High-dose Systemic Corticosteroids Research Articles

Risk of Future Type 2 Diabetes Mellitus in Patients Developing Steroid-Induced Hyperglycemia During Hospitalization for Chronic Obstructive Pulmonary Disease Exacerbation.

We evaluated the future risk of developing impaired glucose tolerance and type 2 diabetes mellitus (T2DM) in patient without T2DM who develop hyperglycemia with short-term systemic glucocorticoid therapy during hospitalization. Retrospective analysis was performed on charts of non-diabetic patients admitted with COPD exacerbation and treated with a course of high dose systemic corticosteroid during hospitalization. Patients with BMI over 40kg/m2, endocrinopathy and on medications that could impair glucose tolerance were excluded. Patient data were collected for 1year after initial hospitalization. Diagnosis of T2DM or IGT was based on the ADA criteria. 311 charts were reviewed, of which 64 patients met our inclusion criteria. Depending on the blood glucose readings during hospitalization, the patients were categorized into two groups: hyperglycemic (> 140mg/dL; n = 42) and normoglycemic (≤ 140mg/dL; n = 22). In the hyperglycemic group, 17/42 (40%) patients developed prediabetes and 5/42 (12%) developed T2DM on follow-up. Interestingly, none of the patients developed IGT or T2DM in the normoglycemic group. Both the groups were well matched in terms of family history of DM, history of hypertension, hyperlipidemia, BMI > 25kg/m2, weight change, tobacco and alcohol use, corticosteroid therapy duration, and cumulative steroid dose. After adjusting for all these risk factors, on logistic regression analysis, hyperglycemic patients had 37 times higher chance of developing IGT, compared to normoglycemic patients (p = 0.003). Our study suggests that patients without T2DM with acute exacerbation of COPD who develop steroid-induced hyperglycemia in response to systemic corticosteroid treatment have an increased risk for developing future IGT or T2DM. Bigger studies are needed to support our findings since results drawn from our study have the limitations of smaller sample size (wider confidence interval) in a single center.

Pyoderma gangrenosum complicating a permanent pacemaker implantation: a case report and literature review.

BackgroundPocket complications are common after cardiac implantable electronic device implantation. We report a rare case of pyoderma gangrenosum (PG) complicating a permanent pacemaker implantation, and the first literature review of 10 published cases.Case summaryFive days after pacemaker implantation for heart failure and 2:1 atrioventricular block, a 93-year-old man had pain in the scar and bleeding on contact. Two days later, he had fever, inflammatory syndrome, and a necrotic 7-cm wound. The pacemaker was removed and he was started on antibiotics. Due to a lack of bacterial growth in samples, PG (a rare aseptic, destructive inflammatory cutaneous condition) was suspected, and histology was compatible with this diagnosis. High-dose corticosteroids vastly improved his condition within 1 week, and after 2 months of decreasing-dose corticosteroid therapy, complete healing and normalization of the inflammatory syndrome were observed.DiscussionPyoderma gangrenosum should be considered if there is aseptic skin ulceration that is not controlled by antibiotic treatment. The first-line treatment for PG is high-dose systemic corticosteroids.

Toxic epidermal necrolysis occurring with immune checkpoint inhibitors

Nivolumab and ipilimumab are immune checkpoint inhibitors (ICIs) used in the management of advanced malignancies including malignant melanoma. Although several cutaneous adverse events have been reported with these immunotherapy agents, toxic epidermal necrolysis (TEN) secondary to ICIs is rare. We report a 67-year-old man with TEN occurring during nivolumab and ipilimumab co-therapy and review published cases to highlight the challenges in recognizing and managing these patients. ICI-induced TEN can present atypically with delayed onset in comorbid, immunosuppressed patients with an associated high mortality rate. Prompt recognition and drug withdrawal are essential to improve outcomes. High dose systemic corticosteroid has also been recommended for the management of ICI-induced TEN, unlike other drug-induced TEN for which optimal immunomodulatory treatment is still debated.

