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Background: In recent years, an increase of allergies and asthma has been observed throughout the world, more so in Western countries than in less developed ones. Although genetics may play a role in this increase, there are many other factors that may have contributed to the upsurge. Objective: The purpose of the present report was to review the many factors associated with modernization and lifestyle that may have contributed to the allergy and/or asthma epidemic, with a particular focus on those aspects that have particular relevance for the allergist/immunologist. Results: The marked rise in allergy and asthma has been significantly seen in more-developed countries, greater in urban than in rural areas, more pronounced in affluent than in poorer societies, and in individuals who have migrated from developing countries to industrialized countries. A widely accepted explanation for this rise is the “hygiene hypothesis,” which postulates a critical dependence on microbial infection for maintenance of a healthy balanced immune system and that extremely clean external environments, often found in the developed world, can derail equilibrated immune development. With the control of infectious diseases, the immune system shifts from a balanced equilibrated immunologic structure to a more Th2 driven proinflammatory state often associated with IgE and eosinophil-related disorders. Conclusion: Modernization has been associated with increased development of allergies and asthma through a cleaner environment and more exposure to allergens and to multiple other contributory factors. The marked reduction in infectious diseases in recent decades permitted the immune system to switch from fighting infectious disease agents and parasites to reacting adversely (hypersensitivity) to benign environmental agents (allergens) and even to self-antigens (autoimmunity).

The practice of food allergy (FA) for clinicians has boomed, with a dramatic rise in the number of patients and families seeking care and with many advances on several fronts. The practice itself sometimes is evidence-based science and sometimes an art of pattern and phenotype recognition. This article examines the tools for diagnosis and management and therapy options available to physicians providing care for patients with FA. The article touches on pressing needs of clinicians and highlights the rapid and important movements in national and international support and advances that will have a positive impact on the field of FA.

Introduction: The development of new biologic agents has provided definite therapeutic advances but, like with any new medications, safety remains a concern.Areas covered: Using PubMed, we reviewed the literature on the adverse effects (AE) to five biologics approved for asthma and/or allergic diseases: one anti-IgE (omalizumab), three anti-IL5 (mepolizumab, reslizumab, benralizumab), and one anti-IL4 (dupilumab).Expert opinion: Biologic agents approved for asthma and allergic diseases are generally safe. Most common AE are benign and tolerated, though long-term safety is lacking for most of them. A slightly increased risk of anaphylaxis to omalizumab and reslizumab required the inclusion of a black box warning, informing the patient, the need for post-injection observation period, and the provision of epinephrine autoinjectors for self-administration when needed. Hypersensitivity reactions, mainly urticaria and very rarely serum sickness have occurred.

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration.

The practice of food allergy (FA) for clinicians has boomed, with a dramatic rise in the number of patients and families seeking care and with many advances on several fronts. The practice itself sometimes is evidence-based science and sometimes an art of pattern and phenotype recognition. This article examines the tools for diagnosis and management and therapy options available to physicians providing care for patients with FA. The article touches on pressing needs of clinicians and highlights the rapid and important movements in national and international support and advances that will have a positive impact on the field of FA.

We describe the case of a woman presenting with rash and fever 3 weeks after starting oxcarbazepine. She had a convoluted, prolonged hospital course involving reactions to multiple structurally-different medications, with a variety of severe manifestations including drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and complicated with MRSA septic shock and death. This case illustrates the high risk in subjects with a drug reaction that initiated excessive T cell stimulation with subsequent reactions to multiple drugs.

Objective To provide a brief summary on food additives and to outline a practical approach for evaluating subjects suspected of having reactions to food additives. Data sources Information was derived from selected reviews and original articles published in peer-reviewed journals, supplemented by the clinical experience of the authors. Study selection Priority was given to studies that used blinded, placebo controlled, oral challenges to confirm adverse reactions to food additives. In addition, selected, appropriately evaluated case reports were included. Results A large number of food additives are widely used in the food industry. Allergic reactions to additives seem to be rare but are very likely underdiagnosed, primarily due to a low index of suspicion. A wide variety of symptoms to food additives have been reported, but a cause-and-effect relationship has not been well documented in the majority of cases. Conclusion Reactions to food additives should be suspected in patients who report symptoms related to multiple foods or to a certain food when commercially prepared but not when home made. It is also prudent to investigate food additives in subjects considered to have "idiopathic" reactions. Except for a limited number of natural additives, there is a small role for skin tests or in vitro testing. Oral challenge, in stages, with commonly used additives is the definitive procedure for detecting the offending agent. Once the specific additive is identified, management is strict avoidance, which can be difficult.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others. ispartof: WORLD ALLERGY ORGANIZATION JOURNAL vol:14 issue:12 ispartof: location:United States status: published

As a chronic inflammatory disease with eosinophilic infiltrate of the esophagus, eosinophilic esophagitis (EoE) causes a variety of gastrointestinal (GI) clinical manifestations. None of the symptoms, endoscopic features, or biopsy findings is pathognomonic of the disease, even with high degrees of esophageal eosinophilia. The pathogenesis has been explored by several studies, yet it still far from being completely understood. Evidence supports a role of allergen-driven Th2 lymphocyte mechanism, though not in every patient. This article addresses the disease's clinical manifestations, endoscopic findings, diagnosis, and differential diagnoses. In addition to the current diagnostic criteria, we summarize some recently emerging procedures that promise of enhancing more precise diagnosis and institution of early appropriate management, with consequent better quality of life and reduction of complications.

We presented a case of a male infant with annular patchy rash on his torso since 2 weeks of age. This was initially diagnosed as tinea corporis but did not respond to oral antifungal treatment. Because of the appearance of the rash and a history of a certain disease in a maternal aunt, we suspected the most probable cause of the rash and the diagnosis was confirmed by laboratory testing. Furthermore, laboratory screening of the mother, who was asymptomatic, revealed that she was seropositive for the disease and was counseled on the importance of follow-up. The infant's rash gradually improved and completely disappeared, without any sequalae by 8 months of age.

Objective To alert physicians about the peculiar adverse effects of antiepilepsy drugs (AEDs) on the immune system. Data Sources PubMed literature during the past 25 years. Study Selections Reports and review articles on the hypersensitivities of AEDs and their effect on immunity. Results AEDs have significant effects on the immune system in the form of hypersensitivity or immune suppression. IgE-mediated reactions can be urticaria, angioedema, bronchospasm, or anaphylaxis. Non–IgE-mediated reactions, more commonly associated with aromatic AEDs, can be in the form of nonspecific rashes or serious reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptom syndrome, and acute generalized exanthematous pustulosis. Because of strong genetic predispositions for certain AEDs in causing severe reactions, HLA analysis before initiation of the drug is advised in certain populations. Immunoglobulin levels can be reduced to various degrees, particularly by carbamazepine, valproate, phenytoin, levetiracetam, zonisamide, and lamotrigine. Spontaneous return to normal levels can be rapid or take months to a few years, and intravenous immunoglobulin supplementation may be needed. Cellular effects can be in the form of cytopenias, inhibition of lymphocyte function, or cytokine dysregulation. Conclusion When prescribing AEDs, physicians should pay special attention to their potential adverse effects on immunity or hypersensitivity, which can be severe and even fatal. For early recognition and intervention, monitoring such patients is necessary. The cornerstone of management is discontinued use of the suspected medication and avoidance of drugs of similar structure, particularly among members of the aromatic group.

Background: Scoring systems are increasingly being developed for various diseases, including asthma and allergic disorders, with the objective of improving the classification of disease severity and the assessment of efficacy of therapeutic modalities. Objective: This review provided concise summaries of published scoring systems used for allergic rhinitis, asthma, atopic dermatitis, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis, eosinophilic esophagitis, and systemic allergic reactions (anaphylaxis). Methods: We searched the medical literature between 1985 and 2018 for published scoring systems that have been developed and used in clinical trials or in practice for assessment of asthma and a variety of allergic disorders. Results: The scoring systems for each of these diseases were briefly presented in the text in chronological order of publication, and selected information was presented in the tables for easy comparisons. For more details, the reader should refer to the original relevant publications. Conclusion: Such assessment methods are useful for sound designing of clinical trials, fair comparisons of findings of studies, and objective measurements of patients' progress in clinical practice. The choice of using one scoring system over another would depend on its proven degree of validity, the purpose, and applicability.

Anemia can be caused by, or be associated with, many clinical conditions, including pulmonary diseases, some of which are rare and can be misdiagnosed. Nontraumatic pulmonary bleeding may be caused by a variety of conditions and results in anemia and pulmonary hemosiderosis, even when it is subtle. The differential diagnosis in such cases is extensive. We present the case of a diagnostic dilemma in a 17-month-old child hospitalized for severe anemia and respiratory distress in which the diagnosis was settled through an allergy/immunology consultation.

Background Some previous reports revealed suboptimal management of anaphylaxis (ANX) in the emergency department (ED). Objective To evaluate the recorded diagnosis and management of patients who presented with ANX at our university hospital ED and to assess how the management correlated with the severity of the case and the training level of the ED staff. Methods A descriptive study that involved reviewing the electronic medical records of patients who presented with ANX at the ED during a period of 4 years. Results When reviewing 1341 charts of potential cases, 60 met the criteria for ANX, but only 23% were correctly coded. Inaccurate coding was noted in 77%, mainly as an "allergic reaction." Systemic corticosteroids were administered in the ED to 85% of the patients and H1-antihistamines to 73%; only 20% received epinephrine. Ten patients required hospital admission, and, on discharge, only four patients (40%) were given epinephrine autoinjector prescriptions. Of the 50 who were discharged home, 48% were given epinephrine autoinjector prescriptions and 16% were given a referral for allergy evaluation. Conclusion The observed low rates of appropriate diagnostic coding of ANX, of epinephrine administration, epinephrine autoinjector prescribing at discharge, and referral for allergy evaluation call for more education on these issues. Some of these pitfalls can be partly attributed to the setting in a university ED where health providers are usually busy in rendering urgent care.

Objective Provide a brief overview of the clinical presentation, common offending agents, management, prognosis, and mortality of selected six high-risk drug rashes, namely Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), multiple drug hypersensitivity syndrome (MDH), acute generalized exanthematous pustulosis (AGEP), and drug-induced bullous pemphigoid (DIBP). Data sources Review of published literature using PubMed, supplemented with authors' clinical experience. Study selections The most recent clinically relevant literature was chosen, as well as older seminal works. Results Most of the published data on these uncommon rashes was based on small observational series or case reports. SJS and TEN have specific genotypes association with certain drugs, have high morbidity and mortality, and require aggressive management by a team of multiple specialists. DRESS is a severe, prolonged multi-organ reaction, yet has a better prognosis than TEN. MDH is a syndrome of repeated reactions to unrelated drugs, often imposes diagnostic and management difficulties. AGEP consists of generalized sterile small pustules, usually mistaken for infection with subsequent inappropriate treatment. Bullous pemphigoid presents with tense pruritic bullae and characteristic linear basement membrane deposition of IgG and C3; DIBP has much better prognosis than the autoimmune variety. Conclusion In such high-risk drug rashes, early recognition, immediate withdrawal of the suspected drug(s), prompt individualized management, and monitoring vital organs function are mandatory for reducing morbidity and mortality. The lack of reliable tests for identification of the causative agent imposes difficulty, particularly in patients receiving multiple medications.

Background: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Objectives & methods: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. Results: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. Conclusions: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.

Dysregulation of the immune system appears to be a major contributing factor in the development of epilepsy, particularly in certain types. Altered cellular and cytokine profiles have been reported in patients with various types of epilepsy. Glia and neurons overexpress inflammatory cytokines, particularly IL 1β, TNF-α, and IL-6. IL-1β is chronically expressed after an acute seizure ceases and contributes to continued inflammation leading to onset of spontaneous seizures. One-third of epilepsy patients do not respond to antiepilepsy medication and multiple alternative therapies are evolving. Immunoglobulins, corticotropin, cannabinoids, plasmapheresis, and corticosteroids have been utilized in refractory cases, with promising results.

"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet (GFD). Wheat allergy has a prevalence of

Food protein–induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.

Purpose of review To raise awareness among healthcare providers about the clinical and laboratory findings in acute and chronic food protein-induced enterocolitis syndrome (FPIES). Recent findings FPIES can be caused by trivial exposure or rare foods. Summary FPIES is a non-IgE-mediated reaction that usually presents with acute severe repetitive vomiting and diarrhea associated with lethargy, pallor, dehydration, and even hypovolemic shock. Manifestations resolve usually within 24-48 h of elimination of the causative food. In chronic cases, symptoms may include persistent diarrhea, poor weight gain, failure to thrive, and improvement may take several days after the food elimination. In the acute cases, laboratory evaluation may reveal thrombocytosis and neutrophilia, peaking about 6 h postingestion. Depending on the severity, metabolic acidosis and methemoglobinemia may occur. In chronic cases, anemia, hypoalbuminemia and eosinophilia may be seen. Radiologic evaluation or other procedures, such as endoscopy and gastric juice analysis may show nonspecific abnormal findings. The diagnosis is based on clinical manifestations. Further studies looking at the phenotypes of FPIES are needed to identify clinical subtypes, and to understand the predisposing factors for developing FPIES compared with immediate-type, IgE-mediated gastroenteropathies.

Introduction Little is known about potential consequences of stopping mepolizumab therapy in asthmatic patients. This is a case of a 43 yr female diagnosed with eosinophilic myocarditis six months after cessation of mepolizumab. Case Description A 43 yr female with severe eosinophilic asthma was started on mepolizumab. She remained compliant for 2 yr with significant improvement of symptoms but due to a lapse of insurance coverage, therapy was interrupted. Six months later, she developed low-grade fever, cough, and dyspnea with infiltrates on CXR. She was diagnosed with atypical pneumonia and treated with antibiotics without improvement. Within a few days, she developed hypoxic respiratory failure requiring noninvasive ventilation support. WBC was 26.2 K/uL with eosinophilia of 9.69 K/uL. She had elevated troponin (7.58); EKG had lateral ST elevation myocardial infarction, and echocardiogram showed pericardial effusion with EF of 20-25%. Infectious workup was unremarkable. Heart catheterization revealed normal coronaries. Pericardiocentesis cytology demonstrated 89% eosinophils. Cardiac MRI showed circumferential subendocardial hyperenhancement of left ventricle and global ventricular hypokinesis. Bone marrow biopsy and cytogenetic testing were negative. She was diagnosed with eosinophilic myocarditis and started on IV methylprednisolone with marked improvement in symptoms. The patient was discharged on high dose prednisone and heart failure therapy. Three months later, she resumed mepolizumab and has been tolerating a slow prednisone taper. Discussion To our best knowledge, this is the first reported case of eosinophilic myocarditis and pneumonia after mepolizumab cessation. This patient may have had a rebound hypereosinophilia or an underlying hypereosinophilic syndrome which was masked by mepolizumab therapy.

Background Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.Objective A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.Methods A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.Results Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.Conclusions Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful. Keywords: probiotics, prevention of allergy, pediatric allergy

PURPOSE OF REVIEW Modalities and timing of the introduction of solid foods to infants may influence growth, obesity, atherosclerosis, hyperlipidemia, hypertension, diabetes, and metabolic disease. The most debated effects of solid foods introduction are those on the development of food allergy. RECENT FINDINGS For the first time, in recent years prospective studies have been published about the effects of early vs. delayed introduction of allergenic foods into the infants' diet on food allergy. According to these studies, the early introduction of peanut may be a powerful protecting factor against peanut allergy in some risk categories. This seems not be true for wheat, cow's milk, sesame, and whitefish. The effect of early introduction of egg on egg allergy are controversial. SUMMARY The recent studies have changed the practice recommendations given by healthcare providers to families. We review the modifications of the recommendations of international societies on the introduction of solid foods, both to the general population and to infants at risk for allergy.

The number of infant formulas intended for food allergy treatment or prevention has been increasing. Some products fulfill the criteria for hypoallergenicity, such as extensively hydrolyzed protein (casein or whey) and synthesized amino acid formulas (elemental diet). Numerous partially hydrolyzed formulas have been derived from bovine milk, soybean, and rice. They are not hypoallergenic and are not recommended for children allergic to the parent protein, yet certain preparations have shown efficacy for allergy prevention. Soybean-derived preparations, although not hypoallergenic, have been tolerated by a majority of children allergic to bovine milk. Studies on the addition of probiotics or prebiotics to infant formulas have shown inconsistent findings. Numerous hypoallergenic formulas or milk substitutes are available for pediatricians to choose for children with food allergy. Caution is needed in prescribing formulas that are erroneously marketed as hypoallergenic. [ Pediatr Ann . 2016;45(4):e150–e156.]

