Neutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied.
We studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery.
Compared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76).
Patients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.
Chemotherapy Induced neutropenia is a frequent and serious complication of cytotoxic cancer treatment.
Granulocyte colony stimulating factors (G-CSF) are frequently used to counter neutropenia, attempt rapid recovery of patients and allow for continuation of treatment without compromise on dose, especially in curative malignancies. Generally regarded as safe, G-CSF use has been very rarely reported to have resulted in serious side effects, such as, splenic rupture.
We are reporting a case of a twenty years old man, who was being treated for T cell acute lymphoblastic leukemia and received colony stimulating factors for treatment of severe neutropenia and suffered from splenic rupture, He was treated with splenectomy.
Although extremely rare, splenic rupture can be a serious and sometimes life threatening complication of high dose colony stimulating factors therapy.
A well known complication in the treatment of infectious endocarditis is development of neutropenia caused by treatment with antibiotics in high concentrations over long periods. Neutropenia often necessitates discontinuation of antibiotic treatment. Three patients with infectious endocarditis who developed neutropenia are reported. The patients were treated with granulocyte colony stimulating factor (G-CSF), a haematopoietic growth factor that stimulates neutrophils. G-CSF induced an immediate increase in white blood cell count, primarily neutrophils. G-CSF may be effective in ameliorating neutropenia in patients who receive antibiotics for treatment of infectious endocarditis.
Keywords: granulocyte colony stimulating factor; neutropenia; endocarditis
LÓPEZ-POUSA A., RIFÀ J., CASAS DE TEJERINA A., GONZÁLEZ-LARRIBA J.L., IGLESIAS C., GASQUET J.A. & CARRATO A. (2010) European Journal of Cancer Care Risk assessment model for first-cycle chemotherapy-induced neutropenia in patients with solid tumours
Chemotherapy-induced neutropenia, the major dose-limiting toxicity of chemotherapy, is directly associated with concomitant morbidity, mortality and health-care costs. The use of prophylactic granulocyte colony-stimulating factors may reduce the incidence and duration of chemotherapy-induced neutropenia, and is recommended in high-risk patients. The objective of this study was to develop a model to predict first-cycle chemotherapy-induced neutropenia (defined as neutropenia grade ≥3, with or without body temperature ≥38°C) in patients with solid tumours. A total of 1194 patients [56% women; mean age 58 ± 12 years; 94% Eastern Cooperative Oncology Group (ECOG) status ≤1] with solid tumours were included in a multi-centre non-interventional prospective cohort study. A predictive logistic regression model was developed. Several factors were found to influence chemotherapy-induced neutropenia. Higher ECOG status values increased toxicity (ECOG 2 vs. 0, P= 0.003; odds ratio 3.12), whereas baseline lymphocyte (P= 0.011; odds ratio 0.67) and neutrophil counts (P= 0.026; odds ratio 0.90) were inversely related to neutropenia occurrence. Sex and treatment intention also significantly influenced chemotherapy-induced neutropenia (P= 0.012). The sensitivity and specificity of the model were 63% and 67% respectively, and the positive and negative predictive values were 17% and 94% respectively. Once validated, this model should be a useful tool for clinical decision making.
solid tumours; neutropenia; predictive model
During the period of neutropenia induced by chemotherapy, patients have a high risk of infection. The use of antibiotic prophylaxis to reduce neutropenia-related complications in patients with cancer is still disputed. Recent meta-analysis and clinical trials demonstrated that antibiotic prophylaxis with quinolones reduces febrile episodes, bacterial infections and mortality in adult oncological patients with neutropenia induced by chemotherapy in acute leukaemia. In paediatric patients, the only randomized, double-blind, prospective study until now suggests that amoxicillin/clavulanate may represent an effective prophylactic treatment in reducing fever and infections in oncological children with neutropenia, with an efficacy that is statistically demonstrated only in patients with acute leukaemia. Considering the risk of resistances, antibiotic-prophylaxis should be used only in selected patients.
neutropenia; antibiotic; prophylaxis; cancer; fever.
Neutropenia is a rare complication of Diamond-Blackfan syndrome (congenital hypoplastic anaemia). Three patients are reported: all had neutropenia as well as anaemia, and to investigate the cause of the neutropenia culture of bone marrow for granulocyte-macrophage colony forming cells (GMCFCs) was performed. Two cases had a low incidence of GMCFCs, but the third case had a high incidence. These findings suggest that myeloid precursors can be abnormal in Diamond-Blackfan syndrome and that the mechanism of neutropenia may, like that of anaemia, vary from patient to patient.