A case of diacerein-induced DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome with thromboembolic complications

Diacerein is a safe drug for osteoarthritis due to its inhibitory effect on proinflammatory cytokines. Its common side effects, such as diarrhea, abdominal pain and skin rash, are relatively mild. There have been a few cases of drug reactions with eosinophilia and sys temic symptoms (DRESS) syndrome accompanied by thromboembolic complications. We report the first case of diacerein-induced DRESS syndrome with thromboembolic complications. A 64-year-old man developed fever, skin rash, increase in liver enzymes, eo sinophilia, deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) after taking diacerein. DVT and PTE were improved after anticoagulation therapy; however, fever, skin rash, eosinophilia and increase in liver enzymes were aggravated. A high-dose systemic corticosteroid (methylprednisolone 1 mg/kg/day) was administered, after which his clinical conditions improved. (Allergy Asthma Respir Dis 2020;8:150-154)

Atypical Stevens–Johnson syndrome caused by pembrolizumab in the treatment of metastatic melanoma – Are corticosteroids a safe treatment option?

Pembrolizumab is a humanized monoclonal antibody that targets programmed cell death receptor-1. Stevens–Johnson syndrome (SJS) secondary to pembrolizumab has rarely been described in the treatment of malignant melanoma (MM). A 62-year-old woman developed a widespread bullous eruption following administration of her third dose of pembrolizumab for the treatment of MM. A skin biopsy showed sub-epidermal bulla formation with lymphocytic infiltrate and a necrotic roof, consistent with a SJS/toxic epidermal necrolysis (TEN) disorder. Intravenous methylprednisolone was administered. Upon cessation of oral prednisolone, there was a recrudescence of the eruption. A repeat skin biopsy confirmed recurrent SJS. Following a prolonged taper with oral prednisolone, there was no further relapse of SJS. Severe cutaneous adverse reactions such as SJS/TEN have been reported with pembrolizumab and can be associated with significant morbidity and even mortality. High-dose systemic corticosteroids are frequently used in its treatment. Concerns about the potential negative effect of high-dose steroids have re-surfaced, given the observed reduced overall survival in patients with MM. Due to difficulties in performing studies in this population, the benefits and risk of steroids should be considered on a case-by-case basis.

A case of vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome with failure to respond to cyclosporine treatment

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare delayed drug reaction that often occurs 2-6 weeks after initiation of therapy and may develop into a life-threatening systemic reaction. Besides immediate discontinuation of the suspected inciting drug, initiation of high dose systemic corticosteroids has long been the mainstay of treatment for severe cases. Nevertheless, significant drawbacks associated with systemic corticosteroid therapy, such as the requirement of a long tapering period post resolution and extensive adverse side effects profile, have motivated clinicians to seek alternative treatment options. Over the past decade, an undisputed increasing number of favorable case reports has highlighted cyclosporine as an emerging, safe, and effective alternative despite inconsistent dosing regimens reported. Herein, we report a severe case of vancomycin-induced DRESS syndrome in which the patient failed initial intervention with cyclosporine and needed rescue with methylprednisolone. To the best of our knowledge, this constitutes the first unsuccessful report of cyclosporine treatment for DRESS syndrome.

Diffuse Alveolar Haemorrhage: A Single Centre Experience

Introduction: Diffuse alveolar hemorrhage results from an accumulation of red blood cells into the alveolar space. Symptoms of alveolar hemorrhage are dyspnea, hemoptysis, anemia, diffuse pulmonary infiltrates and hypoxemic respiratory failure. Diagnosis is established by bronchoalveolar lavage and treatment includes a combination of high dose systemic corticosteroids, immunosuppressant and plasma exchange. The aim of this study is to evaluate the clinical radiological profile and laboratory findings and utility of bronchoalveolar lavage in the diagnosis of diffuse alveolar hemorrhage.Materials and Methods: In a retrospective review between February 2017 and December 2017, medical records of patients with a diagnosis of diffuse alveolar hemorrhage presenting at the National Academy of Medical Sciences, Kathmandu, Nepal, were analyzed. Clinical, radiology and laboratory results along with bronchoalveolar lavage results were extracted. Treatment received and clinical responses were evaluated.Results: A total of five patients were diagnosed to have diffuse alveolar hemorrhage based on bronchoalveolar lavage analysis. Three had hemorrhage secondary to Antineutrophil Cytoplasmic Antibody associated vasculitis, one had Systemic Lupus Erythematosus and the other Idiopathic Pulmonary Hemosiderosis. Renal involvement was present in three patients. All patients received systemic corticosteroids, three received Cyclophosphamide and one Rituximab for remission induction. Plasma exchange was done in two patients with severe hypoxemia. Of the five patients, four improved whereas one died.Conclusions: Diffuse alveolar hemorrhage presents with non-specific symptoms. Bronchoalveolar lavage is extremely useful to establish the diagnosis and exclude infections. Early initiation of immunosuppressant prevents respiratory failure and death.

