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Pneumatocele complicating hyperimmunoglobulin E syndrome (Job's Syndrome).

The case of a boy with hyperimmunoglobulin E syndrome or Job's syndrome is presented to demonstrate the occurrence of pneumatoceles in this syndrome as well as their unusual natural history and failure to spontaneously resolve. Surgical resection was required for two complications in this patient, persistent bronchopleural fistula and a pulmonary abscess that destroyed one lung and required pneumonectomy. Pathologic examination of the specimens demonstrated the wall of the cysts consisted of granulation tissue with chronic active inflammation surrounded by infarcted pulmonary parenchyma with coagulative necrosis. The mechanism responsible for increased immunoglobulin E production in this syndrome is unknown, as is the manner in which elevated immunoglobulin E levels impair normal immune function.

Aspergillosis

[The hyper IgE syndrome. Job's syndrome].

Since 1972, 150 cases of the hyper-IgE-syndrome have been reported. The clinical manifestations are rather homogeneous with recurrent subcutaneous infections and infections in the respiratory tract, mostly with juvenile onset. Laboratory tests show minor eosinophilia and elevated immunoglobulin E-levels are always seen, partly specific to Staphylococcus aureus. Also varying decreases of polymorphonuclear leucocyte-chemotactic response are seen. There is no specific treatment of the disorder, only treatment of current infections has proved valuable. A case history is presented.

Humans

Use of recombinant human interferon gamma to enhance neutrophil chemotactic responses in Job syndrome of hyperimmunoglobulinemia E and recurrent infections.

Recombinant human interferon gamma enhances neutrophil respiratory burst and bactericidal activity in patients with chronic granulomatous disease. Mononuclear leukocytes of patients with the hyperimmunoglobulinemia E syndrome (Job syndrome) produce low or undetectable levels of this lymphokine. For these reasons we have restudied neutrophil chemotaxis in a group of our patients with the syndrome and determined the effect of recombinant human interferon gamma on the responses. Each of the patients had neutrophil chemotactic responses ranging from 22% to 55% of simultaneous control values (p less than 0.001). After incubation with interferon gamma, a significant improvement in chemotactic responsiveness was observed in the neutrophils of each of the patients (mean 301% of baseline chemotaxis; p less than 0.008). These data suggest the need for a double-blind, placebo-controlled trial of interferon gamma in a larger group of patients with the syndrome of hyperimmunoglobulinemia E and recurrent infections.

Adolescent

[Hyperimmunoglobulinemia E (Job) syndrome].

A patient with hyperimmunoglobulin E (Job's) syndrome is presented. The authors review the clinical and immunological characteristics of the disease and sum up the different explanations for the pathogenesis of the syndrome.

Anti-Bacterial Agents

Atopic dermatitis and impaired neutrophil chemotaxis in Job's syndrome.

A 22-year-old white woman with Job's syndrome was found to have atopic dermatitis and impaired neutrophil chemotaxis in vitro. Major clinical features of Job's syndrome included large, "cold" and recurrent staphylococcal abscesses, and intermittent bacterial and yeast infections. Evidence for atopic disease included infantile eczema progressing to flexural dermatitis, a family history of atopy, positive immediate hypersensitivity skin tests, and hyperimmunoglobulinemia E. Defective erythema responses to histamine, methyl niacinate, and methacholine (Mecholyl) chloride may explain the lack of redness, heat, or pain signalling the development of abscesses (hence the term "cold"). Impaired chemotaxis was probably due to an intrinsic neutrophil defect since patient's serum generated normal amounts of chemotactic factors and did not contain an inhibitor of neutrophil chemotaxis. A delay in neutrophil exudation in vivo may explain the abscess formations and the atopic diathesis may explain the absence of clinical signs of inflammation that have been described in this and other patients with Job's syndrome.

Adult

Ileocecal histoplasmosis mimicking Crohn's disease in a patient with Job's syndrome.

A 16-years-old male with a history of Job's syndrome and a recent diagnosis of Crohn's disease was admitted to the hospital because of abdominal pain, nonbloody diarrhea, weakness, and fever. Due to failure to respond to medical therapy it was decided that an operation was indicated, and resection of the terminal ileum and right colon was performed. Cecum and ileum were inflamed, and pathologic studies revealed the presence of budding yeasts which on special stain were diagnostic of Histoplasma species. Successful management was accomplished with oral ketoconazole.

Adolescent

Job's syndrome: a rare cause of recurrent lung abscess in childhood.

A clinical syndrome characterized by recurrent staphylococcal infection of the skin and respiratory tract from birth was described in 1966 and referred to as Job's syndrome. Marked hyperimmunoglobulinemia E was later found to be associated with this syndrome. This article describes a case of Job's syndrome as a cause of recurrent lung abscess during childhood necessitating lung resection.

