Hyper-IgE syndrome: Difference between revisions
No edit summary |
No edit summary |
||
Line 26: | Line 26: | ||
* HIES was first described by Davis et al in 1966 and it was named as [[Job's syndrome]]. | * HIES was first described by Davis et al in 1966 and it was named as [[Job's syndrome]]. | ||
* The criterai included triad of [[eczema]], recurrent skin and lung infections and high serum IgE . | * The criterai included triad of [[eczema]], recurrent skin and lung infections and high serum [[IgE]] . | ||
==Classification== | ==Classification== | ||
Line 36: | Line 36: | ||
* Hyper IgE syndrome is caused due to mutations in STAT 3 and [[Tyrosine kinase]] 2 genes. | * Hyper IgE syndrome is caused due to mutations in STAT 3 and [[Tyrosine kinase]] 2 genes. | ||
* Signal transducer and activator of transcription 3 (STAT3) is a [[Cytoplasm|cytoplasmic]] protein and a component of the JAK-STAT pathway of signal [[transduction]]. | * Signal transducer and activator of transcription 3 ([[STAT3]]) is a [[Cytoplasm|cytoplasmic]] protein and a component of the [[JAK-STAT signaling pathway|JAK-STAT]] pathway of signal [[transduction]]. | ||
* The binding of various [[Cytokine|cytokines]] to their receptors on the cell surface results in activation of [[Janus kinase|JAK]] proteins, which in turn [[Phosphorylation|phosphorylate]] [[STAT protein|STAT]] proteins. | * The binding of various [[Cytokine|cytokines]] to their receptors on the cell surface results in activation of [[Janus kinase|JAK]] proteins, which in turn [[Phosphorylation|phosphorylate]] [[STAT protein|STAT]] proteins. | ||
* The STATs then form [[Dimer|dimers]], translocate to the [[Cell nucleus|nucleus]], bind to specific sites on the [[DNA]], and activate target genes. | * The STATs then form [[Dimer|dimers]], translocate to the [[Cell nucleus|nucleus]], bind to specific sites on the [[DNA]], and activate target genes. | ||
Line 51: | Line 51: | ||
** Defect in neutrophil chemotaxis results in [[Skin|cutaneous]] cold abscess formation, in which signs of acute [[inflammation]] are absent. | ** Defect in neutrophil chemotaxis results in [[Skin|cutaneous]] cold abscess formation, in which signs of acute [[inflammation]] are absent. | ||
* '''T cell defects''' — | * '''T cell defects''' — | ||
** STAT3 plays a crucial role in the differentiation of naïve T cells into IL-17 producing [[T helper cell|CD4+ T cells]] (Th17 cells). | ** [[STAT3]] plays a crucial role in the differentiation of naïve T cells into IL-17 producing [[T helper cell|CD4+ T cells]] (Th17 cells). | ||
** Th17 cells are involved in the response to [[Fungus|fungal]] and extracellular bacterial infections. | ** [[T helper 17 cell|Th17]] cells are involved in the response to [[Fungus|fungal]] and extracellular bacterial infections. | ||
** These cells are significantly reduced or absent in patients with HIES . | ** These cells are significantly reduced or absent in patients with HIES . | ||
* '''B cell defects and abnormal IgE regulation''' — | * '''B cell defects and abnormal IgE regulation''' — | ||
** B cells are resonsible for the synthesis of [[Immunoglobulin E|IgE.]] | ** [[B cell|B cells]] are resonsible for the synthesis of [[Immunoglobulin E|IgE.]] | ||
** A defect in the B cells leads to abnormal synthesis of IgE. | ** A defect in the B cells leads to abnormal synthesis of IgE. | ||
** IgE regulation involves T cell stimulation, appropriate [[cytokine]] production, and the ability of B cells to class switch toward the production of IgE. | ** [[Immunoglobulin E|IgE]] regulation involves T cell stimulation, appropriate [[cytokine]] production, and the ability of B cells to class switch toward the production of IgE. | ||
** Thus, defects in IFN-gamma production or regulation contribute to the elevated levels of IgE. | ** Thus, defects in [[Interferon-gamma|IFN-gamma]] production or regulation contribute to the elevated levels of IgE. | ||
== Causes == | == Causes == | ||
* Hyper IgE syndrome is caused due to mutations in the signal transducer and activator of transcription 3 (''[[STAT3]]'') and [[Tyrosine kinase 2|tyrosine kinase]] 2 (''TYK2'') gene. | * Hyper IgE syndrome is caused due to mutations in the signal transducer and activator of transcription 3 (''[[STAT3]]'') and [[Tyrosine kinase 2|tyrosine kinase]] 2 (''TYK2'') gene. | ||
* STAT 3 gene is essential for the differentiation of helper T cells, mutation causes autosomal dominant type. | * STAT 3 gene is essential for the differentiation of helper T cells, mutation causes autosomal dominant type. | ||
* Tyrosine kinase 2 (''TYK2'') gene mutation causes autosomal recessive type. | * [[Tyrosine kinase 2]] (''TYK2'') gene mutation causes autosomal recessive type. | ||
==Differentiating {{PAGENAME}} from Other Diseases== | ==Differentiating {{PAGENAME}} from Other Diseases== | ||
Line 114: | Line 114: | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
===Natural History=== | ===Natural History=== | ||
* Patients of hyper IgE syndrome are born with [[Pustular rash|pustular]] or eczematoid rashes, or they may appear in first month of life. | * Patients of hyper IgE syndrome are born with [[Pustular rash|pustular]] or [[Eczema|eczematoid]] rashes, or they may appear in first month of life. | ||
* Recurrent eczema, boils and skin abscesses. | * Recurrent [[Eczema|eczema,]] [[Boil|boils]] and skin [[Abscess|abscesses]]. | ||
* Recurrent infections such as chronic otitis media, sinusitis, pneumonias, mucocutaneous infections, neurological and systemic. | * Recurrent infections such as chronic [[otitis media]], [[Rhinosinusitis|sinusitis]], [[Pneumonia|pneumonias]], [[Mucocutaneous zone|mucocutaneous]] infections, neurological and systemic. | ||
* Hyperextensible joints/recurrent bone fractures, and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood. | * Hyperextensible joints/recurrent bone [[Bone fracture|fractures]], and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood. | ||
* Eczema complicated by mucocutaneous candidiasis involving the mouth and diaper areas. | * Eczema complicated by mucocutaneous [[candidiasis]] involving the mouth and diaper areas. | ||
* Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease. | * Skeletal abnormalities include [[scoliosis]], [[Osteoporosis|osteopenia]], minimal trauma [[Bone fracture|fractures]], hyperextensibility, and [[Osteoarthritis|degenerative joint disease]]. | ||
* Retained primary teeth past the age of normal dental exfoliation. | * Retained primary teeth past the age of normal dental [[exfoliation]]. | ||
* | * | ||
===Complications=== | ===Complications=== | ||
* Pustular and eczematoid rashes usually begin within the first month of life, usually affecting the face and scalp. | * [[Psoriasis|Pustular]] and [[Eczema|eczematoid]] [[Rash|rashes]] usually begin within the first month of life, usually affecting the face and scalp. | ||
* Recurrent | * Recurrent [[pneumonia]]<nowiki/>s start in childhood. | ||
* Recurrent lung infections cause bronchiectasis and formation of pneumatocoeles that lead to secondary infections such as fungal and gram negative bacterial infections resulting in pulmonary vessels rupture and haemoptysis. | * Recurrent lung infections cause [[bronchiectasis]] and formation of [[Pneumatocoele|pneumatocoeles]] that lead to secondary infections such as [[Fungus|fungal]] and gram negative bacterial infections resulting in pulmonary vessels rupture and [[Hemoptysis|haemoptysis]]. | ||
* Mucocutaneous candidiasis is common, manifesting typically as oral thrush, vaginal candidiasis or onychomycosis. | * Mucocutaneous [[candidiasis]] is common, manifesting typically as oral thrush, vaginal [[candidiasis]] or [[onychomycosis]]. | ||
* Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease. | * Skeletal abnormalities include [[scoliosis]], [[Osteoporosis|osteopenia]], minimal trauma fractures, hyperextensibility, and [[Osteoarthritis|degenerative joint disease]]. | ||
