High-dose Systemic Glucocorticoids Research Articles

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznań between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Biologics and airway remodeling in severe asthma.

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

Systemic glucocorticoid-free therapy with adalimumab plus immunosuppressants versus conventional therapy in treatment-naïve Vogt-Koyanagi-Harada disease patients.

BackgroundHigh dose systemic glucocorticoid is the main therapy of treatment-naïve Vogt-Koyanagi-Harada (VKH) disease. However, series side effects induced by high dose systemic glucocorticoid frequently occur, which makes alternative therapy necessary for certain patients. This study sought to compare the efficacy and safety of systemic glucocorticoid-free (SGF) therapy with conventional therapy (CT) as an initial treatment for VKH patients.MethodsVKH patients who had not been systemically treated were enrolled. Patients were allocated into 2 therapeutic groups depending on their treatments. In CT group, patients received systemic glucocorticoid plus immunosuppressants (IS), and in SGF group, patients received adalimumab (ADA) plus IS. Patients received approximately 12 months treatment and visit monthly. The outcome parameters included the changes of best-corrected visual acuity (BCVA), intraocular inflammation (including anterior chamber cell grade and vitritis grade) and central macular thickness (CMT) (the change values define as the final-visit values subtracted from baseline counterparts). Other outcomes included the relapses times of ocular inflammation, adverse events (AEs), changes of optic nerve inflammation (ONI) and intraocular/extraocular manifestations.ResultsA total of 30 patients (60 eyes) were included. with 19 patients (38 eyes) in CT group and 11 patients (22 eyes) in SGF group. After approximately 1 year of treatment, the improvements of BCVA were slight better in the SGF group (0.57±0.23) than in the CT group (0.40±0.26), (P=0.014). In both groups, the ocular inflammatory improvements in both groups were similar, with an improvement of AC cell grade of −1.5 (−2, −0.5) in CT group versus −1 (−2, −1) in SGF group (P=0.367); improvement of vitritis grade was 0 (−1.25, 0) in CT group and −1 (−1, −1) in SGF group (P=0.050). The improvement in CMT was similar in both groups, with −523.47±412.09 µm in CT group and −362.73±375.73 µm in SGF group (P=0.572). The mean number of relapses was 1 (0, 2) in the CT group and 0 (0, 2) in the SGF group (P=0.372). No severe AEs were observed in this study.ConclusionsSGF therapy is effective, safe, and well-tolerated in treatment-naïve VKH patients. SGF therapy seems to be a feasible option in patients with existing systemic diseases intolerant to glucocorticoid.

In utero exposure to glucocorticoids and risk of anxiety and depression in childhood or adolescence

Glucocorticoid use is prevalent in pregnant women, but whether in utero exposure impacts mental health in the offspring has not been fully explored. The aim of this study was to investigate if in utero exposure to synthetic glucocorticoids increases the risk of anxiety and depression in childhood or adolescence. The study was conducted as a nationwide cohort study, including negative control exposure analyses and a sibling design to optimize control of confounding. The study population comprised 1,275,909 children born in 1996–2015 in Denmark (median follow-up of 13 years). Exposure was divided into systemic and local glucocorticoid exposure, levels of cumulative dose, generic type and according to trimester of exposure. The comparison cohort was children without exposure born to maternal never-users. Negative control exposures included children without glucocorticoid exposure born to: maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of systemic glucocorticoids, maternal users of systemic glucocorticoids in the postnatal period, and fathers who were prescribed glucocorticoids. The sibling design compared siblings with and without exposure. 9307 (0.7%) children were exposed to systemic glucocorticoids and 116,389 (9.1%) children were exposed to local glucocorticoids. High-dose systemic glucocorticoids (≥500 mg prednisolone equivalents) increased the risk of anxiety compared to the comparison cohort [aIRR 1.79 (95% CI: 1.36–2.37), cumulative risk 16% vs. 7.8% by age 20]. A similar result was found for depression [aIRR 1.45 (95% CI: 0.80–2.63), cumulative risk 3.6% vs. 2.6% by age 20]. The association with anxiety was consistent in the sibling design [aIRR 1.83 (95% CI: 1.03–3.66), exposed siblings (≥ 500 mg) vs. unexposed]. Sex did not modify the associations. Negative control exposure analyses indicated robustness towards confounding from genetics and family environment. No association was found with low doses of systemic exposure or local use. In conclusion, potential adverse mental health effects of in utero exposure to high-dose glucocorticoids merit clinical attention.

Clinical Features and Mortality of COVID-19-Associated Mucormycosis: A Systematic Review and Meta-Analysis

The recent increase of COVID-19-associated mucormycosis (CAM) has been commanding global attention. However, basic epidemiologic characteristics have not firmly been established. In this systematic review and meta-analysis, we sought to determine the clinical manifestations, potential risk factors, and outcomes of CAM. Observational studies reporting CAM were searched with PubMed and EMBASE databases in January 2022. We collected data on comorbidities and treatment for COVID-19, and performed a one-group meta-analysis on the frequency of orbital exenteration procedure and mortality of CAM using a random-effect model. Fifty-one observational studies, including a total of 2,312 patients with proven CAM, were identified. Among the 51 studies, 37 were conducted in India, 8 in Egypt, and 6 in other countries. The most common comorbidity was diabetes mellitus (82%). While 57% required oxygenation, 77% received systemic corticosteroids. Among CAM, 97% were rhino-orbital-cerebral (ROCM), and 2.7% were pulmonary mucormycosis. Usual presentations were headache (54%), periorbital swelling/pain (53%), facial swelling/pain (43%), ophthalmoplegia (42%), proptosis (41%), and nasal discharge/congestion (36%). Regarding the outcomes, orbital exenteration was performed in 17% (95% CI: 12–21%, I2 = 83%) of the COVID-19-associated ROCM patients. The mortality of CAM was 29% (95% CI; 22–36%, I2 = 92%). In conclusion, this systematic review and meta-analysis indicated that the most prevalent type of CAM was ROCM, and most CAM patients had diabetes mellitus and received systemic glucocorticoids. Clinicians in the endemic areas should have a high index of suspicion for this invasive fungal complication of COVID-19 when a diabetic patient who received high-dose systemic glucocorticoids developed rhino-orbital symptoms.

Modulation of tissue resident memory T cells by glucocorticoids after acute cellular rejection in lung transplantation.

Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators after therapy with glucocorticoids but accumulate around airways. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in situ expansion. We thus highlight the accumulation of cytotoxic, recipient-derived tissue resident memory T cells within the lung allograft that persist despite the administration of high-dose systemic glucocorticoids. The long-term clinical consequences of this persistence have yet to be characterized.

Prenatal exposure to glucocorticoids and the prevalence of overweight or obesity in childhood.

ObjectivePrenatal exposure to excess cortisol can affect postnatal metabolic health by epigenetic mechanisms. We aimed to investigate if prenatal exposure to pharmacological glucocorticoids increases the risk of overweight/obesity in childhood.DesignA nationwide population registry-based cohort study.MethodsWe identified 383 877 children born in Denmark (2007–2012), who underwent routine anthropometric evaluation at 5–8 years of age. Prenatal exposure to glucocorticoids was divided into systemic and topical glucocorticoids, cumulative systemic dose, and use by trimester. The comparison cohort included children without exposure, born to maternal never-users. Negative control exposures were used to investigate confounding from an underlying disease or unmeasured characteristics. Such exposures included children without glucocorticoid exposure born to maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of glucocorticoids, or paternal users of glucocorticoids during the pregnancy of their partner. We estimated sex-stratified adjusted prevalence ratios (aPR) of overweight/obesity at 5–8 years of age, as epigenetic modifications have shown to be sex-specific.ResultsIn the study, 21 246 (11%) boys and 27 851 (15%) girls were overweight/obese at 5–8 years of age. Overall, neither systemic nor topical glucocorticoids were associated with overweight/obesity. In boys, high-dose systemic glucocorticoids was associated with higher prevalence of overweight/obesity vs the comparison cohort (aPR: 1.41 (95% CI: 1.07–1.86), prevalence: 16% vs 11%). Negative control exposures indicated robustness to confounding.ConclusionOverweight/obesity might be an adverse effect of prenatal exposure to high-dose systemic glucocorticoids in boys. We found no association for neither prenatal exposure to lower doses of systemic nor topical glucocorticoids. These results merit clinical attention.

