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Biomedical subjects

K M Leiferman

Publications and source records attributed to K M Leiferman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Nodules, eosinophilia, rheumatism, dermatitis and swelling (NERDS): a novel eosinophilic disorder.

This study presents the clinical and laboratory findings of a novel syndrome associated with eosinophilia. Two young women presented with marked eosinophilia, and large, non-tender compressible articular nodules arising from the tenosynovium of extensor tendons, dermatitis, episodic swelling of the hands and/or feet and pain in adjacent muscles and joints. Tissue specimens were examined by routine haematoxylin and eosin staining, immunofluorescent staining for eosinophil granule major basic protein (MBP) and rhodamine-avidin or tryptase staining for mast cells. Plasma levels of MBP and eosinophil-derived neurotoxin (EDN) were quantitated by immunoassay. The first patient presented in 1967 at the age of 20 and had, in addition to nodules and eosinophilia, dermographism, recurrent episcleritis and axillary urticaria. Biopsy of a nodule showed tenosynovitis with necrotizing granulomas, non-specific vasculitis, eosinophils and eosinophil degranulation as shown by extracellular deposition of eosinophil granule MBP. Her symptoms responded to low-dose, alternate-day prednisone and have remained quiescent over the past 15 yr. The second patient presented in 1990 at the age of 28 with generalized pruritic dermatitis for 15 yr, eosinophilia for 2 yr, subcutaneous nodules and non-limiting pain in several joints. Biopsy of a nodule showed chronic mild tenosynovitis, numerous eosinophils and extracellular deposition of MBP. She remains untreated. Serum IgE values and plasma levels of MBP and EDN were elevated in both patients; mast cells were numerous in their synovial tissue. Based on their clinical courses, these patients reveal the existence of a distinctive, relatively benign eosinophilic disorder with good long-term prognosis.

Adult↗
PubMed1993

Paraneoplastic pemphigus: a subset of patients with pemphigus and neoplasia.

We reviewed the clinical, histologic, and immunofluorescence features of 20 patients with pemphigus and neoplasia and compared them with a control group of 17 patients with pemphigus without neoplasia. Patients with neoplasia were divided according to clinical, histologic, and immunofluorescence findings into those with paraneoplastic pemphigus syndrome (12 patients) and those with classic pemphigus vulgaris or pemphigus foliaceus with neoplasia (8 patients). The histologic findings in patients with paraneoplastic pemphigus included acantholysis, interface dermatitis, spongiosis, and satellite keratinocyte necrosis. Histologic findings in the 8 patients with classic pemphigus and neoplasia included acantholysis and spongiosis. Direct immunofluorescence in both paraneoplastic pemphigus and pemphigus with neoplasia showed IgG staining of cell-surface proteins (intercellular substance) and deposition of immunoglobulin at the basement membrane zone. Indirect immunofluorescence with rat bladder substrate was used to differentiate paraneoplastic pemphigus from classic pemphigus. Circulating IgG anti-cell-surface protein antibodies were detected in 4 patients with paraneoplastic pemphigus syndrome; they were absent in 2 patients with pemphigus and neoplasia. Immunoprecipitation of sera from the 4 patients with epithelial staining showed the complex of bands identified in studies of paraneoplastic pemphigus syndrome. We conclude that paraneoplastic pemphigus syndrome has distinct clinical, histologic, and immunologic features that differentiate it from classic pemphigus with underlying neoplasia.

Aged↗
PubMed1993

The biology of the eosinophilic leukocyte.

The eosinophil is characterized by specific cytoplasmic granules that contain a series of cationic toxins able to kill many targets, including helminths, protozoa, bacteria, and other cells. In bronchial asthma, considerable evidence exists that the eosinophil releases granule proteins, especially the major basic protein (MBP), which in turn mediate tissue abnormalities. Among eosinophil-activating factors, IL-5 has been associated with helminth infection and hypersensitivity diseases and would appear to be an attractive target for pharmacological intervention.

Biology↗
PubMed1993

Mast cells, neutrophils, and eosinophils in prurigo nodularis.

BACKGROUND AND DESIGN: Prurigo nodularis is a disease of unknown cause. To characterize the involvement of mast cells, neutrophils, and eosinophils in lesional tissue, we analyzed seven skin biopsy specimens by an indirect immunofluorescence technique for localization of mast cell tryptase, neutrophil elastase, and eosinophil granule major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin. RESULTS: Mast cells were detected in all of the specimens, with prominent numbers of mast cells in three specimens; there was minimal or no extracellular deposition of tryptase in any of the tissues. Neutrophil infiltration was observed in all specimens, but few cells were observed in four; extracellular elastase was minimal or absent in all but one specimen in which prominent dermal elastase deposition was found. Scanty eosinophil infiltration was present in all specimens; however, extracellular deposition of the eosinophil granule proteins including major basic protein, eosinophil-derived neurotoxin, and eosinophil cationic protein was present in all but one specimen and striking deposition of at least one eosinophil granule protein was present in six of the seven specimens. CONCLUSIONS: These studies suggest that mast cell numbers are increased in prurigo nodularis and that eosinophil degranulation as evidenced by striking extracellular deposition of granule proteins is prominent in lesions. In contrast, extracellular deposition of mast cell and neutrophil proteins is absent. The distinctive proteins of the eosinophil granule have potent effects on tissues; the toxicity of these proteins and their deposition in lesional tissue suggest a pathogenic role for the eosinophil in prurigo nodularis.

Adult↗
PubMed1992

Elevated serum levels of interleukin-5 in patients with the syndrome of episodic angioedema and eosinophilia.

The syndrome of episodic angioedema and eosinophilia is characterized by cyclic edema, marked peripheral blood eosinophilia, and eosinophil degranulation in the dermis. Using a sensitive immunoenzymetric method, we measured serum interleukin (IL)-5 levels in four patients with this syndrome. We also determined the percentage of activated T cells in the peripheral blood of a new patient before and during an attack. In the patient presented, IL-5 levels peaked several days before maximal eosinophilia and then declined. This patient's lymphocytes showed an increased percentage, 28% (normal 2% to 3%), of activated T cells staining for both CD3 and HLA-DR 10 days before maximal eosinophilia, but no increase at the time of peak eosinophilia. In serum from three previously reported cases, elevated serum IL-5 levels were found during attacks. After glucocorticoid administration, IL-5 levels became undetectable in three of the four patients. Production of IL-5 is likely an important determinant of the pathophysiology of this syndrome.

Adult↗
PubMed1992

Pyoderma gangrenosum-like ulcer in a patient with large granular lymphocytic leukemia.

Large granular lymphocytic leukemia refers to a clonal expansion of lymphocytes that have abundant cytoplasm and azurophilic granules. The disease is characterized clinically by chronic neutropenia and it may be associated with recurrent pyogenic infections. Except for these infections, cutaneous manifestations of this disease have not been well characterized. We describe a patient with large granular lymphocytic leukemia, which was confirmed by molecular genetics studies, who had a pyoderma gangrenosum-like ulcer on his leg. Results of an evaluation of the histologic characteristics and the leukocytic immunophenotype of a skin biopsy specimen from the ulcer demonstrated large granular lymphocytes within the blood vessels. Cutaneous ulceration may be a manifestation of large granular lymphocytic leukemia, and this disease should be considered when diagnosing patients with otherwise unexplained pyoderma gangrenosum-like ulcers of the skin.

Complement C3↗
PubMed1992

Adhesion molecule expression in polymorphic light eruption.

Endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are cytokine-regulated cell-surface leukocyte adhesion molecules. We have investigated the in vivo kinetics and pattern of expression of these adhesion molecules in relation to tissue accumulation of leukocytes in the photodermatosis, polymorphic light eruption (PMLE), which is characterized by dense perivascular leukocytic infiltration. Immunohistology was performed on biopsies taken at varying time points from PMLE lesions induced in 11 subjects by suberythemal solar simulated irradiation. Vascular endothelial ELAM-1 expression was first observed at 5 h, maximal at 24 to 72 h, and remained elevated at 6 d. VCAM-1, minimally expressed in control skin, was induced above background levels on endothelium and some perivascular cells after 24 h and maintained at 6 d. Endothelial cell ICAM-1 expression was increased above control levels at 72 h and 6 d. Keratinocyte ICAM-1 expression, most marked overlying areas of dermal leukocytic infiltration, began at 5 h and was strong at 72 h and 6 d. In addition to lymphocytes, significant numbers of neutrophils but not eosinophils were detected in the dermal leukocytic infiltrate that appeared at 5 h and persisted at 6 d. The pattern of adhesion molecule expression that we have observed is similar to that seen in normal skin during a delayed hypersensitivity reaction. These observations support an immunologic basis for PMLE.

Biopsy↗
PubMed1992

Cutaneous reactions to granulocyte-monocyte colony-stimulating factor.

BACKGROUND AND DESIGN: Granulocyte-monocyte colony-stimulating factor (GMCSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of neutrophils, eosinophils, and monocytes. We reviewed the cutaneous reactions that developed in 26 patients who received GMCSF as part of a chemotherapeutic protocol. RESULTS: Fourteen patients developed immediate localized angioedematous reactions at the subcutaneous GMCSF injection site, and 21 developed generalized cutaneous reactions. Four biopsy specimens were obtained from three patients who had generalized erythrodermic reactions. All specimens showed perivascular and periadnexal lymphocytic inflammation in the dermis, and two showed perivascular and periadnexal eosinophilia. Staining for eosinophil granule major basic protein showed infiltration by eosinophils and extracellular deposition of major basic protein in three specimens from two patients with eosinophilia. Extracellular deposition of neutrophil elastase and mast cell tryptase was minimal. CONCLUSIONS: Cutaneous reactions are prominently associated with GMCSF administration. Eosinophils, known to release toxic products after being activated, may have a role in these skin reactions through stimulation by GMCSF.

Adult↗
PubMed1991

Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer.

Peripheral eosinophilia is almost invariably observed during the course of interleukin-2 (IL-2) therapy and is frequently accompanied by the development of a capillary leak syndrome characterized by edema, weight gain, and oliguria. We studied five patients with advanced malignancy treated with IL-2. Eosinophilia was not present initially but developed in all patients late in the course of therapy, with counts ranging from 2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship between the infusion of IL-2 and the appearance of elevated plasma concentrations of IL-5, a growth factor for eosinophils. Granulocyte-macrophage colony-stimulating factor was not detectable in plasma. IL-4 and gamma-interferon plasma levels were variably elevated. Plasma concentrations of major basic protein, a toxic eosinophil granule protein, began increasing before eosinophil counts increased. By the time of the third IL-2 infusion, high concentrations of major basic protein were present in all five patients (up to 5,600 ng/mL) and skin biopsies showed major basic protein deposition in the dermis. Four patients developed significant capillary leak syndrome and all of these patients showed markedly elevated major basic protein levels. The lowest peak plasma concentration of major basic protein (1,751 ng/mL) was observed in the one patient who did not develop edema and weight gain. These results suggest that IL-2 induces IL-5 leading to marked peripheral eosinophilia and extravascular eosinophil degranulation. The release of toxic eosinophil products at extravascular sites and in the circulation may contribute to the pathogenesis of the capillary leak syndrome complicating IL-2 therapy.

Aged↗
PubMed1991

Eosinophil and neutrophil degranulation in ophthalmic lesions of Wegener's granulomatosis.

Although eosinophils and neutrophils have been identified in orbital and corneoscleral tissues in some patients with Wegener's granulomatosis, their role in the pathogenesis of the disorder is not completely understood. Nine specimens from six patients with Wegener's granulomatosis and autopsy controls from patients without ophthalmic disease were evaluated with indirect immunofluorescence for eosinophil granule major basic protein and neutrophil elastase. Extracellular deposition of both major basic protein and elastase was identified in orbital tissues from all the patients with Wegener's granulomatosis. Two of the specimens were from enucleated eyes with corneoscleral disease; extracellular deposition of eosinophil major basic protein was identified in one eye, and extracellular neutrophil elastase was deposited in both eyes in lesional areas. None of the control tissues showed major basic protein or elastase deposition. These findings suggest that both eosinophils and neutrophils participate in the pathogenesis of the orbital and corneoscleral manifestations of Wegener's granulomatosis.

Blood Proteins↗
PubMed1991

A current perspective on the role of eosinophils in dermatologic diseases.

Eosinophils are frequently observed in cutaneous inflammation, but little is known of their significance in the pathophysiology of cutaneous disease. Recent studies of the structure, content, and activities of the eosinophil have shown that it has potent toxic proteins with the potential to mediate tissue damage. Furthermore, immunofluorescent localization of eosinophil granule proteins has shown that eosinophils disrupt in tissue and deposit toxic granule proteins. The deposition of granule proteins in several diseases is vastly out proportion to the number of identifiable cells and indicates that eosinophil involvement in cutaneous disease cannot be judged by the number of intact eosinophils in the tissue. Specifically, deposition of eosinophil granule proteins outside of eosinophils has been observed in eczematous lichenified disorders with elevated serum levels of immunoglobulin E, in urticarial and angioedematous disorders, and in bullous diseases. The structural, compositional, and functional characteristics of eosinophils are reviewed, and evidence of eosinophil degranulation in cutaneous diseases is presented. Mechanisms whereby eosinophil degranulation may mediate pathophysiologic effects are also discussed.

Asthma↗
PubMed1991

Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor.

To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis.

Adolescent↗
PubMed1991

Extracellular deposition of eosinophil major basic protein in orbital histiocytosis X.

Although eosinophils are prominent in orbital lesions of patients with histiocytosis X (Langerhans' cell histiocytosis), little is known of their pathogenic significance in the disease. To determine whether eosinophils degranulate and deposit toxic proteins in orbital histiocytosis X, the authors examined lesions by indirect immunofluorescence for localization of the core granule protein (major basic protein) outside of eosinophils. Four patients with histiocytosis X were studied: three with eosinophilic granuloma and one with Hand-Schüller-Christian disease. Tissue eosinophilia was prominent in all specimens; striking extracellular deposition of eosinophil major basic protein was noted in three patients, and focal deposition was present in the fourth patient. Orbital specimens obtained at autopsy from patients without orbital disease were studied as control specimens; no tissue eosinophilia or deposition of eosinophil major basic protein was observed. These findings indicate that eosinophils likely degranulate in lesions of orbital histiocytosis X and may participate in the pathogenesis of the disease.

