Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

Gernez, Yaël; Freeman, Alexandra F.; Holland, Steven M.; Garabedian, Elizabeth; Patel, Niraj; Puck, Jennifer M.; Sullivan, Kathleen E.; Akhter, Javeed; Secord, Elizabeth; Chen, Karin; Buckley, Rebecca H.; Haddad, Élie; Ochs, Hans D.; Fuleihan, Ramsay; Routes, John M.; Muskat, Mica; Lugar, Patricia L.; Mancini, Julien; Cunningham‐Rundles, Charlotte

doi:10.1016/j.jaip.2017.06.041

Cited by 70 publications

(61 citation statements)

References 40 publications

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“…Cohen et al found no atopy in patients with AT. In HIES unspecified, AD‐HIES and AR‐HIES, all of the atopic symptoms, if reported, were present in about half of the patients . Renner et al described the presence of atopy in most Comèl‐Netherton patients.…”

Section: Resultsmentioning

confidence: 99%

Skin disorders are prominent features in primary immunodeficiency diseases: A systematic overview of current data

Wit

Brada

Veldhuizen

et al. 2018

Allergy

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Primary immunodeficiency diseases (PIDs) are characterized by an increased risk of infections, autoimmunity, autoinflammation, malignancy, and allergic disorders. Skin disorders are also common clinical features in PIDs and may be among the presenting manifestations. Recognition of specific PID-associated skin conditions in combination with other clinical features as described in the currently used warning signs could raise suspicion of an underlying PID. We aimed to provide a systematically obtained overview of skin disorders and their prevalence in PIDs. Secondary, the prevalence of Staphylococcus (S.) aureus-associated skin disorders and atopy was reviewed, as these are the most prominent skin features in PIDs. A systematic search was performed in EMBASE, MEDLINE, Web of Science, Cochrane, and Google Scholar (up to May 9, 2018). All original observational and experimental human studies that address the presence of skin disorders in PIDs were selected. We rated study quality using the Institute of Health Economics Quality Appraisal Checklist for Case Series Studies. Sixty-seven articles (5030 patients) were included. Study quality ranged from 18.2% to 88.5%. A broad spectrum of skin disorders was reported in 30 PIDs, mostly in single studies with a low number of included patients. An overview of associated PIDs per skin disorder was generated. Data on S. aureus-associated skin disorders and atopy in PIDs were limited. In conclusion, skin disorders are prominent features in PIDs. Through clustering of PIDs per skin disorder, we provide a support tool to use in clinical practice that should raise awareness of PIDs based on presenting skin manifestations.

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Section: Resultsmentioning

confidence: 99%

Skin disorders are prominent features in primary immunodeficiency diseases: A systematic overview of current data

Wit

Brada

Veldhuizen

et al. 2018

Allergy

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“…Thus, STAT3 deficiency explains the delayed shedding of primary teeth, susceptibility to bone fractures, development of aneurysms and the coarse facial features which are hallmarks of Job syndrome. It is therefore not surprising that patients with AD‐HIES because of STAT3 mutations present with broad immunological and non‐immunological manifestations …”

Section: Stat3 Loss‐of‐function Mutations With Dominant Negative Effectmentioning

confidence: 99%

“…Neonatal onset eczema (present in 57% of patients), recurrent cutaneous staphylococcal infections with abscess formation (74%), recurrent pneumonias caused by Staphylococcus aureus (72%) and Aspergillus fumigatus (27%) often resulting in pneumatoceles, deep organ abscesses, mucocutaneous candidiasis (MCC), along with skeletal, dental and connective tissue abnormalities sum up the clinical features of AD‐HIES . While thought to be uncommon, a recent report listed food (37%) and environmental (18%) allergies as being present in a cohort of 58 patients with AD‐HIES collected in the USIDnet registry; nonetheless this is less frequent than reported by patients with DOCK8 deficiency, possibly related to impaired mast cell degranulation .…”

Section: Stat3 Loss‐of‐function Mutations With Dominant Negative Effectmentioning

confidence: 99%

“…Non‐immunological manifestations such as skeletal, dental and connective tissue abnormalities are key distinguishing features. These include characteristic facial features (increased interalar distance, prominent forehead and facial asymmetry), retained primary teeth (41%), hyperextensible joints (4%), scoliosis (34%), recurrent pathological fractures (39%) and vascular anomalies . It is important to recognize that these features accumulate over time, and may be absent early in life, posing a diagnostic challenge.…”

Section: Stat3 Loss‐of‐function Mutations With Dominant Negative Effectmentioning

confidence: 99%

“…While marked elevation in serum IgE (2000–100,000 IU mL −1 ) is observed in almost all patients (because of impaired IL‐10 and IL‐21 signaling), IgE levels start to rise only after birth and decrease or even normalize during adulthood, being inversely correlated with patient age . Hence, a normal or an IgE level <2000 is not exclusive of the diagnosis.…”

Section: Stat3 Loss‐of‐function Mutations With Dominant Negative Effectmentioning

confidence: 99%

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Hyper IgE syndromes: clinical and molecular characteristics

2018

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Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels. Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders. However, several other genetically characterized immunodeficiency disorders have been identified over the past decade and joined the umbrella of hyper IgE syndromes including autosomal recessive mutations in the DOCK8, ZNF431 and PGM3 genes and heterozygous mutations with dominant negative effect in the CARD11 gene. Moreover, a number of phenotypically distinct immunodeficiency disorders can mimic hyper IgE syndromes, adding to the diagnostic challenge. Herein, we will concisely review these disorders, their molecular bases, highlighting key distinguishing clinical and laboratory findings and therapeutic options.

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