amphotericin-b and Granulomatous-Disease--Chronic

Aspergillus myofasciitis is a rare infection of the muscles and their fascial sheaths that has been reported in patients with immune deficiencies of various kinds but, until now, not with chronic granulomatous disease (CGD). Patients affected by CGD are at high risk of invasive aspergillus infections. The case described involves a 14-year-old boy with a severe autosomal recessive CGD who was admitted to hospital with an Aspergillus myofasciitis of the left forearm. He was treated with liposomal amphotericin for 14 days and then with oral voriconazole for three months with an excellent clinical outcome. He did not evidence any recurrence in the following 30 months using itraconazole prophylaxis.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Fasciitis; Forearm; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Itraconazole; Male; Pyomyositis; Trimethoprim, Sulfamethoxazole Drug Combination

Aspergillus spp. are a leading cause of mortality in chronic granulomatous disease (CGD), but other fungi have emerged in the era of mould prophylaxis. Of these, Phellinus spp. are an under-recognised cause of invasive fungal infections (IFIs) in CGD, and data on their presentation and management are scarce. We present a patient with CGD who developed disseminated IFI involving the lungs and brain. Surgical specimens grew a basidiomycete which was disregarded as a contaminant. After three months of progressive disease despite antifungals, he was diagnosed with Phellinus tropicalis by internal transcribed spacer (ITS) sequencing. He improved with amphotericin B and isavuconazole but required haematopoietic stem cell transplantation (HSCT). We review the literature on Phellinus infections in CGD and conclude that: (i) these infections emerge on mould-active prophylaxis and are indolent; (ii) they typically cause locally destructive disease but can disseminate; (iii) diagnosis is delayed and requires molecular methods; (iv) amphotericin B is most active in vitro; and (v) treatment is protracted and requires surgery and possibly HSCT. In conclusion, Phellinus spp. are emerging pathogens in CGD. Every effort should be made to establish the diagnosis of non-Aspergillus IFIs in patients with CGD by sending tissue specimens for molecular diagnostics.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Basidiomycota; Brain; DNA, Ribosomal Spacer; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Lung; Male; Nitriles; Pyridines; Tomography, X-Ray Computed; Triazoles; Young Adult

Chronic granulomatous disease (CGD) is a rare inherited disorder characterised by inability of phagocytes to kill catalase-positive organisms including certain fungi. Aspergillus species are the most frequent fungal pathogens. This study is a systematic review of the reported cases of osteomyelitis due to Aspergillus species in CGD patients. Retrospective analysis of 46 osteomyelitis cases caused by Aspergillus species in 43 CGD patients (three females) published in the English literature (PubMed) was performed. Twenty-three cases were due to Aspergillus fumigatus (50%), 20 to Aspergillus nidulans (43.5%), one to Aspergillus flavus and two to unspecified Aspergillus species. The median age was 8 years (range 1.5-21). Osteomyelitis due to A. nidulans was associated with pulmonary infection and involved 'small bones' more frequently than A. fumigatus osteomyelitis (P = 0.001). Amphotericin B was used in 91.3% and surgical debridement in 67.4% of all cases. The overall mortality of osteomyelitis due to Aspergillus species in CGD patients was 37%; 55% for A. nidulans compared to 13% for A. fumigatus (P = 0.008). Aspergillus fumigatus causes osteomyelitis in CGD patients almost as frequently as A. nidulans and much more frequently than A. flavus. Osteomyelitis due to A. nidulans is associated with higher mortality than A. fumigatus.

Topics: Age Distribution; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Debridement; Granulomatous Disease, Chronic; Humans; Osteomyelitis; Retrospective Studies

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Child; Granulocytes; Granulomatous Disease, Chronic; Humans; Itraconazole; Male; Osteomyelitis; Spinal Diseases

An 8-year-old boy who had chronic granulomatous disease developed a soft tissue infection of the right heel after riding on a motor scooter. Infection was insidious, and minor heel pain and fevers occurred only on the day interferon-gamma was injected. Soft tissue biopsy showed hyphal elements, and Paecilomyces varioti grew in culture. The infection was treated with amphotericin B for 7 weeks (total dose, 40 mg/kg) followed by 1 year of therapy with itraconazole (100 mg twice daily). Complete cure was achieved during the follow-up period of 10 months.

