Among the various drug induced dermatological entities toxic epidermalnecrolysis (TEN) and Stevens-Johnson syndrome (SJS) occupy a primary place in terms of mortality. Toxic epidermal necrolysis also known as Lyell's syndrome was first described by Lyell in 1956. Drugs are by far the most common cause of toxic epidermal necrolysis, in which large sheets of skin are lost from the body surface making redundant the barrier function of the skin, with its resultant complications. Drug-induced toxic epidermal necrolysis are severe adverse cutaneous drug reactions to various precipitating agents that predominantly involve the skin and mucous membranes. Toxic epidermal necrolysis is rare but considered medical emergencies as they are potentially fatal. Drugs are the most common cause accounting for about 65%-80% of the cases. The most common offending agents are sulfonamides, NSAIDs, butazones and hydrantoins. An immune mechanism is implicated in the pathogenesis, but its nature is still unclear. There is a prodormal phase in which there is burning sensation all over the skin and conjunctivae, along with skin tenderness, fever, malaise and arthralgias. Early sites of cutaneous involvement are the presternal region of the trunk and the face, but also the palms and soles, rapidly spread to their maximum extent, the oral mucosa and conjunctiva being affected. Initial lesions are macular, followed by desquamateion, or may be from atypical targets with purpuriccenters that coalesce, from bullae, then slough. The earlier a causative agent is withdrawn the better is the prognosis. Several treatment modalities given in addition to supportive care are reported in the literature, such as systemicsteroids, high-dose intravenous immunoglobulins, ciclosporin, TNF antagonists. Recovery is slow over a period of 14-28 days and relapses are frequent. Mortality is 25%-50% and half the deaths occur due to secondary infection. Here we report a 50-year-old female of drug-induced toxic epidermal necrolysis. She was admitted to the dermatology ward with extensive peeling of skin over the trunk and limbs. She had taken alamotrigine for epilepsy. A week after taking the tablets, the patient developed a severe burning sensation all over the body and followed by a polymorphic erythematous dermatitis and widespread peeling of skin. We treated this patient with high dose corticosteroids, high-dose intravenous immunoglobulins and etanercept, but eventually she died of secondary aspergillus fumigatus infection.
Adrenal Cortex Hormones ; Aspergillosis/diagnosis* ; Aspergillus fumigatus ; Cyclosporine ; Female ; Humans ; Middle Aged ; Skin ; Stevens-Johnson Syndrome/microbiology*

Airway Obstruction ; diagnosis ; etiology ; Aspergillosis ; complications ; diagnosis ; Humans ; Laryngeal Diseases ; complications ; diagnosis ; microbiology ; Larynx

Aspergillosis ; complications ; Aspergillus ; Chemical and Drug Induced Liver Injury ; complications ; microbiology ; Humans

BACKGROUND/AIMS: In this study, the sensitivity-specificity of galactomannan-enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated. METHODS: IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined. RESULTS: Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA > or = 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results. CONCLUSIONS: With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected.
Adult ; Aged ; Antineoplastic Agents/*adverse effects ; Biomarkers/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Hematologic Neoplasms/diagnosis/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/*adverse effects ; Invasive Pulmonary Aspergillosis/*blood/diagnosis/immunology/microbiology ; Male ; Mannans/*blood ; Middle Aged ; Opportunistic Infections/*blood/diagnosis/immunology/microbiology ; Predictive Value of Tests ; Reproducibility of Results ; Time Factors

Invasive aspergillosis (IA), generally considered an opportunistic infection in immunocompromised hosts, is associated with high morbidity and mortality. IA commonly occurs in the respiratory tract with isolated reports of aspergillosis infection in the nasal sinuses, central nervous system, skin, liver, and urinary tract. Extra-pulmonary aspergillosis is usually observed in disseminated disease. To date, there are a few studies regarding primary and disseminated gastrointestinal (GI) aspergillosis in immunocompromised hosts. Only a few cases of primary GI aspergillosis in non-immunocompromised hosts have been reported; of these, almost all of them involved the upper GI tract. We describe a very rare case of IA involving the lower GI tract in the patient without classical risk factors that presented as multiple colon perforations and was successfully treated by surgery and antifungal treatment. We also review related literature and discuss the characteristics and risk factors of IA in the immunocompetent hosts without classical risk factors. This case that shows IA should be considered in critically ill patients, and that primary lower GI aspergillosis may also occur in the immunocompetent hosts without classical risk factors.
Amphotericin B/administration & dosage/therapeutic use ; Antifungal Agents/administration & dosage/*therapeutic use ; Aspergillosis/*diagnosis/drug therapy/microbiology/surgery ; Aspergillus/*isolation & purification ; Colon/microbiology/radiography/*surgery ; Colonic Diseases/diagnosis/therapy ; Combined Modality Therapy ; Humans ; *Immunocompetence ; Laparotomy ; Male ; Middle Aged ; Treatment Outcome ; Voriconazole/administration & dosage/therapeutic use

OBJECTIVETo evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti (DA) and Albino Oxford (AO) rats recognized as being susceptible to some inflammatory diseases in different manners.

METHODSLung fungal burden (quantitative colony forming units, CFU, assay), leukocyte infiltration (histology, cell composition) and their function (phagocytosis, oxidative activity, CD11b adhesion molecule expression) and cytokine interferon-γ (IFN-γ) and interleukin-17 and -4 (IL-17 and IL-4) lung content were evaluated following infection (intratracheally, 1x10(7) conidia).

