A 34-year-old man suddenly developed an erythematous and exfoliative facial rash. Within days, his skin became intensely pruritic and painful, and the rash spread to his entire body. He also acquired malaise with fever of 39.7°C, necessitating hospitalization. Examination revealed thickened and oozing plaques covering his face; in addition, multiple erythematous papules erupted on his torso and bilateral extremities, but no mucosal erosions (Figure 1). His history was notable for lifelong atopic dermatitis self-treated with hydrocortisone ointment/cream 1% (up to 2.5%) multiple times daily, with use of class III potency topical corticosteroids (TCS) intermittently for flares.

Mastocytosis denotes a wide range of disorders characterized by having abnormal growth and accumulation of mast cells. Mast cells contain histamine and other inflammatory mediators, which have diverse actions within the body, and play crucial roles in acquired and innate immunity. The diverse actions of these inflammatory mediators can lead to puzzling symptoms in individuals with mastocytosis. These symptoms can include flushing, pruritis, nausea, vomiting, abdominal pain, diarrhea, vascular instability, and headache. These clinical features generally divide into cutaneous and systemic manifestations, giving rise to the two divisions of mastocytosis: cutaneous mastocytosis (CM) and systemic mastocytosis. CM has a highly favorable clinical prognosis. Systemic mastocytosis has a range of severity, with the milder forms often remaining chronic conditions, while the severe forms have rapid complex courses with poor prognoses. Generally, treatment is aimed at avoiding mast cell degranulation, inhibiting the actions of the constitutive mediators released by mast cells and, in severe cases, cytoreductive and polychemotherapeutic agents. Behavioral intervention includes avoidance of triggers, such as heat, cold, pressure, exercise, sunlight, and strong emotions. Treatment for released histamine and other inflammatory mediators includes H1 antihistamines, H2 antihistamines, proton pump inhibitors, anti-leukotriene agents, and injectible epinephrine (for possible anaphylaxis). For severe cases, treatment includes cytoreductive agents (interferon alpha, glucocorticoids, and cladribine) and polychemotherapeutic agents (daunomycin, etoposide, and 6-mercaptopurine). For very specific and severe cases, tyrosine kinase inhibitors, imatinib and midostaurine, have shown promise.

Objectives: Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by vascular damage, autoimmunity, and excessive collagen deposition. Despite advances in disease-specific treatment of other rheumatologic diseases, disease-targeted treatment in SSc continues to be elusive. In this review, Our goal was to place the contemporary immunoblology of SSc in the perspective of clinical medicine.Methods: We performed a PUbMed search for the period from 1989 to 2007, using the keyword, "systemic sclerosis," resulting in a total of 9099 publications, including 1252 reviews. Articles were then selected based on their discussion Of recent advances in the elusive pathogenesis of SSc. A final total of 259 articles were chosen for the review.Results: The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. T-cells are a major component of the infiltrate in skin and lung, exhibiting increased expression of activation markers and showing signs of antigen-driven expansion. Preliminary, data indicate that induction of oral tolerance with collagen, a target of SSc T-cell responses, is associated with clinical benefits. Although this Suggests that T-cells participate in the pathogenesis of SSc, their precise role and antigen specificity largely remain to be elucidated. Defective numbers and functions of certain T-cell Subsets, such as natural killer and gamma delta T-cells, may be involved in the failure to maintain tolerance. Other data Suggest that gamma delta T-cells may themselves be effector cells in endothelial cell cytotoxicity. There are several lines of evidence for a pathogenic role of B-cells in SSc, in particular, through the production of autoantibodies. Antibody-dependent cell-mediated cytotoxicity is a primary pathogenic event tit art animal model of SSc and is likely to be involved In human SSc. Nonetheless, there is as yet no convincing evidence for the pathogenicity of SSc-specific antibodies. SSc fibroblasts exhibit a specific phenotype characterized not only by excessive collagen production but also by increased responsiveness to and production of cytokines and chemokines. This phenotype is induced by a complex network of cytokines and chemokines but appears to be maintained in the absence of exogenous stimuli via the autocrine production of sonic of these factors by SSc fibroblasts themselves, particularly transforming growth factor, platelet-derived growth factor, monocyte chemoattractant protein 1, and interleukin-1.Conclusions: Significant variations in laboratory, data among patients Suggest that the pathology reflects a heterogeneous disease. Nonetheless, the possibility of achieving clinical benefits by inducing oral tolerance highlights the importance of characterizing SSc T-cell antigens. It is hoped that the identification of some of the key players in the induction and maintenance of the SSc fibroblast phenotype may yield new disease-targeted treatment regimens for patients with SSc. (C) 2008 Elsevier Inc. All rights reserved.

Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably, the clinician will encounter patients with clear indications for aspirin therapy but a history of aspirin sensitivity. Although protocols have been established for aspirin challenge and desensitization, it is not always an efficacious or safe procedure. This article reviews the different classifications of ASA/NSAIDs hypersensitivities to better guide the clinician in dealing with this patient population. History of crossrelativities between multiple NSAIDs implies a non-IgE-mediated process. Similarly, a history of monosensitivity to one NSAID implies an IgE-mediated process, although specific antibodies are often elusive. Despite the name, AERD can potentially be exacerbated by all cyclooxygenase (COX) inhibitors based on dose-dependent inhibition of COX-1. Aspirin desensitization can be achieved to improve both upper and lower respiratory symptoms for most patient with AERD. Aspirin desensitization can usually be achieved for those in need of the antiplatelet effects of aspirin, with the exception of those with aspirin-induced urticaria and baseline chronic urticaria.However, desensitization should only be attempted in those with stable coronary artery disease because the process of desensitization carries the inherent risk of anaphylaxis / anaphylactoid reaction, which may further increase cardiac demand and bring about ischemic injury. Therefore, desensitization is reserved until coronary artery disease is stabilized.

In recent years, an explosion of biologic response modifiers has entered the market to combat a variety of immune-mediated diseases. These can be in the form of recombinant cytokines, as in the case of interferon beta in the treatment of multiple sclerosis, or novel engineered antibodies constructed by combining non-human determinants with a human immunoglobulin scaffold, as in the case of omalizumab in the treatment of allergic asthma. More recently, completely human monoclonal antibodies have also been constructed. Adverse reactions related to these agents can be classified as expected or unexpected events. A number of case studies and a handful of randomized trials have demonstrated the potential toxicities with the use of biologic response modifiers. This article aims to review adverse event profiles of select biologic response modifiers for which the most data is available and are common to a rheumatology, allergy/immunology, and dermatology patient population.

Variants of mastocytosis can present with puzzling cutaneous and systemic symptoms and signs that can result in an erroneous diagnosis of idiopathic urticaria or idiopathic anayphylaxis. The molecular basis of mastocytosis is now better understood, with updated classification based on distinct growth factor and oncogene abnormalities. Elicitation of a full history and careful attention to the skin examination will usually provide the clinician enough information to deduce that the condition is not simply chronic idiopathic urticaria.