Topics: Amphotericin B; Antifungal Agents; Child; Drug Therapy, Combination; Follow-Up Studies; Granulomatous Disease, Chronic; Heel; Humans; Interferon-gamma; Itraconazole; Ketoconazole; Male; Mycoses; Paecilomyces; Treatment Outcome

Antibacterial therapy in chronic granulomatous disease requires antimicrobials active on Staphylococcus aureus and enterobacteria, which also have a good intracellular penetration and activity as rifampicin, fluoroquinolone, fosfomycin, cotrimoxazole. Several trials showed that cotrimoxazole was effective for the prevention of bacterial infection: thus, this antimicrobial can be used as long-term and continuous prophylaxia. Fungal infections require the use of amphotericin B. The place of new imidazole compounds as itraconazole should be assessed.

Topics: Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Drug Combinations; Granulomatous Disease, Chronic; Humans; Mycoses; Premedication; Sulfamethoxazole; Trimethoprim

Mucocutaneous leishmaniasis (MCL) is a rare infection caused by several species within the genus

Topics: Adult; Amphotericin B; Female; Granulomatous Disease, Chronic; Humans; Immunosuppressive Agents; Leishmania; Leishmaniasis, Mucocutaneous

Topics: Amphotericin B; Antifungal Agents; Granulomatous Disease, Chronic; Humans; Lung Diseases; Mycoses

Amphotericin B is a powerful polyene antifungal drug used for treating systemic fungal infections and is usually administered for a short period. Side effects after prolonged use are unknown in humans. Here we report the case of a 28-year-old man suffering from chronic granulomatous disease (CGD), treated for invasive cerebral aspergillosis with liposomal amphotericin B (L-AmB) for a very long time (8 consecutive years). We describe the efficacy and safety of this treatment in the long term. Aspergillosis was kept under control as long as L-AmB therapy was maintained, but relapsed when the dose was reduced. No overt renal toxicity was noted. The patient gradually developed hepatosplenomegaly and pancytopenia. Abnormalities of bone marrow were similar to the sea-blue histiocyte syndrome. Liver biopsy showed images of nodular regenerative hyperplasia related to CGD as well as a histiocytic storage disease. We discuss the very prolonged use of L-AmB leading to the development of a lysosomal storage disease.

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Granulomatous Disease, Chronic; Histocytochemistry; Humans; Liver; Lysosomal Storage Diseases; Male; Neuroaspergillosis

The most common cause of invasive aspergillosis (IA) in patients with chronic granulomatous disease (CGD) is Aspergillus fumigatus followed by A. nidulans; other aspergilli rarely cause the disease. Here we review two clinical cases of fatal IA in CGD patients and describe a new etiologic agent of IA refractory to antifungal therapy. Unlike typical IA caused by A. fumigatus, the disease caused by the new species was chronic and spread from the lung to multiple adjacent organs. Mycological characteristics and the phylogenetic relationship with other aspergilli based on the sequence analysis of Mcm7, RPB2, and Tsr1 indicated that the new species, which we named as A. tanneri, belongs to Aspergillus section Circumdati. The species has a higher amphotericin B, voriconazole, and itraconazole MIC and causes more chronic infection in CGD mice than A. fumigatus. This is the first report documenting IA in CGD patients caused by a species belonging to the Aspergillus section Circumdati that is inherently resistant to azoles and amphotericin B. Unlike the results seen with many members of Aspergillus section Circumdati, ochratoxin was not detected in filtrates of cultures grown in various media. Our phenotypic and genetic characterization of the new species and the case reports will assist future diagnosis of infection caused by A. tanneri and lead to more appropriate patient management.

