased susceptibility to recurrent bacterial infections, malignancies, and autoimmune disorders. In this report, 2 siblings with CVID who developed Hodgkin lymphoma are presented: a 16-year-old girl at stage IIB and her 12-year-old brother at stage IIIB of Hodgkin lymphoma. Their father and 1 uncle were also affected by the same cancer with no immunodeficiency state. The presence of lymphoma should be considered in the patients with CVID, especially in those with family history of malignancies.

Hemophagocytic Lymphohistiocytosis in a Neonate: Case Report.

 Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, occurring as either a familial disorder or a sporadic condition, in association with a variety of triggers. This article will introduce a neonate with HLH in Iran. We report a case of HLH presenting with respiratory distress and fever, hepatosplenomegaly, jaundice and pancytopenia on the second day of life. Typical clinical and laboratory findings were detected in the neonate. HLH was diagnosed according to HLH-2004 guidelines. In spite of initiating the treatment, the disease did not cure. Post-mortem, extensive hemophagocytosis was found in multiple organs. No specific genetic defect was identified. Since HLH is a potentially lethal childhood illness, early diagnosis of this disorder and commences the therapy is important for pediatricians.

Bilateral basal ganglia involvement in a patient with Griscelli syndrome.

We report a 6-year-old Iranian boy with silvery-gray hair, eyelashes and the eyebrows who was admitted because of seizures and subsequent stupor. He had previous history of acute hemiparesis at 1 year of age and hepatitis-like syndrome 3 months ago. Microscopic examination of the patient's hair shaft revealed different sized clumps of melanin seen in the center of the shafts. Bone marrow aspiration revealed erythroid hyperplasia and erythrophagocytic cells. Bilateral frontal cortical and subcortical high signal lesions, dirty white matter, high signal areas in the upper pons and in both caudates and lentiform nuclei in T2 WI were the brain MRI findings of the patient. He died in the accelerated phase of Griscelli Syndrome (GS) type 2. To our knowledge we report the first case of GS from Iran.

Hemophagocytic lymphohistiocytosis in a neonate with cutis marmorata telangiectatica congenita.

In this case report we describe the first case of hemophagocytic lymphohistiocytosis with concurrent cutis marmorata telangiectatica congenita. She had pancytopenia and hepatosplenomegaly, hemophagocytic cells in spleen necropsy, and she died with respiratory failure and pseudomonas induced septicemia.

Features of Childhood Acute Myeloid Leukemia in Iran: a Report from Double Center Study.

Acute Myeloblastic Leukemia is one of the important malignancies in children. For better managing the prognosis of this disease, there should be enough information about common features of this malignancy. The aim of this study was to evaluate these common features in children with Acute Myeloblastic Leukemia. A total of 104 eligible children less than 15-year-old have been referred from 2007-2011 to two referral centers for childhood malignancies. Basic epidemiological information recorded in checklists for each individual. Analyzes have been done by SPSS version 22. Out of patients, 57 cases were males (54.8%). The male/female ratio was 1.2. The mean age of patients was 6.5 ± 4.3 years. The majority subtypes of patients were M3, M4, non-M3, and M2, respectively. The common molecular abnormalities were t (15;17) and inv (16). Of patients, 19.2% had an early relapse. The mean age of relapse in patients was 6.7 ± 3.9 years. Sixty patients (57.7%) were alive, and 44 cases (42.3%) died during or after therapy. The three years overall survival rate of patients was 42% in this study. According to our data, AML has the same frequency as compared with data from developing countries. But different epidemiological characteristic was a lower rate of three years overall survival in patients. These data may serve the health authorities for more effective environmental and preventive measurements, purposeful allocation of resources for facilitating up-to-date diagnostic and treatment modalities, psychological support programs for respective family members and educational purposes.

A neonate with indurate dermal papules and nodules and pneumonia: a case report.

We presents an infant with several indurated plaques and nodules scattered on her body. She was brought to the hospital because of fever, runny nose and cough from one month ago. During the examination and investigation the plaques and nodules grabbed the attention of the clinicians and the skin biopsy and other lab works revealed the diagnosis of congenital leukemia.

Relapse of Acute Lymphoblastic Leukemia as a Conjunctival Mass in a 9-Year-Old Girl.

A 9-year-old girl with a history of acute lymphoblastic leukemia in remission presented with a right subconjunctival mass and ipsilateral preauricular lymphadenopathy despite normal findings on blood cell profile. Excisional biopsy of the lesion was performed to exclude extramedullary relapse of acute lymphoblastic leukemia. Histopathologic examination showed infiltration of leukemic cells at the conjunctival substantia propria. The patient was referred to her oncologist, and bone marrow aspiration showed medullary relapse of acute lymphoblastic leukemia for which systemic and intrathecal chemotherapy was administered. Leukemic infiltration of the conjunctiva in the presence of normal findings on blood cell profile can be a rare manifestation of relapsed acute lymphoblastic leukemia.

Cytologic phenotypes of B-cell acute lymphoblastic leukemia-a single center study.

Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

Presence of Idiopathic Thrombocytopenic Purpura and autoimmune hemolytic anemia in the patients with common variable immunodeficiency.

Common Variable Immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and an increased susceptibility to recurrent infections as well as autoimmunity and malignancies. Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA) are two autoimmune disorders which may be seen in association with CVID. Among 85 CVID patients, seven cases had ITP and/or AIHA (8%). Four of these patients had one or more episodes of ITP, one patient had AIHA, and two patients had both ITP and AIHA (Evans syndrome). Almost, all patients experienced chronic and recurrent infections mostly in respiratory and gastrointestinal systems during the course of the disease. Among the seven patients, five presented their underlying disease with recurrent respiratory and/or gastrointestinal tract infections, while in two remaining patients, CVID was presented with ITP. Three patients died until now; two because of hepatic failure and one due to pulmonary hemorrhage. As CVID is prone to autoimmune disorders, it should be considered as a differential diagnosis of adult-onset ITP and possibly in children. Chronic and recurrent ITP, especially in the presence of propensity to respiratory and gastrointestinal infections mandate the evaluation for an underlying immune dysregulation such as CVID.

The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia.

Severe congenital neutropenia (SCN) is a rareE primary immunodeficiency disorder characterized by early onset recurrent infections in association with persistent severe agranulocytosis. To identify the clinical, immunohematological, and molecular characteristics of patients with SCN, 18 Iranian patients with the mean age of 8.8 +/- 5.8 years were investigated in this study. All of these patients experienced severe neutropenia; the mean of absolute neutrophil count was 281.4 +/- 137.7 cells/mm3. Bone marrow findings were typified by a myeloid maturation arrest at the promyelocyte-myelocyte stage in these patients. Molecular analysis revealed different mutations in the ELA-2 gene of one patient and in the HAX-1 gene of another three patients. The most common presenting complaints in these patients were superficial abscesses, oral ulcers, cutaneous infections, omphalitis, and pneumonia. During the course of illness, all patients developed mucocutaneous manifestations, and 16 cases had respiratory infections. The most commonly manifestations were abscesses, oral ulcers, pneumonia, periodontitis, otitis media, cutaneous infections, mucocutaneous candidiasis, and acute diarrhea. Three patients died because of a severe infection. Although SCN is a rare disorder, early onset of severe and recurrent infections should always raise a suspicion, which deserves further evaluation for detecting such disorder.

Congenital neutropenia and primary immunodeficiency disorders: a survey of 26 Iranian patients.

Inherited neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. The current study was performed to determine the clinical and laboratory findings of Iranian patients with inherited neutropenias. Records of 26 patients (14 male, 12 female) with inherited neutropenia were reviewed in this study. The patients had been referred to Children's Medical Center, a referral center for immunodeficiency disorders in Iran, during a 22-year period (1981-2003). Primary immunodeficiency disorders of these patients were as follows: cyclic neutropenia (8 patients), Shwachman-Diamond syndrome (7 patients), Kostmann syndrome (6 patients), and Chediak-Higashi syndrome (5 patients). The mean absolute neutrophil count of patients was 398.2 +/- 259.3 cells/mm (range 74-1,152/mm) at the first visit. Twenty-one patients showed severe, four moderate, and one mild neutropenia. Sixteen of these patients had leukopenia, seven anemia, two thrombocytopenia, and one monocytosis. The most common presenting complaints in these patients were oral ulcer, otitis, pneumonia, diarrhea, cutaneous abscess, and oral candidiasis. The patients first manifested symptoms of infection suggesting neutropenia at a median age of 7.5 months (range 1 month to 10 years). During follow-up, respiratory infections developed in 24 cases, oral manifestations in 20 patients. The most common infections, in descending order of frequency, were otitis media, abscesses, pneumonia, oral ulcers, acute diarrhea, cutaneous infections, oral candidiasis, and periodontitis. Less frequent infections were sinusitis, cystitis, conjunctivitis, meningitis, and osteomyelitis. Nonspecific symptoms (hepatomegaly and splenomegaly) were also detected in 10 patients and 1 patient, respectively. Three patients died of recurrent infections. The infectious manifestations both at presentation and during follow-up in inherited neutropenia were similar. Although inherited neutropenias are rare, recurrent infections always deserves further evaluation for detecting such disorders.

Clinical and laboratory findings in Iranian children with cyclic neutropenia.

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia (3 males and 4 females), who experienced neutropenic periods every 3 weeks (5 with severe and 2 with moderate neutropenia), were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years (1980-2003). The range of patients' ages was from 7 to 13 years (median 11 years). The median age at the onset of the disease was 12 months (1 month- 2 years) and the median age of diagnosis was 2 (1.5-5) years, with a median diagnosis delay of 1 year (2 months- 5 years). Neutropenia was associated with leukopenia (3 patients), anemia (3 patients), and thrombocytopenia (1 patient). Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media (6 cases), oral ulcers (5 cases), abscesses (4 cases), pneumonia (3 cases), diarrhea (3 cases), oral candidiasis (3 cases), cutaneous infections (2 cases), and periodontitis (2 cases). One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient.