Practical Dermatology
Differential Diagnosis of Genetic Disorders Associated with Moderate to Severe Refractory Eczema and Elevated Immunoglobulin E
Trastornos genéticos con eccema moderado-grave refractario y elevación de inmunoglobulina E: diagnóstico diferencial
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The patient was diagnosed with inverse psoriasis and was found to be sensitized to all 3 groups of corticosteroids. Reading at 96<span class="elsevierStyleHsp" style=""></span>hours with the modified standard series revealed positive results for budesonide (++) and hydrocortisone 17-butyrate (+) (group 1). Testing with the corticosteroid series revealed positive results to triamcinolone acetonide (+) (group 2). Testing with the patient's own corticosteroids revealed allergy to group 3 drugs, with positive results for the commercially available creams Diproderm (+), Elocom (+), Fucibet (+), Nasonex (+), Peitel (+), and Suniderma (+).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Berbegal, F.J. DeLeon, J.F. Silvestre" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Berbegal" ] 1 => array:2 [ "nombre" => "F.J." "apellidos" => "DeLeon" ] 2 => array:2 [ "nombre" => "J.F." 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Arjona Aguilera, C. Albarrán Planelles, J. Tercedor Sánchez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Arjona Aguilera" "email" => array:1 [ 0 => "cintiaarjona@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "Albarrán Planelles" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Tercedor Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Dermatología y Venereología, Hospital Universitario Puerta del Mar, Servicio Andaluz de Salud, Cádiz, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Dermatología y Venereología, Hospital Universitario Virgen de las Nieves, Servicio Andaluz de Salud, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trastornos genéticos con eccema moderado-grave refractario y elevación de inmunoglobulina E: diagnóstico diferencial" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3765 "Ancho" => 3381 "Tamanyo" => 472503 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Suggested Diagnostic Algorithm for Clinical Diagnosis of Genodermatosis of Moderate-to-Severe Presentation and Elevated IgE.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The association between moderate-to-severe eczema and elevated plasma immunoglobulin (Ig) E levels is characteristic of atopic dermatitis and is also seen in other genetic diseases. Many patients also have concurrent congenital immunodeficiency. When faced with a patient with clinical signs and symptoms consistent with severe atopic dermatitis<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> who does not respond to traditional treatments (hygiene and dietary interventions, topical or systemic corticosteroids, cyclosporin, methotrexate, or azathioprine)<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> and has elevated IgE from the first days of life, we should suspect the presence of one of these syndromes.</p><p id="par0010" class="elsevierStylePara elsevierViewall">One group, hyper-IgE syndromes, has been described and extensively studied. These entities are classified according to the pattern of transmission: autosomal dominant (AD) or autosomal recessive (AR). Both types are characterized by elevated IgE and a clinical picture dominated by skin involvement, with moderate or severe acute and subacute eczema that resembles atopic dermatitis, and by recurrent skin and respiratory infection.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The other group comprises a series of low-prevalence congenital diseases that often present with episodes of refractory eczema associated with elevated IgE and that should be included in our diagnostic algorithm. Omenn syndrome is a serious combined immunodeficiency of AR transmission that presents in the first year of life. Wiskott-Aldrich syndrome is a primary X-linked immunodeficiency characterized essentially by bleeding diathesis secondary to thrombocytopenia or platelet dysfunction, along with recurrent eczemas and bacterial infections from birth. Prolidase deficiency is a multisystemic disease of AR transmission with a very variable clinical presentation and severity, associated with limited or no prolidase enzyme in erythrocytes, leukocytes, or fibroblasts. Loeys-Dietz syndrome is a connective tissue disease of AD transmission that is associated with a marfanoid appearance and abnormalities in the great arteries. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a serious congenital autoimmune disease in which refractory diarrhea, infections, and multiple endocrine disorders are present in addition to skin involvement. STAT5B deficiency is a condition of AR transmission included in the group of syndromes related to growth hormone insensitivity. This entity is notable for the occurrence of primary immunodeficiency. Pentasomy X is a congenital disease caused by chromosomal abnormalities in women leading to gonadal dysfunction, delayed development, short stature, and musculoskeletal and craniofacial malformations. Netherton syndrome is an AR genodermatosis characterized by ichthyosiform erythroderma, trichorrhexis invaginata, and atopic manifestations present almost from birth. Finally, we include 2 very recently described genodermatosis related to Netherton syndrome from the pathophysiological point of view: peeling skin syndrome type B (PSS-B) and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome. PSS-B is an AR genodermatosis with ichthyosiform erythroderma from birth which, in addition, presents with severe food allergies, angioedema, and urticaria. Finally, SAM is another rare AR genodermatosis in which skin involvement is combined with notable food allergies, esophageal involvement, and other characteristics that will be discussed later in this article.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Differential diagnosis of these syndromes can be very complex, given that there may be considerable overlap and many clinical characteristics are shared. The phenotypic expression of each of these conditions may also vary from one individual to another. Thus, in this article, we provide key information to enable differential diagnosis from the clinical point of view, with the intention of guiding which genetic studies to request. Definitive diagnosis is made by identifying the causal mutation. In <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, we have compiled the main genodermatosis that should be included in the differential diagnosis, indicating the main characteristics to investigate in the diagnostic procedure to enable us reach a full diagnosis. A complete detailed description of each of these diseases is not an objective of this article. For this, the reader is referred to literature for more information.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">It should be noted from the outset that the skin manifestations have a very early onset and many of these are common to several entities. Dermatitis (erythema, intense pruritus, dry skin, and lichenification) is moderate or severe in both types of hyper-IgE syndromes,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2–5</span></a> Wiskott-Aldrich syndrome,<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,7</span></a> Netherton syndrome,<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,8</span></a> SAM,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> IPEX syndrome,<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">3,9</span></a> and STAT5 deficiency,<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9,10</span></a> but is less frequent in PSS-B,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Loeys-Dietz syndrome,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> and prolidase deficiency.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> Generally, these conditions follow a severe course with poor response to the traditional topical and systemic treatments used in atopic dermatitis. However, seborrheic dermatitis-like lesions are much more common in Omenn syndrome. In all entities, erythroderma may present with variable frequency, and even in Netherton syndrome and PSS-B, ichthyosiform erythroderma will be a dominant feature of the clinical picture and will present at a very early stage.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> The differential diagnosis should include all these possible causes of erythroderma in children. It should also be mentioned that cases of IPEX syndrome with psoriasiform dermatitis, exfoliative dermatitis, and pemphigoid nodularis have been reported.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">From the dermatopathological point of view, we can find features of great help in the diagnosis of these diseases. Perivascular dermatitis with abundant eosinophils and spongiosis is common in hyper-IgE syndromes. Histological study of skin biopsy in Netherton syndrome is characterized by hypogranulosis, parakeratosis, and subcorneal detachment, while premature secretion of lamellar bodies is also observed in electron microscopy; immunohistochemical staining demonstrates the absence of LEKTI in the granular layer and inner root sheaf. This is all a result of abnormal differentiation and accelerated scaling of the epidermis in this disease.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,8</span></a> In contrast, skin histology in PSS-B is noteworthy because of the presence of subcorneal acantholysis, superficial inflammatory infiltrate, and lack of expression of epidermal <span class="elsevierStyleItalic">CDSN</span> in the immunohistochemical study. Electron microscopy demonstrates loss of corneodesmosomes.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Finally, in SAM, subcorneal and intragranular acantholysis and psoriasiform dermatitis alternating with orthoparakeratosis/parakeratosis and hypogranulosis or hypergranulosis are also found.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,14</span></a> Electron microscope study shows the irregular distribution of desmosomes in the upper half of the epidermis, with normal follicular histology.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,14</span></a> Direct immunofluorescence shows the anomalous cytoplasmic distribution of desmoglein 1 in epidermal keratinocytes.