GUHA KRISHNASWAMY, MD, FACP, FCCP, FAAAI, FACAAI

Methods3 cases of malignancy following dupilumab use in our hospitals were studied. The literature was reviewed for published cases of dupilumab-related malignancy. Mechanisms of oncogenesis were extrapolated from published IL-4-JAK-STAT axis abnormalities.ResultsIn our single institution three patients treated with dupilumab for fungal sinusitis, asthma and eczema developed rapidly progressive and aggressive cancers including glioblastoma multiforme, fatal pancreatic cancer and advanced sinonasal cancer. Over 30 cases of cutaneous T-cell lymphoma (CTCL) related to dupilumab use have been published. Hematological malignancies such as anaplastic lymphoma, Sezary syndrome and Hodgkin’s lymphoma, and solid tumors, specifically sinonasal, pancreatic, lung, testicular and prostate cancers, have been reported.ConclusionsMulticenter and single institutional studies have shown sporadic …

The management of atopic diseases has been revolutionised by precision therapies and biological drugs that target specific immune proteins. This report elucidates a unique complication from the use of the monoclonal antibody, dupilumab, that primary care providers and subspecialists need to be aware of. A patient in her 40s consulted us for severe atopic asthma, food allergy and eczema involving the face and body. She had previously failed treatments and was started on dupilumab (which binds to the interleukin-4 [IL4] receptor and inhibits both IL-4 and IL-13). She quickly achieved remission of asthma, rhinitis and eczema. Therapy was, however, complicated by severe blepharoconjunctivitis, dry eyes and periorbital dermatitis, consistent with dupilumab-induced ocular surface disease and dupilumab-associated mucin deficiency. Following aggressive treatment of ocular disease, the patient was able to …

Human eosinophils develop in the bone marrow in response to specific hematopoietic factors including interleukin-5. They circulate in the peripheral blood in small numbers (usually less than 500 cells/mm3 or less than 5% of total leukocytes) and migrate to various tissues, where they are responsible for host defense, cancer immunity and homeostasis. Activated eosinophils are capable of expressing multiple, pleiotropic, and redundant mediators that complement the immune response and can enhance tissue healing and fibrosis. The finding of elevated eosinophil counts in the blood is referred to as hypereosinophilia (HE) while hypereosinophilic syndrome (HES) describes HE with evidence of end-organ damage. Many categories of the HES have been described, including the familial, secondary, or reactive, myeloid (related to myeloid neoplasia with typical mutations, fusions, or gene rearrangements), lymphoid …

Figure 1: Clichés d’œsophagogastroduodénoscopie chez un homme de 31 ans présentant une impaction alimentaire aiguë; on voit (A) l’aspect en anneaux concentriques ou «félinisation»(flèches blanches), un signe caractéristique de l’œsophagite à éosinophiles et (B) bouchée de steak coincée (flèche noire) à 30 cm.

Budesonide for nebulizer use can be administered as a slurry mixed with a flavoured sugar substitute (off-label use). Du pilumab, an antibody to interleukin-4, has recently received approval from the United States Food and Drug Administration for patients with refractory eosinophilic esophagitis, but its use is limited by availability and cost. Impacted food may require endoscopic extraction, while strictures may require dilatation.

What does Generation Z mean? Generation Z is the name given to the current generation of young people by many demographic researchers. According to the Pew Research Center (1), Generation Z is the generation of people born between 1997 and 2010. It is the successor to Generation Y and precedes Generation Alpha. It is defined as the first generation to be born into a world with the Internet, smart devices and apps. As a result, these individuals have radically different views on the meaning of privacy, trust and relationships in the digital world. They are also more dedicated to overall personal wellness—but everything it encompasses, including economic security, nutrition, fitness, sleep and stress management. Members of Generation Z are fighting for social change, racial equity and environmental protection. They are also more likely to be highly educated and include many participants in medical professions. These are aspects that the healthcare industry has never addressed.Caring for patients is a form of priesthood, we've been taught, and we know stories of physicians who have dedicated their lives to caring for others, some even losing their lives in the process (for example during wars, environmental disasters and pandemics). The recent experience with the COVID-19 outbreak has shown us how physicians have risked their lives to save patients.

IntroductionThe management of severe, recalcitrant viral warts (extragenital warts or verucca vulgaris, palmar and plantar warts) is far from clear. Inability to clear human papilloma virus (HPV) may be followed by neoplastic transformation. Immunity to HPV includes type 1 T-helper cells, CD8+ T cell, neutrophils and chemokines acting via CXCR4 receptors. Acquired (HIV infection, malignancy, chemotherapeutic drugs etc) and inborn errors of immunity (such as the WHIM syndrome and epidermodysplasia verruciformis/EV) can predispose to refractory warts. We describe the management of an immunocompetent young man with refractory warts.Case DescriptionThe patient is a 42-year-old male who had undergone multiple surgical resections of large cutaneous veruccae followed by prolonged pain and slow healing. Wart recurrences were common and resulted in significant disability. The patient had failed topical …

IntroductionAquagenic urticaria (AquaU) is a rare chronic inducible urticaria (CINDU) characterized by hives occurring within 30 minutes of exposure to water and resolving within two hours. AquaU is classified into two subtypes: familial and acquired. Quality of life can be diminished due to difficulty of daily tasks such as bathing and handwashing. Omalizumab has been used in refractory cases of CINDU including AquaU. We present 2 cases of refractory aquagenic urticaria that went into remission following short term treatment with high dose omalizumab.Case DescriptionsA 64-year-old male, after showering, presented with pruritic wheals over his trunk and limbs, refractory to high dose anti-histamines, montelukast and monthly Omalizumab 300 mg. Laboratory data was unrevealing. Omalizumab was increased to 450 mg, with complete resolution after two doses, and was discontinued 6 months later.A 62-year …

IntroductionDelayed pressure urticaria (DPU) is an uncommon type of severe, inducible urticaria that can present independently or as a complicating form of chronic spontaneous urticaria. The disorder is characterized by wheal eruption and tissue edema within hours following exposure to mechanical pressure. Wearing tight clothing, carrying weights, sitting, walking and even sleeping are common triggers. Management can be challenging. We present two cases of dramatic resolution of DPU following administration of omalizumab.Case DescriptionA 42 year-old male presented with frequent episodes of painful swelling of the face, hands, and feet preceded by pruritis and warmth. These attacks occurred as often as twenty times per year and continued to progress despite management with histamine blockade (H1 and H2) and leukotriene receptor antagonists. Laboratory testing was unremarkable for immune …

Recurrent pneumonia related to a Haemophilus influenzae-specific antibody deficiency and its alleviation by vaccination Recurrent pneumonia related to a Haemophilus influenzae-specific antibody deficiency and its alleviation by vaccination Ann Allergy Asthma Immunol. 2022 Jul;129(1):106-107. doi: 10.1016/j.anai.2022.03.032. Epub 2022 Apr 9. Authors Samantha Minh Thy Nguyen 1 , Merin Anna Reji 2 , Aaisha Haque 3 , Guha Krishnaswamy 4 Affiliations 1 Wake Forest Baptist Health, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina. 2 Wake Forest Baptist Health, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina. Electronic address: mreji@wakehealth.edu. 3 Department of Veterans Affairs, WG (Bill) Hefner VA Medical Center, Salisbury, North Carolina. 4 Wake Forest Baptist Health, Wake Forest School of Medicine, Wake Forest …

An immunocompetent man in his 20s presented with a 24-hour history of severe odynophagia, nausea, vomiting and throat pain. Esophagogastroduodenoscopy (EGD) revealed severe esophagitis with ulcerated mucosa, exudative debris, haemorrhage and multiple erosions. Biopsy of the oesophageal tissue demonstrated marginated chromatin, multinucleated giant cells and molding of nuclei, consistent with herpes simplex virus esophagitis (HSE). Treatment with oral acyclovir led to the complete resolution of symptoms. The patient subsequently developed dysphagia again, 8 months later. EGD showed furrowing and concentric rings typical of eosinophilic esophagitis (EoE), a diagnosis confirmed by biopsy. Treatment with a proton pump inhibitor and swallowed topical corticosteroids led to symptomatic improvement. Thus, HSE can occur in immunocompetent hosts and on occasion, HSE may be a harbinger of …

Food allergy (FA) directly affects 1 in 13 children, 1 and accumulating research has highlighted a plethora of psychosocial difficulties faced by families of children with FA. 2-5 However, psychosocial research and interventions to date have tended to focus on young children and caregivers, with a dearth of literature dedicated to the unique psychosocial needs of adolescents with FA. 5, 6 Existing research on adolescents with FA has largely focused on medical risk, as the highest rates of anaphylaxis and fatalities occur among this population. 7, 8 Although it is important to acknowledge risk taking, it is also necessary to more broadly explore how FA interact with the developmental context of adolescence. As the prevalence of FA increases, and more children with FA become adolescents with FA, it is imperative to (1) identify the psychosocial needs of adolescents with FA and (2) subsequently develop resources to …

Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify …

Anaphylaxis is a severe, acute, life-threatening multisystem allergic reaction resulting from the release of a plethora of mediators from mast cells culminating in serious respiratory, cardiovascular and mucocutaneous manifestations that can be fatal. Medications, foods, latex, exercise, hormones (progesterone), and clonal mast cell disorders may be responsible. More recently, novel syndromes such as delayed reactions to red meat and hereditary alpha tryptasemia have been described. Anaphylaxis manifests as sudden onset urticaria, pruritus, flushing, erythema, angioedema (lips, tongue, airways, periphery), myocardial dysfunction (hypovolemia, distributive or mixed shock and arrhythmias), rhinitis, wheezing and stridor. Vomiting, diarrhea, scrotal edema, uterine cramps, vaginal bleeding, urinary incontinence, dizziness, seizures, confusion, and syncope may occur. The traditional (or classical) pathway is mediated via T cells, Th2 cytokines (such as IL-4 and 5), B cell production of IgE and subsequent crosslinking of the high affinity IgE receptor (FcεRI) on mast cells and basophils by IgE-antigen complexes, culminating in mast cell and basophil degranulation. Degranulation results in the release of preformed mediators (histamine, heparin, tryptase, chymase, carboxypeptidase, cathepsin G and tumor necrosis factor alpha (TNF-α), and of de novo synthesized ones such as lipid mediators (cysteinyl leukotrienes), platelet activating factor (PAF), cytokines and growth factors such as vascular endothelial growth factor (VEGF). Of these, histamine, tryptase, cathepsin G, TNF-α, LTC4, PAF and VEGF can increase vascular permeability. Recent data …

OBJECTIVES:Anaphylaxis is a rapidly progressive life-threatening syndrome manifesting as pruritus, urticaria, angioedema, bronchospasm and shock. The goal of this synthetic review is to provide a practical, updated approach to the evaluation and management of this disorder and associated complications.DATA SOURCES:A MEDLINE search was conducted with the MeSH of anaphylaxis, anaphylactic reaction, anaphylactic shock, refractory anaphylaxis and subheadings of diagnosis, classification, epidemiology, complications and pharmacology. The level of evidence supporting an intervention was evaluated based on the availability of randomized studies, expert opinion, case studies, reviews, practice parameters and other databases (including Cochrane).STUDY SELECTION:Selected publications describing anaphylaxis, clinical trials, diagnosis, mechanisms, risk factors and management were retrieved …

Stiff Person Syndrome (SPS), a rare autoimmune neurologic disorder characterized by fluctuating muscle spasms and rigidity, is mediated by autoantibodies to glutamic acid decarboxylase (GAD) antibodies. Symptoms of SPS have been shown to improve after administration of intravenous immunoglobulin (IVIG) however, there is a paucity of information regarding use of SCIg in SPS. Four patients with Stiff Person Syndrome were treated with SCIgPro20 for a period between 31 to 101 months. Most reactions were local and mild. All patients reported improvement in spasticity, and 2 patients reported improvement in seizure frequency. SCIgPro20 was well tolerated in patients with SPS and was associated with improvement in symptoms.