Topics: Adolescent; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus; Cluster Analysis; DNA, Fungal; Drug Resistance, Fungal; Fungal Proteins; Granulomatous Disease, Chronic; Humans; Itraconazole; Lung; Male; Mice; Microbial Sensitivity Tests; Microscopy; Molecular Sequence Data; Phylogeny; Pyrimidines; Sequence Analysis, DNA; Tomography, X-Ray Computed; Treatment Failure; Triazoles; Voriconazole; Young Adult

A 26-year-old man with chronic granulomatous disease complicated by multiple liver abscess was admitted to our hospital for hepatic resection and allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling. We diagnosed the patient with Aspergillus liver abscesses based on computed tomographic findings, elevated serum levels of beta-D-glucan, positive test for galactomannan antigen, and the findings of laboratory cultures. Since the liver abscess could not be treated by drainage and administration of antifungals, we resected the posterior segments of the liver, which contained the abscess (S1, S6). However, abscess recurred in the remaining part of the liver 1 month later. The patient received allogeneic BMT from an HLA-matched sibling. During BMT, we continuously administered liposomal amphotericin B (L-AMB) via the hepatic artery (25 mg/day) to treat the liver abscess. There were no adverse effects during hepatic arterial infusion of L-AMB, and the liver abscess disappeared after BMT. These results suggest that hepatic arterial infusion of L-AMB is effective in treating fungal abscess in the liver.

Topics: Adult; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Granulomatous Disease, Chronic; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Abscess; Male; Treatment Outcome

Visceral leishmaniasis is a severe form of infection caused by a parasite endemic along the Mediterranean coast. Complications such as infection-associated hemophagocytic syndrome can occur despite correct therapy. We report visceral leishmaniasis-associated infection-associated hemophagocytic syndrome in 3 patients with chronic granulomatous disease.

Topics: Adolescent; Amphotericin B; Animals; Antiprotozoal Agents; Child; Fatal Outcome; Female; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male; Recombinant Proteins

We describe a case of sporotrichosis that disseminated to involve multiple nerves after initiation of immunosuppressive therapy and then precipitously worsened after withdrawal of therapy. This case illustrates that multiple mononeuropathies are not always caused by vasculitis, and a correct pathological diagnosis should be established before treatment. Based on clinical and pathological features, the mechanism of neuropathy may have been due to either direct nerve infection or a bystander effect of inflammatory/immune damage or, perhaps more likely, to both mechanisms.

Topics: Abscess; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents; Debridement; Dermatitis; Diagnostic Errors; Disease Progression; Forearm; Granulomatous Disease, Chronic; Humans; Immunosuppressive Agents; Inflammation; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Pain; Peripheral Nerves; Peripheral Nervous System Diseases; Sporothrix; Sporotrichosis; Treatment Outcome; Wrist Joint

Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase characterized by recurrent life-threatening bacterial and fungal infections. We characterized the effects of single and combination antifungal therapy on survival, histopathology, and laboratory markers of fungal burden in experimental aspergillosis in the p47phox-/- knockout mouse model of CGD. CGD mice were highly susceptible to intratracheal Aspergillus fumigatus challenge, whereas wild-type mice were resistant. CGD mice were challenged intratracheally with a lethal inoculum (1.25 x 10(4) CFU/mouse) of A. fumigatus and received one of the following regimens daily from day 0 to 4 after challenge (n = 19 to 20 per treatment group): (i) vehicle, (ii) amphotericin B (intraperitoneal; 1 mg/kg of body weight), (iii) micafungin (intravenous; 10 mg/kg), or (iv) amphotericin B plus micafungin. The rank order of therapeutic efficacy based on prolonged survival, from highest to lowest, was as follows: amphotericin B plus micafungin, amphotericin B alone, micafungin alone, and the vehicle. Lung histology showed pyogranulomatous lesions and invasive hyphae, but without hyphal angioinvasion or coagulative necrosis. Treatment with micafungin alone or combined with amphotericin B produced swelling of invasive hyphae that was not present in mice treated with the vehicle or amphotericin B alone. Assessment of lung fungal burden by quantitative PCR showed no significant difference between treatment groups. Serum galactomannan levels were at background despite documentation of invasive aspergillosis by histology. Our findings showed the superior efficacy of the amphotericin B and micafungin combination compared to either agent alone after A. fumigatus challenge and also demonstrated unique features of CGD mice as a model for experimental aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Therapy, Combination; Echinocandins; Granulomatous Disease, Chronic; Lipopeptides; Lipoproteins; Lung; Micafungin; Mice; NADPH Oxidases; Peptides, Cyclic; Phosphoproteins

Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absence of superoxide and hydrogen peroxide production in phagocytes predisposes patients to bacterial and fungal infections. The most common fungal infections in these patients are caused by Aspergillus species.. Here, we describe Aspergillus osteomyelitis of the ribs and hepatic abscess in a 5-year-old boy. The patient was successfully treated with Amphotericin B and INF-gamma.. With respect to the high frequency of aspergillosis in the CGD patient, immune deficiency should be investigated in patients with invasive aspergillosis. Moreover, using antifungal drugs as prophylaxis can improve the quality of life in these patients.

Topics: Amphotericin B; Aspergillosis; Child, Preschool; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Male

Chronic granulomatous disease is an inherited defect in host defense mechanisms mainly affecting neutrophil function. Pulmonary infection with Aspergillus nidulans in a child with chronic granulomatous disease could not be eliminated by a combination of caspofungin and liposomal amphotericin B. Voriconazole was successful in clearing the infection.

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus nidulans; Caspofungin; Drug Therapy, Combination; Echinocandins; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Lipopeptides; Lung Diseases, Fungal; Male; Opportunistic Infections; Peptides; Peptides, Cyclic; Pyrimidines; Risk Assessment; Salvage Therapy; Treatment Outcome; Triazoles; Voriconazole

13 cases of osteomyelitis caused by Aspergillus nidulans have been previously reported in patients with chronic granulomatous disease (CGD). All of them have been associated with simultaneous pulmonary infection and have had an extremely poor outcome. We report an unusual case of femoral osteomyelitis due to A. nidulans in a 16-year-old male with CGD, without pulmonary involvement. Treatment with liposomal amphotericin B and granulocyte colony-stimulating factor as well as extensive surgical debridement followed by prolonged treatment with itraconazole resulted in an excellent clinical response.

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus nidulans; Femur; Granulomatous Disease, Chronic; Humans; Male; Osteomyelitis; Tomography, X-Ray Computed

A 3-month-old boy born to a mother carrying an X-linked form of chronic granulomatous disease presented with persistent fever and hepatosplenomegaly. The diagnosis was confirmed as a gp91phox defect by genetic analysis, and the patient was managed with broad spectrum antibacterial agents, gamma-interferon and later amphotericin B. A liver biopsy revealed granulomata with budding yeast forms, and cultures of blood and urine grew Candida lusitaniae. The patient died 26 days after admission.

Topics: Amphotericin B; Anti-Infective Agents; Antiviral Agents; Candidiasis; Fatal Outcome; Granulomatous Disease, Chronic; Humans; Infant; Interferon-gamma; Male

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Crohn Disease; Diagnosis, Differential; Female; Granulomatous Disease, Chronic; Humans; Sarcoidosis; Tomography, X-Ray Computed

To report an unusual ocular presentation of Candida glabrata in a patient with chronic granulomatous disease.. Interventional case report. A 15-year-old boy with chronic granulomatous disease presented with bilateral limbal infiltrates. He had been receiving broad-spectrum systemic antibiotics for recurrent liver abscesses. The keratitis did not respond to antibiotics and did not resolve after a course of topical steroids.. Corneal cultures revealed Candida glabrata. The same species was simultaneously isolated from the surgical drainage of the liver abscesses. The ocular and hepatic findings resolved on intravenous amphotericin B.. Candida glabrata has recently emerged as an important nosocomial pathogen. It may present as a limbal keratitis in the setting of systemic infection.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cornea; Eye Infections, Fungal; Granulomatous Disease, Chronic; Humans; Keratitis; Liver Abscess; Male; Staphylococcal Infections; Visual Acuity