We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.
Human Immunodeficiency Virus; Lymphoma; Neutropenia
Purpose of review
This review updates treatment of neutropenia from articles published from January 2008 through April 2009.
Chemotherapy-induced neutropenia occurs most commonly in the first cycle of treatment. Older patients, patients with multiple co-morbidities, and those receiving more myelotoxic drugs are prone to develop neutropenia and its complications. Current guidelines recommend use of the myeloid growth factors for the first cycle of chemotherapy for patients with more that a 20 % risk of febrile neutropenia. Meta-analysis from randomized trials shows that granulocyte colony-stimulating factor (G-CSF) prophylaxis is associated with patients receiving more intensive chemotherapy, having better survival, but also having a higher risk of secondary AML. Antibiotic remain the mainstay of treatment of febrile neutropenia and are increasingly used for prophylaxis in “low risk” patients. Diagnosis and treatment of other type of neutropenia is also steadily improving.
The myeloid growth factor G-CSF has radically changed our approach to the management of neutropenia. Antibiotics remain the mainstay of treatment of febrile neutropenia.
neutrophil; neutropenia; granulocyte colony-stimulating factor (G-CSF); chemotherapy-induced neutropenia
Glycogen storage disease type Ib is an autosomal recessive transmitted disorder of glycogen metabolism caused by mutations in the glucose-6-phosphate translocase gene on chromosome 11q23 and leads to disturbed glycogenolysis as well as gluconeogenesis. Besides hepatomegaly, growth retardation, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia, patients suffer from neutropenia associated with functional defects predisposing for severe infections. In order to attenuate these complications, long-term treatment with granulocyte colony-stimulating factor is common but this is associated with an increased risk for acute myeloid leukemia or myelodysplastic syndromes in patients with inherited bone marrow failures such as severe congenital neutropenia. Onset of these myeloid malignancies is linked to cytogenetic aberrations involving chromosome 7. In addition, granulocyte colony-stimulating factor is known to stimulate proliferation of monosomy 7 cells in vitro. To our knowledge, we report for the first time a case report of a patient with glycogen storage disease type Ib, who developed acute myeloid leukemia with a classical monosomy 7 and acute myeloid leukemia-associated translocation t(3;8)(q26;q24) after 14 years of continuous treatment with granulocyte colony-stimulating factor.
A 28-year-old Turkish man with glycogen storage disease type Ib was admitted to our department because of dyspnea and increasing fatigue. He also presented with gum bleeding, bone pain in his legs, night sweats, recurrent episodes of fever with temperatures up to 39°C and hepatosplenomegaly.
A blood count taken on the day of admission showed pancytopenia and a differential count displayed 30% blasts. A bone marrow biopsy was taken which showed a hypercellular marrow with dysplastic features of all three cell lines, while blast count was 20%. Classical cytogenetic analyses as well as fluorescence in situ hybridization showed a monosomy 7 with a translocation t(3;8)(q26;q24). Based on these findings, the diagnosis of acute myeloid leukemia was made.
Our observations suggest that bone marrow examinations including cytogenetic analysis should be carried out on a regular basis in patients with glycogen storage disease type Ib who are on long-term treatment with granulocyte colony-stimulating factor for severe neutropenia, since this treatment might also contribute to an increased risk for acute myeloid leukemia or myelodysplastic syndromes.
Severe congenital neutropenia (SCN) is a heterogeneous bone marrow failure syndrome predisposing to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We studied 82 North American and Australian SCN patients enrolled in the Severe Chronic Neutropenia International Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced. There was no significant difference in the risk of MDS/AML in patients with mutant versus wild-type ELA2: the respective cumulative incidences at 15 years were 36% and 25% (P = 0·96). Patients with either mutant or wild-type ELA2 should be followed closely for leukaemic transformation.
severe congenital neutropenia; neutrophil elastase ELA2; acute myeloid leukaemia; myelodysplastic syndromes; granulocyte colony-stimulating factor
Immune reconstitution inflammatory syndrome (IRIS) in the setting of antiretroviral therapy is well described, but it is not as common in non-HIV patients; here, we present a case of immune reconstitution inflammatory syndrome presenting as acute respiratory distress syndrome in a leukemia patient who had neutropenic fever and septic shock after high-dose cytarabine. During neutropenia recovery, his chest X-ray showed progressive worsening despite being on adequate therapy, we started him on steroids which resulted in significant clinical improvement.