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">A predisposition to skin infections is present in all entities, although with certain particularities. The most frequent are pyodermatitis and cutaneous abscesses, as reflected in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Mucocutaneous candidiasis appears in hyper-IgE syndromes.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> In AR hyper-IgE syndrome, as well as in Wiskott-Aldrich syndrome, viral infections such as molluscum contagiosum and HPV, are also common.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2–4</span></a> STAT5B deficiency has frequently been associated with severe cases of chicken pox or herpes zoster.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Apart from these common characteristics, there are specific cutaneomucosal and morphological manifestations of certain entities which, if present, can greatly facilitate clinical diagnosis. Typical facies is often present with AD hyper-IgE syndrome<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> (but not in the AR variant), Loeys-Dietz syndrome,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> Omenn syndrome, prolidase deficiency, and STAT5B deficiency.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9,10</span></a> Purpuric lesions are characteristic of Wiskott-Aldrich syndrome and, less frequently, prolidase deficiency, generally in form of petechiae and ecchymosis after minimal trauma. In SAM palmoplantar keratoderma striata, skin erosions, substantial peeling, and hypotrichosis are often present.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The skin fragility characteristic of prolidase deficiency is responsible for the development, in addition, of ulcers, predominantly on the lower limbs and, less frequently, in the anogenital region. These are generally recurrent, with an onset in early infancy, and with partial response to suitable topical treatment.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Abnormalities in the hair follicles are varied. In Netherton syndrome, trichorrhexis invaginata (<span class="elsevierStyleItalic">bamboo hair</span>) is observed. This is more apparent after the first year of life and is a key characteristic to differentiate this entity from PSS-B, which is phenotypically very similar although children have normal hair.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,8</span></a> STAT5B deficiency is associated with sparse fine hair,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> and some cases of alopecia areata universalis have been reported in IPEX syndrome.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> Diffuse alopecia may develop in Omenn syndrome and very early greying may present in patients with prolidase deficiency, with diffuse alopecia in adults.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Second, respiratory manifestations are frequent in all these children. In prolidase deficiency, of note is the high frequency of upper respiratory infections, which may help differential diagnosis with hyper-IgE syndromes.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> In fact, in AD hyper-IgE syndrome, the development of pneumatocele as a result of recurrent lung infections is relatively common.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> Recurrent pneumonia typically appears in all entities, except in Netherton syndrome and PSS-B, in which allergic asthma is more characteristic.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> In IPEX syndrome, infections are uncommon<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> and are often a side effect of immunosuppressive treatment. Finally, rhinitis occurs principally in Loeys-Dietz syndrome.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Third, we have musculoskeletal manifestations, which are key for differential diagnosis. Thus, AD hyper-IgE syndrome is associated with osteopenia, scoliosis, and pathological fractures in more than half of those affected<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a>; however, in the AR form, postnatal growth retardation is the only musculoskeletal manifestation in some cases. On the other hand, PSS-B<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> and SAM<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> also show a delayed growth with short final stature, whereas in Omenn syndrome,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> prolidase deficiency,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> and Netherton syndrome,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> the delayed growth is limited, uncommon, and children will not necessarily have a short adult stature. Prolidase deficiency can be associated at times with osteoporosis and joint hypermobility.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> Loeys-Dietz syndrome<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> usually presents with marfanoid features and joint hypermobility, and in type <span class="elsevierStyleSmallCaps">i</span>, bone abnormalities may also present, including craniosynostosis, pectus excavatum, pectus carinatum, cavus foot, and joint contractures. In Loeys-Dietz syndrome type <span class="elsevierStyleSmallCaps">ii</span>, bone abnormalities are mild or absent. The type <span class="elsevierStyleSmallCaps">iii</span> syndrome is essentially associated with multifocal osteoarthritis. Pentasomy X is associated with cranial malformations, often microcephaly, as well as other bone abnormalities such as syndactylia.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> Finally, dwarfism may occur with STAT5B deficiency from birth as a result of growth hormone (GH) receptor failure, which is known as GH insensitivity syndrome.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">We will now review the main laboratory findings to discriminate between these diseases. Determination of immunoglobulins is key. Elevated IgE is observed in all entities, although we should remember that IgE levels may be normal in some patients with Loeys-Dietz syndrome and pentasomy X.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11,19</span></a> In Wiskott-Aldrich syndrome and IPEX syndrome, IgA is also elevated, and in prolidase deficiency and STAT5B deficiency, polyclonal hypergammoglobulinemia is common.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11,19</span></a> Multiple autoantibodies such as antiperoxidase and antivillin antibodies, among others, will be observed in IPEX syndrome and STAT5B deficiency.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The hematology parameters may also show notable abnormalities. Eosinophilia would point towards hyper-IgE syndromes,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2–5</span></a> Omenn syndrome,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> PSS-B,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> and IPEX syndrome.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> Eosinophilia is usually more marked in the recessive variant of hyper-IgE syndrome, and progressive lymphopenia is also observed. The absence of B cells is a key finding for the diagnosis of Omenn syndrome. In Wiskott-Aldrich syndrome,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> prolidase deficiency,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> and IPEX syndrome,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> thrombocytopenia, and occasionally lymphopenia are observed. With regards red blood cell parameters, hemolytic anemia is present in IPEX syndrome,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> Wiskott-Aldrich syndrome,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> and, to a lesser extent, hyper-IgE syndromes.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">3,5</span></a> Hypochromic microcytic anemia is most characteristic of prolidase deficiency, and here we should also mention massive iminodipeptiduria along with elevated iminodipeptides (with proline or hydroxyproline at the carboxy-terminal end) as key laboratory findings pointing to diagnosis.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> In turn, and very characteristically, in STAT5B deficiency, we can find T cell lymphopenia along with low levels of <span class="elsevierStyleItalic">IGF1</span> and <span class="elsevierStyleItalic">IGFBP3</span> and normal or elevated GH.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Manifestations of atopy and allergy are characteristic of AR hyper-IgE syndrome,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> Netherton syndrome, PSS-B, SAM, and often Loeys-Dietz syndrome.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">15,19</span></a> The most frequent such manifestations are rhinitis and episodes of urticaria. In PSS-B, and above all in hyper-IgE syndrome, episodes of anaphylaxis and angioedema have been reported. These may be recurrent. In SAM, food allergies are usually particularly severe.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> The radioallergosorbent test, an analytical technique that quantitatively determines specific IgE levels for a range of allergens, is usually abnormal in all these entities, particularly in the case of alimentary antigens, and more frequently in individuals with atopic dermatitis.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">16,19</span></a> Pathological radioallergosorbent test results are less common in AD hyper-IgE syndrome than in the recessive form.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">19,20</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Finally, we highlight other manifestations that do not fit into the above categories and that might be useful in the differential diagnosis.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The clinical picture in IPEX syndrome and STAT5B deficiency is dominated by autoimmune phenomena.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9,10</span></a> In the case of IPEX syndrome, type 1 diabetes mellitus, thyroid disease, and autoimmune enteropathy are almost always present. In addition, hemolytic anemia, thrombocytopenia, leukopenia, hepatitis, and tubular nephropathy may also be present. In STAT5B deficiency, enteropathy, thyroid disease, and lymphocytic interstitial pneumonitis are the most characteristic. Autoimmune manifestations also occur in Wiskott-Aldrich syndrome (in up to 40% of patients),<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,7</span></a> and hyper-IgE syndromes,<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">3,5,20</span></a> above all in AR forms; they are less common in AD forms.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> Hemolytic anemia, leukocytoclastic vasculitis, isolated cerebral vasculitis, systemic small-vessel vasculitis, arthritis, and autoantibody-mediated glomerulonephritis can be present in hyper-IgE syndromes and Wiskott-Aldrich syndrome and, in the case of Wiskott-Aldrich syndrome, inflammatory bowel disease may also occur.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,7</span></a> In hyper-IgE syndromes, isolated cases associated with systemic lupus erythematosus and dermatomyositis have also been reported.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> In addition, an increased risk of cancer at any age has been documented for these 3 entities. Specifically, in AD hyper-IgE syndrome<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">3,20</span></a> and Wiskott-Aldrich syndrome,<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,7</span></a> lymphoproliferative diseases predominate. In AR hyper-IgE syndrome,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> a higher risk ratio has been reported with respect to the AD variant, and this higher risk is also present for neoplasms of epithelial and other origins.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The appearance of neurological manifestation, such as hemiplegia, encephalopathy, strokes, and facial paralysis may point to AR hyper-IgE syndrome.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> However, the delay in psychomotor development, which may be very variable, is mainly associated with pentasomy X<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> and prolidase deficiency.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A manifestation common to IPEX syndrome, STAT5B deficiency, Netherton syndrome, and Omenn syndrome is chronic diarrhea syndrome.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">3,9,10,17</span></a> In the latter 2 entities, hepatosplenomegaly and inflammatory adenopathies are also often reported. The esophagus is affected more often in SAM<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> in the form of eosinophilic esophagitis and gastroesophageal reflux.</p><p id="par0100" class="elsevierStylePara elsevierViewall">From the cardiovascular point of view, it is important to note that arterial aneurysms and episodes of aortic dissection are characteristic of Loeys-Dietz syndrome.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> In more than 80% of cases of AD hyper-IgE syndrome, peripheral, cerebral, and, to a lesser extent, coronary vascular malformations are present.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">4,5</span></a> SAM is sometimes associated with minor cardiac defects,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> whereas cardiovascular abnormalities can be very varied in the case of pentasomy X.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">With regards genital abnormalities, gonadal dysfunction is only characteristic of pentasomy X<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> although the external genitals are normal.</p><p id="par0110" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a> shows a diagnostic algorithm based on laboratory results (presence of eosinophilia and abnormalities in the radioallergosorbent test) and preliminary classification of the patients to subsequently study the presence of other findings that may guide clinical diagnosis for each of the genetic disorders discussed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">In conclusion, this article aims to provide practical assistance in the differential diagnosis of a child with refractory eczema and elevated IgE. The medical history, physical exploration, and laboratory results can guide us to the most appropriate genetic study for a definitive molecular diagnosis. This will enable individualized treatment according to the most recent evidence available for each of these entities.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of Interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres818344" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec815372" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres818345" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec815373" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 5 => array:2 [ "identificador" => "xack274600" "titulo" => "Acknowledgments" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-06-29" "fechaAceptado" => "2015-09-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec815372" "palabras" => array:6 [ 0 => "Immunoglobulin E" 1 => "Atopic dermatitis" 2 => "Atopic eczema" 3 => "Genetic diseases" 4 => "Differential diagnosis" 5 => "Immunodeficiency" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec815373" "palabras" => array:6 [ 0 => "Inmunoglobulina E" 1 => "Dermatitis atópica" 2 => "Eccema atópico" 3 => "Enfermedades genéticas" 4 => "Diagnóstico diferencial" 5 => "Inmunodeficiencia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The association of moderate to severe eczema and elevated plasma levels of immunoglobulin E is a characteristic not only of atopic dermatitis but also of various genodermatoses: hyperimmunoglobulin E syndromes, Omenn syndrome, Netherton syndrome, peeling skin syndrome type B, severe dermatitis, multiple allergies, and metabolic wasting syndrome, Wiskott-Aldrich syndrome, prolidase deficiency, Loeys-Dietz syndrome, IPEX syndrome, STAT5B deficiency, and pentasomy X. The clinical presentation of these genodermatoses –typically in children– is consistent with severe atopic dermatitis. Immunoglobulin E is elevated from birth and response to conventional treatments is poor. Diagnosis is further complicated by the fact that these genodermatoses often share other clinical manifestations and laboratory findings. We present practical guidelines for differentiating among these various entities, with the aim of helping physicians decide what type of genetic test should be carried out –and when– in order to establish a definitive diagnosis.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La asociación de eccema moderado-grave y niveles elevados de IgE en plasma es característica no solo de la dermatitis atópica, sino también de diversas genodermatosis: síndromes hiper-IgE, síndrome de Omenn, síndrome de Netherton, síndrome de la piel exfoliada tipo B, síndrome de dermatitis grave-alergias múltiples-desgaste metabólico, síndrome de Wiskott-Aldrich, déficit de prolidasa, síndrome de Loeys-Dietz, síndrome IPEX, déficit de STAT5B y pentasomía X. Se trata de pacientes pediátricos que presentan un cuadro clínico compatible con dermatitis atópica grave, con mala respuesta a los tratamientos clásicos y que asocian elevación de IgE desde el nacimiento. Además, comparten con frecuencia otras manifestaciones clínicas y analíticas, lo cual dificulta el diagnóstico. Presentamos una guía práctica para orientar el diagnóstico diferencial entre todas estas entidades y, por lo tanto, ayudar a decidir cuándo y el tipo de test genético a realizar para establecer el diagnóstico definitivo.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Arjona Aguilera C, Albarrán Planelles C, Tercedor Sánchez J. Trastornos genéticos con eccema moderado-grave refractario y elevación de inmunoglobulina E: diagnóstico diferencial. Actas Dermosifiliogr. 2016;107:116–124.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3765 "Ancho" => 3381 "Tamanyo" => 472503 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Suggested Diagnostic Algorithm for Clinical Diagnosis of Genodermatosis of Moderate-to-Severe Presentation and Elevated IgE.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">BC, B cells; DIF, direct immunofluorescence; DM, diabetes mellitus; DPT, dermatopathology; DSG1, desmoglein 1; GH, growth hormone; HPV, human papillomavirus; HSV, herpes simplex virus; IBD, inflammatory bowel disease; IGF-1, insulin growth factor, type 1; IGFBP3, insulin growth factor binding protein 3; IHC, immunohistochemistry; IPEX, immune-polyendocrinopathy-enteropathy, X-linked dysregulation syndrome; RAST, radioallergoasorbent test; SAH, subarachnoid hemorrhage; SLE, systemic lupus erythematosus; TC, T cells; VZV, varicella-zoster virus.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Skin and Appendages \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Respiratory System \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Musculoskeletal system \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Autoimmunity \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Others \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Laboratory \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genetics \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autosomal dominant hyper-IgE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate-to-severe eczema<br>Pyodermatitis Abscesses<br>Mucocutaneous candidiasis<br>Typical facies<br>Facial punctiform scars \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent pneumonia<br>Pneumatocele \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Osteopenia<br>Scoliosis (50%)<br>Fractures (60%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Infrequent</span><br>Vasculitis (leukocytoclastic, isolated cerebral, systemic small vessel)<br>Glomerulonephritis<br>Hemolytic anemia<br>SLE, dermatomyositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lymphomas<br>Vascular malformations: peripheral, cerebral, or coronary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>Eosinophilia<br>RAST: normal or positive to food antigens<br>DPT: perivascular dermatitis with eosinophilia, spongiosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">STAT3</span> gene mutations (70%)<br>Autosomal dominant<br>Unknown (30%). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autosomal recessive hyper-IgE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate-to-severe eczema<br>Urticaria<br>Pyodermatitis Abscesses<br>Mucocutaneous candidiasis<br>Viral infections (HSV, HPV, molluscum, etc) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma (30%-50%), rhinitis<br>Pneumonia uncommon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Postnatal growth retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vasculitis (leukocytoclastic, isolated cerebral, systemic small vessel)<br>Glomerulonephritis<br>Hemolytic anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cancer: 17% (hematological, epithelial, others)<br>Central nervous system: SAH, encephalopathy, stroke, facial paralysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>Extreme eosinophilia<br>Progressive lymphopenia<br>RAST: positive to food allergens<br>DPT: perivascular dermatitis with abundant eosinophils, spongiosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">DOCK8</span> gene mutations<br>Others (rare): TYK2, PGM3 gene mutations, unknown<br>Autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wiskott-Aldrich syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate-to-severe eczema<br>Seborrheic dermatitis<br>Piodermitis<br>Viral infection<br>Petechaie, purpura \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemolytic anemia<br>Vasculitis<br>Nephritis<br>Arthritis<br>IBD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bleeding<br>Lymphomas: 13% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE and IgA<br>Thrombocytopenia<br>normal/low BC and TC<br>RAST: normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">WAS</span> gene mutations<br>X-linked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Omenn syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Seborrheic dermatitis<br>Erythroderma<br>Eczemas (uncommon)<br>Diffuse alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Postnatal growth retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hepatosplenomegaly<br>Adenopathies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chronic multifactorial diarrhea syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>Eosinophilia<br>B cells absent<br>Anomalous TC clone<br>RAST: normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">RAG1-2</span> gene mutations. Less often: <span class="elsevierStyleItalic">RMRP, ADA, IL2RG, IL7RA, DCLRE1</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">C, CHD7, LIG4, AK2</span><br>Autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Netherton syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate-to-severe eczema<br>Urticaria<br>Pyodermatitis<br>Ichthyosiform erythroderma; ichthyosis linearis circumflexa<br>Trichorrhexis invaginata \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Allergic asthma, rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Postnatal growth retardation<br>Short stature \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chronic multifactorial diarrhea syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>TC differentiation abnormality<br>RAST: positive to food allergens<br>DPT: psoriasiform dermatitis, hypogranulosis/agranulosis, parakeratosis, premature lamellar body secretion, subcorneal acantholysis<br>IHC: LEKTI absence in granular layer and inner root sheaf \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">SPINK5</span> gene mutations<br>Autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peeling skin syndrome, type B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ichthyosiform erythroderma<br>Urticaria, angioedema<br>Pyodermatitis (<span class="elsevierStyleItalic">Staphylococcus aureus</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Allergic asthma, rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Postnatal growth retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>Eosinophilia<br>RAST: positive to food allergens<br>DPT: perivascular dermatitis, subcorneal acantholysis IHC: absence CDSN in epidermis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">CDSN</span> gene mutations<br>Autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe dermatitis, multiple allergies, metabolic wasting syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Congenital erythroderma, peeling<br>Palmoplantar keratoderma striata<br>Hypotrichosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pneumonia<br>Upper respiratory tract infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Postnatal growth retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eosinophilic esophagitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metabolic wasting<br>Gastroesophageal reflux<br>Minor cardiac defects \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>RAST: positive to food allergens<br>DPT: subcorneal and intragranular acantholysis, psoriasiform dermatitis, orthokeratosis/parakeratosis, hypogranulosis/hypergranulosis DIF: anomalous DSG1 cytoplasmic distribution \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">DSG1, DSP</span> gene mutations<br>Autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prolidase deficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Skin fragility, ulcers (legs, perianal)<br>Purpura, telangiectasias<br>Photosensitivity<br>Acute eczema<br>Typical facies<br>Poliosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent upper airway infection<br>Pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Joint hypermobility<br>Short stature<br>Osteoporosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Splenomegalia<br>Mental retardation<br>Less often: deafness, hepatomegalia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE/hypergammaglobulinemia<br>Microcytic anemia<br>Thrombocytopenia<br>Imidodipeptiduria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">PEPD</span> gene mutations<br>Autosomal recessive (very variable age and phenotype) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Loeys-Dietz syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marfanoid appearance, cleft palate<br>Fine skin, anomalous healing<br>Mild eczema/occasionally severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pneumonia<br>Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermobility<br>I: bone abnormalities (cranium, sternum, phalanges, etc.)<br>III: Osteoarthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Arterial aneurysms<br>Aortic dissection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal/elevated IgE<br>RAST: normal/positive to food and respiratory allergens \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGFBR1, TGFBR2, SMAD3</span> gene mutations<br>Autosomal dominant \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pentasomy X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Typical facies<br>Mild eczema/occasionally severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cranial malformations (microcephaly)<br>Syndactylia, other bone malformations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cardiovascular malformations<br>Gonadal dysfunction<br>Mental retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal/elevated IgE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pentasomy X (no maternal disjunction in meiosis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IPEX syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe atopic dermatitis<br>Uncommon: erythroderma, exfoliative dermatitis, psoriasiform dermatitis, pemphigoid nodularis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pneumonia uncommon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Enteropathy<br>Endocrine disorders: DM-1, thyroiditis, others<br>Hemolytic anemia<br>Thrombocytopenia<br>Neutropenia<br>Hepatitis<br>Tubular nephropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sometimes severe systemic infections due to immunosuppression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated IgE<br>Elevated/normal IgA<br>Eosinophilia<br>Cytopenias<br>Autoantibodies (pancreatic, thyroid, intestinal mucosa antigens, etc) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">FOXP3</span> gene mutations<br>X-linked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">STAT5B deficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe eczema<br>Pyodermatitis<br>Severe viral infection (VZV)<br>Craniofacial dysmorphia<br>Thin, fine hair \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Infectious pneumonia<br>Interstitial lymphocytic pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dwarfism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thyroid disease<br>Enteropathy<br>Interstitial lymphocytic pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GH insensitivity syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypergammaglobulinemia<br>Lymphopenia (TC)<br>Normal/elevated GH<br>Decreased IGF1, IGFBP3<br>Autoantibodies (thyroid, intestinal mucosa antigens, others) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">STAT5B</span> gene mutations<br>Autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1375502.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Differential Clinical and Laboratory Diagnosis of Genodermatoses That Present With Moderate-to-Severe Eczema and Elevated IgE.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tratamiento sistémico de la dermatitis atópica grave en la infancia. 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| año/Mes | Html | Total | |
|---|---|---|---|
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| 2023 Septiembre | 64 | 40 | 104 |
| 2023 Agosto | 53 | 20 | 73 |
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| 2022 Marzo | 70 | 53 | 123 |
| 2022 Febrero | 63 | 30 | 93 |
| 2022 Enero | 93 | 50 | 143 |
| 2021 Diciembre | 88 | 42 | 130 |
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| 2021 Octubre | 102 | 56 | 158 |
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| 2021 Agosto | 78 | 34 | 112 |
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| 2019 Noviembre | 4 | 0 | 4 |
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| 2019 Agosto | 7 | 0 | 7 |
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| 2019 Febrero | 1 | 0 | 1 |
| 2019 Enero | 4 | 0 | 4 |
| 2018 Diciembre | 3 | 0 | 3 |
| 2018 Noviembre | 4 | 0 | 4 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 5 | 0 | 5 |
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| 2018 Marzo | 1 | 9 | 10 |
| 2018 Febrero | 41 | 14 | 55 |
| 2018 Enero | 51 | 20 | 71 |
| 2017 Diciembre | 45 | 17 | 62 |
| 2017 Noviembre | 43 | 24 | 67 |
| 2017 Octubre | 47 | 16 | 63 |
| 2017 Septiembre | 30 | 17 | 47 |
| 2017 Agosto | 26 | 11 | 37 |
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| 2017 Enero | 25 | 26 | 51 |
| 2016 Diciembre | 42 | 26 | 68 |
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| 2016 Octubre | 48 | 39 | 87 |
| 2016 Septiembre | 0 | 9 | 9 |
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