In experimental visceral leishmaniasis, in which the tissue macrophage is the target, in vivo responsiveness to conventional chemotherapy (pentavalent antimony [Sb]) requires a T-cell-dependent mechanism. To determine if this mechanism involves gamma interferon (IFN-gamma)-induced activation and/or specific IFN-gamma-regulated macrophage leishmanicidal mechanisms (generation of reactive nitrogen or oxygen intermediates, we treated gene-deficient mice infected with Leishmania donovani. In IFN-gamma gene knockout (GKO) mice, Sb inhibited but did not kill intracellular L. donovani (2% killing versus 76% in controls). Sb was active (>94% killing), however, in both inducible nitric oxide synthase (iNOS) knockout (KO) and respiratory burst (phagocyte oxidase)-deficient chronic granulomatous disease (X-CGD) mice. Sb's efficacy was also maintained in doubly deficient animals (X-CGD mice treated with an iNOS inhibitor). In contrast to Sb, amphotericin B (AmB) induced high-level killing in GKO mice; AmB was also fully active in iNOS KO and X-CGD animals. Although resolution of L. donovani infection requires iNOS, residual visceral infection remained largely suppressed in iNOS KO mice treated with Sb or AmB. These results indicate that endogenous IFN-gamma regulates the leishmanicidal response to Sb and achieves this effect via a pathway unrelated to the macrophage's primary microbicidal mechanisms. The role of IFN-gamma is selective, since it is not a cofactor in the response to AmB. Treatment with either Sb or AmB permits an iNOS-independent mechanism to emerge and control residual intracellular L. donovani infection.

Topics: Amphotericin B; Animals; Antimony; Antiprotozoal Agents; Disease Models, Animal; Enzyme Inhibitors; Female; Granulomatous Disease, Chronic; Guanidines; Interferon-gamma; Leishmaniasis, Visceral; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase; Nitric Oxide Synthase Type II

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impaired microbial killing and susceptibility to bacterial and fungal infections. Cure of the disease can be achieved by stem cell transplantation when performed early in its course, and before severe infections have developed. Invasive aspergillosis constitutes a very high risk for transplantation. We report a 4-year-old boy with X-linked CGD who underwent successful HLA-identical peripheral blood stem cell (PBSC) transplantation during invasive pulmonary aspergillosis and osteomyelitis of the left fourth rib, which was unresponsive to antifungal treatment. During the 2 months prior to the transplant he received G-CSF-mobilized granulocyte transfusions (GTX) from unrelated donors three times a week in addition to the antifungal treatment. This resulted in clinical improvement in his respiratory status. He also received GTX during the aplastic period after the conditioning regimen, until he had engrafted. Post-transplant superoxide generation test revealed that neutrophil function was within normal range. One year post transplant the CT scan showed almost complete clearance of the pulmonary infiltrates and a marked improvement in the osteomyelitic process. Based on other reports and our own experience, GTX can serve as important treatment in patients with CGD who have failed conventional anti-fungal treatment and for whom stem cell transplantation is the only chance for cure.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Child, Preschool; Combined Modality Therapy; Drug Resistance, Microbial; Flucytosine; Granulocyte Colony-Stimulating Factor; Granulocytes; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Itraconazole; Leukocyte Transfusion; Lung Diseases, Fungal; Male; Neutrophils; Osteomyelitis; Pyrimidines; Respiratory Burst; Ribs; Triazoles; Voriconazole

Here we describe Aspergillus osteomyelitis of the tibia in a 9-year-old boy who has an autosomal recessive form of chronic granulomatous disease (CGD). The patient showed a p67-phagocyte oxidase (phox) deficiency, which is rare type of CGD in Japan. The initial treatment which consisted of surgical debridement and antibiotic therapy with amphotericin B (AMPH), did not control the infection. Aspergillus fumigatus (A. fumigatus) pure isolated from drainage fluid and necrotic bone tissue demonstrated less susceptible to antifungal agents, including AMPH, fluconazole and flucytosine. Recombinant interferon gamma was then administrated, and it was effective in controlling the course of severe invasive aspergillosis. This report indicates the use of interferon gamma might be helpful in control for Aspergillus osteomyelitis of the tibia in a child with CGD demonstrated p67-phox deficiency refractory to conventional therapy with AMPH.