In patients with severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long-term risk remains uncertain. We updated a prospective study of 374 SCN patients on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry (SCNIR) with longer follow-up. After 10 years on G-CSF, the annual risk of MDS/AML was 2.3%/year. After 15 years on G-CSF, the cumulative incidence was 10% for death from sepsis and 22% for MDS/AML. The data continue to support the hypothesis that SCN patients with high G-CSF requirements are also at high risk of MDS/AML. The risk per year of MDS/AML in SCN now appears similar to, rather than higher than, the reported risk of AML in Fanconi anemia and dyskeratosis congenita.
severe congenital neutropenia; acute myeloid leukaemia; myelodysplastic syndromes; granulocyte colony-stimulating factor
Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.
Canadian recommendations; neutropenia; febrile neutropenia; supportive care; colony-stimulating factors; chemotherapy-induced neutropenia; safety
Chemotherapy-induced neutropenia often occurs in our routine work and presents an obstacle for adequate (dose and continuance) treatment, which may affect patients’ outcome. Granulocyte colony-stimulating factors (GCSFs) effectively prevent myelosuppression and thus improve the standard treatment. Through their application cases of chemotherapy-induced neutropenia have been reduced. Still these factors cannot remove entirely the danger of encountering neutropenia, which can cause dangerous complications. We present a case of a fulminate anaerobic infection with unknown origin in a patient with metastatic breast cancer after standard treatment with chemotherapy supported by GCSFs.
neutropenia; granulocyte colony-stimulating factors; anaerobic infection; phlegmon
Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy. This phase III, double-blind, randomized, active-controlled, noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy.
Patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5 × 109 cells/L were randomized to a single 6-mg subcutaneous injection of lipegfilgrastim (n = 101) or pegfilgrastim (n = 101) on day 2 of each 21-day chemotherapy cycle (4 cycles maximum). The primary efficacy endpoint was the duration of severe neutropenia during cycle 1.
Cycle 1: The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days, respectively (λ = −0.218 [95% confidence interval: –0.498%, 0.062%], p = 0.126), and no severe neutropenia was observed in 56% and 49% of patients in the lipegfilgrastim and pegfilgrastim groups, respectively. All cycles: In the efficacy population, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and zero lipegfilgrastim-treated patients. Drug-related adverse events in the safety population were reported in 28% and 26% of patients i006E the lipegfilgrastim and pegfilgrastim groups, respectively.
This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.
The study protocol, two global amendments (Nos. 1 and 2), informed consent documents, and other appropriate study-related documents were reviewed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees (IECs).
Neutropenia; Febrile neutropenia; Breast cancer; Recombinant granulocyte-colony stimulating factor; Lipegfilgrastim; Pegfilgrastim
Bone marrow culture in semi-solid agar was used to assess the proliferative activity and the response to sodium aurothiomalate of the myeloid precursor cells from patients during and after recovery from neutropenia associated with the use of this drug. Colony formation was reduced during the neutropenia and returned to normal after recovery. The rheumatoid process itself did not impair colony formation even in patients with Felty's syndrome. Sodium aurothiomalate inhibited colony formation by normal marrow in a dose-dependent manner. Bone marrow colonies from patients who had recovered from neutropenia induced by sodium aurothiomalate were not abnormally sensitive to the inhibitory effect of the drug in vitro. The metabolism of gold is probably altered in a small proportion of patients, which causes high local concentrations within the bone marrow leading directly to marrow depression.
Neutropenic enterocolitis (NEC) can be a life-threatening complication of chemotherapy in leukemic patients. Early diagnosis and treatment is therefore crucial.
A 38-year-old woman with acute lymphoblastic leukemia and chemotherapy-induced neutropenia suddenly developed symptoms suspicious of NEC. Transabdominal ultrasound showed features consistent with NEC, later confirmed by computed tomography (CT) scan.
The patient was scanned using portable ultrasound (US) equipment (Esaote My Lab 25). US findings showed involvement of the cecum, appendix, ascending colon and proximal middle transverse colon, with features resembling gas containing fissures within the colon wall itself. The risk of colon rupture was confirmed by CT scan. The patient underwent successful hemicolectomy after intravenous treatment with broad spectrum antibiotics, granulocyte-colony stimulating factor (G-CSF), platelets and fresh frozen plasma transfusion.
