Pneumonic tularemia in a patient with chronic granulomatous disease

We report the case of a 14-year-old boy with granulomatous pneumonia caused by Francisella tularensis. In addition, an autosomal recessive form of chronic granulomatous disease was diagnosed. Both F. tularensis and chronic granulomatous disease are associated with pulmonary granulomas. To our knowledge, this is the first report of F. tularensis infection in a patient with chronic granulomatous disease. The relationship between these two processes is discussed.     

Cutaneous purulent aspergillosis in a young man with chronic granulomatous disease

We describe a case of cutaneous purulent aspergillosis in a 19-year-old man with chronic granulomatous disease (CGD) treated successfully with a 6-month regimen of itraconazole. The therapeutic effect of the drug was seen after 1 month of administration. Surgical treatment of the skin lesions, although first planned, was not necessary.     

Bronchiolitis obliterans organizing pneumonia and chronic graft-versus-host disease in a child after allogeneic bone marrow transplantation

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype O infections are not reliably detected by commonly used anti-HIV-1/2 screening assays. Therefore, anti-HIV-1/2 assays have been modified to increase their sensitivity in detecting antibodies to HIV-1 subtype O. STUDY DESIGN AND METHODS: Two new anti-HIV-1/2 enzyme-linked immunosorbent assays (ELISAs) (Abbott Plus and Ortho Enhanced) were compared with a currently used anti-HIV-1/2 ELISA (Abbott Recombinant) in various serum panels: 91 Western blot-confirmed anti-HIV-1-positive samples, 20 samples from Western blot-confirmed HIV-1-infected patients in log3 serial dilutions, and 1463 samples from consecutive, volunteer, nonremunerated blood donors. RESULTS: Among 91 anti-HIV-1 Western blot-positive samples, 2 (2.2%) were missed by the Abbott Recombinant ELISA, but all 91 were detected by the Abbott Plus and Ortho Enhanced ELISAs. In contrast, two discrepant samples were found to react in viral lysate-based assays. In serial dilutions, Ortho Enhanced ELISA was significantly less sensitive than the Abbott Recombinant and Abbott Plus ELISAs, with the latter two being of comparable sensitivity. The specificities of Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs in 1463 blood donors were 100, 99.93, and 99.86 percent, respectively. Routine testing of 29,102 donations with the enhanced Abbott Plus ELISA revealed a specificity of 99.93 percent. CONCLUSION: Two Western blot-confirmed anti-HIV-1-positive samples were missed by the Abbott Recombinant ELISA but detected by the Abbott Plus and Ortho Enhanced ELISAs. The analytic sensitivity of the Ortho Enhanced ELISA was inferior to that of both Abbott ELISAs. The specificities of the Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs were comparable.     

Arcuate dermal erythema in a carrier of chronic granulomatous disease

A female carrier of chronic granulomatous disease developed arcuate, erythematous dermal plaques on her back and face. The lesions were clinically and histopathologically suggestive of Jessner benign lymphocytic infiltration of the skin. Some women with relatively fixed arcuate or annular, erythematous, dermal plaques may be carriers of chronic granulomatous disease.     

Bone marrow transplantation in chronic granulomatous disease

We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was without complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft. CONCLUSION: Bone marrow transplantation in cases of chronic granulomatous disease is controversial, although it could be useful in selected very severe cases in which prophylactic therapy is problematic.     

Treatment with rhG-CSF for osteomyelitis in a patient with p47-phox-deficient chronic granulomatous disease

A 24-year-old woman with osteomyelitis was diagnosed as having p47-phox-deficient chronic granulomatous disease (CGD). The patient showed a marked deficiency of p47-phox, which is very rare in Japan. As the clinical response to various antibiotics including sulfamethoxazole-trimethoprim was not satisfactory, we added recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the treatment protocol. We report the beneficial clinical course of the patient, together with the effect of rhG-CSF on the granulocyte function, and the present report indicates that rhG-CSF is useful for the treatment of antibiotic-resistant infection in the variant type of p47-phox-defective CGD.     

Genitourinary involvement in chronic granulomatous disease of childhood

A second case of symptomatic renal involvement of chronic granulomatous disease of childhood is reported, and all previous cases of documented genitourinary lesions in this disease are reviewed. Although frequent infections of other organ systems are a well recognized part of chronic granulomatous disease, involvement of the urinary tract has been rarely reported. The nature of the few cases described suggests that extensive insidious destruction occurs before urinary tract involvement is clinically suspected.     