IS ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA AN EMERGING CAUSE OF DIFFUSE ALVEOLAR HEMORRHAGE?

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare and poorly understood form of interstitial lung disease that can present either acutely or insidiously. Among the acute manifestations of AFOP, diffuse alveolar hemorrhage (DAH) has only been described once before in the literature. CASE PRESENTATION: A 25 year old male with a history of end stage renal disease secondary to bilateral posterior urethral valves (on hemodialysis) and cutaneous neutrophilic dermatosis (Sweet syndrome) presented with the abrupt onset of severe dyspnea. Given concern for flash pulmonary edema on initial chest radiograph (Figure 1), he was placed on a nitroglycerine drip and underwent emergent hemodialysis with ultrafiltration. He subsequently developed rapidly progressive acute hypoxic respiratory failure with worsening pulmonary infiltrates (Figure 2) requiring emergent intubation and mechanical ventilation. Copious bloody secretions were noted during intubation, and the patient required multiple blood transfusions following admission. Despite mechanical ventilation with paralysis and proning, the patient developed severe adult respiratory distress syndrome with a P:F ratio nadir of 74. Chest CT revealed diffuse severe consolidative lung injury of unclear etiology (Figure 3). Bronchoscopy with serial aliquots on bronchoalveolar lavage confirmed the presence of diffuse alveolar hemorrhage. The patient’s condition improved rapidly with initiation of systemic glucocorticoids, and he was subsequently extubated on hospital day 5. Shortly after discharge home, the patient was readmitted with recurrent severe acute hypoxic respiratory failure in the setting of tapering his glucocorticoids, but he was successfully extubated within 24 hours following reinitiation of high-dose systemic glucocorticoids. Bronchoscopically-guided cryobiopsy during this admission revealed a diagnosis of AFOP, and the patient was ultimately discharged home with plans for a prolonged course of steroids and possible transition to steroid-sparing agents. DISCUSSION: Further investigations are needed to determine whether AFOP represents a distinct clinical entity, or rather the sequelae of concomitant inflammatory or autoimmune processes such as those present in this patient. Regardless of the etiology, data from case reports suggest that AFOP can be highly responsive to systemic glucocorticoids and other forms of immunosuppression. Delay in diagnosis, however, remains a significant barrier to the treatment of AFOP and portends poor prognosis in the acute form of this illness. CONCLUSIONS: The addition of this case to the literature suggests that DAH may represent an emerging manifestation of AFOP. Prompt recognition of this rare and heterogeneous disease process is imperative, as increasing evidence suggests favorable outcomes with early initiation of systemic glucocorticoids. REFERENCE #1: Crowley N, Sessler C, Miller K, Robila V, Debesa, O. Relapsing acute fibrinous and organizing pneumonia complicated by diffuse alveolar hemorrhage. Chest. 2018;154(4)(suppl):409A-410A. doi: 10.1016/j.chest.2018.08.375. REFERENCE #2: Lee JH, Yum HK, Jamous F, Santos C, Campisi A, Surani S, Lococo F, Goo JM, Yoon SH. Diagnostic procedures and clinico-radiological findings of acute fibrinous and organizing pneumonia: a systematic review and pooled analysis. Eur Radiol. 2021 Mar 31. doi: 10.1007/s00330-021-07868-z. Epub ahead of print. REFERENCE #3: Santos C, Oliveira RC, Serra P, Baptista JP, Sousa E, Casanova P, Pimentel J, Carvalho L. Pathophysiology of acute fibrinous and organizing pneumonia - Clinical and morphological spectra. Pathophysiology. 2019 Sep-Dec;26(3-4):213-217. doi: 10.1016/j.pathophys.2019.04.001. DISCLOSURES: No relevant relationships by Andrew Davis, source=Web Response No relevant relationships by Nathan Sandbo, source=Web Response

Risk of ocular hypertension in children treated with systemic glucocorticoid.