A prompt bedside US examination upon development of symptoms allowed an early diagnosis of NEC and identified features consistent with imminent colon wall rupture, shifting the management of this life-threatening complication from medical to surgical. Multidisciplinary intervention was crucial for a successful hemicolectomy in a severely affected neutropenic patient.
Neutropenic; Enterocolitis; Leukemia; Ultrasound sonography; Hemicolectomy
The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l.
When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease.
Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant.
About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia.
Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified.
Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.
Neutropenia; Childhood; G-CSF; Severe congenital neutropenia; Adverse effects; ELANE; G6PC3; Shwachman Diamond Syndrome; Review
We descibe the case of a girl of Indian origin who presented with recurrent infections. The only abnormality detected in the armoury of the immune system was consistent neutropenia. Mutation analysis revealed ELA2 (neutrophil elastase) gene mutation that has been associated with severe congenital neutropenia phenotype. Patient was treated with the granulocyte-colony stimulating factor (G-CSF) as prevention of infectious manifestations along with appropriate measure to curb secondary complications. She showed poor response to the G-CSF during stringent surveillance. After being on treatment for 1 year, she developed acute myelogenous leukemia as inherit complication of this disease.
Acute myelogenous leukemia; ELANE (elastase neutrophil expressed) gene – related neutropenia; granulocyte-colony stimulating factor; hematopoietic stem-cell transplant; kostmann syndrome; severe congenital neutropenia
Colony-stimulating factors (CSFs) are commonly used for the treatment of neutropenia following chemotherapy and for the mobilization of peripheral blood stem cells (PBSC). We recently experienced a rare case of a new onset of psoriasiform eruption by GM-CSF (granulocyte-macrophage colony-stimulating factor) which was exacerbated by G-CSF (granulocyte colony-stimulating factor) in a patient with breast cancer. A 36-year-old woman had received neoadjuvant chemotherapy (cyclophosphamide, epirubicin and 5-fluorouracil), modified radical mastectomy and adjuvant chemotherapy with paclitaxel and mitoxantrone followed by GM-CSF administration for the treatment of locally advanced breast cancer. She had developed a psoriatic skin lesion on face and both upper arms during leukocyte recovery in spite of no previous history of psoriasis. Next, the chemotherapy course was complicated by a flare of mild psoriatic skin lesion, although CSF was changed into G-CSF due to GM-CSF-associated psoriasis. Subsequently, she had had high-dose chemotherapy and autologous peripheral blood stem cell transplantation for consolidation therapy. GM-CSF was administered for the mobilization of PBSC and post-transplant period, but psoriatic skin lesion did not appear. During 6 months after PBSCT, psoriasiform eruption did not appear.
A case of severe combined immunodeficiency (SCID) in monozygotic twin sisters was detected at 3 months of age with neutropenia in one twin and a normal differential count in the other. The neutropenic twin, suffering from severe skin ulcers, was successfully treated with granulocyte colony stimulating factor (G-CSF). Discordant occurrence of neutropenia in identical twins shows that there may be a non-genetic cause for the neutropenia in SCID. Suppression of myelopoiesis was probably induced by activated maternal T cells. The neutropenia in this case may thus be classified as SCID associated neutropenia, as opposed to reticular dysgenesis, in which the neutropenia is G-CSF refractory and is most probably caused by a genetic stem cell defect. A response to G-CSF in a neutropenic child with SCID can be clinically beneficial and might help to distinguish between G-CSF unresponsive reticular dysgenesis and G-CSF responsive SCID associated neutropenia.
Barth syndrome (BS) is an X-linked infantile-onset cardioskeletal disease characterized by cardiomyopathy, hypotonia, growth delay, neutropenia and 3-methylglutaconic aciduria. It is caused by mutations in the TAZ gene encoding tafazzin, a protein involved in the metabolism of cardiolipin, a mitochondrial-specific phospholipid involved in mitochondrial energy production.
Clinical, biochemical and molecular characterization of a group of six male patients suspected of having BS. Three patients presented early with severe metabolic decompensation including respiratory distress, oxygen desaturation and cardiomyopathy and died within the first year of life. The remaining three patients had cardiomyopathy, hypotonia and growth delay and are still alive. Cardiomyopathy was detected during pregnancy through a routine check-up in one patient. All patients exhibited 3-methylglutaconic aciduria and neutropenia, when tested and five of them also had lactic acidosis.
