The effects on mucociliary clearance of prednisone associated with bronchial section

OBJECTIVE: Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance. METHODS: A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated. RESULTS: Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05). CONCLUSION: Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.

Evaluation of Adrenal Reserve in Children with Acute Lymphocytic Leukemia Treated with Prednisone or Dexamethasone

Background/Aims: The purpose of this study was to compare adrenal gland reserve in acute lymphocytic leukemia (ALL) patients 8 weeks after treatment with either prednisone (PRED) or dexamethasone (DEX) during the induction phase of therapy. Methods: A double-blind comparative study of patients treated with PRED and DEX was performed. Sixteen patients received PRED (40 mg/m(2)/day) and 13 patients received DEX (6 mg/m(2)/day), both for 28 days. A low-dose adrenocorticotropic hormone test (1.0 mu g/m(2), IV) was performed before and weekly for 8 weeks after abrupt cessation of glucocorticoid therapy. Sixteen children without ALL were used as controls to determine the cutoff peak cortisol level (14.2 mu g/dl). Results: Both groups (PRED and DEX) displayed similar mean peak cortisol levels before treatment and during the 8 weeks of evaluation (p = 0.652). No relationship was observed between the incidence of infection/stress and peak cortisol level within each group, nor was there a difference in the frequency of infection/stress between groups (p = 0.359). Although the patients presented variations in peak cortisol during the study period, no signs or symptoms of adrenal insufficiency were observed. Conclusion: Patients who received PRED or DEX for 4 weeks showed similar adrenal reserves and infection rates for 8 weeks after abruptly stopping glucocorticoid therapy, suggesting that DEX, which is a better antileukemic drug than PRED, has similar adrenal suppression and recovery rates. Copyright (c) 2012 S. Karger AG, Basel

Acne fulminans successfully treated with prednisone and dapsone

Acne fulminans is a rare condition and the most severe form of acne. It involves the sudden onset of febrile and multisystemic symptoms, with poor response to ordinary therapy in patients who previously had mild to moderate acne. It is characterized by hemorrhagic ulcerative crusting lesions on the face, chest and upper back. The authors report a case of acne fulminans that was successfully treated with oral prednisone and dapsone.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.

Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radio therapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0.5 ng/mL were surrogates for PCSM. Findings Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0.5 ng/mL than were those treated with radiotherapy alone (p<0.0001). Presence of candidate surrogates (ie, PSA end and PSA nadir values >0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p >= 0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. Interpretation After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p < .001). Both groups had comparable disease duration (2.6 +/- 3.0 vs. 5.6 +/- 7.0 years, p = .151) and median SLEDAI scores [17.5 (2 to 32) vs. 17.5 (3 to 28), p = 1.000]. At AH onset, a higher frequency of JSLE were already on a high prednisone dose ( > 0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p = .042). The mean drop of hemoglobin was significantly lower in JSLE (2.9 +/- 0.9 vs. 5.5 +/- 2.9 g/dL, p = .006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p > .050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p = .055) and also significant mortality (69% vs. 13%, p = .006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p = .433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients. Lupus (2012) 21, 872-877.

Oral Lesions in Renal Transplant

To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy.

Minimal change disease associated with type 1 and type 2 diabetes mellitus

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents. Arq Bras Endocrinol Metab. 2012;56(5):331-5

Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

Disseminated histoplasmosis in a juvenile lupus erythematosus patient

Introduction: Histoplasmosis is an infection caused by dimorphic fungus, Histoplasma capsulatum, and it has not been reported in juvenile systemic lupus erythematosus (JSLE) patients, particularly progressive disseminated histoplasmosis (PDH) subtype. Case report: We reported herein a 14-year old girl who was diagnosed with JSLE. Six months later, she had abdominal distension and received prednisone, hydroxychloroquine and azathioprine. Computer tomography evidenced hepatosplenomegaly and multiple mesenteric, mediastinal and retroperitoneal enlarged lymph nodes, forming large conglomerates at the mesentery, suggestive of lymphoproliferative disorder. After 10 days, she had acute surgical abdominal, and underwent a laparotomy and intestinal perforation and conglomerates of lymph nodes were observed. The jejunum biopsy showed perforated acute enteritis with hemorrhage and necrosis, and Grocott staining identified Histoplasma sp. and the culture showed a heavy growth of Histoplasma capsulatum. At that moment liposomal amphotericin B (1.0 mg/Kg/day) was introduced. Despite this treatment she died due to septic shock eight days later. Diffuse Histoplasma capsulatum was evidenced at autopsy. Conclusion: We reported a severe opportunistic infection in JSLE patient with adenopathy and multiple intestinal perforations. This study reinforces the importance of early diagnosis and antifungal therapy, especially in patients with these uncommon clinical manifestations.