Bronchiectasis

Neonatal Job's syndrome featuring a vesicular eruption.

A newborn infant who developed a vesicular eruption, clinically indistinguishable from herpetic lesions, eventually developed the classic features of Job's syndrome. The initial ares of involvement included the hands and feet, then the scalp, face, and suprapubic skin. The clear, tense vesicles varied only slightly in size and appeared as isolated, grouped, or confluent lesions on inflamed skin. Many eventually became umbilicated. The more typical eczematous component appeared over the course of the next several months. Although the child initially had an elevated white blood cell count and eosinophilia, his IgE level did not become dramatically elevated until after 1 year of age. Job's syndrome should be considered as part of the differential diagnosis of a vesicular eruption in the newborn.

Chronic Disease

[Hyperimmunoglobulinemia E, recurring staphylococcal infections and a defect in granulocyte chemotaxis in adults. A variant of Job's syndrome].

Two cases in adults with recurrent staphylococcal infections associated with abnormal granulocytic chemotaxis and hyperimmunoglobulinaemia E (Job's syndrome) are described. The pathophysiological mechanisms seems to consist of an abnormal IgE reaction against staphylococcal antigens causing secondary abnormality of granulocyte function. Abnormal cellular immune function was demonstrated in vitro and in vivo. Corticosteroid administration at first proved effective in both patients. One patient developed Hodgkin's disease of the mixed type in the course of the disease.

Adrenal Cortex Hormones

[Chemotaxis and cellular migration in respiratory pathology].

Numerous types of cells have a capacity for movement in physiological or pathological situations. For example, this is the case for inflammatory cells in the lung, during acute lobar pneumonia, sarcoidosis and idiopathic pulmonary fibrosis. Cellular migration is a general process which rests on the interaction between different chemotactic factors and specific receptors which are present on the target cells. On the other hand the addition of inhibitors can significantly decrease the cellular migration in the presence of chemotactic factors. In respiratory pathology, congenital chemotactic defects are exceptional (and the Chediak-Higashi syndrome and Job syndrome are examples). In contrast during the course of lung cancer, circulating monocytes often show a significant decrease in their chemotactic responsiveness.

Chemotactic Factors

Leukocyte functions.

Knowledge concerning leukocyte functions has increased enormously over the last two decades, largely because techniques have become available to assess them. It has provided insights into many disease entities, as well as on immunologic functioning as a whole. In addition to some classical clinical entities, such as severe combined immunodeficiency disease and chronic granulomatous disease, new entities have been discovered and described, in which subtle disturbances in white blood cell function are sufficient to cause disease. Furthermore, much has been learned about the effect of drugs and disease conditions on leukocyte functions. This review is not intended as a comprehensive description of white blood cell function testing, rather, it is meant to provide a practical guide for clinical laboratories. Therefore only those functional tests are presented which have a direct impact on patient management. These are primarily those functional derangements in white cells which either define a disease entity or without which a diagnosis cannot be made. Granulocytes, monocytes, and lymphocytes will be discussed separately. A short review of their physiology and function is presented to provide a context for the further discussion of their dysfunctions. This discussion of dysfunction and the techniques for laboratory testing thereof includes the evaluation of diagnostic usefulness and implications for patient management. Clinically, the most important granulocyte defects involve chemotaxis, respiratory burst, and intracellular microbial killing. Defects of granulocyte chemotaxis define the lazy leukocyte syndrome, Job's syndrome, and a series of relatively rare idiopathic neutrophil disorders. In addition, chemotaxis is a relatively easily measured sign of actin dysfunction. Defective generation of the respiratory burst with consequent impaired microbial killing defines chronic granulomatous disease and its variants as well as glutathione peroxidase deficiency. The most reliable clinical laboratory testing of granulocyte chemotaxis is performed by using granulocyte migration in response to a chemoattractant, either across a filter or in agarose. For clinical testing of respiratory burst, nitroblue tetrazolium (NBT) reduction is simple, quantitative, and has recently been adapted to automated measurement. Direct measurement of microbial killing is generally not indicated, since clinically important defects are recognized by measurement of respiratory burst generation. Although the monocyte's functions are numerous, they are somewhat less well characterized than those of granulocytes and lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome.

A 29-yr-old woman presenting with granulomatous colitis and a chronic perirectal abscess was found to have localized cryptococcosis associated with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Similarity to previous cases of esophageal cryptococcosis and ileocecal histoplasmosis suggests an association between the hyperimmunoglobulinemia E-recurrent infection syndrome and localized fungal infections of the alimentary tract. To our knowledge, this is the first well-documented case of cryptococcosis confined to the colon and perirectal tissues.

Adult