Assessment of high-dose inhalational corticosteroids vs systemic corticosteroids in acute exacerbations of COPD in diabetic patients

BackgroundSystemic corticosteroids (SCS) are effective in the management of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, they are not without adverse effects, especially hyperglycemia. Inhaled corticosteroids (ICS) showed satisfactory outcomes with good safety. These benefits were not evaluated in patients with AECOPD with diabetes mellitus. The aim was to compare the efficacy and safety of high dose of ICS vs SCS in the treatment of AECOPD in diabetic patients.Patients and methodsA total of 126 patients with AECOPD were screened, and thirty of them were found to be eligible and were enrolled into two groups: group 1 (n=15) received 1mg budesonide by jet nebulizer four times daily, and group 2 (n=15) received 40mg prednisolone or equivalent systemically. Postbronchodilator forced expiratory volume in 1 s (FEV1%) of predicted was measured at day 1 and day 7, and random blood sugar (RBG) was measured twice daily in all patients.ResultsThere was a significant increase in the mean FEV1 at day 7 as compared with mean FEV1 at day 1 in groups 1 and 2, with the increase in mean FEV1 being 19.6 and 21% in groups 1 and 2, respectively. There was a significant difference, with higher mean RBG in group 2 when compared with group 1, at day 4 of treatment and continued onward. Interestingly, there was a significant elevation in mean RBG among patients in group 2 (SCS) starting by day 3 of treatment and continued onward, with no significant rise in the first two days, although there was no evident effect of ICS on the mean RBG among patients in group 1 (ICS) during the follow-up days.ConclusionBoth ICS and SCS improve airflow in patients with AECOPD, taking into consideration the existence of diabetes mellitus. ICS may be an excellent substitute to SCS in the treatment of AECOPD in diabetic patients.

Pneumocystis jirovecii pneumonia in inflammatory rheumatic systemic diseases under immunosuppressive therapy: Two case reports, current overviews

Infection with pneumocystis jirovecii is one of the most common AIDS (Acquired Immune Deficiency Syndromes) defining diseases. There is an increased risk of clinical apparent pneumocystis jirovecii infections due to cellular immunodeficiency. Other patients with a higher risk for an infection with pneumocystis jirovecii are those with malignant diseases, condition after stem cell transplantation or after transplantation of solid organs, and patients receiving immunosuppressive therapy due to autoimmune disorders. Therefore, patients with inflammatory rheumatic diseases are often at an increased risk for opportunistic infections such as pneumocystis jirovecii pneumonia (PcP). The PcP is transmitted aerogenically or it can be a result of reactivation of a latent infection after immunosuppression. Leading symptoms are dyspnea on effort, coughing and sub febrile temperature. For detection of the pathogen staining methods or molecular genetic methods are used. Furthermore, imaging, in particular highresolution computed tomography, plays an essential role. The most important medication for treatment is Trimethoprim and Sulfamethoxazole. Sometimes an adjuvant corticosteroid treatment is recommended, whereas evidence for benefits in patients with inflammatory rheumatic disease is lacking. A primary chemoprophylaxis is recommended for patients on high intensive or combined immunosuppression or under high-dose systemic corticosteroid treatment. Also in this case Trimethoprim/Sulfamethoxazole are treatment of choice. Here we describe two case reports on clinical pneumocystis jirovecii infection under immunosuppressive medication in patients with rheumatic diseases and we give an overview on current literature with regard to rheumatic therapy options.

SUBCUTANEOUS C1-INHIBITOR FOR LONG-TERM PROPHYLAXIS IN HEREDITARY ANGIOEDEMA WITH NORMAL C1 INHIBITOR

Introduction Hereditary angioedema (HAE) is a rare disorder characterized by episodes of swelling without urticaria. HAE presents with decreased C1 inhibitor (C1INH) antigen (type I) or function (type II), or with normal C1INH (HAE-nC1INH). Case Description A 25-year-old female presented with intermittent airway, abdominal and extremity angioedema without hives every 2-4 weeks for 3 years, often coinciding with ovulation or menstruation. She had up to 24 emergency room (ER) visits and 5 hospitalizations annually, historically requiring intubation, abdominal laparoscopy and appendectomy. Pathology revealed normal appendix. C4, ANA, tryptase, C1INH antigen level, C1INH function, C1q and Factor XII gene testing were normal. Angioedema was unresponsive to high-dose antihistamines, systemic corticosteroids, and omalizumab. She was diagnosed with suspected HAE-nC1INH. Progesterone contraceptives and fresh frozen plasma were ineffective. On-demand ecallantide or icatibant reduced episode duration but she continued with frequent symptoms. Prophylactic tranexamic acid and subsequently IV C1INH 1000 units every 3-4 days resulted in modest preventative effects but she had ER visits, hospitalizations and decreased quality of life due to angioedema. In September 2017, she transitioned to prophylactic subcutaneous C1INH replacement 60 IU/kg twice weekly and has since experienced only 3 ER visits with rapid recovery, no hospitalizations, international travel and permanent employment. Discussion Plasma-derived human C1-INH has been reported as a successful acute treatment in HAE-nC1INH. A lower threshold for contact system activation might explain the benefit of higher C1INH levels in some HAE-nC1INH patients. Our report demonstrates that SQ C1INH may be effective for long-term prophylaxis in a subset of HAE-nC1INH.

Three-Dimensional High-Resolution Black-Blood Magnetic Resonance Imaging for Detection of Arteritic Anterior Ischemic Optic Neuropathy in Patients With Giant Cell Arteritis.

Arteritic anterior ischemic optic neuropathy (A-AION) caused by inflammatory occlusion of the posterior ciliary arteries is the most common reason for irreversible vision loss in patients with giant cell arteritis. Atypical clinical presentation and negative funduscopy can delay systemic high-dose corticosteroid therapy to prevent impending permanent blindness and involvement of the contralateral eye.The purpose of this study was to assess the diagnostic accuracy of 3-dimensional (3D) high-resolution T1-weighted black-blood magnetic resonance imaging (T1-BB-MRI) for the detection of posterior ciliary artery involvement in patients with giant cell arteritis and funduscopic A-AION. After institutional review board approval and informed consent, 27 patients with suspected giant cell arteritis and vision disturbances were included in this monocentric prospective cohort study. Giant cell arteritis was diagnosed in 18 patients according to the diagnostic reference standard (6 men, 73.8 [69.0-78.0] years); 14 of those were positive for A-AION. Precontrast and postcontrast 3D T1-BB-MRI was performed in all 27 patients. Two radiologists separately assessed image quality and local fat suppression (4-point scale), visual contrast enhancement (3-point scale), and diagnostic confidence (5-point scale) regarding arteritic posterior ciliary artery involvement. Magnetic resonance imaging findings were assessed in comparison to funduscopy. Statistical analysis included accuracy parameters and interrater agreement. Sensitivity of 3D T1-BB-MRI was 92.9% (95% confidence interval, 66.1%-99.8%) and specificity was 92.3% (95% confidence interval, 64.0%-99.8%) for detection of A-AION-positive patients. Image quality and local fat suppression were assessed with 3.2 ± 0.8 (median 3) and 3.8 ± 0.5 (median 4). Visual contrast enhancement with 2.3 ± 0.8 (median 3) and diagnostic confidence was rated at 4.7 ± 0.5 (median 5). Interrater agreement was high (κ = 0.85, P < 0.001). Three-dimensional T1-BB-MRI displayed bilateral findings in 50% of the cases, whereas only unilateral A-AION was detected in funduscopy as a possible indication for the contralateral eye at risk. Three-dimensional T1-BB-MRI allows accurate detection of arteritic posterior ciliary artery involvement in patients with A-AION. Further, 3D T1-BB-MRI seems to display arteritic involvement of the posterior ciliary arteries earlier than funduscopy and might, therefore, display "vision-at-risk" in patients with visual impairment and suspected giant cell arteritis but unremarkable funduscopy.

Kimura’s Disease: Presenting as a Giant Head and Neck Mass

We report an interesting case of Kimura’s disease (KD) that presented as a giant head and neck mass. KD is a rare chronic inflammatory disorder and usually presents as small subcutaneous swellings in the head and neck region. Such a large mass of 15 × 17.5 cm as seen in our patient has previously not been reported, to the best of our knowledge. The radiological picture was that of an enlarged subcutaneous mass with heterogeneous enhancement of the salivary gland. The histological findings were helpful in identifying the lesion as KD. The combination of these two aided us in differentiating it from other lesions such as follicular lymphoma, angiolymphoid hyperplasia with eosinophilia (ALHE) and Langerhan’s histiocytosis. There is no standard protocol for management of this disease owing to its rarity. Due to the extensive and ill-defined nature of the lesion in our patient, we have started the patient on systemic high-dose corticosteroid therapy to downsize the lesion and we plan to follow up with surgical excision if needed.

