Biomedical subjects

Karina A Keogh

Publications and source records attributed to Karina A Keogh.

7 recordsLinked to original sources

PubMed2006

Microscopic polyangiitis associated with thymoma, exacerbating after thymectomy.

A variety of autoimmune diseases has been associated with thymoma, and thymectomy does not always induce remission of these disorders. This case report describes a 50-year-old man who presented with migratory polyarthritis and an anterior mediastinal mass that proved to be a thymoma. Five months after thymectomy, the patient presented with worsening polyarthritis, hematuria, and azotemia. Based on elevated titers of antineutrophil cytoplasmic antibodies directed against myeloperoxidase and renal biopsy showing crescentic necrotizing glomerulonephritis, microscopic polyangiitis was diagnosed. After remission-induction therapy with prednisone and cyclophosphamide, articular symptoms and renal manifestations resolved. Microscopic polyangiitis was not associated previously with thymoma, and this case broadens the spectrum of autoimmune disorders seen with this tumor. Progressive disease seen after thymectomy in this patient has potential implications regarding the pathophysiological characteristics of microscopic polyangiitis and management of patients with this clinical association.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2006

Churg-Strauss syndrome.

Churg-Strauss syndrome was originally called "allergic granulomatosis and angiitis," describing the combination of eosinophilic inflammation, extravascular granulomas, and necrotizing vasculitis occurring in patients with severe asthma. It is now classified as a small-vessel vasculitis and, together with Wegener's granulomatosis and microscopic polyangiitis, as one of the vasculitides associated with antineutrophil cytoplasmic autoantibodies (ANCA). Glucocorticoid-sparing agents used in the treatment of asthma, such as leukotriene receptor antagonists, may unmask this particular form of vasculitis as oral glucocorticoids are withdrawn. ANCA occur in 40-75% of patients with active disease and typically react with myeloperoxidase. Patients' symptoms are defined by various degrees of eosinophilic inflammation and necrotizing vasculitis, which may affect any organ. On presentation, Churg-Strauss syndrome needs to be differentiated from other eosinophilic pneumonias, idiopathic hypereosinophilic syndrome, and Wegener's granulomatosis and microscopic polyangiitis. Churg-Strauss syndrome remains a rare disease with a poorly understood pathogenesis. Treatment consists primarily of glucocorticoids. Patients who have ANCA at the time of presentation should be treated according to the treatment principles for ANCA-associated vasculitides. However, the exact role of glucocorticoid-sparing immunosuppressive agents and treatment options for refractory disease remain poorly studied.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2006

Churg-Strauss syndrome: update on clinical, laboratory and therapeutic aspects.

Originally described over fifty years ago as a disorder of asthma, eosinophilic inflammation and small vessel vasculitis, Churg-Strauss syndrome is now defined as one of the ANCA-associated vasculitides. The predilection of disease manifestations for the respiratory tract, preferred affliction of small vessels including capillaries, and the frequent occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) justify this grouping together with Wegener's granulomatosis and microscopic polyangiitis. However, the allergic background in which the vasculitis presents, typically characterized by asthma and prominent peripheral blood and tissue eosinophilia, render it unique among the primary systemic vasculitis syndromes. Despite recent interest in a potential link between leukotriene receptor antagonist use for asthma and the onset of Churg-Strauss syndrome, it remains a rare disease with poorly understood pathogenesis. This review provides an update on the clinical diagnosis of Churg-Strauss syndrome in light of changing disease definitions and classifications, and focuses on evolving therapeutic approaches for this challenging systemic disorder.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2005

Characterization of lymphocyte populations in nonspecific interstitial pneumonia.

STUDY OBJECTIVES: Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. DESIGN: Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. RESULTS: In ten NSIP tissue samples 41.4 +/- 4% of mononuclear cells expressed CD3, 24.7 +/- 1.8% CD4, 19.1 +/- 2% CD8, 27.4 +/- 3.9% CD20, and 14.3 +/- 1.6% had CD68 expression. Mononuclear cells expressed INFgamma 21.9 +/- 1.9% of the time and IL-4 in 3.0 +/- 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFgamma; 4.6 +/- 1.7% and IL-4; 0.6 +/- 0.3%). Significant populations of CD20 positive B-cells were also identified. CONCLUSION: The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP.

Adolescent↗

PubMed2005

Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial.