Ureteral obstruction in a patient with chronic granulomatous disease, receiving combined prophylaxis with IFN-gamma and antibiotics

For a successful take, skin grafts must be immobilized when applying dressings. Surgical beds requiring a stent to maintain contact between the graft and wound bed can be treated with Biobrane (Dow B. Hickam, Inc., Sugarland, Texas), which is held in place with skin staples at the periphery. Moistened gauze is placed over the grafted area, the redundant Biobrane stretched over the gauze, and this top layer again stapled at the periphery. When the stent is no longer needed, the top layer of Biobrane and gauze are removed, leaving a graft adherent to the bed and covered with Biobrane. This allows the surgeon to quickly construct an effective stent.     

Phagocytic NADPH oxidase and its role in chronic granulomatous disease

Case-control and cohort studies support the hypothesis that postmenopausal oestrogen-replacement therapy reduces the risk of atherosclerotic disease manifestations. The evidence for a cardioprotective effect of such a therapy is, however, incomplete because randomized prospective studies are missing. Because it may be almost impossible to conduct placebo-controlled trials in the future, other study designs will be needed to minimize selection bias. Further work is required to define the optimal dose and administration schedule of oestrogen and to determine whether addition of progestogens alters the beneficial effect of oestrogen on the cardiovascular system. Such studies may also provide mechanistic insight into the interaction between lipoprotein metabolism and haemostasis and its relation to the atherosclerotic disease process.     

Successful polymerase chain reaction-based diagnosis of fungal meningitis in a patient with chronic granulomatous disease

The structural and electronic properties of seventeen alkylxanthine derivatives were calculated using the MO program PM3 to elucidate the key features related to their inhibitory activity on phosphodiesterase (PDE) IV isoenzyme. Except for 7-alkylxanthine derivatives, a good correlation could be established between the distance between the tops of the two alkyl groups at the N1 and N3 positions of the xanthine skeleton (molecular length) and the PDE IV inhibitory activity (r=0.973, n=13). The same inhibitory activity could also be significantly correlated with the following electronic parameters of alkylxanthines: HOMO energy (r=0.850), absolute hardness (r=-0.806), and absolute electronegativity (r=-0.825). These results suggest that the electronic properties are partly responsible for PDE IV inhibition as far as the effects of structural properties associated with molecular length are concerned. Alkylxanthines may also act as electron donors in the charge-transfer interaction with the active sites on PDE IV isoenzyme.     

Safety and effectiveness of long-term interferon gamma therapy in patients with chronic granulomatous disease

In chronic granulomatous disease (CGD), diminished or absent neutrophil NADPH oxidase function leads to recurrent pyogenic infections and granuloma formation. In a recent randomized, placebo-controlled trail, short-term prophylactic use of recombinant human interferon gamma (rIFN-gamma 1b) reduced the risk of serious infection in CGD patients by 67%, The current study evaluated the safety and effectiveness of long-term rIFN-gamma therapy in CGD patients. Patients were treated three times weekly with rIFN-gamma and evaluated semiannually. Serious infections (requiring hospitalization and parenteral antibiotic therapy), adverse clinical events, and measures of growth and development were noted. Thirty patients were evaluated for 12 months. The total average duration of rIFN-gamma therapy was 2.5 years. Three patients developed a total of four serious infections (0.13 infections per patient year). This rate compare favorably with rates of 1.10 and 0.38 infections per patient year found in the placebo and rIFN-gamma groups, respectively, during a previous study. Common adverse events were fever (23%), diarrhea (13%), and flu-like illness (13%). No serious adverse event was attributable to rIFN-gamma therapy and no obvious effects on growth and development were observed. rIFN-gamma is a safe and effective adjunctive therapy for reducing the frequency and severity of serious infections in CGD patients.     

Outpatient management with oral corticosteroid therapy for obstructive conditions in chronic granulomatous disease

We report the outpatient management of three patients with X-linked chronic granulomatous disease, two of whom had episodes of gastric outlet obstruction and another, urinary bladder obstruction. These obstructive conditions were successfully treated with 2-week courses of orally administered corticosteroids with or without the addition of orally administered clindamycin. There were no infectious or other adverse reactions.     

Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden

To estimate the prevalence of chronic granulomatous disease (CGD) in Sweden, an inquiry asking for known and possible CGD cases was mailed to paediatric, internal medicine and infectious disease departments all over Sweden. The detected patients were characterized as to genetics and the clinical presentation. Twenty-one patients (belonging to 16 different families) were found, corresponding to a prevalence of approximately 1/450,000 individuals. The patients with X-linked disease, lacking a functional gp91phox protein (n = 12), comprised 57% and 43% of the patients had an autosomal recessive (AR) disease lacking p47phox (n = 7) or p67phox (n = 1), respectively. All unrelated patients with X-linked disease displayed different gene abnormalities such as point mutations predicting nonsense (n = 3), missense (n = 1) or splice site mutations (n = 2), but also a total deletion and a unique 40 base pair duplicature insertion. The patients with p47phox-deficiency showed a GT deletion at a GTGT tandem repeat, and the p67phox-deficient patient displayed a heterozygous in-frame deletion of AAG combined with a large deletion in the other allele. Three patients died during the study period, two from pseudomonas cepacia infections. Patients with X-linked disease had more frequent infections (mean of 1.7 per year), than the patients with AR inheritance (0.5 infections per year). The most common infections were dermal abscesses (n = 111), followed by lymphadenitis (n = 82) and pneumonias (n = 73). Inflammatory bowel disease-like symptoms, mimicking Crohn's disease of the colon, was seen in three CGD patients.     

Disseminated infection due to Chrysosporium zonatum in a patient with chronic granulomatous disease and review of non-Aspergillus fungal infections in patients with this disease

BACKGROUND: Insulin-like growth factor-2 (IGF-2) is considered one of the autocrine growth factors in colorectal carcinoma. In addition, it is well known that IGF-2 is produced in the liver. However, the role of IGF-2 in liver metastasis is not yet understood clearly. METHODS: Immunohistochemical staining of IGF-2 and IGF-1 receptor (IGF-1R) was performed on tissue samples of liver metastases from 30 colorectal carcinoma patients. In situ hybridization of IGF-2 also was conducted on the same tissue samples. Furthermore, proliferating cell nuclear antigen (PCNA) was immunohistochemically stained for use as an indicator of the proliferative activity of cancer cells. RESULTS: Invasive margins of liver metastases were stained highly by both IGF-2 (70%) and IGF-1R (83%). Overexpression of IGF-2 protein and mRNA was observed in the normal liver adjacent to the tumor. The PCNA labeling indices (LIs) of the IGF-2 positive groups were significantly higher than those of the IGF-2 negative group (P < 0.0001). In addition, the PCNA LIs for the IGF-1R positive groups also were significantly higher than those for the IGF-1R negative group (P=0.0002). CONCLUSIONS: These findings suggest that hepatocyte-derived IGF-2 stimulates tumor cell proliferation by a paracrine mechanism and plays an important role in tumor progression in colorectal carcinoma patients with liver metastases.     

"Flexispira rappini" bacteremia in a child with pneumonia

We describe a case of "Flexispira rappini" bacteremia from a 9-year-old girl who presented with a 5-day history of fever, productive cough, and malaise. A chest X-ray result was compatible with right middle lobe pneumonia. Blood culture grew a gram-negative spiral fusiform bacterium 2 days after the inoculation. Biochemical tests showed the organism to be catalase negative, oxidase positive, sodium hippurate hydrolysis negative, and urea hydrolysis negative. 16S rRNA gene sequencing identified this organism as "F. rappini," showing a six-base substitution from the type strain. This is the first report of "F. rappini" bacteremia in a human, suggesting that this organism has the potential of causing invasive infection, but its role in pneumonia is uncertain and could be unrelated to the bacteremia.     

Invasive pulmonary infection due to Scedosporium apiospermum in two children with chronic granulomatous disease

The aim of this study was to investigate of the relationship of ovarian stromal volume, measured using three-dimensional ultrasound, to serum androgen concentrations in patients with polycystic ovaries. Serum gonadotrophin, oestradiol and androgen concentrations and ovarian volume measurements were obtained in the early follicular phase from 100 women undergoing assisted conception treatment cycles. Group 1 contained 50 women with regular menstrual cycles and normal ovarian morphology, group 2 contained 24 women with regular menstrual cycles and polycystic ovaries seen on ultrasound scan and group 3 contained 26 women with polycystic ovary syndrome. Statistical analysis included analysis of variance, Scheffé's procedure and Pearson's correlation. Total ovarian volume (15.7-16.1 versus 11 ml, P < 0.05), stromal volume (14.5 versus 9.4 ml, P < 0.05) and thecal steroid concentrations were significantly greater in groups 2 and 3. Stromal volume was positively correlated with serum androstenedione concentrations (r = 0.45, P = 0.0019 in group 3) but was not correlated with any other endocrine parameter. It was concluded that polycystic ovaries are characterized by increased ovarian stroma with associated overproduction of theca-derived steroids, particularly androstenedione.