Adolescent↗
PubMed1991

Localization of eosinophil granule major basic protein in incontinentia pigmenti.

We report a case of incontinentia pigmenti and demonstrate the deposition and localization of eosinophil major basic protein (MBP) in the vesicular stage of this neurocutaneous syndrome. The initial stage of incontinentia pigmenti is histologically characterized by intraepidermal vesicles associated with eosinophilic spongiotic dermatitis. Pathologic examination of a lesional tissue specimen from our patient demonstrated epidermal necrosis, spongiosis, and vesicle formation. Indirect immunofluorescence with affinity-chromatography purified antibody to human eosinophil granule MBP demonstrated many intact eosinophils within vesicles and scattered throughout the epidermis and dermis, and extracellular deposition of granular MBP in the tissue. The characteristic finding of extensive tissue eosinophilia in incontinentia pigmenti, as well as the new finding of extracellular deposition of an eosinophil granule protein in lesional tissue, suggests the involvement of eosinophils in the pathogenesis of the disease.

Blood Proteins↗
PubMed1991

Neonatal lupus erythematosus syndrome.

Three cases of neonatal lupus erythematosus (NLE) syndrome are described. The key diagnostic sign is the erythematous and annular clinical appearance of lesions. The histopathologic findings may be subtle in NLE syndrome compared with discoid or subacute cutaneous lupus erythematosus. Direct immunofluorescence testing may be useful in supplementing the histopathologic evaluation. Detection of immunoglobulins, complement, or both at the basement membrane zone in lesional skin by immunofluorescence occurs in approximately half of cases; a negative study does not preclude the diagnosis of NLE syndrome. Clinical and serologic evaluation of both the infant and the mother are important in establishing a diagnosis of NLE syndrome, particularly when histopathologic findings are subtle.

Fluorescent Antibody Technique↗
PubMed1990

Sequestration of eosinophil major basic protein in human mast cells.

Previous studies showed that lung and skin mast cells do not contain eosinophil granule major basic protein (MBP). However, MBP has been localized by immunofluorescence to mast cells from a recently established human mast cell line. Analysis of MBP in human mast cell-1 cell lysates by radioimmunoassay showed immunochemical similarity to eosinophil MBP as judged by comparison of dose-response regression lines. Based on these findings and other new information about mast cell heterogeneity, we tested whether mast cells contain MBP. Mast cells were preserved in Carnoy's fixative and were identified by staining with rhodamine-conjugated avidin or for chloroacetate esterase or aminocaproate esterase activity. MBP was localized by immunofluorescence to mast cells in 6 of 7 nasal polyps, 4 of 4 ileal tissue specimens, and 12 of 14 cutaneous mastocytosis specimens. Furthermore, by immunoelectron microscopy MBP was localized to mast cell granules in cutaneous mastocytosis lesions. In contrast, normal skin mast cells preserved in Carnoy's fixative did not contain MBP. After injection of MBP into normal skin and fixation in Carnoy's fluid, mast cells became MBP-positive within 3 minutes, suggesting that endocytosis of MBP by mast cells had occurred. These results suggest that human mast cells in several tissues may sequester toxic eosinophil proteins by endocytosis.

Blood Proteins↗
PubMed1990

Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction.

Intradermal injection of allergens in sensitive subjects produces an IgE-dependent prolonged inflammatory reaction, the late phase reaction (LPR). Histologically, eosinophils are present in the LPR but are not as numerous as neutrophils or mononuclear cells. We determined whether extracellular deposition of eosinophil and neutrophil granule proteins occurs in the LPR by immunofluorescent localization of eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase. Before intradermal challenge, eosinophils and neutrophils were present only in blood vessels, and MBP, EDN, and elastase were localized to cells. At 15 minutes, small amounts of MBP, EDN and elastase were found outside of cells in focal areas. By 1 to 3 hours, MBP, EDN and elastase were extensively deposited throughout the dermis in a granular and diffuse manner; these deposits persisted up to 56 hours. Both actively and passively sensitized subjects showed similar MBP and elastase deposition. Skin sites passively sensitized by sera depleted of IgE showed essentially no MBP or elastase deposition. Electron microscopy showed degenerating eosinophils and free eosinophil granules in the dermis. Mast cell numbers diminished during the LPR when extracellular eosinophil and neutrophil granule protein deposition was maximal. These results demonstrate that striking dermal eosinophil and neutrophil granule protein deposits are prominent features of the cutaneous LPR, are IgE-dependent and precede the maximal clinical expression of the LPR. The possible significance of these findings in the pathophysiology of the LPR is discussed.

Administration, Cutaneous↗