To investigate the risk of steroid-induced ocular hypertension in children treated with systemic glucocorticoid. Prospective cohort study of children treated with high-dose systemic glucocorticoid (prednisolone-equivalent >0.5 mg/kg/day) for more than 2 weeks. Intraocular pressure (IOP) was measured by an Icare tonometer. An intraocular hypertensive response was defined as a net increase in IOP ≥6 mmHg from baseline or a peak IOP ≥21 mmHg in either eye. Patients with a peak IOP ≥31 mmHg or a net increase in IOP ≥15 mmHg were considered as high responders. Sixteen children with median age 12 years (range 5-17) were included in the study. Nine children (56%) developed a steroid-induced ocular hypertensive response. Two children (12%) were high responders with peak IOP between 32 and 44 mmHg and a net increase in IOP between 15 and 23 mmHg. All children were asymptomatic and IOP was normalized in all after withdrawal of steroid. Steroid responders were significantly younger than nonresponders (p = 0.03). No associations were found between net IOP increase and time to peak pressure, steroid dose at peak pressure or accumulated prednisolone dose at peak IOP. Systemic treatment of children with glucocorticoid can cause a significant increase in IOP which indicates the need for IOP screening of these children. The risk of steroid-induced ocular hypertension may depend on age and ethnicity. In this perspective, further studies on Caucasian children are needed.

Evaluating tertiary adrenal insufficiency in rheumatology patients on long-term systemic glucocorticoid treatment.

Patients with rheumatic diseases are often treated with prolonged, high-dose systemic glucocorticoids which can cause hypothalamic-pituitary-adrenal (HPA) axis suppression and development of tertiary adrenal insufficiency. Adrenal insufficiency carries the risk of serious, potentially life-threatening adrenal crisis. Our study evaluated the prevalence, characteristics and recovery of patients with underlying rheumatology conditions who had received prolonged glucocorticoid treatment. Retrospective, cross-sectional study. We evaluated 238 patients seen in outpatient rheumatology clinic, managed in accordance with current nationally and internationally accepted clinical guidelines. Data collected included patient demographics, historical steroid data, 09.00h cortisol/short synacthen test (SST) results and follow-up data on those with repeat assessments. Overall, 65% of our cohort had a 09.00h cortisol <350nmol/L. On SST, 43% of patients demonstrated evidence of possible tertiary adrenal insufficiency. Prednisolone equivalent dose at time of SST was significantly higher in the group who failed SST vs. those who passed; mean of 5.57mg vs. 3.59mg (p=.005). 09.00h cortisol result correlated with 30-min cortisol on SST (R2 =.20, p=.002). 0-min cortisol on SST correlated more strongly with 30-min cortisol than 09.00h cortisol (R2 =.59, p-value<.001). Patients with 0-min cortisol >350nmol/L, all passed their SST. Patients who remained on prednisolone were more likely to recover (71%) vs. those switched to hydrocortisone (27%), P=.02. Peak steroid dose was predictive of recovery; significantly lower in those who recovered (mean of 22.3mg vs. 33.8mg, P=.03). Steroid duration was not found to be a predictor of recovery [recovery (64.2months) vs. non-recovery (55.6months), P=.58]. There was no correlation found to outcome on SST with age, sex, peak steroid dose, steroid duration, underlying rheumatological condition, additional exogenous steroid use or serum sodium. Forty three percent of our patients demonstrated sub-optimal adrenal function on SST. Steroid dose at the time of SST was the only significant predictive risk factor for tertiary adrenal insufficiency. 09.00h cortisol demonstrated good correlation with outcome on SST and could represent a valid screening test to reduce need for SST if 09.00h >350nmol/L. Further prospective data are required to further characterize risk factors, predictive features of recovery and establish optimal management strategy of steroids (prednisolone vs hydrocortisone) to encourage adrenal recovery.

Benralizumab for severe DRESS in two COVID-19 patients

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare severe hypersensitivity reaction that clinically manifests with exanthema, facial edema, enlarged lymph nodes, fever, and organ damage at variable degrees.1 Eosinophil expansion in blood is a hallmark of DRESS, and eosinophil tissue infiltration a main contributor to the observed organ damage and dysfunction.2 Although high-dose systemic glucocorticoids have not been evaluated in randomized clinical trials, they are currently the first-line therapy for DRESS with organ involvement.