* Chiari 1 malformations are common. | * [[Chiari malformation|Chiari]] 1 malformations are common. | ||
* Arterial aneurysms are fairly common. Aneurysms can be present in brain circulation or Aorta. It can lead to myocardial infarction or stroke. | * Arterial [[Aneurysm|aneurysms]] are fairly common. [[Aneurysm|Aneurysms]] can be present in brain circulation or [[Aorta]]. It can lead to [[ST elevation myocardial infarction|myocardial infarction]] or [[stroke]]. | ||
* Malignancies such as squamous cell carcinoma, cutaneous T-cell lymphoma/leukemia, Burkitt lymphoma, Hodgkin's and non-Hodgkin's lymphoma . | * Malignancies such as [[Squamous cell carcinoma laboratory tests|squamous cell carcinoma]], cutaneous [[T-cell lymphoma]]/[[leukemia]], [[Burkitt's lymphoma|Burkitt lymphoma]], [[Hodgkin's lymphoma|Hodgkin's]] and [[Non-Hodgkin lymphoma|non-Hodgkin's lymphoma]] . | ||
* Systemic vasculitis. | * Systemic [[vasculitis]]. | ||
===Prognosis=== | ===Prognosis=== | ||
Infectious pulmonary complications are the leading cause of death in patients with HIES, followed by lymphoma: | Infectious pulmonary complications are the leading cause of death in patients with HIES, followed by [[lymphoma]]: | ||
* Prognosis depends on the complications arising from the disease. | * Prognosis depends on the complications arising from the disease. | ||
* Pneumatoceles can become colonized with fungi and gram-negative bacteria, including ''A. fumigatus'' and ''P. aeruginosa''. | * Pneumatoceles can become colonized with fungi and gram-negative bacteria, including ''A. fumigatus'' and ''[[Pseudomonas aeruginosa|P. aeruginosa]]''. | ||
* Infected pneumatoceles can cause subsequent pneumonia, systemic infection, or sudden pulmonary hemorrhage. | * Infected pneumatoceles can cause subsequent [[pneumonia]], systemic infection, or sudden pulmonary [[Bleeding|hemorrhage]]. | ||
* Vascular invasion by fungi may give rise to mycotic aneurysms with subsequent hemorrhagic complications in the lungs and other organs. | * Vascular invasion by fungi may give rise to [[Mycosis|mycotic]] [[Aneurysm|aneurysms]] with subsequent [[hemorrhagic]] complications in the lungs and other organs. | ||
* Patients developing lymphoma have a poor prognosis, with death resulting from superimposed infections. | * Patients developing [[lymphoma]] have a poor prognosis, with death resulting from superimposed infections. | ||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic Criteria=== | ===Diagnostic Criteria=== | ||
Diagnosis requires clinical interepretation of symptoms | Diagnosis requires clinical interepretation of symptoms along with laboratory findings.. | ||
* Serum IgE levels above 2,000 IU/ml(100 times greater than normal). | * Serum IgE levels above 2,000 IU/ml(100 times greater than normal). | ||
* Increased levels of | * Increased levels of [[Eosinophil|eosinophils]] with normal levels of [[Neutrophil|neutrophils]] and [[Lymphocyte|lymphocytes]]. | ||
* A scoring system devised by NIH for the diagnosis of hyper IgE syndrome, score >30 suggests the presence of the disease. | * A scoring system devised by NIH for the diagnosis of hyper IgE syndrome, score >30 suggests the presence of the disease. | ||
{| class="wikitable" | {| class="wikitable" | ||
Line 417: | Line 417: | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
* Patients of hyper IgE syndrome are born with pustular or eczematoid rashes, or they may appear in first month of life. | * Patients of hyper IgE syndrome are born with pustular or eczematoid rashes, or they may appear in first month of life. | ||
* Recurrent eczema, boils and skin abscesses. | * Recurrent [[eczema]], [[Boil|boils]] and skin [[Abscess|abscesses]]. | ||
* Recurrent infections such as chronic otitis media, sinusitis, pneumonias, mucocutaneous infections, neurological and systemic. | * Recurrent infections such as chronic [[otitis media]], [[Rhinosinusitis|sinusitis]], [[Pneumonia|pneumonias]], [[Mucocutaneous zone|mucocutaneous infections]], neurological and systemic. | ||
* Hyperextensible joints/recurrent bone fractures, and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood. | * Hyperextensible joints/recurrent bone [[Bone fracture|fractures]], and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood. | ||
* Eczema complicated by mucocutaneous candidiasis involving the mouth and diaper areas. | * Eczema complicated by mucocutaneous [[candidiasis]] involving the mouth and diaper areas. | ||
* Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease. | * Skeletal abnormalities include [[scoliosis]], [[Osteoporosis|osteopenia]], minimal trauma fractures, hyperextensibility, and [[Osteoarthritis|degenerative joint disease]]. | ||
* Retained primary teeth past the age of normal dental exfoliation. | * Retained primary teeth past the age of normal dental [[exfoliation]]. | ||
===Physical Examination=== | ===Physical Examination=== | ||
* Coarse facial features( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance). | * Coarse facial features( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance). | ||
* Dental abnormalities- retained primary teeth. | * Dental abnormalities- retained primary teeth. | ||
* Facial pain(sinusitis), ear pain and discharge(otitis media). | * Facial pain ([[Rhinosinusitis|sinusitis]]), ear pain and discharge ([[otitis media]]). | ||
* Purulent sputum producing cough or dry cough due to recurrent pneumonias. | * Purulent sputum producing cough or dry cough due to recurrent pneumonias. | ||
* Eczematous dermatitis and lichenification affect the face, trunk, and extremities. | * [[Dermatitis|Eczematous dermatitis]] and [[lichenification]] affect the face, trunk, and extremities. | ||
* Boils and multiple skin abscesses. | * [[Boil|Boils]] and multiple skin [[Abscess|abscesses]]. | ||
* Purpural rash. | * [[Purpura|Purpural]] [[rash]]. | ||
* Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease. | * Skeletal abnormalities include [[scoliosis]], [[Osteoporosis|osteopenia]], minimal trauma fractures, hyperextensibility, and degenerative joint disease. | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Line 444: | Line 444: | ||
There are no specific findings for IgM deficiency on x ray but signs of lung disease may be present. | There are no specific findings for IgM deficiency on x ray but signs of lung disease may be present. | ||
* Increased bronchovascular markings in [[bronchitis]]. | * Increased bronchovascular markings in [[bronchitis]]. | ||
* ''' | * '''Lung''' hyperinflation with flattened hemidiaphragms in [[emphysema]]. | ||
* [[Consolidation (medicine)|Consolidation]] in [[pneumonia]]. | * [[Consolidation (medicine)|Consolidation]] in [[pneumonia]]. | ||
* Tram track opacities in [[bronchiectasis]]. | * Tram track opacities in [[bronchiectasis]]. | ||
Line 471: | Line 471: | ||
Treatment of hyper IgE syndrome includes prevention of infections, administering prohphylactic antibiotics, treating current infections and bone marrow transplant.<ref>{{cite journal |author=Kimata H |title=High-dose intravenous gamma-globulin treatment for hyperimmunoglobulinemia E syndrome |journal=J Allergy Clin Immunol |volume=95 |issue=3 |pages=771-4 |year=1995 |pmid=7897163}}</ref> | Treatment of hyper IgE syndrome includes prevention of infections, administering prohphylactic antibiotics, treating current infections and bone marrow transplant.<ref>{{cite journal |author=Kimata H |title=High-dose intravenous gamma-globulin treatment for hyperimmunoglobulinemia E syndrome |journal=J Allergy Clin Immunol |volume=95 |issue=3 |pages=771-4 |year=1995 |pmid=7897163}}</ref> | ||
* Skin care with antiseptic wash prevents infection with bacterias and fungi. | * Skin care with antiseptic wash prevents infection with bacterias and fungi. | ||
** Eczematous dermatitis is treated with a topical corticosteroid, a moisturizing cream, and an antihistamine . | ** Eczematous [[dermatitis]] is treated with a topical [[corticosteroid]], a moisturizing cream, and an [[antihistamine]] . | ||
* Prophylactic administration of trimethoprim-sulfamethoxazole is useful in the prevention of cutaneous | * Prophylactic administration of [[Sulfamethoxazole-Trimethoprim|trimethoprim-sulfamethoxazole]] is useful in the prevention of cutaneous [[Staphylococcaceae|staphylococca]]<nowiki/>l infections, including [[Abscess|abscesses]], as well as [[Rhinosinusitis|sinusitis]], [[otitis media]], and [[pneumonia]]. | ||
** 5 to 8 mg/kg/day of the trimethoprim component administered orally in two divided daily doses, or from 0 to 6 months, 120 mg/day; 6 months to 5 years, 240 mg/day; 6 to 12 years, 480 mg/day; and >12 years, 960 mg/day. | ** 5 to 8 mg/kg/day of the [[trimethoprim]] component administered orally in two divided daily doses, or from 0 to 6 months, 120 mg/day; 6 months to 5 years, 240 mg/day; 6 to 12 years, 480 mg/day; and >12 years, 960 mg/day. | ||
* Treatment of active infections: | * Treatment of active infections: | ||
** Pneumonia and deep-seeded abscesses caused by ''S aureus'' are treated intravenously with nafcillin and with vancomycin if it is methicillin-resistant. | ** [[Pneumonia]] and deep-seeded [[Abscess|abscesses]] caused by ''[[Staphylococcus aureus|S aureus]]'' are treated intravenously with [[Nafcillin sodium|nafcillin]] and with [[vancomycin]] if it is [[methicillin]]-resistant. | ||
** Lung abscesses superinfected with ''Aspergillus'' species require intravenous amphotericin B. | ** Lung [[Abscess|abscesses]] superinfected with ''[[Aspergillus]]'' species require intravenous [[amphotericin B]]. | ||
** ''P aeruginosa,'' requires an aminoglycoside and a third-generation cephalosporin or another synergistic antibiotic. | ** ''P aeruginosa,'' requires an [[aminoglycoside]] and a third-generation [[cephalosporin]] or another synergistic antibiotic. | ||
* Bone marrow transplantation (BMT) is also being studied to be used for treatment. | * Bone marrow transplantation (BMT) is also being studied to be used for treatment. | ||
Line 484: | Line 484: | ||
===Primary Prevention=== | ===Primary Prevention=== | ||
There are no established measures for the primary prevention of IgM deficiency | There are no established measures for the primary prevention of [[Immunoglobulin M deficiency|IgM deficiency]] | ||
===Secondary Prevention=== | ===Secondary Prevention=== | ||
Secondary prevention includes prevention of infections by: | Secondary prevention includes prevention of infections by: | ||
* Avoidance- reduce exposure to others with potentially contagious illnesses, proper hand washing and [[Vaccination|immunization]] of family members and close contacts. | * Avoidance- reduce exposure to others with potentially contagious illnesses, proper hand washing and [[Vaccination|immunization]] of family members and close contacts. | ||
* Vaccination with conjugate vaccines -conjugated pneumococcal vaccine, conjugated haemophillus influenza B and conjugated meningococcal vaccine administered to prevent infections. | * [[Vaccination]] with conjugate vaccines - conjugated [[pneumococcal vaccine]], conjugated [[haemophillus influenza B]] and conjugated [[Meningococcal|meningococcal vaccine]] administered to prevent infections. | ||
* Use of prophylactic broad spectrum antibiotics. | * Use of prophylactic broad spectrum [[Antibiotic|antibiotics]]. | ||
* Skin care with antiseptic wash prevents infection with bacterias and fungi. | * Skin care with [[antiseptic]] wash prevents infection with [[Bacteria|bacterias]] and [[Fungus|fungi]]. | ||
==References== | ==References== |
Revision as of 20:54, 9 October 2018
Hyper-IgE syndrome | |
ICD-10 | D82.4 |
---|---|
ICD-9 | 288.1 |
OMIM | 29572 147060 |
DiseasesDB | 29572 |
eMedicine | derm/845 ped/1074 |
MeSH | D007589 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jogeet Singh Sekhon, M.D. [2]
Synonyms and keywords: Job-Buckley syndrome; Job syndrome; Buckley syndrome.
Overview
Hyper IgE syndrome (HIES) is a group of disorders characterized by recurrent staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of serum IgE. Some patients have an autosomal dominant form of the disease; these patients have problems with their bones including recurrent fractures and scoliosis. Many patients with autosomal dominant hyper IgE syndrome fail to lose their baby teeth and have two sets of teeth simultaneously.
Historical Perspective
- HIES was first described by Davis et al in 1966 and it was named as Job's syndrome.
Classification
Hyper IgE syndrome is classified into 2 types:
- Autosomal dominant.
- Autosomal recessive.
Pathophysiology
- Hyper IgE syndrome is caused due to mutations in STAT 3 and Tyrosine kinase 2 genes.
- Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic protein and a component of the JAK-STAT pathway of signal transduction.
- The binding of various cytokines to their receptors on the cell surface results in activation of JAK proteins, which in turn phosphorylate STAT proteins.
- The STATs then form dimers, translocate to the nucleus, bind to specific sites on the DNA, and activate target genes.
- Tyrosine kinase 2 (TYK2) is part of the JAK family of kinases that are associated with cytokine receptors.
- A deletion in TYK2 resulting in a truncated protein that is associated with abnormal signaling for type I interferon, IL-6, IL-10, IL-12, and IL-23.
- Both STAT3 and TYK2 defects lead to impaired Th17 function.
- A defect in Th17 function, results in decreased neutrophil proliferation and chemotaxis, decreased inflammation, and increased susceptibility to Candida and bacterial infections.
Pathogenesis:
- Neutrophil chemotactic defect-
- Th17 cell production of IL-17 is involved in neutrophil chemotaxis and proliferation .
- Defective Th17 leads to defects in neutrophil chemotaxis and proliferation .
- Interferon (IFN)-gamma production is also decreased which results in cutaneous and pulmonary infections.
- Defect in neutrophil chemotaxis results in cutaneous cold abscess formation, in which signs of acute inflammation are absent.
- T cell defects —
- STAT3 plays a crucial role in the differentiation of naïve T cells into IL-17 producing CD4+ T cells (Th17 cells).
- Th17 cells are involved in the response to fungal and extracellular bacterial infections.
- These cells are significantly reduced or absent in patients with HIES .
- B cell defects and abnormal IgE regulation —
- B cells are resonsible for the synthesis of IgE.
- A defect in the B cells leads to abnormal synthesis of IgE.
- IgE regulation involves T cell stimulation, appropriate cytokine production, and the ability of B cells to class switch toward the production of IgE.
- Thus, defects in IFN-gamma production or regulation contribute to the elevated levels of IgE.
Causes
- Hyper IgE syndrome is caused due to mutations in the signal transducer and activator of transcription 3 (STAT3) and tyrosine kinase 2 (TYK2) gene.
- STAT 3 gene is essential for the differentiation of helper T cells, mutation causes autosomal dominant type.
- Tyrosine kinase 2 (TYK2) gene mutation causes autosomal recessive type.
Differentiating Hyper-IgE syndrome from Other Diseases
Hyper IgE syndrome can be differentiated from other diseases of the same kind by measuring the serum IgE levels.
Disease | IgM levels | IgG levels | IgA levels | IgE levels | B cell defect | T cell defect |
---|---|---|---|---|---|---|
IgM deficiency | ↓ | - | - | - | - | - |
IgA deficiency | - | - | ↓ | - | - | - |
IgG deficiency | - | ↓ | - | - | - | - |
IgE deficiency | - | - | - | ↓ | - | - |
Hypoproteinemia/Proteinuria | ↓ | ↓ | ↓ | ↓ | - | - |
Comined Immunodeficiency | ↓ | ↓ | ↓ | ↓ | + | + |
X linked agammaglobulinemia | ↓ | ↓ | ↓ | ↓ | + | - |
Hyperimmunoglobulin M syndrome | ↑ | ↓ | ↓ | ↓ | + | - |
Common variable immunodeficiency | ↓ | ↓ | ↓ | ↓ | + | - |
Wiskott-Aldrich syndrome | ↓ | ↓ | ↑ | ↑ | - | + |
Hyper IgE syndrome | - | - | - | ↑ | - | + |
Epidemiology and Demographics
- Incidence of hyper IgE syndrome is less than 1 in 100,000 individuals.
Screening
Screening is not recommended for hyper IgE syndrome.
Natural History, Complications, and Prognosis
Natural History
- Patients of hyper IgE syndrome are born with pustular or eczematoid rashes, or they may appear in first month of life.
- Recurrent eczema, boils and skin abscesses.
- Recurrent infections such as chronic otitis media, sinusitis, pneumonias, mucocutaneous infections, neurological and systemic.
- Hyperextensible joints/recurrent bone fractures, and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood.
- Eczema complicated by mucocutaneous candidiasis involving the mouth and diaper areas.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
- Retained primary teeth past the age of normal dental exfoliation.
Complications
- Pustular and eczematoid rashes usually begin within the first month of life, usually affecting the face and scalp.
- Recurrent pneumonias start in childhood.
- Recurrent lung infections cause bronchiectasis and formation of pneumatocoeles that lead to secondary infections such as fungal and gram negative bacterial infections resulting in pulmonary vessels rupture and haemoptysis.
- Mucocutaneous candidiasis is common, manifesting typically as oral thrush, vaginal candidiasis or onychomycosis.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
- Chiari 1 malformations are common.
- Arterial aneurysms are fairly common. Aneurysms can be present in brain circulation or Aorta. It can lead to myocardial infarction or stroke.
- Malignancies such as squamous cell carcinoma, cutaneous T-cell lymphoma/leukemia, Burkitt lymphoma, Hodgkin's and non-Hodgkin's lymphoma .
- Systemic vasculitis.
Prognosis
Infectious pulmonary complications are the leading cause of death in patients with HIES, followed by lymphoma:
- Prognosis depends on the complications arising from the disease.
- Pneumatoceles can become colonized with fungi and gram-negative bacteria, including A. fumigatus and P. aeruginosa.
- Infected pneumatoceles can cause subsequent pneumonia, systemic infection, or sudden pulmonary hemorrhage.
- Vascular invasion by fungi may give rise to mycotic aneurysms with subsequent hemorrhagic complications in the lungs and other organs.
- Patients developing lymphoma have a poor prognosis, with death resulting from superimposed infections.
Diagnosis
Diagnostic Criteria
Diagnosis requires clinical interepretation of symptoms along with laboratory findings..
- Serum IgE levels above 2,000 IU/ml(100 times greater than normal).
- Increased levels of eosinophils with normal levels of neutrophils and lymphocytes.
- A scoring system devised by NIH for the diagnosis of hyper IgE syndrome, score >30 suggests the presence of the disease.
Clinical findings | Points* | |||||||||
0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 10 | |
Highest serum-IgE level (international units/mL)¶ | <200 | 200 to 500 | 501 to 1000 | 1001 to 2000 | >2000 | |||||
Skin abscesses | None | 1 to 2 | 3 to 4 | >4 | ||||||
Pneumonia (episodes over lifetime) | None | 1 | 2 | 3 | >3 | |||||
Parenchymal lung anomalies | Absent | Bronchiectasis | Pneumatocele | |||||||
Retained primary teeth | None | 1 | 2 | 3 | >3 | |||||
Scoliosis, maximum curvature | <10° | 10 to 14° | 15 to 20° | >20° | ||||||
Fractures with minor trauma | None | 1 to 2 | >2 | |||||||
Highest eosinophil count (cells/microL)Δ | <700 | 700 to 800 | >800 | |||||||
Characteristic face | Absent | Mildly present | Present | |||||||
Midline anomaly◊ | Absent | Present | ||||||||
Newborn rash | Absent | Present | ||||||||
Eczema (worst stage) | Absent | Mild | Moderate | Severe | ||||||
Upper respiratory infections per year | 1 to 2 | 3 | 4 to 6 | >6 | ||||||
Candidiasis | None | Oral | Fingernails | Systemic | ||||||
Other serious infections | None | Severe | ||||||||
Fatal infection | Absent | Present | ||||||||
Hyperextensibility | Absent | Present | ||||||||
Lymphoma | Absent | Present | ||||||||
Increased nasal width§ | <1 SD | 1 to 2 SD | >2 SD | |||||||
High palate | Absent | Present | ||||||||
Young-age correction | >5 years | 2 to 5 years | 1 to 2 years | ≤1 year |
History and Symptoms
- Patients of hyper IgE syndrome are born with pustular or eczematoid rashes, or they may appear in first month of life.
- Recurrent eczema, boils and skin abscesses.
- Recurrent infections such as chronic otitis media, sinusitis, pneumonias, mucocutaneous infections, neurological and systemic.
- Hyperextensible joints/recurrent bone fractures, and distinctive coarse faces( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance) in early childhood.
- Eczema complicated by mucocutaneous candidiasis involving the mouth and diaper areas.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
- Retained primary teeth past the age of normal dental exfoliation.
Physical Examination
- Coarse facial features( prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance).
- Dental abnormalities- retained primary teeth.
- Facial pain (sinusitis), ear pain and discharge (otitis media).
- Purulent sputum producing cough or dry cough due to recurrent pneumonias.
- Eczematous dermatitis and lichenification affect the face, trunk, and extremities.
- Boils and multiple skin abscesses.
- Purpural rash.
- Skeletal abnormalities include scoliosis, osteopenia, minimal trauma fractures, hyperextensibility, and degenerative joint disease.
Laboratory Findings
- Serum IgE levels above 2,000 IU/ml(100 times greater than normal).
- Increased levels of eosinophills ( >700) with normal levels of neutrophils and lymphocytes.
Electrocardiogram
There are no ECG findings associated with IgM defiicency.
X-ray
There are no specific findings for IgM deficiency on x ray but signs of lung disease may be present.
- Increased bronchovascular markings in bronchitis.
- Lung hyperinflation with flattened hemidiaphragms in emphysema.
- Consolidation in pneumonia.
- Tram track opacities in bronchiectasis.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with IgM deficiency
CT scan
- There are no CT scan findings associated with IgM deficiency.
- Changes of chronic lung disease, if present will be visible on CT and can help differentiate the cause and extent of the disease.
- Chronic sinusitis- mucosal thickening, complete opacification, bone remodeling and thickening due to osteitis, and polyposis.
MRI
There are no MRI findings associated with IgM deficiency.
However, signs of chronic lung disease or chronic sinsuitis may be present.
Other Imaging Findings
There are no other imaging findings associated with IgM deficiency.
Other Diagnostic Studies
There are no other diagnostic studies associated with IgM deficiency.
Treatment
Treatment of hyper IgE syndrome includes prevention of infections, administering prohphylactic antibiotics, treating current infections and bone marrow transplant.[1]
- Skin care with antiseptic wash prevents infection with bacterias and fungi.
- Eczematous dermatitis is treated with a topical corticosteroid, a moisturizing cream, and an antihistamine .
- Prophylactic administration of trimethoprim-sulfamethoxazole is useful in the prevention of cutaneous staphylococcal infections, including abscesses, as well as sinusitis, otitis media, and pneumonia.
- 5 to 8 mg/kg/day of the trimethoprim component administered orally in two divided daily doses, or from 0 to 6 months, 120 mg/day; 6 months to 5 years, 240 mg/day; 6 to 12 years, 480 mg/day; and >12 years, 960 mg/day.
- Treatment of active infections:
- Pneumonia and deep-seeded abscesses caused by S aureus are treated intravenously with nafcillin and with vancomycin if it is methicillin-resistant.
- Lung abscesses superinfected with Aspergillus species require intravenous amphotericin B.
- P aeruginosa, requires an aminoglycoside and a third-generation cephalosporin or another synergistic antibiotic.
- Bone marrow transplantation (BMT) is also being studied to be used for treatment.
Surgery
Surgery is not recommended for the treatment of hyper IgE syndrome.
Primary Prevention
There are no established measures for the primary prevention of IgM deficiency
Secondary Prevention
Secondary prevention includes prevention of infections by:
- Avoidance- reduce exposure to others with potentially contagious illnesses, proper hand washing and immunization of family members and close contacts.
- Vaccination with conjugate vaccines - conjugated pneumococcal vaccine, conjugated haemophillus influenza B and conjugated meningococcal vaccine administered to prevent infections.
- Use of prophylactic broad spectrum antibiotics.
- Skin care with antiseptic wash prevents infection with bacterias and fungi.