RATIONALE: Standard therapy for Wegener's granulomatosis is fraught with substantial toxicity and not always effective. B lymphocytes have been implicated in the pathogenesis of Wegener's granulomatosis. Their depletion has been proposed as salvage therapy for refractory disease. Earlier encouraging reports are confounded by concomitant immunosuppressive medications and include only limited available biomarker data. OBJECTIVES: To evaluate the efficacy and safety of rituximab for remission induction in refractory Wegener's granulomatosis. METHODS: A prospective open-label pilot trial was conducted with 10 patients monitored for 1 yr. Included were patients with active severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, ANCA positivity, and resistance to (or intolerance of) cyclophosphamide. The remission induction regimen consisted of oral prednisone (1 mg/kg/d) and four weekly infusions of rituximab (375 mg/m(2)). Prednisone was tapered and discontinued over 5 mo. Failure to achieve remission, a clinical flare in the absence of B lymphocytes, and inability to complete the glucocorticoid taper were considered treatment failures. MAIN RESULTS: Three women and seven men (median age, 57 yr; range, 25-72 yr) were enrolled. All had ANCA reacting with proteinase-3. The median activity score at enrollment was 6 (range, 5-10). All patients tolerated rituximab well, achieved swift B-lymphocyte depletion and complete clinical remission (activity score, 0) by 3 mo, and were tapered off glucocorticoids by 6 mo. Five patients were retreated with rituximab alone for recurring/rising ANCA titers according to protocol. One patient experienced a clinical flare after B lymphocyte reconstitution. CONCLUSION: In this cohort, rituximab was a well-tolerated and effective remission induction agent for severe refractory Wegener's granulomatosis.

Adult↗

PubMed2005

Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: To assess the clinical effects of rituximab therapy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: The study group comprised 11 patients who had active AAV despite receiving maximally tolerated doses of cyclophosphamide or had contraindications for cyclophosphamide use. All patients had ANCA reactive against proteinase 3. The patients received rituximab infusions and glucocorticoids to induce remission. Three patients also received plasma exchange. No other immunosuppressive agents were used. Glucocorticoids were tapered as soon as control of disease activity was achieved. Disease activity was monitored using the Birmingham Vasculitis Activity Score, modified for Wegener's granulomatosis. RESULTS: Rituximab therapy was well tolerated by all patients, and adverse events were rare. Following the rituximab infusions, circulating B lymphocytes became undetectable, and ANCA titers decreased significantly. Remission was achieved in all patients and was maintained while B lymphocytes were absent. CONCLUSION: The ability to achieve stable remissions with rituximab in patients with AAV refractory to conventional therapy suggests that B lymphocyte depletion may be a safe, effective, mechanism-based treatment modality for treatment of patients with these conditions.

Adolescent↗

PubMed2003

Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists.

PURPOSE: To determine the association of antineutrophil cytoplasmic antibodies (ANCA) and leukotriene receptor antagonists with disease activity in a large series of patients with Churg-Strauss syndrome. METHODS: Potential subjects were identified by a computerized search of the Mayo Clinic Rochester database for the years 1990 to 2000. Patients meeting one of three classification schemes for Churg-Strauss syndrome were included. RESULTS: Ninety-one patients met the inclusion criteria. Clinical manifestations were similar to those in previous reports. Mortality was similar to that in the general population. ANCA testing was performed in 74 patients. Seventy-three percent (n = 22) of the 30 patients tested before therapy were ANCA positive, as were 75% (n = 12) of the 16 patients tested during a disease flare. In comparison, 16% (n = 8) of the 49 tested during remission were ANCA positive. Serial measurements indicated a correlation of ANCA levels with disease activity. Central nervous system involvement was the only clinical manifestation that correlated with ANCA status (P = 0.05). Twenty-three patients received leukotriene receptor antagonists, of whom 16 (70%) began treatment before diagnosis and 6 (27%) began during remission. Two of those treated after diagnosis relapsed. In 1 patient the relation between disease and leukotriene receptor antagonist use could not be determined. Use of leukotriene receptor antagonists did not affect the time between onset of asthma and manifestations of vasculitis, and was not correlated with organ manifestations, except sinus disease. CONCLUSION: No one classification scheme identified all patients. Churg-Strauss syndrome has a better prognosis than other ANCA-associated vasculitides. ANCA status correlates with disease activity, whereas a pathogenic role for leukotriene receptor antagonists in the development of Churg-Strauss syndrome was not noted.

Acetates↗