Acute exacerbation of idiopathic pulmonary fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is defined as an acute clinically significant respiratory deterioration characterized by evidence of new, widespread alveolar abnormalities, such as diffuse bilateral ground-glass opacification and/or consolidation, and the absence of other obvious clinical causes like fluid overload, left heart failure, or pulmonary embolism, etc. AE-IPF is subcategorized as “triggered” (where specific causes are identified, for example, infections, surgery procedures, drug toxicity, etc.) or “idiopathic” (where no specific causes are identified). In randomized trials, the annual incidence of AE-IPF is about 8%, in retrospective studies it reaches 19%. Severe forms of IPF are an important risk factor for the development of AE-IPF. In-hospital mortality from AE-IPF is more than 50%, and the average survival of patients with AE-IPF is 1–4 months. Currently, there remain no proven, effective therapies for AE-IPF. In real clinical practice patients with AE-IPF still receive high doses of systemic corticosteroids and antibiotics. Antifibrotic therapy can reduce the risk of exacerbations; it has been shown that therapy with nintedanib leads to a reduction in the number of confirmed/suspected AE-IPF by 68%. It is necessary to further study the potential methods of prevention and therapy of AE-IPF in future clinical trials.

Use of Oral Steroids and Immunosuppressant / Immunomodulators in the Treatment of Behcet's Disease-Related Uveitis

Behçet’s disease is a multisystemic inflammatory disease of unknown etiology. Unpredictable severe inflammatory ocular exacerbations are usual during the course of the disease and if these acute attacks did not treat in a fast and effective manner, permanent ocular complications would be inevitable. Immune suppressive drugs combined with high-dose systemic corticosteroids are used in resistant uveitis attacks with severe posterior segment involvement, while topical therapy is sufficient only in cases with anterior segment involvement. But unfortunately, refractory uveitis exacerbations could be seen despite the conventional immunosuppressive treatment.

29-Year-Old Woman With Fever and Bilateral Lower Extremity Lesions

29-Year-Old Woman With Fever and Bilateral Lower Extremity Lesions

Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma

BackgroundSebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck.Case presentationA 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab. After 6 months, he developed a near complete response to therapy by irRECIST and RECIST v.1.1. The response was associated with circulating CD8+ T cells with central memory (CM) and effector memory (EM) phenotype and mature CD16 + CD57+ NK cells. During treatment the patient developed adrenal insufficiency requiring high-dose systemic corticosteroids and later adrenal replacement therapy. After 12-months of follow-up he showed imaging evidence of progression in liver, mediastinum, and abdominal lymph nodes. Given persistent, strong PD-L1 expression he resumed pembrolizumab therapy and showed radiographic evidence of an ongoing response to therapy.ConclusionsThis is the first report describing objective clinical and radiographic responses following immunotherapy for widely metastatic sebaceous carcinoma. The dramatic therapeutic response to pembrolizumab was associated with peripheral blood circulating memory T cells and mature Natural Killer cells after 6 months (24 weeks) of therapy. This report supports prospective clinical trials of anti-PD1 checkpoint blockade for metastatic sebaceous carcinoma.

Age and Sex Associations with Systemic Corticosteroid-Induced Morbidity in Asthma

Treatment of severe asthma may include high-dose systemic corticosteroid therapy, which is associated with substantial comorbidity. There is evidence to suggest that this burden is not evenly distributed across age, sex, and corticosteroid exposure levels. To examine the associations between age, sex, comorbidity, and patterns of health care cost across groups differentiated by corticosteroid exposure. Patients with severe asthma (n= 808) were matched by age and sex with patients with mild/moderate asthma (n= 3975) and nonasthma control subjects (n=2412) from the Optimum Patient Care Research Database. Regression analysis was used to investigate the oddsof a number of corticosteroid-induced comorbidities as it varied by cohort, age group, and sex. Prescribed drugs and publicly funded health care activity were monetized and annual costs per patient estimated. Patients aged 60 years or younger with high oral corticosteroid (OCS) exposure had greater odds of osteopenia, osteoporosis, glaucoma, dyspeptic disorders, chronic kidney disease, cardiovascular disease, cataracts, hypertension, and obesity (P < .01) relative to those with mild/moderate asthma (low OCS exposure) as well as to those with no asthma. This difference in odds was much less evident in older patients. Sex-related differences for the odds of most comorbidities related to high-dose OCS were also observed. This differential pattern ofcomorbidity prevalence was reflected in mean health care costs per patient per year. Results demonstrate important differential prevalence of corticosteroid-induced morbidity by age and sex, which is paralleled by differences in health care costs. This is important for clinicians in better understanding the risks of placing different age groups or sexes on systemic corticosteroids.