We confirmed the diagnosis of BS with sequence analysis of the TAZ gene, and found five new mutations, c.641A>G p.His214Arg, c.284dupG (p.Thr96Aspfs*37), c.678_691del14 (p.Tyr227Trpfs*79), g.8009_16445del8437 and g.[9777_9814del38; 9911-?_14402del] and the known nonsense mutation c.367C>T (p.Arg123Term). The two gross rearrangements ablated TAZ exons 6 to 11 and probably originated by non-allelic homologous recombination and by Serial Replication Slippage (SRS), respectively. The identification of the breakpoints boundaries of the gross deletions allowed the direct detection of heterozygosity in carrier females.
Lactic acidosis associated with 3-methylglutaconic aciduria is highly suggestive of BS, whilst the severity of the metabolic decompensation at disease onset should be considered for prognostic purposes. Mutation analysis of the TAZ gene is necessary for confirming the clinical and biochemical diagnosis in probands in order to identify heterozygous carriers and supporting prenatal diagnosis and genetic counseling.
Barth syndrome; TAZ gene mutation; In utero cardiomyopathy; Metabolic decompensation; Lactic acidosis; 3-methylglutaconic aciduria; Gross deletions; Metabolic cardiomyopathy
Zygomycoses caused by fungi of the mucorales order (mucormycoses) are emerging
fungal diseases with a high fatality rate. The most important risk factors
include neutropenia or functional neutropenia, diabetic ketoacidosis, iron
overload, major trauma, prolonged use of corticosteroids, illicit intravenous
drug (ID) use, neonatal prematurity, malnourishment, and maybe a previous
exposure to antifungal agents with no activity against zygomycetes, such as
voriconazole and echinocandins.
A high index of suspicion is crucial for the diagnosis, as prompt and appropriate
management can considerably reduce morbidity and mortality. Suspicion index can
be increased through recognition of the differential patterns of clinical
presentation. In the non- haematological immunocompromised patients,
mucormycosis can manifest in various clinical forms, depending on the underlying
condition: mostly as rhino-orbital or rhino-cerebral in diabetes patients,
pulmonary infection in patients with malignancy or solid organ transplantation,
disseminated infection in iron overloaded or deferoxamine treated patients,
cerebral - with no sinus involvement - in ID users, gastrointestinal in
premature infants or malnourishment, and cutaneous after direct inoculation in
immunocompetent individuals with trauma or burns.
Treating a patient’s underlying medical condition and reducing
immunosuppression are essential to therapy. Rapid correction of metabolic
abnormalities is mandatory in cases such as uncontrolled diabetes, and
corticosteroids or other immunosuppressive drugs should be discontinued where
feasible. AmphotericinB or its newer and less toxic lipid formulations are the
drugs of choice regarding antifungal chemotherapy, while extensive surgical
debridement is essential to reduce infected and necrotic tissue. A high number
of cases could be prevented through measures including diabetes control
programmes and proper pre- and post-surgical hygiene.
Felty's syndrome is an uncommon but severe extra-articular manifestation of rheumatoid arthtitis. Felty's syndrome is characterized by the triad of rheumatoid arthtitis, neutropenia, and splenomegaly. The lifetime risk of Felty's syndrome for a rheumatoid arthtitis patient is less than 1% and there are only few case reports of Felty's syndrome with neutropenia preceded clinical evidence of arthritis. We present a case which is atypical presentation of Felty's syndrome without arthritis.
We present a case of 31-year-old man who presented with fever and skin infection, found to have neutropenia. The work up showed splenomegaly and other evidences support Felty's syndrome diagnosis without arthritis presentation.
Patients with unexplained, continuous neutropenia without arthristis but with high level of rheumatoid factor and positive antibodies to cyclic citrullinated peptides should be suspected of developing Felty's syndrome as an initial presentation of rheumatoid arthtitis.
Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious infections and exhibits a self-limited course. Chronic idiopathic neutropenia of adults is characterized by occurrence in late childhood or adulthood, greater prevalence among females than among males, and rare spontaneous remission. Secondary AIN is more commonly seen in adults and underlying causes include collagen disorders, drugs, viruses and lymphoproliferative disorders. In most patients with AIN, antibodies recognize antigens located on the IgG Fc receptor type 3b but other target antigens have been recently identified in secondary AIN. Granulocyte colony-stimulating factor is a proven treatment in patients with AIN of all types and is now preferred to other possible therapies.