Biomedical subjects

Cynthia M Magro

Publications and source records attributed to Cynthia M Magro.

65 records · Page 4Linked to original sources

PubMed2003

Progress in the understanding of the pathology and pathogenesis of cutaneous drug eruptions : implications for management.

Cutaneous drug eruptions are among the most common adverse reactions to drug therapy. The etiology may reflect immunologic or nonimmunologic mechanisms, the former encompassing all of the classic Gell and Combs immune mechanisms. Cumulative and synergistic effects of drugs include those interactions of pharmacokinetic and pharmacodynamic factors reflecting the alteration by one drug of the effective serum concentration of another and the functions of drugs and their metabolites that interact to evoke cutaneous and systemic adverse reactions. Recent observations include the role of concurrent infection with lymphotropic viruses and drug effects that, through the enhancement of lymphoid blast transformation and/or lymphocyte survival and the contribution of intercurrent systemic connective tissue disease syndromes, promote enhanced lymphocyte longevity and the acquisition of progressively broadening autoantibody specificities. The latter are particularly opposite to drug-induced lupus erythematosus and to drug reactions in the setting of HIV infection. Specific common types of cutaneous drug eruptions will be discussed in this review. Successful management of cutaneous drug eruptions relies upon the prompt discontinuation of the causative medication; most drug eruptions have a good prognosis after this is accomplished. Oral or topical corticosteroids can be administered to aid in the resolution of some types of eruptions. Antihistamines or anti-inflammatory agents may also be administered for some eruptions.

Drug Eruptions↗

PubMed2002

Humorally mediated posttransplantation septal capillary injury syndrome as a common form of pulmonary allograft rejection: a hypothesis.

BACKGROUND: Cellular immunity is the reputed mechanism of lung allograft failure. Humoral immunity is not a commonly recognized pathway. MATERIAL AND METHODS: We describe 22 patients who developed a posttransplantation septal capillary injury syndrome in the absence of panel-reactive antibodies. Factor VIII levels served as an index of microvascular injury. Routine light microscopic studies were performed in a total of 73 biopsies; 54 biopsy specimens were analyzed for deposition of C1q, C4d, C5b-9, and immunoglobulin (IgG, IgM, and IgA). Indirect immunofluorescent testing to assess for antiendothelial cell antibodies was performed using patient serum and human pulmonary microvascular endothelial cell cultures as substrate. Control samples were based on patients who were clinically well at the time of the biopsy. RESULTS: All presented with a deterioration in respiratory function. All patients had elevated factor VIII levels; the levels were significantly greater compared with pretransplantation baseline values (P =<0.03). The biopsy specimens were remarkable for septal capillary necrosis with significant septal capillary deposition of C1q, C3, C4d, and/or C5b-9 along with immunoglobulin, including IgG, with variable endothelial cell localization. The degree of septal capillary necrosis was significantly less in posttransplantation patients who were clinically doing well ( P<0.0001) as was the degree of C1q, C3, C4d, and C5b-9 ( P<0.05). Indirect antiendothelial cell antibody studies were positive in most patients. Treatment interventions included plasmapheresis, resulting in functional improvement: the postpheresis biopsy specimens showed a reduction in both the degree of septal capillary injury (P <0.0003) and the amount of C1q, C3, C4d, and C5b-9 deposition (P <0.05). CONCLUSIONS: Septal capillary injury accompanied by direct and indirect immunofluorescent evidence of humoral immunity is a frequent finding on transbronchial biopsies. The findings suggest that humoral immunity to endothelial-based alloantigen is a common occurrence in lung grafts and may be a critical factor in chronic graft dysfunction.

Adult↗

PubMed2002

The precursors of malignant melanoma.

The precursors to melanoma are generally considered to be related to nevi of different types. Here we emphasize the dysplastic nevus, the congenital nevus, and lentigo maligna as specific lesions. The dysplastic nevus is discussed not only as a formal precursor but also as a marker of cutaneous melanoma. The clinical and histologic characteristics are outlined, as well as evidence of progression in dysplastic nevi. The congenital nevus is briefly reviewed and emphasis is placed upon clues to malignant degeneration. The concept of lentigo maligna as a precursor as distinct from an in situ phase is detailed.

Cell Transformation, Neoplastic↗

PubMed2002

Primary anti-phospholipid antibody syndrome caused by isolated anti-phosphatidylethanolamine antibodies presenting as cryptogenic fibrosing alveolitis with recurrent pulmonary hemorrhage after single-lung transplantation.

A 28-year-old man underwent a single-lung transplantation for rapidly progressive usual interstitial pneumonitis. Following transplantation, primary anti-phospholipid antibody syndrome was diagnosed after a thromboembolic event and continued dyspnea. Review of his native lung and allograft tissue showed diffuse hemorrhage secondary to capillary injury, probably reflecting anti-phospholipid antibody effects on endothelia.

Adult↗

PubMed2002

Immunoglobulin A-associated lymphocytic vasculopathy: a clinicopathologic study of eight patients.

INTRODUCTION: Cutaneous IgA-associated vasculitis can be a clue to Henoch-Schönlein purpura (HSP), which typically comprises renal and gastrointestinal tract disease and arthritis, whereby prominent and predominant IgA deposits within the cutaneous vasculature provoke a pustular leukocytoclastic vasculitis. DESIGN: We describe eight patients with a novel expression of a cutaneous IgA vascular injury syndrome, namely a lymphoid vasculopathy which clinically and light microscopically resembled a pigmentary purpura (PP) in six, and correlate direct immunofluorescence (DIF) and clinical features to light microscopy. RESULTS: Among associated diseases were prior viral infection, an HSP symptom complex, an undifferentiated connective tissue disease syndrome, lupus erythematosus profundus (LEP), Degos' disease and Berger's disease. Skin lesions comprised non-palpable petechial lesions involving lower extremities in all cases and also the upper extremities in two. A superficial perivascular lymphocytic infiltrate unaccompanied by vascular fibrin deposits was associated with prominent erythrocyte extravasation including into the epidermis. Mural and extravascular fibrin deposition was seen in one biopsy from a PP-like lesion and mural fibrinoid necrosis was seen in the cases of LEP and Degos' disease; in biopsies from these three cases, the presence of fibrin deposition warranted use of the appellation 'lymphocytic vasculitis'. In all patients, DIF showed prominent and predominant IgA deposits. CONCLUSIONS: A non-necrotizing lymphocytic purpuric vascular reaction is one manifestation of vascular IgA deposition in the skin. A subpopulation of human lymphocytes bear surface Fc receptor and/or C3 receptors ('complement receptor lymphocytes') which can bind circulating immune complexes (ICs) or C3 generated via activation of the alternative complement cascade. Thus, circulating ICs are a potential pathogenic basis of this eruption, the histologic differential diagnosis of which is idiopathic PP and PP of drug or viral etiology.

Adolescent↗

PubMed2002

Parvovirus B19 associated adult Henoch Schönlein purpura.

BACKGROUND: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated. METHODS: Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies. CASE PRESENTATION: A 64-year-old-female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA-associated mesangioproliferative glomerulonephritis and IgA-associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor alpha DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells. CONCLUSION: This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19-associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti-TNFalpha therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.

DNA, Viral↗

PubMed2002

The eosinophilic pneumonias.

Acute and chronic eosinophilic pneumonia can be distinguished by their clinical, laboratory, and radiographic features. Patients with both acute and chronic eosinophilic pneumonia present with cough, dyspnea, and fever. Patients with chronic eosinophilic pneumonia present subacutely over weeks to months but patients with acute eosinophilic pneumonia present within 5 days of symptom onset. Chest radiographs in chronic eosinophilic pneumonia show peripheral alveolar infiltrates. In contrast, radiographs in acute eosinophilic pneumonia show mixed interstitial and alveolar infiltrates, Kerley B lines, and pleural effusions. Both disorders are characterized by high percentages of bronchoalveolar lavage eosinophils, but high numbers of blood eosinophils accompanies only chronic eosinophilic pneumonia. The diagnosis of both disorders can usually be made based on clinical and radiographic findings; however, lung biopsy is occasionally necessary to distinguish the eosinophilic pneumonias from other eosinophilic lung diseases. In both conditions, patients will respond rapidly and completely to corticosteroids but patients with chronic eosinophilic pneumonia usually relapse if less than 6 months of treatment is given, whereas patients with acute eosinophilic pneumonia do not relapse after a brief course of treatment.

Journal Article↗

PubMed2002

Parvoviral infection of endothelial cells and its possible role in vasculitis and autoimmune diseases.

OBJECTIVE: To analyze a series of biopsies from 16 patients who, on the basis of clinical and dermatopathologic findings, had a spectrum of connective tissue diseases (CTD), autoinflammatory or CTD-like syndromes for parvoviral DNA, RNA, and protein. METHODS: Most of the patients were initially screened for parvoviral-related IgG and IgM antibodies. Parvoviral DNA was analyzed by solution phase polymerase chain reaction (PCR). In situ localization of viral VP1 RNA was accomplished by in situ reverse transcriptase (RT) PCR; viral protein (VP2) was detected by immunohistochemistry and these results correlated with the histologic findings. (J Rheumatol 2002;29:xxxx) RESULTS: Of 11 people tested, 10 had either IgG or IgM specific antibodies against parvovirus. Common histologic features of the 16 cases included an interface dermatitis, interstitial histiocytic infiltration with variable collagen necrobiosis, a mononuclear cell dominant vasculitis, and interstitial neutrophilia. Detection of parvoviral RNA by in situ RT-PCR in 14 of 16 cases corroborated solution phase PCR data and demonstrated that the endothelial cells and surrounding mononuclear cells were the viral target. Viral protein as revealed by immunohistochemisty showed an equivalent histologic distribution. Anti-tumor necrosis factor-alpha (TNF-alpha) therapy (etanercept) yielded dramatic improvement after worsening of symptoms with traditional immunosuppressive therapy in the 3 patients in whom this drug was administered; TNF-alpha mRNA was detected by in situ RT-PCR in the area of parvoviral infected cells. CONCLUSION: Parvoviral induced endothelialitis may be responsible for cases of "idiopathic" CTD.

Adolescent↗

PubMed2002

Henoch-Schonlein purpura secondary to subacute bacterial endocarditis.

Henoch-Schönlein purpura (HSP), a systemic, small-vessel vasculitic syndrome, is characterized by a nonthrombocytopenic purpuric rash, arthralgia, abdominal pain, and nephritis. These signs and symptoms may occur in any order, and not all are necessary for the diagnosis. Although most common in 4- to 7-year-olds, HSP is well documented in adults and is often preceded by a history of mucosal-based infections, especially of the upper respiratory tract. We report a case of HSP that occurred coincident with the onset of subacute bacterial endocarditis (SBE) in an otherwise healtny 41-year-old white woman. The patient presented with a purpuric rash and arthralgia and was found to have left-sided streptococcal SBE. She subsequently developed abdominal pain and immune complex glomerulonephritis. The bacterial endocarditis was treated with antibiotics and mitral valve replacement, followed by a spontaneous resolution of the associated signs and symptoms of HSP.

Adult↗

PubMedDate not supplied

Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment.

Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis, and thrombosis. This syndrome occurs predominantly in individuals with renal failure and results in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscle. The syndrome causes significant morbidity in the form of infection, organ failure, and pain. Mortality rates are high. In individuals with renal failure, risk factors for the development of calciphylaxis include female sex, Caucasian race, obesity, and diabetes mellitus. Many cases occur within the first year of dialysis treatment. Several recent reports demonstrate that prolonged hyperphosphatemia and/or elevated calcium x phosphorus products are associated with the syndrome. Protein malnutrition increases the likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or protein S deficiency. Recent advances in diagnostic tools and therapeutic strategies have helped in the management of patients with calciphylaxis.

Calciphylaxis↗

PubMedDate not supplied

Ultrastructure as a diagnostic adjunct in the evaluation of lung allograft biopsies.

Humoral immunity contributes significantly to lung graft dysfunction. Recognizing a role of ultrastructural studies in the evaluation and diagnosis of chronic humoral allograft rejection in the kidney, the authors sought to explore its utility as a diagnostic adjunct in lung allograft biopsies. Ultrastructural studies were conducted on 44 biopsies from 26 lung transplant recipients. Endothelial cell activation and necrosis were seen in the setting of acute humoral allograft rejection. Septal chronic vasculopathic changes of thickening and lamellation of the basement membrane zone (BMZ) and BMZ collagen deposition were correlated with greater numbers of humoral allograft rejection episodes and with the development of chronic graft dysfunction/bronchiolitis obliterans syndrome. There was a positive correlation between the extent of septal fibrosis and certain chronic vasculopathic changes, namely collagen deposition in the BMZ and BMZ wrinkling. Patients with chronic graft dysfunction and multiple rejection episodes manifested low diffusion capacities (less than 50% predicted). The results indicate that ultrastructural analysis is useful in identification of septal fibrosis and chronic vasculopathy of the septal microvasculature, correlating with chronic graft dysfunction, encompassing not only fibrotic sequelae of the bronchial wall but also irreversible terminal lung parenchymal changes, the latter associated with repeated episodes of humoral rejection.

Adult↗