High doses of systemic corticosteroids in patients hospitalized for exacerbation of chronic obstructive pulmonary disease. A cohort study

ObjectivesTo assess the effect of high doses of corticosteroids in patients hospitalized for exacerbation of chronic obstructive pulmonary disease (COPD). Patients and methodsA prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. ResultsWe analyzed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67–82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597–2.007; p=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392–2.082; p=.811), and the mortality was 1.832 (95% CI 0.229–16.645; p=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. ConclusionsA daily dose greater than 40mg of prednisone in patients hospitalized for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months.

A Rare Case of Sulfasalazine-Induced DRESS Syndrome With Acute Liver Injury

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening, drug-induced hypersensitivity syndrome, characterized by rash, fever, lymphadenopathy, eosinophilia, and internal organ involvement. Most cases of DRESS involve the liver with transaminitis less than 10 times the upper limit of normal, however, severe disease can also rarely be seen - as presented in this case. A 39-year-old woman with psoriatic arthritis (PsA) presents with progressive whole body pruritic rash for one week. Ten months prior to admission, she started apremilast and then one month prior to presentation also started sulfasalazine for her PsA. One week prior to presentation, she noticed an erythematous, pruritic maculopapular rash on her face, chest, arms, legs, and with associated fever. At that time, her rheumatologist discontinued all PsA medications, and she was treated with penicillin for suspected scarlet fever. Her rash worsened, developing facial edema and confluent blistering of her arms and legs. She also developed painful cervical lymphadenopathy. Upon admission, she had a new transaminitis (AST and ALT > 1000 IU/L), elevated INR (1. 4), leukocytosis (30 x103/uL) with eosinophilia (3300 cells/uL), positive HHV-6, and negative viral and autoimmune hepatitis serologies. She had no infectious or neurologic evidence of symptomatic HHV-6 infection. Dermatology, gastroenterology and infectious disease were consulted. A skin biopsy showed a robust lymphomatoid cellular immune reaction with dermal infiltration of eosinophils, consistent with DRESS syndrome. She was started on intravenous and topical steroids and transitioned to a long oral steroid taper, with subsequent resolution of her rash, leukocytosis, and acute liver injury. DRESS syndrome is associated with a range of drugs, including anticonvulsants (phenytoin), sulphonamides, and rarely sulfasalazine. As seen in our case, the onset of the disease is delayed, and ranges from 2 to 6 weeks after the initiation of the therapy. While most cases of DRESS involve only a mild hepatoxicity, severe disease can rarely induce severe transaminitis (AST and ALT >1000 IU/L), hepatomegaly and fulminant liver failure. Treatment involves withdrawal of the causative drug, systemic high dose corticosteroids, and in rare cases with fulminant liver failure even liver transplantation. DRESS syndrome has a mortality rate of 10%, most commonly due to liver failure, making liver involvement a poor prognostic marker.Figure: Trend of Laboratory Values During Hospital Course.Figure: All samples were stained with Hematoxylin-eosin. The biopsy revealed a striking interface dermatitis with marked papillary edema leading to focal areas of epidermaldermal separation (A, B). The supervening epidermis showed spongiosis and eczematous changes (C, D). Many dermal vessels were surrounded by a dense lymphocytic infiltrate containing scattered transformed immunoblastic elements as well as eosinophils (E). There was vascular mural fibrin deposition with mural edema and concomitant endothelial cell swelling, consistent with a lymphomatoid vasculitis (F). ((A) 4x; (B) 10x; (C) 20x; (D) 40x; (E) 100x; (F) 100x).

A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations \u2013 The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol

BackgroundThe most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects.Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.MethodsThis is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage.DiscussionThis will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD.Trial registrationClinicaltrials.gov, NCT02857842, 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.