Severe combined immunodeficiency (SCID) is a fatal childhood disease unless immune reconstitution is performed early in life, with either hematopoietic stem cell transplantation or gene therapy. One of its subtypes is caused by adenosine deaminase (ADA) enzyme deficiency, which leads to the accumulation of toxic metabolites that impair lymphocyte development and function. With the development of polyethylene glycol–conjugated adenosine deaminase (PEG-ADA) enzyme replacement therapy, many ADA-deficient children with SCID who could not receive a hematopoietic stem cell transplantation or gene therapy survived and had longer and healthier lives. We report a 24-year course of treatment in a patient who was diagnosed with ADA deficiency at 4 months of age. The patient was treated with PEG-ADA, which was the only therapy available for him. The patient’s plasma ADA level was regularly monitored and the PEG-ADA dose adjusted accordingly. This treatment has resulted in near-normalization of lymphocyte counts, and his clinical course has been associated with only minor to moderate infections. Thus far, he has had no manifestations of autoimmune or lymphoproliferative disorders. This patient is among the longest to be maintained on PEG-ADA enzyme replacement therapy.

Specialists in allergy/immunology are often asked to evaluate patients with eosinophilia, with the general assumption of an underlying allergic or immunologic disease. We present a case of an infant referred for marked eosinophilia. Although atopic disease may be in the differential diagnosis, it is rarely associated with hypereosinophilia, and other conditions need to be investigated. Until the underlying cause is identified, systemic corticosteroid therapy may be initiated, mainly in severe cases.

Allergist/clinical immunologist maintenance of certification and training program reaccreditation are mandatory in some countries. The World Allergy Organization conducted surveys in 2009 and 2011 to assess where such programs were available and to promote the establishment of such programs on a global level. This was done with the presumption that after such an ''inventory,'' World Allergy Organization could offer guidance to its Member Societies on the promotion of such programs to assure the highest standards of practice in the field of allergy and clinical immunology. This review draws on the experience of countries where successful programs are in place and makes recommendations for those wishing to implement such programs for the specialty. Keywords: allergy and clinical immunology, allergist, physician skills, physician competencies, physician performance measurement

6 Sou .com The issue of apostrophe “s” in eponyms has frequently arisen during our Journal Clubs and other seminars. On multiple occasions, we have encountered an eponym of a particular disease or syndrome including an “s” with an apostrophe by certain medical writers and without an “s” apostrophe by other medical writers. By the way, these 2 terms (disease and syndrome) too are sometimes used interchangeably. Generally speaking, when the illness has several clinical features or laboratory findings or both, but not all are present in every patient or are required to establish the diagnosis, it is usually called a syndrome rather than a disease. Let us go back to the controversy of the incorrect use of apostrophe “s,” which has prevailed throughout scientific writings and oral presentations. Over the years, the medical literature has been inconsistent, predominated by the incorrect use. Strictly speaking, apostrophe “s” reflects possessiveness. It is correct when the syndrome or disease is named after the first described patient (e.g., Lou Gehrig’s disease, Job’s syndrome or Duncan’s disease). Much more commonly, a syndrome or disease has been linked to the name of the physician or the scientist who first described it, as an honorific eponym (e.g., Bruton hypogammaglobulinemia, Churg-Strauss syndrome, DiGeorge syndrome, Hodgkin lymphoma, Sjogren syndrome and Wiskott-Aldrich syndrome). In such instances, an apostrophe or an “s” should not be used. The same applies to physical signs, microorganisms, procedures or tests. Apostrophe before or after the “s” would be inappropriate in cases like Wilms tumor and Coombs test because the “s” here is a part of the name of the scientist. By searching the history of common eponyms in a variety of textbooks, Wikipedia and other sources, we created a list (Table) of common eponyms with