Stevens-Johnson syndrome

The literature review of the epidemiology, etiology and pathogenesis, clinical presentation and diagnosis of the syndrome of Stevens-Johnson severe life-threatening disease characterized by extensive lesions of the skin and mucous membranes, fever and bone and muscle aches, often induced by medication is presented. A review on the methods of treatment and prevention of this disease is presented. The clinical case of patient with the syndrome of Stevens-Johnson is described. The successful treatment of Syndrome Stevens-Johnson with high-dose systemic glucocorticoids was performed.

OP0006 Eular evidence-based recommendations on the management of medium to high dose systemic glucocorticoid therapy in rheumatic diseases

ObjectivesTo develop recommendations for the management of medium to high dose systemic glucocorticoid (GC) therapy in rheumatic diseases.MethodsA multidisciplinary EULAR task force was formed, comprising of 8 rheumatologists, 1 endocrinologist,...

Perioperative glucocorticoids in hip and knee surgery – benefit vs. harm? A review of randomized clinical trials

Glucocorticoids are frequently used to prevent post-operative nausea and vomiting (PONV), and may be part of multimodal analgesic regimes. The objective of this review was to evaluate the overall benefit vs. harm of perioperative glucocorticoids in patients undergoing hip or knee surgery. A wide search was performed in PubMed, Embase, and Cochrane Central to identify relevant randomized clinical trials. A systematic approach was used, starting from the PRISMA recommendations. The Cochrane Collaboration's tool was used for risk of bias assessment. Studies were divided into three groups: systemic glucocorticoid administration analogous to > 10 mg or ≤ 10 mg dexamethasone, and local glucocorticoid administration. Seventeen studies with data from 1081 patients were included in the final qualitative synthesis. Benefit (of any kind) with glucocorticoid vs. placebo was reported in 15 studies. PONV was reduced with systemic glucocorticoid. Pain was reduced with high-dose systemic and local glucocorticoid, but not with low-dose systemic glucocorticoid. Systemic inflammatory markers were reduced with low-dose and high-dose systemic glucocorticoid, and with local glucocorticoid. Functional recovery was improved with local glucocorticoid. All studies were small-sized and none sufficiently powered to meaningfully evaluate uncommon adverse events. Most of the local administration studies had poor scientific quality (high risk of bias). Due to clinical heterogeneity and poor scientific quality, no meta-analysis was performed. In conclusion, in addition to PONV reduction with low-dose systemic glucocorticoid, this review supports high-dose systemic glucocorticoid to ameliorate post-operative pain after hip and knee surgery. However, large-scale safety and dose-finding studies are warranted before final recommendations.

Protocolo de diagnóstico y tratamiento de la oftalmopatía tiroidea

Thyroid ophthalmopathy is the most frequent extrathyroidal manifestation of Graves' disease with autoimmune mechanism which is still incompletely understood. The severity and activity of ophthalmopathy should be evaluated reliably for planning subsequent therapy. When needed, complementary imaging techniques (orbital ultrasonography, computerized tomography or nuclear magnetic resonance) to confirm the diagnosis must be used. Management of Graves' ophthalmopathy is preferably done in a multidisciplinary setting. Management of orbitopathy can be either medical and surgical. All subjects with this ophtalmopathy should benefit from euthyroidism restoration, smoking withdrawal and local measures. The medical therapy relies on the use of high dose systemic glucocorticoids or retro-orbital irradiation, either alone or in combination. Later on, surgery (orbital decompression, squint surgery, eyelid surgery, in this order) will eventually be needed for inactive disease.

An update on medical management of Graves’ ophthalmopathy

Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease, is a disorder of autoimmune origin, the pathogenic mechanisms of which are still incompletely understood. Although GO is severe in only 3-5% of affected individuals, quality of life is severely impaired even in patients with mild GO. Management of severe GO can be either medical or surgical (orbital decompression, eye muscle or lid surgery). Medical management relies on the use of high-dose systemic glucocorticoids or orbital radiotherapy, either alone or in combination. Studies carried out in the last 5 yr have shown that glucocorticoids are more effective through the i.v. route than through the oral route. However, particular attention should be paid to possible liver toxicity of i.v. glucocorticoids. Recent randomized clinical trials have, with one exception, confirmed that orbital radiotherapy is an effective and safe therapeutic procedure for GO. At variance with previous encouraging data, recent randomized clinical trials have shown that currently available SS analogs are not very effective in the management of GO. Antioxidants might have a role, at least in mild forms of GO. Particular attention should be paid to correction of risk factors (cigarette smoking, thyroid dysfunction, radioiodine therapy) involved in GO progression.

