nonsyndromic types of ichthyoses – an update

109 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1202 109

Nonsyndromic types of ichthyoses an update

SummaryIchthyoses are genetically determined Mendelian disorders of cornification (MEDOC) that are characterized by universal scaling. Today we distinguish between non-syndromic and syndromic forms. Ichthyosis vulgaris is the most frequent type (prevalence 1:100) and is caused by autosomal semi-dominant filaggrin mutations. It is associated with a higher risk for the development of atopic diseases, such as atopic eczema and allergic rhinitis. Recessive X-linked ichthyosis (RXLI) occurs almost exclu-sively in boys; in Germany it has a prevalence of around 1:4,000. It is caused by ste-roid sulfatase deficiency and is often associated with further clinical problems, such as cryptorchidism (~20 %) or social communication deficits, such as attention defi-cit hyperactivity syndrome (40 %) or autism (25 %). Autosomal recessive congenital ichthyosis (ARCI) is genetically very heterogeneous and 8 different genes have been identified so far. The most frequent cause of ARCI is a transglutaminase 1 deficiency (prevalence 1:200, 000). Mutations in keratin genes are the cause of the keratinopa-thic ichthyoses, such as epidermolytic ichthyosis. They manifest at birth and often feature episodes of blistering. Most of these types are inherited as autosomal do-minant traits, but autosomal recessive forms have also been described on occasion.

Introduction

Ichthyoses belong to the large and clinically and genetically heterogeneous group of Mendelian disorders of cornification (MEDOC) [1]. Ichthyoses are characteri-zed by universal scaling, which usually involves the entire skin surface. In the pa-tients first year of life, congenital ichthyosis in particular may be life-threatening; the disease is often accompanied by severe skin inflammation and problems such as hypothermia and dehydration as a result of transepidermal water loss. In palmoplantar keratosis or palmoplantar keratoderma, unlike ichthyosis, the cor-nification disorder is not widespread, but almost exclusively affects the hands and feet. The previous distinction commonly made between ichthyoses and erythro-keratodermia is no longer used; rather, erythrokeratodermia is now considered a type of ichthyosis.

An important result of the consensus conference on ichthyosis was that we now distinguish between syndromic and non-syndromic forms of the disease. This distinction was first proposed by Traupe in 1989. The former division between congenital onset and non-congenital manifestation has fallen out of favor. Certain diseases such as X-linked recessive ichthyosis appear at birth in some

Submitted: 5.8.2013Accepted: 29.8.2013Conflicts of interestNone.

CME ArticleDOI: 10.1111/ddg.12229

Heiko Traupe1, Judith Fischer2, Vinzenz Oji1

(1) Department of Dermatology, Univer-sity of Mnster, Germany(2) Institute for Human Genetics, Uni-versity Hospital of Freiburg, Freiburg im Breisgau, Germany

Section EditorProf. Dr. Jan C. Simon, Leipzig

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110 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1202

patients and after several months in others. Instead, we distinguish between com-mon and rare forms of ichthyosis. Common forms include ichthyosis vulgaris, with a prevalence of 1:100, as well as recessive X -linked ichthyosis. The latter has a prevalence of about 1:4,000. Based on European Union criteria, it is considered a rare disease. In non-syndromic ichthyosis, phenotypic expression of the underlying genetic defect is limited to the skin; in syndromic ichthyosis, the disorder is part of a larger syndrome as the genetic defect also affects other organs.

This review addresses only non-syndromic ichthyoses. It discusses recent fin-dings on the biology of the diseases as well as surprising insights into their clinical variability.

