Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity

Renner, Eleonore D.; Puck, Jennifer M.; Holland, Steven M.; Schmitt, M L; Weiss, Michael E.; Frosch, Michael; Bergmann, Markus; Davis, Joie; Belohradsky, Bernd H.; Grimbacher, Bodo

doi:10.1016/s0022-3476(03)00449-9

Cited by 256 publications

(251 citation statements)

References 20 publications

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“…1 The autosomal dominant form (AD-HIES), caused by dominant negative mutations in the STAT3 gene, 2 is additionally characterized by anomalies of the osseous and connective tissue, which do not exist in the autosomal recessive forms of HIES (AR-HIES). In the latter, we observe a high susceptibility to cutaneous viral infections, 3,4 allergies, and malignancies. However, autoimmune diseases are rarely reported.…”

mentioning

confidence: 86%

“…COMMENTARY AR-HIES was identified as a separate entity in 2004 4 and was linked to mutations in DOCK8 in 2009. 5,6 Early in the course of the disease and especially in children, the clinical distinction between the 2 forms of HIES (recessive and dominant) is difficult because of the similarity of the first symptoms, such as respiratory tract infections, eczema, and skin infection, combined with elevated levels of serum IgE and eosinophilia.…”

Section: Geneticsmentioning

confidence: 99%

“…3,4,7 Viral skin infections most commonly seen are severe and sometimes mutilating infections with Herpes simplex, Varicella zoster, Molluscum contagiosum, and human papilloma virus, which are often diffuse and resistant to usual therapies. 5,8,9,10 Some authors have reported efficiency of topical cidofovir for recalcitrant molluscum contagiosum in immunocompromised children.…”

Section: Geneticsmentioning

confidence: 99%

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Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Jouhadi¹,

Khadir²,

Ailal³

et al. 2014

Pediatrics

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Dedicator of cytokinesis 8 (DOCK8) deficiency is an innate error of adaptive immunity characterized by recurrent infections with viruses, bacteria, and fungi, typically high serum levels of immunoglobulin E, eosinophilia, and a progressive deterioration of T-and B-cell-mediated immunity. DOCK8 mutations are the second most common cause of hyper-immunoglobulin E syndromes (HIES). We report a case of DOCK8 deficiency associated with systemic lupus erythematosus (SLE). Association of SLE with HIES is very rare; to our knowledge, this is the sixth such case reported in the literature. A 10-year-old girl of consanguineous parents was followed in our clinic because of HIES since early childhood. She developed SLE with purpuric and necrotic skin lesions, diffuse arthritis, and glomerulonephritis. These autoimmune features were corroborated by the presence of antinuclear, anti-DNA, and antiphospholipid antibodies. The combination of HIES and autoimmunity makes treatment difficult, because the use of immunosuppressive drugs needed for SLE may worsen existing symptoms caused by the immunodeficiency. Our observation is the first case of association of SLE with HIES in the literature where the primary immune disease is genetically documented and labeled as DOCK8 deficiency.

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mentioning

confidence: 86%

Section: Geneticsmentioning

confidence: 99%

Section: Geneticsmentioning

confidence: 99%

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Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Jouhadi¹,

Khadir²,

Ailal³

et al. 2014

Pediatrics

Self Cite

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“…1,2 The disorder has recently been characterized at the molecular level by Zhang et al, who described mutations in DOCK8, a member of a family of Rho-Rac GTP-exchange factors, in 11 patients from 8 families suffering from AR-HIES. Four of the presented patients had died at the age between 13 and 21 years, three of these patients had developed squamous cell carcinoma, most likely because of persistent human papillomavirus infections.…”

Section: Introductionmentioning

confidence: 99%

Curative treatment of autosomal-recessive hyper-IgE syndrome by hematopoietic cell transplantation

Gatz

Benninghoff

Schütz

et al. 2010

Bone Marrow Transplant

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Autosomal-recessive hyper-IgE syndrome (AR-HIES) is a combined immunodeficiency recently found to be associated with mutations of DOCK8. Clinically, this disorder is characterized beside recurrent bacterial complications, in particular by an unusual susceptibility to extensive cutaneous viral complications and by a high risk for squamous cell carcinoma. Here, we report on lasting control over the disorder in two patients by hematopoietic cell transplantation (HCT). Both patients were suffering from extensive long-lasting cutaneous viral complications, in particular from disfiguring molluscum contagiosum infections, when treated at the age of 10 and 17 years. Donors were matched unrelated, and conditioning was carried out with a combination of fludarabine, melphalan and BM-targeted radioimmunotherapy. Both patients developed stable, full donor cell chimerism, with the exception of persistent lowIgA serum levels and the exception of normal immune functions. Over the course of several months, cutaneous manifestations of viral disease resolved completely and both patients remain clinically well and free of infectious complications at 4 and 2 years, respectively, after transplantation. This represents the first report indicating HCT to be curative in patients with AR-HIES, which should be considered early before life-threatening complications develop, which include malignancies.

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“…Recently, a homozygous mutation of tyrosine kinase 2 was discovered in a patient with eczema, moderately elevated serum IgE, and a mild T-cell deficiency 7) . However, some patients who was clinically diagnosed with HIES had no stat3 mutations 6,18) , indicating further genetic heterogeneity of the disease. In our patient, we found R382W mutation of the DNA-binding domain, which was reported to be the most frequent stat3 mutation in previous studies [5][6][7] .…”

Section: Discussionmentioning

confidence: 99%

A case of Hyper-IgE syndrome with a mutation of the STAT3 gene

et al. 2010

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Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disease which is characterized by high serum IgE levels, eczema, and recurrent infections. Herein we present the case of a patient with HIES associated with STAT3 gene (stat3) mutation. A 16 year-old girl was admitted to our hospital due to hemoptysis caused by pneumonia with bronchiectasis. She had a history of recurrent skin and respiratory tract infections, such as pneumonia caused by MRSA (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa. On physical examination, a broad round shaped nose, oral thrush, and chronic eczematous skin rash over her whole body were found. Laboratory data showed an elevated eosinophil count (750/&micro;L) and total IgE level (5,001 U/mL). The patient’s National Institutes of Health (NIH) score for HIES was 44. Direct sequencing of the STAT3 gene revealed that the patient was heterozygous for a missense mutation in the DNA binding domain of the STAT3 protein (c.1144C&gt;T, p. Arg382Trp). HIES should be suspected in patients with recurrent infections and can be confirmed by clinical scoring and genetic analysis

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Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity

Cited by 256 publications

References 20 publications

Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Curative treatment of autosomal-recessive hyper-IgE syndrome by hematopoietic cell transplantation

A case of Hyper-IgE syndrome with a mutation of the STAT3 gene

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