Topics: Amphotericin B; Aspergillosis; Child; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Male; Osteomyelitis; Phosphoproteins; Recombinant Proteins; Tibia

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Brain Abscess; Granulomatous Disease, Chronic; Humans; Male; Recurrence

A 5-year-old boy with chronic granulomatous disease (CGD) was treated with amphotericin B for an invasive pulmonary Aspergillus nidulans infection. The infection progressed during 6 wk of treatment despite the addition of interferon-gamma (IFN-gamma), filgrastim, and transfusions with donor granulocytes. Treatment with a novel antifungal triazole, voriconazole, resulted in an excellent clinical response.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus nidulans; Child, Preschool; Granulomatous Disease, Chronic; Humans; Lung Diseases, Fungal; Male; Pyrimidines; Triazoles; Voriconazole

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with complete absence or malfunction of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagocytic cells. Life-threatening infections especially with aspergillus are common despite optimal antimicrobial therapy. Bone marrow transplantation (BMT) is contraindicated during invasive aspergillosis in any disease setting. We report an 8-year-old patient with CGD who underwent HLA-genoidentical BMT during invasive multifocal aspergillus nidulans infection, nonresponsive to treatment with amphotericin-B and gamma-interferon. During the first 10 days post-BMT, the patient received granulocyte colony-stimulating factor (G-CSF)-mobilized, 25 Gy irradiated granulocytes from healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the transfused granulocytes. This was confirmed in vitro by apoptosis assays and in vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral blood 12 and 36 hours after the transfusions. Clinical and biological signs of infection began to disappear on day 7 post-BMT. Positron emission tomography with F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months post-BMT showed complete disappearance of infectious foci. At 2 years post-BMT, the patient is well with full immune reconstitution and no sign of aspergillus infection. Our results show that HLA-identical BMT may be successful during invasive, noncontrollable aspergillus infection, provided that supportive therapy is optimal.

Topics: Amphotericin B; Antifungal Agents; Apoptosis; Aspergillosis; Aspergillus nidulans; Bone Marrow Transplantation; Child; Combined Modality Therapy; Drug Carriers; Graft Survival; Granulocyte Colony-Stimulating Factor; Granulocytes; Granulomatous Disease, Chronic; Humans; Itraconazole; Leukocyte Count; Leukocyte Transfusion; Liposomes; Lung Diseases, Fungal; Male; Tomography, Emission-Computed; Treatment Outcome

A 12 year old boy suffering from p67-phox deficient chronic granulomatous disease presented with a bullous skin disease and a lung infection with paecilomyces species. The histopathology of a bullous lesion showed subepidermal blister formation and microabcesses containing eosinophils in the dermal papillae. By direct immunofluorescence, linear staining of IgA at the dermal-epidermal junction was detected which confirmed the clinical diagnosis of chronic bullous disease of childhood (linear IgA dermatosis).

Topics: Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Autoimmune Diseases; Child; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Itraconazole; Lung Diseases, Fungal; Male; Paecilomyces; Phosphoproteins; Prednisolone; Skin Diseases, Vesiculobullous

We describe a patient with chronic granulomatous disease who presented with erythematous papular skin lesions on the chest, back, and arm. Examination of biopsy specimens from the lesions on the arm and back showed suppurative granulomata in association with acute and chronic inflammation. Histopathologic examination of a specimen from the lesion on the arm revealed fungal elements, and cultures yielded Microascus cinereus. The patient was treated with 2.5 g of intravenous amphotericin B, and the lesions resolved. We report what is, to our knowledge, the first case of invasive disease due solely to M. cinereus.

Topics: Amphotericin B; Ascomycota; Child; Dermatomycoses; Female; Granuloma; Granulomatous Disease, Chronic; Humans; Opportunistic Infections

A 3-yr-old boy with known chronic granulomatous disease presented with a left-sided chest wall mass. Extensive intrathoracic and extrathoracic aspergillosis was confirmed by CT scan-guided percutaneous biopsy. Initially, he was treated intravenously with liposomal amphotericin and subcutaneous gamma-interferon, but his clinical condition deteriorated over 7 wk of treatment. The amphotericin was therefore discontinued, and itraconazole in an oral suspension was begun. There was progressive clinical improvement after 3 months of this regime, and marked radiologic clearing was apparent after 8 months of treatment. A multicenter trial of this mode of therapy in patients with invasive aspergillosis is indicated.

