Primary immunodeficiency update

Pichard, Dominique C.; Freeman, Alexandra F.; Cowen, Edward W.

doi:10.1016/j.jaad.2015.01.054

Cited by 34 publications

(7 citation statements)

References 56 publications

(70 reference statements)

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“…The diagnosis of AD is made clinically, and currently, there are no biomarkers available to distinguish it from other conditions. Skin biopsy is not routinely used or [27][28][29][30][31][32][33].…”

Section: Diagnosismentioning

confidence: 99%

Atopic Dermatitis in the Adult Population

R¹,

D²,

L³

2023

Arch Fam Med Gen Pract

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Atopic Dermatitis (AD) is a chronic inflammatory disease of the skin characterized by cutaneous findings of dry skin, erythematous scaly papules, or plaques, and lichenification. The hallmark of AD is pruritis, which drives most of the disease burden. While this disease is thought to primarily affect children, it commonly affects adults as well [1]. In the adult population, AD may be persistent from childhood, relapsing AD that was thought to be resolved, or adult-onset AD. Although AD is commonly seen in the adult population and is associated with a significant disease burden, many providers are inadequately educated about the recognition and treatment of AD in adults. This paper will review the clinical features, pathophysiology, diagnosis, treatment, and management of AD in the adult population. Working to better understand AD and its impact on patients may be beneficial in minimizing the burden of this disease on the adult population. Check for updatesAD patients have a family history of atopy [8]. There are also several genes associated with an increased risk for AD, many of which code for proteins involved in the skin barrier or immune regulation [9]. One major genetic alteration associated with an increased risk for AD is a loss-of-function mutation in the FLG gene. This gene codes for the filaggrin protein, which is a component of natural moisturizing factors and is key for the barrier function of the skin.Environmental risk factors include living in an urban area, stress, increased domestic water hardness, exposure to irritants (e.g., tobacco smoke), increased adiposity, and a Western diet [10]. It is also believed that increased exposure to pathogens early in life can be protective against AD, termed the "hygiene hypothesis." This hypothesis theorizes that exposure to dirt and pathogens early in life can steer the immune system away from allergic inflammation [11]. This hypothesis may explain regional differences in the incidence of AD, as well as the increasing prevalence of AD over the past half-century [10].

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Section: Diagnosismentioning

confidence: 99%

Atopic Dermatitis in the Adult Population

R¹,

D²,

L³

2023

Arch Fam Med Gen Pract

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“…Primary immunodeficiency disorders (PIDs), also termed inborn errors of immunity (IEI), encompass a variable group of hereditary diseases harboring defects in innate and adaptive immune responses. Patients often present with recurrent infections, failure to thrive, and have an elevated risk of autoimmunity, allergy, and malignancy ( 1 , 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…Many immunodeficiencies have associated cutaneous eruptions, which can be specific for the disorder or nonspecific. For example, “Eczematous dermatitis,” characterized by erythema, inflammatory papules or plaques, scale, and pruritus, is a common cutaneous presentation of a subset of PIDs [e.g., Omen syndrome, severe combined immunodeficiency (SCID)] ( 1 – 5 ). In addition, primary immunodeficiencies may present with nonspecific inflammatory eruptions, including granulomatous nodules, cold abscesses, urticaria, and ulcers ( 2 , 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

A horse or a zebra? Unusual manifestations of common cutaneous infections in primary immunodeficiency pediatric patients

Ollech

Simon²,

Lev³

et al. 2023

Front. Pediatr.

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BackgroundPatients with primary immunodeficiency disorders (PIDs) often suffer from recurrent infections because of their inappropriate immune response to both common and less common pathogens. These patients may present with unique and severe cutaneous infectious manifestations that are not common in healthy individuals and may be more challenging to diagnose and treat.ObjectiveTo describe a cohort of patients with PIDs with atypical presentations of skin infections, who posed a diagnostic and/or therapeutic challenge.MethodsThis is a retrospective study of pediatric patients with PID with atypical presentations of infections, who were treated at the immunodeficiency specialty clinic and the pediatric dermatology clinic at the Sheba Medical Center between September 2012 and August 2022. Epidemiologic data, PID diagnosis, infectious etiology, presentation, course, and treatment were recorded.ResultsEight children with a diagnosis of PID were included, five of whom were boys. The average age at PID diagnosis was 1.7 (±SD 3.2) years. The average age of cutaneous infection was 6.9 (±SD 5.9) years. Three patients were born to consanguineous parents. The PIDs included the following: common variable immunodeficiency, severe combined immunodeficiency, DOCK8 deficiency, ataxia telangiectasia, CARD11 deficiency, MALT1 deficiency, chronic granulomatous disease, and a combined cellular and humoral immunodeficiency syndrome of unknown etiology. The infections included the following: ulcerative-hemorrhagic varicella-zoster virus (two cases) atypical fungal and bacterial infections, resistant Norwegian scabies, giant perianal verrucae (two cases), and diffuse molluscum contagiosum.ConclusionsIn this case series, we present unusual manifestations of infectious skin diseases in pediatric patients with PID. In some of the cases, recognition of the infectious process prompted life-saving treatment. Increasing familiarity with these dermatological manifestations, as well as keeping a high index of suspicion, is important to enabling early diagnosis of cutaneous infections in PIDs and initiation of prompt suitable treatment.

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“…This endotyping approach could be of interest as immune dysregulation may play an important role in the pathogenesis of the atopic syndrome. Interestingly, the atopic syndrome is a prevalent comorbidity in primary immunodeficiency diseases (PIDs), for example in hyper IgE syndrome (HIES), Comèl Netherton syndrome and immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, which suggests that the atopic syndrome could be caused by a genetic defect in pathways that are also involved in these monogenic PIDs [26, 27]. This is supported by the hypothesis of autoallergy, in which atopy seems to stand at the boundary between allergy and auto-immunity, given the presence of IgE antibodies against self-proteins [28–30].…”

Section: Introductionmentioning

confidence: 99%

Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?

Wit

Wijck

Dalm

et al. 2019

Clin Transl Allergy

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Background The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity. Based on the genetic defects in PIDs, novel gene/pathway-targeted therapies have been evaluated, which could be relevant in the atopic syndrome as well. Therefore, we aimed to define subclasses within the atopic syndrome based on the expression profiles of immune cell lineages of healthy mice. Methods Overlap between known atopy-related genes as described in the Human Gene Mutation Database and disease-causing genes of monogenic PIDs was evaluated. Clusters of atopy-related genes were based on the overlap in their co-expressed genes using the gene expression profiles of immune cell lineages of healthy mice from the Immunological Genome Project. We analyzed pathways involved in the atopic syndrome using Ingenuity Pathway Analysis. Results Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and PID-related genes (n = 278). We identified seven distinct clusters of atopy-related genes. Functional pathway analysis of all atopy-related genes showed relevance of T helper cell-mediated pathways. Conclusions This study shows a model to define clusters within the atopic syndrome based on gene expression profiles of immune cell lineages. Our results support the hypothesis that both genetic mechanisms and immune dysregulation play a role in the pathogenesis. It also opens up the possibility for novel therapeutic targets and a more tailored approach towards personalized medicine. Electronic supplementary material The online version of this article (10.1186/s13601-019-0273-8) contains supplementary material, which is available to authorized users.

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Primary immunodeficiency update

Cited by 34 publications

References 56 publications

Atopic Dermatitis in the Adult Population

Atopic Dermatitis in the Adult Population

A horse or a zebra? Unusual manifestations of common cutaneous infections in primary immunodeficiency pediatric patients

Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?

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