De Novo Thrombotic Microangiopathy After Kidney Transplantation: Clinical Features, Treatment, and Long-Term Patient and Graft Survival

Introduction. Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. Methods. A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. Results. Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 +/- 15 years, and serum creatinine was 6.1 +/- 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CM) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). Conclusion. De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CM withdrawal and FFP infusions and/or plasmapheresis.

Influenza A H1N1/2009 vaccine in juvenile dermatomyositis: reduced immunogenicity in patients under immunosuppressive therapy

Objectives The aim of the present paper is to assess the influence of demographic, muscle enzymes, JDM scores and treatment on non-adjuvanted influenza A H1N1/2009 vaccine immunogenicity in juvenile dermatomyositis (JDM) patients. Methods Thirty JDM patients and 81 healthy age-matched controls were vaccinated. All participants were evaluated pre- and 21 days post-vaccination and serology for anti-HI NI was performed by haemagglutination inhibition assay. Muscle enzymes, JDM scores and treatment were evaluated before and after vaccination. Adverse events were reported. Results After immunisation seroconversion rates were significantly lower in JDM patients compared to age-matched controls (86.7 vs. 97.5%, p=0.044), whereas seropmtection (p=0.121), geometric mean titres (GMT) (p=0.992) and factor increase (FI) in GMT (p=0.827) were similar in both groups. Clinical and labomtorial evaluations revealed that JDM scores and muscle enzymes remained stable throughout the study (p>0.05). A higher frequency of chronic course was observed in non-seroconverted compared to seroconverted (100% vs. 27%, p=0.012). Regarding treatment, a lower rate of seroconversion was observed in patients under prednisone>20mg/day (50% vs. 4%, p=0.039), and in those treated with a combination of prednisone, methotrexate and cyclosporine (50% vs. 4%, p=0.039). Local and systemic vaccine adverse events were mild and similar in patients and controls (p>0.05). Conclusion This study identified that chronic course and immunosuppressive therapy are the major factors hampering seroconversion was JDM, suggesting that a specific protocol may be required for this subgroup of patients. In spite of that, a single dose of non-adjuvanted influenza A/H1N1 2009 vaccine was generally seroprotective in this disease with no evident deleterious effect in disease itself (ClinicalTrials.gov, no. NCT01151644).

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study

Background: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy. Methods: Twenty-eight patients (51 eyes) with long-standing (>= 6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis. Results: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes). Conclusion: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.

Cochleovestibular nerve involvement in multifocal fibrosclerosis

Objectives: To report a case of multifocal fibrosclerosis with a nine-year follow up, and to discuss this disease's radiological appearance and management. The disease is a rare systemic disorder of unknown cause characterised by fibrous proliferation involving multiple anatomical sites. Case report: A 50-year-old woman presented with histological findings characterised by similar inflammatory processes involving the meninges, pituitary gland, peritoneum, retroperitoneum and orbits, prompting a search for a common pathophysiology. A diagnosis of multifocal fibrosclerosis was postulated. Symptom improvement was noted after treatment with prednisone and azathioprine. Conclusion: This is the first documented case of involvement of the cochleovestibular nerve in a patient with multifocal fibrosclerosis. The rare association between fibrotic diseases and masses showing various clinical patterns should be kept in mind by otolaryngologists, and imaging performed to investigate for multifocal fibrosclerosis. However, diagnosis can only be confirmed with tissue biopsy and histopathological examination.

Subconjunctival Loa loa worm: first case report in Brazil

We report the first case of ocular infestation by Loa loa in Brazil. Loiasis is caused by infestation with Loa loa, a filarial parasite originally found in the rainforests of western and central Africa. It is transmitted by the bite of the fly Chrysops and has been recently described in other places other than Africa, in African immigrants or travellers. Our case is a 33 year-old woman from Cameroon who was living in Sao Paulo, Brazil, for 5 years. She was asymptomatic until one morning she started feeling "something moving" in the left eye. Under topical anesthesia, on the slit lamp, a moving worm was removed from the subconjunctival space, which later was confirmed to be a male Loa loa adult specimen. Blood tests revealed microfilaraemia of 129 mf/mL. The patient was treated with 400 mg oral albendazole for 3 weeks and 60 mg prednisone. This report illustrates an unusual ocular disease, which is extremely rare outside of Africa, but easily diagnosed and treated. Ophthalmologists should be aware of it, in face of an increasingly globalized world.