RESULTSSlower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CD11b adhesion molecule expression (except for phagocytosis of conidia) in these rats. Differential patterns of changes in proinflammatory cytokine levels (unchanged levels of IFN-γ and transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats) and unchanged levels of IL-4 were observed.

CONCLUSIONGenetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

Animals ; Aspergillus fumigatus ; immunology ; Cytokines ; metabolism ; Lung ; immunology ; metabolism ; microbiology ; pathology ; Male ; Pulmonary Aspergillosis ; immunology ; Rats

Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Humans ; Invasive Pulmonary Aspergillosis ; complications ; drug therapy ; Lipopeptides ; Liver Failure ; complications ; drug therapy ; microbiology ; Male ; Middle Aged ; Voriconazole ; administration & dosage ; therapeutic use

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo determine risk factors of invasive fungal infections (IFI) in patients admitted to non-hematological oncology department and pediatric intensive care unit (PICU), in order to improve diagnostic level of invasive fungal infections.

METHODWe retrospectively assessed 85 hospitalized pediatric patients with invasive fungal infections in Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2007 to Nov.2012. All the cases were either from non-hematological oncology department or the PICU.We reviewed risk factors of invasive fungal infections.

RESULTAmong 85 patients, 42 had invasive candida infection, 20 invasive aspergillus infection, 21 cryptococcus infection, 1 Histoplasma capsulatum infection and 1 Mucor mucedo infection.In the 42 patients with invasive candida infection, 5 were young infants, 3 had combined immunodeficiency, 1 cellular immunodeficiency, 25 secondary infection due to long term use of corticosteroids and/or combined use of more than 2 kinds of antibiotics with primary disease, 5 prior intestinal tract surgery or chronic diarrheal disease, 1 reflux gastritis.In the 20 patients with invasive aspergillosis infection, 10 patients had chronic granulomatous disease, 5 long term use of corticosteroids ≥ 1 month, 3 long term use of corticosteroids and combined use of more than 2 kinds of antibiotics, 2 had no apparent host factors.In the 21 patients with cryptococcus infection, 2 patients had used corticosteroids ≥ 1 month, 2 had immunodeficiency mainly for lack of antibodies, while others had no apparent host factors. The child with Mucor mucedo infection had diabetes mellitus. And the one with Histoplasma capsulatum infection had immunodeficiency.

CONCLUSIONHigh risk factors for IFI in patients admitted to non-hematological oncology department and PICU are primary immunodeficiency disease and long term use of corticosteroids and/or long term combined use of more than 2 kinds of antibiotics. Besides, young infant is also a high risk factor for invasive candida infection. Most of the cryptococcus infections and certain aspergillosis had no obvious host factors.

Adolescent ; Adrenal Cortex Hormones ; administration & dosage ; adverse effects ; Age Factors ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; Aspergillosis ; diagnosis ; etiology ; microbiology ; Aspergillus ; isolation & purification ; Candida ; isolation & purification ; Child ; Child, Preschool ; Cross Infection ; epidemiology ; microbiology ; Female ; Humans ; Immunologic Deficiency Syndromes ; complications ; Infant ; Infant, Newborn ; Male ; Multivariate Analysis ; Mycoses ; diagnosis ; etiology ; microbiology ; Retrospective Studies ; Risk Factors

OBJECTIVETo describe clinical signs, pathology, diagnosis and treatment of Cape vultures in which Aspergillus fumigatus (A. fumigatus) and mixed species of bacteria were isolated.

METHODSSix Cape vultures sourced from South Africa for exhibition at Al Ain Zoo developed illness manifesting as anorexia, dyspnea, polyuria and lethargy. Three vultures died manifesting "pneumonia-like syndrome". These three vultures were necropsied and gross lesions recorded, while organ tissues were collected for histopathology. Internal organs were swabbed for bacteriology and mycology. From live vultures, blood was collected for hematology and biochemistry, oropharyngeal and cloacal swabs were collected for mycology and bacteriology.

RESULTSA. fumigatus was isolated from the three dead vultures and two live ones that eventually survived. One of the dead vulture and two live vultures were co-infected with A. fumigatus and mixed species of bacteria that included Clostridium perfringens, Pseudomonas, Staphylococcus, Escherichia, Proteus, Enterococcus and Enterbacter. One of the Cape vulture and a Lappet-faced vulture, however, were free of Aspergillus or bacterial infections. At necropsy, intestinal hemorrhages were observed and the lungs were overtly congested with granulomas present on caudal air sac. Histopathological examinations demonstrated granulomatous lesions that were infiltrated by mononuclear cells and giant cells.

CONCLUSIONSAspergillosis is a persistent threat to captive birds and we recommend routine health assessments so that early diagnosis may prompt early treatment. It is likely that prompt prophylaxis by broad spectrum antibiotics and antifungals medication contributed to the survival of some of the vultures.

Animals ; Animals, Zoo ; Aspergillosis ; veterinary ; Aspergillus ; Bacteria ; Bacterial Infections ; veterinary ; Bird Diseases ; diagnosis ; microbiology ; Birds ; microbiology ; Granuloma ; pathology ; Necrosis ; Opportunistic Infections