Pathophysiology

The development of hyperkeratosis and ichthyosis as a clinical disease is now un-derstood as a homeostatic repair response due to an abnormal epidermal barrier [1, 2]. Animal experiments in which the causal gene for ichthyosis is switched off have contributed to a better understanding of the disorder. The results of studies on mouse models, e.g., in regard to a transglutaminase deficiency, the lipoxy-genase (ALOX12B) mutation, or the mutation in ABCA12 underlying harlequin ichthyosis (or for severe, lamellar ichthyosis), have shown that in all models, the animals are born with a severe clinical barrier defect. Most die within hours of birth. In nearly all mouse models of ichthyosis, the disease is lethal. The reason is a serious barrier defect, which leads to problems such as massively increased transepidermal water loss, against which mice (unlike humans) cannot compensa-ted. Another difference between mouse models and human beings is that at birth mice do not have hyperkeratosis, but only inflammation of the skin and a deficient barrier. In humans, hyperkeratosis is believed to be part of a repair process. In the mouse models, hyperkeratosis has been observed in transplantation experiments. If a piece of skin is transplanted from a mouse with ichthyosis to an immuno-deficient mouse, the transplant develops hyperkeratosis, which corresponds to ichthyosis in humans [3].

Ichthyosis vulgaris

Epidemiology and cause

The most common type of ichthyosis is ichthyosis vulgaris. Data from Northern England have reported a prevalence of 1:100 [4]. The cause of disease is filaggrin mutations, which are inherited as an autosomal semi-dominant trait. About two-thirds of patients have two filaggrin mutations with relatively serious disease; one-third of those with the disease have only one filaggrin mutation and a milder course [5]. The null mutations in the filaggrin gene lead to a marked reduction of natural moisturizing factors (NMF), which play an important role in hydration of the stratum corneum. Physiological studies have shown that in people with two filaggrin mutations, skin moisture levels are moderately (up to one-third) lower, while at the same time there is a moderate increase in transepidermal water loss [5].

Histology and ultrastructure

Patients with ichthyosis vulgaris have orthohyperkeratosis with a diminished or absent granular layer. In terms of ultrastructure, the filaggrin deficiency

The development of ichthyosis is now believed to result from genetic defects

affecting the epidermal barrier along with a concomitant homeostatic repair

response.

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leads to a characteristic keratohyalin defect, with abnormally small and crum-bly granules.

Clinical presentation

The typical clinical presentation consists of a fine, usually light gray scale. The joint flexures are not involved, and scaling usually does not occur until two to six months after birth (Figure 1a). There is spontaneous improvement during the summer. Many patients say that they do not sweat normally [6]. The furrows on the hands are typically deeper (hyperlinearity) (Figure 1b).

Some 50 % of patients with ichthyosis vulgaris develop atopic dermatitis, and another 20 % develop other atopic manifestations such as allergic rhinitis and bronchial asthma.

Among patients with two filaggrin mutations, about 30 % do not have

atopy; one filaggrin mutation is sufficient for predisposing patients to

atopic eczema or allergic rhinitis.

Figure 1 Ichthyosis vulgaris: fine, light grey scaling (a), hyperlinearity of palms in Ichthyosis vulgaris (b).

Figure 2 Recessive X-linked ichthyosis: rhombic, but light gray, firmly adhering scaling with sparing of the flexures (a), typical finding with dark brown hyperkeratoses (b).

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Recessive X-linked ichthyosis


Recessive X-linked ichthyosis (XRI) nearly always manifests in boys. The preva-lence of disease is about 1:4,000. The disease is caused by mutations in the gene for steroid sulfatase (STS); in about 90 % of patients, there is a deletion affecting the STS gene. This deletion can extend to adjacent genes, which may lead to more complex disease associations such as XRI occurring in Kallmann syndrome, the recessive form of X-linked ichthyosis chondrodysplasia punctata, or the common cryptorchidism (ca. 20 %), with attention-deficit hyperactivity syndrome (ADHS) (40 %), or with autism (25 %) [7]. The high rate of ADHS may also be a direct result of steroid sulfatase deficiency.


Histology reveals orthohyperkeratosis and a well-maintained, sometimes thicker granular layer. Ultrastructurally, there are persistent corneodesmosomes (retention hyperkeratosis).

Clinical presentation

The clinical appearance consists of firmly attached, rhomboid scales covering the whole body. The elbows and the backs of the knees are usually spared. The palms of the hands and the soles of the feet are unaffected. About 70 % of patients have a light brown scale (Figure 2b), and in 30 % the scale is light gray (Figure 2a). Mothers of boys with the disease frequently report complications during birth, including weakness of labour or the need for a Cesarean section.

Autosomal recessive congenital ichthyosis (ARCI)

This term includes all non-syndromic autosomal recessive congenital forms of ichthyosis without a tendency toward blistering; it includes harlequin ichthyosis as well as lamellar ichthyosis and congenital ichthyosiform erythroderma [1]. This group of diseases is caused by diverse genetic defects (Table 1) [8]. There are genotype-phenotype relationships in terms of certain mutations, e.g., in the transglutaminase 1 gene, which may cause bathing suit ichthyosis, while other mutations in the same gene at another site may also be associated with inflammatory forms of ARCI (congenital ichthyosiform erythroderma). Cer-tain ABCA12 mutations as well may cause lamellar ichthyosis, while in CERS3 patients, both phenotypes have been described. The LIPN mutation causes a clinical appearance that is not yet present at birth; nevertheless, it is classified as ARCI by the group that first reported this entity.


Recent data show that the prevalence of ARCI in the German population is 1.7:100,000. The data on the prevalence of ARCI in Spain are similar (1.6 : 100,000) [9]. In regard to the transglutaminase 1 deficiency, the most common cause of ARCI, there is a prevalence of 1:200,000 in Germany.

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The histological appearance of ARCI varies. Given the variety of genetic defects, this is not surprising. Typical features include orthohyperkeratosis, a well-developed, thi-cker granular layer, and usually epidermal thickening as a sign of epidermal hyper-proliferation as well as lymphohistiocytic infiltrates in the dermis as an expression of the accompanying inflammation. Electron microscopy shows genetic defects which are correlated with the typical findings such as the presence of cholesterol clefts in the horny layer in transglutaminase 1 deficiency or balloon-like lamellar bodies in harlequin ichthyosis as a result of an ABCA12 nonsense mutation. Vesicular structu-res in the lamellar bodies are commonly found in mutations in the lipoxygenase ge-nes or in the NIPAL4 gene. In Germany, a transglutaminase 1 deficiency is found in about 30 % of all patients with ARCI; the second most common cause are mutations in the lipoxygenase genes ALOXE3 and ALOX12B, which are found in about 10 % of all patients [8]. NIPAL4 mutations and CYP4F22 mutations are also more com-mon, while mutations in the gene for ABCA12 or PNPLA1 or CERS3 are very rare.

Clinical picture

With the exception of harlequin ichthyosis, ARCI generally manifests at birth as collodion baby. Cyp4F22 patients are rarely born as collodion babies. In harlequin ichthyosis, the babies are born with armor-like skin (Figure 3a), which can considerab-ly impair movement and often limits the ability to breathe and eat or drink. Ectropion and eclabium are also major problems as is the tendency toward infection of the skin and other organs (e.g., lungs). Even today, about 50 % of babies born with harlequin ichthyosis die of the disease. In children who survive the critical phase of disease, the thickening of the stratum corneum resolves somewhat, and large, lamellar scales develop; symptoms are accompanied by marked skin inflammation (erythroderma) (Figure 3b).

The more common clinical presentation of ARCI at birth is collodion baby (Figure 4). The term describes a transient condition in newborns. At birth, child-ren born with the disease are encased in a shiny membrane, which cracks within a few days and then usually peels within the first four weeks of life. Afterward, there may be complete healing, which is temporary. In most instances, collodion

Table 1 Gene defects in autosomal recessive congenital ichthyosis (ARCI).

Clinical entities Genes Function

Harlequin ichthyosis ABCA12 Lipid transporter

Bathing suit ichthyosis (BSI)

TGM1 Formation of the cornified envelope

Congenital ichthyosiform erythroderma

ALOXE3ALOX12BCERS3

Epidermal lipoxygenase/hepoxilin metabolism Ceramide synthesis

Lamellar ichthyosis ALOXE3ALOX12BCYP4F22NIPAL4 (Ichthyin)PNPLA1TGM1LIPN

Hepoxilin metabolismEpidermal lipid barrier

Epidermal lipase

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baby is followed by the development of classic severe congenital ichthyosis. Clinical presentations include lamellar scaling with dark brown keratosis; this is usually accompanied by underlying inflammation (clinical appearance of lamellar ichthyo-sis) (Figure 5a, b). Other presentations include a fine, light gray scaling, often with accompanying inflammation (congenital ichthyosiform erythroderma). Typically, the large joint flexures are involved; many patients also have keratotic lichenifica-tion, i.e., keratotic coarsening of the skin relief. This is also seen in other types of ichthyosis such as Sjgren-Larsson syndrome.

Immediate management problems in harlequin ichthyosis and collodion baby at birth

The infants have a very abnormal epidermal barrier, which leads to transepidermal water loss and thus problems such as hypothermia and hypernatremic dehydration.

Figure 3 Harlequin ichthyosis: at birth (a), typical aspect at an older age (b).

Figure 4 Collodion baby with aspect of glistering membrane.

Newborns with harlequin ichthyosis or who are born as a collodion baby are considered a dermatological emer-

gency and should be transferred to a neonatal intensive care unit.

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They should thus be placed in an incubator with high humidity (7080 %) and their weight continually monitored in order to detect any water loss. Occasionally, infusions and the use of a gastric tube are needed. To treat ectropion, a special eye ointment (e.g., dexpanthenol-based Corneregel) is advisable. During the first year of life, topical treatment should consist of bland ointments.

In about 10 % of collodion babies, there is either long-term clinical healing or the disease transitions into very mild forms of ARCI. The previously used term self-healing collodion baby has been replaced by self-improving congenital ichthyosis (SICI). Ichthyosis types with self-healing or marked spontaneous impro-vement have been reported in patients with transglutaminase 1 deficiency and in those with ALOX12B and ALOXE3 mutations [10].

Another special clinical type is bathing suit ichthyosis (BSI). These are also collodion babies, but then there is long-term healing on the extremities (Figure 6). The cause of BSI are temperature-sensitive mutations in transglutaminase 1.

Figure 5 Transglutaminase 1-deficient ARCI: dark brown hyperkeratosis (a), typical aspect on back with lamellar scaling (b).

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Keratinopathic ichthyosis

The technical term keratinopathic was agreed on at a consensus conference as an umbrella term for all types of ichthyosis whose mutations are due to one of the keratin genes (Table 2). The cause is usually autosomal dominant inheritance, although autosomal recessive inheritance can occasionally occur.


In terms of histology, most types of keratinopathic ichthyosis exhibit epidermolytic hyperkeratosis. The ultrastructure is characterized by collapsed keratin aggregates (tonofilaments). These often aggregate around the cell nucleus; they have lost their connection to the desmosomes. The keratinocytes therefore no longer are connected

Figure 6 Bathing suit ichthyosis (BSI) in a 12-year-old boy, sparing of extremities.

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to each other which promotes an intraepidermal blistering. The clinical appearan-ce may thus include blistering. In mutations involving the keratin genes 1 and 10, the problem develops in the suprabasal layers of the epidermis (for example in the model disease of epidermolytic ichthyosis). In a mutation in the keratin 2 gene, with expression at the level of the granular layer, the corresponding findings are found at higher levels of the epidermis. Clinically, this leads to superficial epider-molytic ichthyosis.

Clinical presentation of epidermolytic ichthyosis (mutation KRT1 or KRT10)

At birth, the presentation usually consists of congenital ichthyosiform erythroder-ma, sometimes with marked blistering. In newborns, differential diagnosis often includes epidermolysis bullosa. In the first months of life, the blistering resolves and hyperkeratosis develops. Often, there is keratotic lichenification (Figure 7), and sometimes there are very prominent spiny scales, especially in regions where the body temperature is somewhat elevated, such as the flexures and axillae. In mutations in KRT1, the palms as well as the soles of the feet are often affected, which can significantly impair walking.

The treatment of patients with KRT1 mutations if often very difficult, and the use of systemic retinoids such as acitretin may worsen disease. Patients with a ke-ratin 10 mutation generally respond well to moderate dosages of systemic retinoids (0.5 mg/kg of body weight).

Superficial epidermolytic ichthyosis (keratin 2 mutation)

At birth, the clinical appearance resembles that of epidermolytic ichthyosis. Yet, over the course of disease, it is milder and more localized. That is, the keratosis is limited to the region around the navel, on the hands and feet (dorsal aspect), or the arm and axillary region, while there is healing on much of the upper body.

Congenital reticular ichthyosiform erythroderma (CRIE, ichthyosis with confetti)

At birth, the clinical appearance consists of severe congenital ichthyosiform ery-throderma, which also dominates the clinical appearance in the first years of life.

Table 2 Gene defects in keratinopathic ichthyoses.

Clinical entities Genes

Epidermolytic ichthyosis* KRT1KRT10

Annular epidermolytic ichthyosis KRT10

Superficial epidermolytic ichthyosis** KRT2

Congenital reticular ichthyosiform erythroderma KRT10

Ichthyosis hystrix of Curth-Macklin KRT1

*Formerly known as Brocq. **Formerly known as ichthyosis bullosa Siemens.

Figure 7 Superficial epidermolytic ichthyosis (keratin 10 mutation).

Patients with ARCI or keratinopathic ichthyosis often have significant

vitamin D deficiency.

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Patients also have keratotic lichenification. At the age of 310 years, multiple white islands form which can later grow to 2 cm in size. In terms of molecular genetics, there may be localized spontaneous healing (i.e., natural gene therapy) due to recombination processes. Many patients with CRIE are severely ill and fail to thrive. Often there are bone remodeling processes, for instance, affecting the ankle joints.

Treatment of non-syndromic ichthyosis

Generally speaking, only non-specific measures are available to alleviate symp-toms. Only for transglutaminase 1-deficient ichthyosis is there a causal topical en-zyme replacement therapy on the horizon. The goal of most treatment measures is to reduce scaling, for example by elevating the moisture level of the skin. Urea-ba-sed ointments (up to 10 %) and lactic acid-based ointments (also up to 10 %) as well as glycerin-based ointments are available. Substances such as macrogol 400 can decrease scaling; this may be incorporated into ointments in concen-trations of up to 20 %. In Germany, ointments with higher water content are preferred for the treatment of ichthyosis. In terms of galenical composition, these correspond to a cream. In other countries, such as Great Britain, petrolatum-like ointments are used. For patients with ichthyosis vulgaris and X-linked recessive ichthyosis, twice daily application of cream with a urea-based or glycerin-ba-sed ointment (e.g., Dexeryl) is sufficient. Patients with ARCI or keratinopathic ichthyosis generally also need to bathe at least once a day. After soaking the skin, the patient or the parents of the patient can use a sponge or microfiber cloth to rub the skin and thus promote desquamation as well as remove any remaining ointment. Afterward, the ointment may be carefully applied. For problem areas, vitamin A acid ointments may also be used, for instance on the knees and el-bow joints. Patients with marked inflammation (e.g., congenital ichthyosiform erythroderma) often cannot tolerate ointments containing urea or lactic acid. Other substances, such as glycerin, dexpanthenol, or macrogol should be used. Systemic retinoids, such as acitretin, are frequently administered to patients over age 16 (who have stopped growing). In women, the possibility of birth defects should be recalled. In patients with harlequin ichthyosis, the use of retinoids is warranted, even in newborns. In Germany, there is a reluctance to use long-term retinoid therapy in children, while in Great Britain there is much less concern with doing so.

Self-help and information for patients and doctors

Membership in a patient organization can be very helpful for patients and their families. One such organization in Germany is Selbsthilfe Ichthyosis e.V. (http://www.ichthyose.de). This gives patients the chance to discuss everyday problems (e.g., scalp care) with others as well as the chance to benefit from their experience. This patient organization is also active on a European level (European Network of Ichthyoses) and is also represented in other umbrella organizations such as Alliance for Chronic Diseases (Allianz fr chronische seltene Erkrankungen, ACHSE) and the Federal Working Group on Self-Help (Bundesarbeitsgemein-schaft Selbsthilfe, BAG). Another resource for general information on the disease is the German Network for Ichthyoses (NIRK [www.netzwerk-ichthyose.de]). In regard to molecular diagnosis, a helpful Website has been set up by the Institute of Human Genetics at the University of Freiburg (http://www.uniklinik-freiburg.de/humangenetik/).

Long daily baths and mechanical keratolysis are essential for patients

with severe ichthyosis.

Patients should be encouraged to contact and join a self-help

organization.

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References1 Oji V, Tadini G, Akiyama M et al. Revised nomenclature and classification of inherited

ichthyoses: results of the First Ichthyosis Consensus Conference in Sorze 2009. J Am Acad Dermatol 2010; 63: 60741.

2 Elias PM, Williams ML, Crumrine D, Schmuth M. Ichthyoses: Clinical, biochemical, pathogenic and diagnostic assessment. Karger, Basel, 2010.

3 Kuramoto N, Takizawa T, Takizawa T et al. Development of ichthyosiform skin com-pensates for defective permeability barrier function in mice lacking transglutaminase 1. J Clin Invest 2002; 109: 24350.

4 Brown SJ, Relton CL, Liao H et al. Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: further delineation of the skin phe-notype in a prospective epidemiological study of 792 school children. Br J Dermatol 2009; 61: 8849.

5 Perusqua-Ortiz AM, Oji V, Sauerland MC et al. Complete filaggrin deficiency in ich-thyosis vulgaris is associated with only moderate changes in epidermal permeability barrier function profile. J Eur Acad Dermatol Venereol 2013; doi: 10.1111/jdv.12079. [Epub ahead of print].

6 Oji V, Seller N, Sandilands A et al. Ichthyosis vulgaris: novel FLG mutations in the German population and high presence of CD1a+ cells in the epidermis of the atopic subgroup. Br J Dermatol 2009; 160: 77181.

7 Kent L, Emerton J, Bhadravathi V et al. X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits. J Med Genet 2008; 45: 51924.

8 Fischer J. Autosomal recessive congenital ichthyosis. J Invest Dermatol 2009; 129: 131921.

9 Hernndez-Martn A, Garcia-Doval I, Aranegui B et al. Prevalence of autosomal reces-sive congenital ichthyosis: a population-based study using the capture-recapture method in Spain. J Am Acad Dermatol 2012; 67: 2404.

10 Vahlquist A, Bygum A, Gnemo A et al. Genotypic and clinical spectrum of self-im-proving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients. J Invest Dermatol 2010; 130: 43843.

Correspondence to

Prof. Dr. med. Heiko TraupeHautklinikUniversitt Mnster

Von-Esmarch-Strae 5848149 Mnster, Germany

E-mail: [email protected]

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Fragen zur Zertifizierung durch die DDA

1. Welche Aussage zur Pathophysio-

logie der kongenitalen Ichthyose ist

zutreffend?a) Die Strung bei Ichthyosis vulgaris

befindet sich im Stratum spinosum.b) Die Ichthyose spiegelt im weitesten

Sinne die Reaktion des Krpers auf einen epidermalen Barrieredefekt wider.

c) Mit Ichthyosis assoziierte Gendefekte zeigen an der Haut ein sehr spezifisches klinisches Bild.

d) Die Verdickung der Hornhaut zeigt, dass bei Ichthyose eine gute epider-male Barrierefunktion besteht.

e) Die hufigste Ursache der lamellren Ichthyose ist in den Keratin-Genen zu suchen.

2. Ein ansonsten gesundes

mnnliches Neugeborenes zeigte nach

einer Woche eine generalisierte weie

Hautschuppung. Welche Aussage

trifft zu?a) Das Vorliegen einer seltenen konge-

nitalen Ichthyose ist ausgeschlossen.b) Zur Behandlung des Neugeborenen

eignen sich Cremes ab 5 % Harnstoff.

c) Das Vorliegen einer X-chromosomal rezessiven Ichthyose ist mglich.

d) Hufiges Baden des Kindes sollte vermieden werden.

e) Ichthyosis vulgaris manifestiert sich meistens bereits bei Geburt.

3. Die bislang als bullse Ichthyose

bezeichneten Formen der Ichthyose

werden nach der neuen Nomenklatur

als keratinopathische Ichthyose (KPI)

bezeichnet. Welche Aussage zu den

KPI trifft zu?a) Bei epidermolytischer Ichthyose (EI)

zeigt sich eine epidermolytische Hyperkeratose entsprechend der Expression von Keratin-1 oder -10 im Stratum basale.

b) Epidermolytische Ichthyose auf-grund von Keratin-1-Mutationen ist mit Palmoplantarkeratose assoziiert.

c) Alle Formen der KPI zeigen eine epidermolytische Hyperkeratose.

d) Die Ichthyose Curth-Macklin ist durch Keratin-9-Mutationen verursacht.

e) Alle KPI werden als autosomal dominante Erkrankungen vererbt.

4. Die Gruppe der autosomal rezes-

siven kongenitalen Ichthyosen (ARCI)

ist klinisch und genetisch heterogen.

Welche Erkrankung gehrt in diesem

Sinne nicht zu den autosomal rezessi-ven kongenitalen Ichthyosen (ARCI)?a) Harlekin-Ichthyoseb) selbstheilendes Kolliumbabyc) lamellre Ichthyosed) kongenitale ichthyosiforme

Erythrodermiee) Netherton-Syndrom

5. Die Diagnose der Ichthyosen

basiert neben der molekularen

Diagnostik auf Klinik und Morphologie.

Welche Aussage zur Diagnostik trifft

nicht zu?a) Die Ichthyosis vulgaris lsst sich

sehr gut elektronenmikroskopisch besttigen.

b) Zur molekularen Diagnostik eignet sich eine EDTA-Blutprobe der/des Betroffenen.

c) Bei vielen kongenitalen Ichthyosen eignen sich ultrastrukturelle Marker zur diagnostischen Eingrenzung.

d) Eine epidermolytische Hyperkera-tose lsst sich nur in der elektro-nenmikroskopischen Untersuchung erkennen.

e) Der Transglutaminase-1-Mangel lsst sich durch Enzymmessung einer Hautprobe bestimmen.

6. Die lamellre Ichthyose (LI) und

kongenitale ichthyosiforme Erythro-

dermie (CIE) werden als ein Krank-

heitsspektrum aufgefasst. Welche

Aussage hierzu trifft nicht zu?a) Die Erkrankungen knnen durch be-

stimmte Mutationen im ABCA12-Gen

verursacht sein, welches ansonsten aber auch mit der Harlekin- Ichthyose assoziiert ist.

b) Im Hautbefund zeigt die lamellre Ichthyose eine dunklere und grobe Schuppung.

c) Die verminderte Fhigkeit zu schwitzen ist klinisch von geringer Relevanz.

d) Fr die Behandlung eignen sich re-gelmige Bder mit Backpulver als Badezusatz (12 Hnde pro Badewanne).

e) Im Spektrum des Transglutamina-se-1Mangels ergeben sich sehr unterschiedliche Krankheitsverlufe.

7. Eine Mutter stellt erstmalig ihren

4-jhrigen Sohn mit einer hellgrauen

mittel-lamellren Ichthyose vor, die im

Sommer nahezu abheilt. Auf Nachfra-

ge gibt sie an, dass ihr Vater ebenfalls

eine Ichthyose gehabt htte. Der Junge

zeigt unauffllige Handinnenflchen.

Welche Aussage ist nicht zutreffend?a) Es knnte ein X-chromosomal

rezessiver Erbgang vorliegen.b) Das Vorliegen eines Netherton-

Syndroms ist denkbar.c) Das Vorliegen einer ausgeprgten

Ichthyosis vulgaris ist unwahrscheinlich.

d) Die Diagnose lsst sich mittels Steroidsulfatase-Messung verifizieren.

e) Weitere Symptome wie ein ADHS knnten vorliegen.

8. Bei der Ichthyosis vulgaris (IV)

handelt es sich um die hufigste Form

der Ichthyosen. Welche Aussage trifft

nicht zu?a) Zirka 5060 % der Betroffenen

leiden gleichzeitig an einer Erkrankung aus dem atopischen Formenkreis.

b) Die Erkrankung ist mit einer Reduktion des natural moisturizing factor assoziiert.

c) Ausgesparte Ellen- und Kniebeugen erlauben die Abgrenzung zur X-chro-mosomal rezessiven Ichthyose.

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Liebe Leserinnen und Leser,

der Einsendeschluss an die DDA fr diese Ausgabe ist der 19. Februar 2014. Die richtige Lsung zum Thema Andrologische Basisdiagnostik in Heft 9 (September 2013) ist: 1c, 2c, 3b, 4e, 5d, 6a, 7e, 8b, 9d, 10c.

Bitte verwenden Sie fr Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lsung online unter http://jddg.akademie-dda.de ein.

d) Charakteristisch ist die palmoplantare Hyperlinearitt.

e) Die Vererbung erfolgt semidominant.

9. Ein Neugeborenes zeigte bei sta-

bilen Vitalparametern eine ausgeprg-

te Erythrodermie, dann entwickelt

es pergamentpapierartige Haut mit

mildem Ektropium und Eklabium. Wie

schtzen Sie den Befund ein?a) Zu befrchten ist, dass es sich

bei der Erkrankung um eine Harlekin-Ichthyose handelt.

b) Der Temperatur- und Flssigkeits-haushalt sollte engmaschig kontrol-liert werden.

c) Das Kind zeigt das typische Bild einer lamellren Ichthyose.

d) Das Kind wird zeitlebens an einer schweren Verhornungsstrung leiden.

e) Auf eine Hautprobe kann verzichtet werden, da das Ergebnis keine Relevanz hat.

10. Eltern einer 6-jhrigen Tochter mit

lamellrer Ichthyose erkundigen sich

vor der Einschulung beim Arzt. Welcher

Hinweis ist am wenigsten hilfreich?a) Teilnahme am Schulsport kann

Probleme bereiten.b) Ichthyose, da kann man nicht viel

machen!c) Vorsicht wegen verminderter

Schwitzfhigkeit und Gefahr der Hyperthermie (Meidung des Fens-terplatzes im Sommer, klimatisierter Raum wre sinnvoll)!

d) Ntzlich ist der Kontakt zur Ichthyosis-Selbsthilfe-Organisation.

e) Der Vitamin-D-Spiegel sollte kontrolliert werden.

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nonsyndromic types of ichthyoses – an update

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