Topics: Administration, Oral; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Biopsy; Child, Preschool; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Injections, Subcutaneous; Interferon-gamma; Itraconazole; Male; Suspensions; Tomography, X-Ray Computed; Treatment Outcome

Chronic granulomatous disease (CGD) is a rare inherited disorder in which neutrophils do not appropriately generate cytotoxic superoxide anion, the respiratory burst, in response to invading bacteria or fungi as a part of normal host defence. We report the case of a child with CGD who had two abdominal wall abscesses caused by Paecilomyces lilacinus, an organism not previously known to cause infections in patients with CGD. The abdominal wall is a location that is rarely associated with Paecilomyces infections. Parenteral amphotericin B eradicated the infection in an immunocompromised child whereas this regimen has heretofore largely been unsuccessful in the treatment of this infection. Paecilomyces species and other fungi from immunocompromised hosts and thought to be laboratory contaminants, need to be carefully investigated for they may become pathogens in this clinical setting.

Topics: Abdominal Muscles; Abscess; Amphotericin B; Child, Preschool; Granulomatous Disease, Chronic; Humans; Male; Mycoses; Paecilomyces; Recurrence

An 18-year-old boy with X-linked chronic granulomatous disease (CGD) developed Aspergillus fumigatus pneumonia and multifocal osteomyelitis. Treatment with amphotericin B resulted in only moderate improvement of the lesions and was accompanied by considerable toxicity. In contrast, administration of the new triazole drug itraconazole led to complete disappearance of all signs of infection. We conclude that itraconazole may be a valuable new drug for treating invasive aspergillosis in patients with CGD, although the duration of treatment remains to be established.

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Chromatography, High Pressure Liquid; Granulomatous Disease, Chronic; Humans; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Male; Osteomyelitis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Aspergillus nidulans var. echinulatus was the sole agent cultured from the left lung, a paraspinal abscess, left ribs, and thoracic vertebral bodies from a patient with chronic granulomatous disease. Hyphal elements were present in histologic sections of lung, vertebral bodies, and infected ribs along with granuloma formation. The patient was treated with two debridement procedures and insertion of a Harrington rod followed by a long course of amphotericin B, flucytosine, and daily white blood cell transfusions.

Topics: Abscess; Amphotericin B; Aspergillosis; Aspergillus nidulans; Blood Transfusion; Child, Preschool; Flucytosine; Granulomatous Disease, Chronic; Humans; Leukocyte Transfusion; Lung Diseases, Fungal; Male; Spinal Diseases; Thoracic Vertebrae

Human PMN and monocytes both possess a mechanism for amplifying Fc receptor-mediated phagocytic function, which is dependent on activation of the respiratory burst. The pathway for augmentation of phagocytosis requires superoxide anion, hydrogen peroxide, and lactoferrin and is independent of the hydrogen peroxide-MPO-halide system. In neither cell type is this mechanism induced upon exposure to the opsonized target. PMN require an additional signal for stimulation of the respiratory burst; this is not true of monocytes. On the other hand, monocytes require an exogenous source of lactoferrin in order to activate this pathway for enhanced ingestion. The dependence of this pathway for both PMN and monocytes on superoxide anion, hydrogen peroxide, and cell-bound lactoferrin is consistent with a role for locally generated reactive oxygen metabolites, possibly hydroxyl radicals, in phagocytosis amplification. Patients with chronic granulomatous disease, who are genetically deficient in the ability to activate the respiratory burst, are unable to amplify Fc receptor-mediated phagocytosis. Thus, these patients may have a previously unrecognized defect in the recruitment of phagocytic function at inflammatory sites.

Topics: Amphotericin B; Benzoates; Benzoic Acid; Biological Factors; Catalase; Cytokines; Free Radicals; Granulomatous Disease, Chronic; Humans; Lactoferrin; Male; Monocytes; NADH, NADPH Oxidoreductases; NADPH Oxidases; Neutrophils; Opsonin Proteins; Oxygen Consumption; Phagocytosis; Phorbol 12,13-Dibutyrate; Receptors, Fc; Zymosan

Chronic granulomatous disease of childhood is a hereditary abnormality of phagocytic cells, frequently associated with Aspergillus infections. From 1969 to 1984, 14 of 37 children with chronic granulomatous disease have presented with pulmonary (13 cases) and/or osteo-articular (1 case) aspergillosis. The paucity of symptoms was a characteristic of these infections. Lung lesions extending to the thoracic chest wall carried the bad prognosis. Neither the Aspergillus skin test nor the Aspergillus serology could definitely confirm the diagnosis. Only broncho-alveolar lavage and biopsy with isolation of Aspergillus could confirm the diagnosis. Long-term therapy with amphotericin B alone or associated with other antifungal agents is necessary. For the past 3 years, ketoconazole prophylaxis has been used in 23 children and none of these children has developed aspergillosis.

Topics: Adolescent; Amphotericin B; Aspergillosis; Child; Child, Preschool; Female; Granulomatous Disease, Chronic; Humans; Infant; Infant, Newborn; Ketoconazole; Lung Diseases, Fungal; Male

We report two patients with chronic granulomatous disease (CGD) and life-threatening infections: a 10 10/12-year-old boy had Aspergillus fumigatus spondylitis with destruction of the 11th vertebral body and paravertebral abscess formation, and an 8 5/12-year-old boy had multiple Staphylococcus aureus hepatic abscesses with subphrenic abscess formation. Both patients failed to respond to intense antimicrobial therapy but showed a remarkable recovery following surgical drainage combined with granulocyte transfusions. These results suggest that antimicrobial therapy and surgical drainage followed by granulocyte transfusions may be the ideal mode of treatment for severe infections in patients with CGD.

Topics: Amphotericin B; Blood Transfusion; Child; Drug Combinations; Flucytosine; Granulocytes; Granulomatous Disease, Chronic; Humans; Liver Abscess; Male; Spondylitis; Staphylococcal Infections; Subphrenic Abscess; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Amphotericin B; Aspergillosis; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Male; Rifampin

In a patient with chronic granulomatous disease of childhood documented by the nitroblue tetrazolium test, an infection of the mediastinal lymph nodes developed that was caused by Hansenula polymorpha, an ascomycetous yeast. To our knowledge, this yeast has not been previously shown to be an etiologic agent of disease in man. The diagnosis was made by growing the yeast from cultures of several biopsy specimens collected at the time of thoracotomy. Susceptibility testing showed that the yeast was sensitive to amphotericin B. Treatment with amphotericin B reversed this life-threatening episode.

Topics: Amphotericin B; Ascomycota; Child, Preschool; Granulomatous Disease, Chronic; Humans; Lymphadenitis; Male; Mycoses; Pichia

A case of systemic infection caused by Aspergillus fumigatus in a seven-year-old boy suffering from chronic granulomatous disease is described. The fungus had infiltrated his lungs, his left foot and the popliteal and inguinal lymph nodes. Amphotericin B, 1 mg/kg daily, was given for three months via a central venous catheter, Progressive anaemia made amputation of his left leg necessary. The bone tissue was heavily infiltrated with fungal elements. The regional lymph nodes were also resected because of fungal growth. After six months no fungi were found in liver aspirates taken on account of liver abscesses due to Staphylococcus aureus. The combined medical and surgical approach resulted in complete eradication of the Aspergillus infection, as verified by the disappearance of Aspergillus precipitins.

Topics: Amphotericin B; Amputation, Surgical; Aspergillosis; Aspergillus fumigatus; Child; Granulomatous Disease, Chronic; Humans; Leg; Male

Topics: Amphotericin B; Aspergillosis; Child, Preschool; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Male; Osteomyelitis; Rifampin