Relationship between cigarette smoking and Graves’ ophthalmopathy

Environmental triggers in the development of Graves' disease (GD) have been suggested from the very first description of the disease. Since 1987 a number of studies from various countries, have assessed the risk for Graves' ophthalmopathy (GO) associated with smoking, and found an odds-ratio of approximately 4 associated with smoking. Smokers have a higher risk for more advanced GO and a dose response relation is evident. Temporality is suggested by a few prospective studies, as is reversibility since former smokers had a lower risk of developing GO than current smokers, even with a comparable lifetime tobacco consumption. In view of the biological plausibility of the association (suggested mechanisms include tissue hypoxia, modulation of circulating pro- and anti-inflammatory cytokines and accentuation of fibroblast HLA-DR expression) it seems that the association is, indeed, causal. Treatment effect of GD/GO is also influenced by cigarette smoking. It is an independent risk factor for relapse of GD after antithyroid drug treatment. Furthermore, it attenuates the effect of orbital radiotherapy and high-dose systemic glucocorticoids in GO and causes a higher rate of progression of eye disease after radioiodine therapy. The possibility of hindering GO or attenuating its course suggests that counselling on smoking cessation should be an integral part of the treatment of any patient with GD.

Influence of cigarette smoking on thyroid function, goiter formation and autoimmune thyroid disorders

Both smoking and thyroid dysfunction are frequent in the general population. Many studies have shown that cigarette smoking interferes with thyroid function and with the evolution of thyroid pathology (e.g. goiter formation and thyroid cancer development). Some studies have also suggested a significant correlation of Graves' hyperthyroidism and Graves' ophthalmopathy with the severity of smoking. In addition, cigarette smoking may reduce the effectiveness of some therapeutic modalities, such as orbital radiotherapy or high-dose systemic glucocorticoid administration for severe thyroid eye disease. Tobacco smoking seems to induce similar changes in thyroid function in the adult and the fetus. This review article discusses the effect of cigarette smoking on thyroid function and morphology as well as on thyroid autoimmunity.

Orbital radiotherapy for Graves' ophthalmopathy.

Orbital radiotherapy is a well-established method of treatment for severe Graves' ophthalmopathy, because of its anti-inflammatory and locally immunosuppressive effects. It has been used for 60 years. Conventional external x-ray and cobalt therapy have been abandoned, and most groups now use supervoltage linear accelerators (4-6 MeV). Cumulative doses may vary, but in most studies a cumulative dose of 20 Gy delivered over 2 weeks was utilized. Successful outcome depends on the selection of patients, because recent onset, active ophthalmopathy is much more favorably affected than longstanding, inactive disease. Inflammatory signs, recent onset eye muscle dysfunction, and optic neuropathy respond well to orbital radiotherapy, while proptosis and longstanding eye muscle restriction respond poorly. Overall, favorable responses have been reported, with few exceptions, in approximately 60% of cases. Combination of irradiation with high-dose systemic glucocorticoids provides better results than either treatment alone. Orbital radiotherapy is well tolerated and safe. Preexisting retinopathy (e.g., in patients with diabetes) is a contraindication to this treatment for the risk of further retinal damage. No case of radiation-induced tumors has so far been described after orbital radiotherapy for Graves' ophthalmopathy.

High-dose systemic glucocorticoid therapy in the treatment of severe asthma: A case of resistance and patterns of response

At some frequent interval, perhaps once a month, REFERENCES these would be reported to a central data collection 1. Yunginger JW. Sweeney KG. Stumer WQ. ct ,jl. Fatal i’ood center. Of course it would be ideal if each patient induced anaphylaxis. JAMA 1988;260: 1450-2 could be evaluated to determine if a food (and which 2. Sampson HA. Mendelson L, Rosen JP. Patal and trear-fatal food food) was actually responsible for the symptoms, but anaphylaxis reactions in children. N Engl J 2lcd 1992327: